Interannual and Spatial Variability in Maturity of Walleye Pollock Gadus chalcogrammus and Implications for Spawning Stock Biomass Estimates in the Gulf of Alaska

PubMed Central

Kruse, Gordon H.; Dorn, Martin W.

2016-01-01

Catch quotas for walleye pollock Gadus chalcogrammus, the dominant species in the groundfish fishery off Alaska, are set by applying harvest control rules to annual estimates of spawning stock biomass (SSB) from age-structured stock assessments. Adult walleye pollock abundance and maturity status have been monitored in early spring in Shelikof Strait in the Gulf of Alaska for almost three decades. The sampling strategy for maturity status is largely characterized as targeted, albeit opportunistic, sampling of trawl tows made during hydroacoustic surveys. Trawl sampling during pre-spawning biomass surveys, which do not adequately account for spatial patterns in the distribution of immature and mature fish, can bias estimated maturity ogives from which SSB is calculated. Utilizing these maturity data, we developed mixed-effects generalized additive models to examine spatial and temporal patterns in walleye pollock maturity and the influence of these patterns on estimates of SSB. Current stock assessment practice is to estimate SSB as the product of annual estimates of numbers at age, weight at age, and mean maturity at age for 1983-present. In practice, we found this strategy to be conservative for a time period from 2003–2013 as, on average, it underestimates SSB by a 4.7 to 11.9% difference when compared to our estimates of SSB that account for spatial structure or both temporal and spatial structure. Inclusion of spatially explicit information for walleye pollock maturity has implications for understanding stock reproductive biology and thus the setting of sustainable harvest rates used to manage this valuable fishery. PMID:27736982

Development of immature stomata: evidence for epigenetic selection of a spacing pattern.

PubMed

Kagan, M L; Sachs, T

1991-07-01

In Sansevieria trifasciata as many as half the potential stomata remain immature. The development of all stomatal structures started at the same time and the early stages of the development of immature stomata had no special characteristics. Statistical analysis showed that the mature stomata were more evenly spaced than all potential stomata, both mature and immature. Furthermore, the distribution of mature stomata per unit area was more predictable or orderly than comparable structures of a random model that developed in the same way. These facts indicate that a nonrandom loss of many stomata by "immaturity" is a major determinant, acting during rather than preceding development, of the distribution of the mature, functional stomata. Thus in Sansevieria there is a selection of an epidermal pattern from an excess of cells that undergo the early stages of stomatal development.

Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus

PubMed Central

Mangala Prasad, Vidya

2017-01-01

Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway. PMID:28575072

Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.

PubMed

Mangala Prasad, Vidya; Klose, Thomas; Rossmann, Michael G

2017-06-01

Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.

Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: structure of the empty capsid assembly intermediate at 2.9 A resolution.

PubMed Central

Basavappa, R.; Syed, R.; Flore, O.; Icenogle, J. P.; Filman, D. J.; Hogle, J. M.

1994-01-01

The crystal structure of the P1/Mahoney poliovirus empty capsid has been determined at 2.9 A resolution. The empty capsids differ from mature virions in that they lack the viral RNA and have yet to undergo a stabilizing maturation cleavage of VP0 to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein shell are very similar to those of the mature virion. The major differences between the 2 structures are focused in a network formed by the N-terminal extensions of the capsid proteins on the inner surface of the shell. In the empty capsids, the entire N-terminal extension of VP1, as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are present in the mature virion are missing. In the empty capsid, the VP0 scissile bond is located some 20 A away from the positions in the mature virion of the termini generated by VP0 cleavage. The scissile bond is located on the rim of a trefoil-shaped depression in the inner surface of the shell that is highly reminiscent of an RNA binding site in bean pod mottle virus. The structure suggests plausible (and ultimately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VP0, and for the role of the cleavage in establishing the ordered N-terminal network and in generating stable virions. PMID:7849583

Prediction of brain maturity based on cortical thickness at different spatial resolutions.

PubMed

Khundrakpam, Budhachandra S; Tohka, Jussi; Evans, Alan C

2015-05-01

Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders can be assessed. In this study, cortical thickness derived from structural magnetic resonance imaging (MRI) scans of a large longitudinal dataset of normally growing children and adolescents (n=308), were used to build a highly accurate predictive model for estimating chronological age (cross-validated correlation up to R=0.84). Unlike previous studies which used kernelized approach in building prediction models, we used an elastic net penalized linear regression model capable of producing a spatially sparse, yet accurate predictive model of chronological age. Upon investigating different scales of cortical parcellation from 78 to 10,240 brain parcels, we observed that the accuracy in estimated age improved with increased spatial scale of brain parcellation, with the best estimations obtained for spatial resolutions consisting of 2560 and 10,240 brain parcels. The top predictors of brain maturity were found in highly localized sensorimotor and association areas. The results of our study demonstrate that cortical thickness can be used to estimate individuals' brain maturity with high accuracy, and the estimated ages relate to functional and behavioural measures, underscoring the relevance and scope of the study in the understanding of biological maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

Predicting Suicidal Ideation in Adolescent Boys and Girls: The Role of Psychological Maturity, Personality Traits, Depression and Life Satisfaction.

PubMed

Morales-Vives, Fabia; Dueñas, Jorge Manuel

2018-04-10

In recent years, suicide rates have increased in adolescents and the young population, so these age groups are considered as populations at risk. Considering that suicidal ideation is the first sign of possible future suicide behavior, the objective of this study is to determine the relative importance of psychological maturity, personality, depression and life satisfaction in predicting suicidal ideation in adolescents. Results show that depressive symptoms is the variable that best predicts suicidal ideation, but psychological maturity, life satisfaction and emotional stability are predictors as well (R2 = .51, p < .001). However, the Multigroup Structural Equation Models analyses carried out show that emotional stability has an indirect relationship with suicidal ideation, through its relationship with depressive symptoms, life satisfaction and identity. Two Multigroup Structural Equation Models were proposed to better understand the relationships between these variables for each sex. The results show that the fit of the model that includes the variable Self-reliance is better for boys than for girls (chi-square contributions of 8.175 for girls and 1.978 for boys) unlike the other model (chi-square contributions of 0.288 for girls and 1.650 for boys). These results suggest that the psychological maturity subscale Self-reliance play a role in suicidal ideation in males but not in females. Although there have been no previous studies on the role of psychological maturity as a predictor of suicidal phenomena, the current study suggests that it is a feature to be considered in the prediction of adolescent suicidal ideation.

Characterizing stand-level forest canopy cover and height using Landsat time series, samples of airborne LiDAR, and the Random Forest algorithm

NASA Astrophysics Data System (ADS)

Ahmed, Oumer S.; Franklin, Steven E.; Wulder, Michael A.; White, Joanne C.

2015-03-01

Many forest management activities, including the development of forest inventories, require spatially detailed forest canopy cover and height data. Among the various remote sensing technologies, LiDAR (Light Detection and Ranging) offers the most accurate and consistent means for obtaining reliable canopy structure measurements. A potential solution to reduce the cost of LiDAR data, is to integrate transects (samples) of LiDAR data with frequently acquired and spatially comprehensive optical remotely sensed data. Although multiple regression is commonly used for such modeling, often it does not fully capture the complex relationships between forest structure variables. This study investigates the potential of Random Forest (RF), a machine learning technique, to estimate LiDAR measured canopy structure using a time series of Landsat imagery. The study is implemented over a 2600 ha area of industrially managed coastal temperate forests on Vancouver Island, British Columbia, Canada. We implemented a trajectory-based approach to time series analysis that generates time since disturbance (TSD) and disturbance intensity information for each pixel and we used this information to stratify the forest land base into two strata: mature forests and young forests. Canopy cover and height for three forest classes (i.e. mature, young and mature and young (combined)) were modeled separately using multiple regression and Random Forest (RF) techniques. For all forest classes, the RF models provided improved estimates relative to the multiple regression models. The lowest validation error was obtained for the mature forest strata in a RF model (R2 = 0.88, RMSE = 2.39 m and bias = -0.16 for canopy height; R2 = 0.72, RMSE = 0.068% and bias = -0.0049 for canopy cover). This study demonstrates the value of using disturbance and successional history to inform estimates of canopy structure and obtain improved estimates of forest canopy cover and height using the RF algorithm.

Changes in the stability and biomechanics of P22 bacteriophage capsid during maturation.

PubMed

Kant, Ravi; Llauró, Aida; Rayaprolu, Vamseedhar; Qazi, Shefah; de Pablo, Pedro J; Douglas, Trevor; Bothner, Brian

2018-03-15

The capsid of P22 bacteriophage undergoes a series of structural transitions during maturation that guide it from spherical to icosahedral morphology. The transitions include the release of scaffold proteins and capsid expansion. Although P22 maturation has been investigated for decades, a unified model that incorporates thermodynamic and biophysical analyses is not available. A general and specific model of icosahedral capsid maturation is of significant interest to theoreticians searching for fundamental principles as well as virologists and material scientists seeking to alter maturation to their advantage. To address this challenge, we have combined the results from orthogonal biophysical techniques including differential scanning fluorimetry, atomic force microscopy, circular dichroism, and hydrogen-deuterium exchange mass spectrometry. By integrating these results from single particle and population measurements, an energy landscape of P22 maturation from procapsid through expanded shell to wiffle ball emerged, highlighting the role of metastable structures and the thermodynamics guiding maturation. The propagation of weak quaternary interactions across symmetric elements of the capsid is a key component for stability in P22. A surprising finding is that the progression to wiffle ball, which lacks pentamers, shows that chemical and thermal stability can be uncoupled from mechanical rigidity, elegantly demonstrating the complexity inherent in capsid protein interactions and the emergent properties that can arise from icosahedral symmetry. On a broader scale, this work demonstrates the power of applying orthogonal biophysical techniques to elucidate assembly mechanisms for supramolecular complexes and provides a framework within which other viral systems can be compared. Copyright © 2018 Elsevier B.V. All rights reserved.

Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

PubMed Central

Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

2017-01-01

Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

PubMed

Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

2017-05-09

Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

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

Carneiro, Karina M. M.; Zhai, Halei; Zhu, Li

We report that enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-likemore » structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. Lastly, we propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.« less

Dynamic complexities in a pest control model with birth pulse and harvesting

NASA Astrophysics Data System (ADS)

Goel, A.; Gakkhar, S.

2016-04-01

In this paper, an impulsive model is discussed for an integrated pest management approach comprising of chemical and mechanical controls. The pesticides and harvesting are used to control the stage-structured pest population. The mature pest give birth to immature pest in pulses at regular intervals. The pest is controlled by spraying chemical pesticides affecting immature as well as mature pest. The harvesting of both immature and mature pest further reduce the pest population. The discrete dynamical system obtained from stroboscopic map is analyzed. The threshold conditions for stability of pest-free state as well as non-trivial period-1 solution is obtained. The effect of pesticide spray timing and harvesting on immature as well as mature pest are shown. Finally, by numerical simulation with MATLAB, the dynamical behaviors of the model is found to be complex. Above the threshold level there is a characteristic sequence of bifurcations leading to chaotic dynamics. Route to chaos is found to be period-doubling. Period halving bifurcations are also observed.

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy.

PubMed

Cho, Gun-Sik; Lee, Dong I; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Chen, Huei-Sheng Vincent; Chen, Xiongwen; Basso, Cristina; Houser, Steven R; Tomaselli, Gordon F; O'Rourke, Brian; Judge, Daniel P; Kass, David A; Kwon, Chulan

2017-01-10

Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

PubMed Central

Cho, Gun-Sik; Lee, Dong I.; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Vincent Chen, Huei-Sheng; Chen, Xiongwen; Basso, Cristina; Houser, Steven R.; Tomaselli, Gordon F.; O’Rourke, Brian; Judge, Daniel P.; Kass, David A.; Kwon, Chulan

2016-01-01

SUMMARY Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of the transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which predominantly manifests in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. PMID:28076798

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

PubMed

Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

2017-02-01

Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study. Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as being a promising source of cells for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. In the current study, we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials and demonstrated that supplementation of mesenchymal niche cells as well as provision of mechanical loading particularly stretching have significantly promoted the maturation of the cardiomyocytes and hence improved the mechanical functional characteristics of the tissue strips. Specifically, with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and spreading of cells, and upregulation of molecular signature in both gene and protein expression of maturation. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of molecular signature markers and functional parameters including twitch force, elastic modulus and sarcomere length, when comparing with static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture, resulting in more mature cardiac strips. Our results contribute to bioengineering of functional heart tissue strips for drug screening and disease modeling. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation: piece by piece.

PubMed

Lundy, David J; Lee, Desy S; Hsieh, Patrick C H

2017-03-01

There is a growing need for in vitro models which can serve as platforms for drug screening and basic research. Human adult cardiomyocytes cannot be readily obtained or cultured, and so pluripotent stem cell-derived cardiomyocytes appear to be an attractive option. Unfortunately, these cells are structurally and functionally immature-more comparable to foetal cardiomyocytes than adult. A recent study by Ruan et al ., provides new insights into accelerating the maturation process and takes us a step closer to solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation.

[Evaluating the maturity of IT-supported clinical imaging and diagnosis using the Digital Imaging Adoption Model : Are your clinical imaging processes ready for the digital era?

PubMed

Studzinski, J

2017-06-01

The Digital Imaging Adoption Model (DIAM) has been jointly developed by HIMSS Analytics and the European Society of Radiology (ESR). It helps evaluate the maturity of IT-supported processes in medical imaging, particularly in radiology. This eight-stage maturity model drives your organisational, strategic and tactical alignment towards imaging-IT planning. The key audience for the model comprises hospitals with imaging centers, as well as external imaging centers that collaborate with hospitals. The assessment focuses on different dimensions relevant to digital imaging, such as software infrastructure and usage, workflow security, clinical documentation and decision support, data exchange and analytical capabilities. With its standardised approach, it enables regional, national and international benchmarking. All DIAM participants receive a structured report that can be used as a basis for presenting, e.g. budget planning and investment decisions at management level.

Debt-maturity structures should match risk preferences.

PubMed

Gapenski, L C

1999-12-01

Key to any debt-maturity matching strategy is financing assets with the appropriate debt structure. Financial managers need to establish an optimal capital structure and then choose the best maturity-matching structure for their debt. Two maturity-matching strategies that are available to healthcare financial managers are the accounting approach and the finance approach. The accounting approach, which defines asset maturities as current or fixed, is a riskier financing strategy than the finance approach, which defines asset maturities as permanent or temporary. The added risk occurs because of the accounting approach's heavy reliance on short-term debt. The accounting approach offers the potential for lower costs at the expense of higher risk. Healthcare financial managers who believe the financing function should support the organization's operations without adding undue risk should use the finance approach to maturity matching. Asset maturities in those organizations then should be considered permanent or temporary rather than current or fixed, and the debt-maturity structure should reflect this.

[Maturity Levels of Quality and Risk Management at the University Hospital Schleswig-Holstein].

PubMed

Jussli-Melchers, Jill; Hilbert, Carsten; Jahnke, Iris; Wehkamp, Kai; Rogge, Annette; Freitag-Wolf, Sandra; Kahla-Witzsch, Heike A; Scholz, Jens; Petzina, Rainer

2018-05-16

Quality and risk management in hospitals are not only required by law but also for an optimal patient-centered and process-optimized patient care. To evaluate the maturity levels of quality and risk management at the University Hospital Schleswig-Holstein (UKSH), a structured analytical tool was developed for easy and efficient application. Four criteria concerning quality management - quality assurance (QS), critical incident reporting system (CIRS), complaint management (BM) and process management (PM) - were evaluated with a structured questionnaire. Self-assessment and external assessment were performed to classify the maturity levels at the UKSH (location Kiel and Lübeck). Every quality item was graded into four categories from "A" (fully implemented) to "D" (not implemented at all). First of all, an external assessment was initiated by the head of the department of quality and risk management. Thereafter, a self-assessment was performed by 46 clinical units of the UKSH. Discrepancies were resolved in a collegial dialogue. Based on these data, overall maturity levels were obtained for every clinical unit. The overall maturity level "A" was reached by three out of 46 (6.5%) clinical units. No unit was graded with maturity level "D". 50% out of all units reached level "B" and 43.5% level "C". The distribution of the four different quality criteria revealed a good implementation of complaint management (maturity levels "A" and "B" in 78.3%), whereas the levels for CIRS were "C" and "D" in 73.9%. Quality assurance and process management showed quite similar distributions for the levels of maturity "B" and "C" (87% QS; 91% PM). The structured analytical tool revealed maturity levels of 46 clinical units of the UKSH and defined the maturity levels of four relevant quality criteria (QS, CIRS, BM, PM). As a consequence, extensive procedures were implemented to raise the standard of quality and risk management. In future, maturity levels will be reevaluated every two years. This qualitative maturity level model enables in a simple and efficient way precise statements concerning presence, manifestation and development of quality and risk management. © Georg Thieme Verlag KG Stuttgart · New York.

Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes.

PubMed

Yang, Xiulan; Pabon, Lil; Murry, Charles E

2014-01-31

The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.

Maturation delay for the predators can enhance stable coexistence for a class of prey-predator models.

PubMed

Banerjee, Malay; Takeuchi, Yasuhiro

2017-01-07

Maturation time delay for the predators is introduced in prey-predator models to implicitly model the stage-structure of predators. Most of the prey-predator models with maturation delay are known to exhibit destabilization of coexistence steady-state. Discrete time delay induced destabilization is a common finding, however, this is due to the introduction of time delay with lack of ecological justification. The main objective of the present work is to show the stabilizing role of maturation delay for a class of delayed prey-predator model. To be specific, we consider prey-predator models with strong and weak Allee effects in prey growth and Michaelis-Menten type functional response. We provide ecological justification for the introduction of maturation delay parameter in predator's growth equation. We obtain the conditions for stable and oscillatory coexistence of prey and their specialist predator in case of strong as well as weak Allee effect for non-delayed and delayed models. Apart from the analytical results for the models under consideration, we perform extensive numerical simulations to construct the relevant bifurcation diagrams. Our analytical and supportive numerical findings reveal that delay is not always a destabilizing factor rather the stable coexistence in the presence of time delay depends upon the formulation of the delayed model. The biological implications of the current investigation are provided in the conclusion section. We also explain the validity of obtained results for other types of prey-predator models with a specialist predator. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-scale modeling of the CD8 immune response

NASA Astrophysics Data System (ADS)

Barbarroux, Loic; Michel, Philippe; Adimy, Mostafa; Crauste, Fabien

2016-06-01

During the primary CD8 T-Cell immune response to an intracellular pathogen, CD8 T-Cells undergo exponential proliferation and continuous differentiation, acquiring cytotoxic capabilities to address the infection and memorize the corresponding antigen. After cleaning the organism, the only CD8 T-Cells left are antigen-specific memory cells whose role is to respond stronger and faster in case they are presented this very same antigen again. That is how vaccines work: a small quantity of a weakened pathogen is introduced in the organism to trigger the primary response, generating corresponding memory cells in the process, giving the organism a way to defend himself in case it encounters the same pathogen again. To investigate this process, we propose a non linear, multi-scale mathematical model of the CD8 T-Cells immune response due to vaccination using a maturity structured partial differential equation. At the intracellular scale, the level of expression of key proteins is modeled by a delay differential equation system, which gives the speeds of maturation for each cell. The population of cells is modeled by a maturity structured equation whose speeds are given by the intracellular model. We focus here on building the model, as well as its asymptotic study. Finally, we display numerical simulations showing the model can reproduce the biological dynamics of the cell population for both the primary response and the secondary responses.

Multi-scale modeling of the CD8 immune response

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

Barbarroux, Loic, E-mail: loic.barbarroux@doctorant.ec-lyon.fr; Ecole Centrale de Lyon, 36 avenue Guy de Collongue, 69134 Ecully; Michel, Philippe, E-mail: philippe.michel@ec-lyon.fr

During the primary CD8 T-Cell immune response to an intracellular pathogen, CD8 T-Cells undergo exponential proliferation and continuous differentiation, acquiring cytotoxic capabilities to address the infection and memorize the corresponding antigen. After cleaning the organism, the only CD8 T-Cells left are antigen-specific memory cells whose role is to respond stronger and faster in case they are presented this very same antigen again. That is how vaccines work: a small quantity of a weakened pathogen is introduced in the organism to trigger the primary response, generating corresponding memory cells in the process, giving the organism a way to defend himself inmore » case it encounters the same pathogen again. To investigate this process, we propose a non linear, multi-scale mathematical model of the CD8 T-Cells immune response due to vaccination using a maturity structured partial differential equation. At the intracellular scale, the level of expression of key proteins is modeled by a delay differential equation system, which gives the speeds of maturation for each cell. The population of cells is modeled by a maturity structured equation whose speeds are given by the intracellular model. We focus here on building the model, as well as its asymptotic study. Finally, we display numerical simulations showing the model can reproduce the biological dynamics of the cell population for both the primary response and the secondary responses.« less

Breaking the solid ground of common sense: undoing "structure" with Michael Balint.

PubMed

Bonomi, Carlo

2003-09-01

Balint's great merit was to question what, in the classical perspective, was assumed as a prerequisite for analysis and thus located beyond analysis: the maturity of the ego. A fundamental premise of his work was Ferenczi's distrust for the structural model, which praised the maturity of the ego and its verbal, social, and adaptive abilities. Ferenczi's view of ego maturation as a trauma derivative was strikingly different from the theories of all other psychoanalytic schools and seems to be responsible for Balint's understanding of regression as a sort of inverted process that enables the undoing of the sheltering structures of the mature mind. Balint's understanding of the relation between mature ego and regression diverged not only from the ego psychologists, who emphasized the idea of therapeutic alliance, but also from most of the authors who embraced the object-relational view, like Klein (who considered regression a manifestation of the patient's craving for oral gratification), Fairbairn (who gave up the notion of regression), and Guntrip (who viewed regression as a schizoid phenomenon related to the ego weakness). According to Balint, the clinical appearance of a regression would "depend also on the way the regression is recognized, is accepted, and is responded to by the analyst." In this respect, his position was close to Winnicott's reformulation of the therapeutic action. Yet, the work of Balint reflects the persuasion that the progressive fluidification of the solid structure could be enabled only by the analyst's capacity for becoming himself or herself [unsolid].

Amyloid-like ribbons of amelogenins in enamel mineralization

DOE PAGES

Carneiro, Karina M. M.; Zhai, Halei; Zhu, Li; ...

2016-03-24

We report that enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-likemore » structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. Lastly, we propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.« less

A structure for maturing intelligent tutoring system student models

NASA Technical Reports Server (NTRS)

Holmes, Willard M.

1990-01-01

A special structure is examined for evolving a detached model of the user of an intelligent tutoring system. Tutoring is used in the context of education and training devices. A detached approach to populating the student model data structure is examined in the context of the need for time dependent reasoning about what the student knows about a particular concept in the domain of interest. This approach, to generating a data structure for the student model, allows an inference engine separate from the tutoring strategy determination to be used. This methodology has advantages in environments requiring real-time operation.

Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons.

PubMed

Robinson, Kelsey A; Sun, Mei; Barnum, Carrie E; Weiss, Stephanie N; Huegel, Julianne; Shetye, Snehal S; Lin, Linda; Saez, Daniel; Adams, Sheila M; Iozzo, Renato V; Soslowsky, Louis J; Birk, David E

2017-12-01

The small leucine-rich proteoglycans (SLRPs), decorin and biglycan, are key regulators of collagen fibril and matrix assembly. The goal of this work was to elucidate the roles of decorin and biglycan in tendon homeostasis. Our central hypothesis is that decorin and biglycan expression in the mature tendon would be critical for the maintenance of the structural and mechanical properties of healthy tendons. Defining the function(s) of these SLRPs in tendon homeostasis requires that effects in the mature tendon be isolated from their influence on development. Thus, we generated an inducible knockout mouse model that permits genetic ablation of decorin and biglycan expression in the mature tendon, while maintaining normal expression during development. Decorin and biglycan expression were knocked out in the mature patellar tendon with the subsequent turnover of endogenous SLRPs deposited prior to induction. The acute absence of SLRP expression was associated with changes in fibril structure with a general shift to larger diameter fibrils in the compound knockout tendons, together with fibril diameter heterogeneity. In addition, tendon mechanical properties were altered. Compared to wild-type controls, acute ablation of both genes resulted in failure of the tendon at lower loads, decreased stiffness, a trend towards decreased dynamic modulus, as well as a significant increase in percent relaxation and tissue viscosity. Collagen fiber realignment was also increased with a delayed and slower in response to load in the absence of expression. These structural and functional changes in response to an acute loss of decorin and biglycan expression in the mature tendon demonstrate a significant role for these SLRPs in adult tendon homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Origin of the biomechanical properties of wood related to the fine structure of the multi-layered cell wall.

PubMed

Yamamoto, H; Kojima, Y; Okuyama, T; Abasolo, W P; Gril, J

2002-08-01

In this study, a basic model is introduced to describe the biomechanical properties of the wood from the viewpoint of the composite structure of its cell wall. First, the mechanical interaction between the cellulose microfibril (CMF) as a bundle framework and the lignin-hemicellulose as a matrix (MT) skeleton in the secondary wall is formulated based on "the two phase approximation." Thereafter, the origins of (1) tree growth stress, (2) shrinkage or swelling anisotropy of the wood, and (3) moisture dependency of the Young's modulus of wood along the grain were simulated using the newly introduced model. Through the model formulation; (1) the behavior of the cellulose microfibril (CMF) and the matrix substance (MT) during cell wall maturation was estimated; (2) the moisture reactivity of each cell wall constituent was investigated; and (3) a realistic model of the fine composite structure of the matured cell wall was proposed. Thus, it is expected that the fine structure and internal property of each cell wall constituent can be estimated through the analyses of the macroscopic behaviors of wood based on the two phase approximation.

Structural, Mechanistic, and Antigenic Characterization of the Human Astrovirus Capsid

PubMed Central

York, Royce L.; Yousefi, Payam A.; Bogdanoff, Walter; Haile, Sara; Tripathi, Sarvind

2015-01-01

ABSTRACT Human astroviruses (HAstVs) are nonenveloped, positive-sense, single-stranded RNA viruses that are a leading cause of viral gastroenteritis. HAstV particles display T=3 icosahedral symmetry formed by 180 copies of the capsid protein (CP), which undergoes proteolytic maturation to generate infectious HAstV particles. Little is known about the molecular features that govern HAstV particle assembly, maturation, infectivity, and immunogenicity. Here we report the crystal structures of the two main structural domains of the HAstV CP: the core domain at 2.60-Å resolution and the spike domain at 0.95-Å resolution. Fitting of these structures into the previously determined 25-Å-resolution electron cryomicroscopy density maps of HAstV allowed us to characterize the molecular features on the surfaces of immature and mature T=3 HAstV particles. The highly electropositive inner surface of HAstV supports a model in which interaction of the HAstV CP core with viral RNA is a driving force in T=3 HAstV particle formation. Additionally, mapping of conserved residues onto the HAstV CP core and spike domains in the context of the immature and mature HAstV particles revealed dramatic changes to the exposure of conserved residues during virus maturation. Indeed, we show that antibodies raised against mature HAstV have reactivity to both the HAstV CP core and spike domains, revealing for the first time that the CP core domain is antigenic. Together, these data provide new molecular insights into HAstV that have practical applications for the development of vaccines and antiviral therapies. IMPORTANCE Astroviruses are a leading cause of viral diarrhea in young children, immunocompromised individuals, and the elderly. Despite the prevalence of astroviruses, little is known at the molecular level about how the astrovirus particle assembles and is converted into an infectious, mature virus. In this paper, we describe the high-resolution structures of the two main astrovirus capsid proteins. Fitting these structures into previously determined low-resolution maps of astrovirus allowed us to characterize the molecular surfaces of immature and mature astroviruses. Our studies provide the first evidence that astroviruses undergo viral RNA-dependent assembly. We also provide new insight into the molecular mechanisms that lead to astrovirus maturation and infectivity. Finally, we show that both capsid proteins contribute to the adaptive immune response against astrovirus. Together, these studies will help to guide the development of vaccines and antiviral drugs targeting astrovirus. PMID:26656707

Dynamic complexities in a pest control model with birth pulse and harvesting

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

Goel, A., E-mail: goelanju23@gmail.com; Gakkhar, S., E-mail: sungkfma@iitr.ernet.in

In this paper, an impulsive model is discussed for an integrated pest management approach comprising of chemical and mechanical controls. The pesticides and harvesting are used to control the stage-structured pest population. The mature pest give birth to immature pest in pulses at regular intervals. The pest is controlled by spraying chemical pesticides affecting immature as well as mature pest. The harvesting of both immature and mature pest further reduce the pest population. The discrete dynamical system obtained from stroboscopic map is analyzed. The threshold conditions for stability of pest-free state as well as non-trivial period-1 solution is obtained. Themore » effect of pesticide spray timing and harvesting on immature as well as mature pest are shown. Finally, by numerical simulation with MATLAB, the dynamical behaviors of the model is found to be complex. Above the threshold level there is a characteristic sequence of bifurcations leading to chaotic dynamics. Route to chaos is found to be period-doubling. Period halving bifurcations are also observed.« less

trans- cis Isomerism and acylimine formation in DsRed chromophore models: Intrinsic rotation barriers

NASA Astrophysics Data System (ADS)

Olsen, Seth; Smith, Sean C.

2006-07-01

The chromophore of the red fluorescent protein DsRed contains an acylimine substituent to a GFP-like chromophore structure. The acylimine is formed from the trans peptide linkage between residues F65 and Q66 in immature DsRed, but has a cis configuration in the mature protein. The relationship between acylimine formation and trans- cis isomerization is unresolved. We have calculated bond rotation profiles for models of mature and immature DsRed chromophores using B3LYP DFT. The isomerization barrier is substantially reduced in acylimine-substituted models, providing prima facie evidence that acylimine formation precedes trans- cis isomerization in DsRed chromophores.

Optical clearing of the pancreas for visualization of mature β-cells and vessels in mice.

PubMed

Nishimura, Wataru; Sakaue-Sawano, Asako; Takahashi, Satoru; Miyawaki, Atsushi; Yasuda, Kazuki; Noda, Yasuko

2018-05-04

Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells. Reconstruction of confocal images demonstrated mature β-cells and the glomerular-like structures of β-cell vasculatures labeled with DyLight 488-conjugated lectin in normal mice as well as in low-dose streptozotocin-injected diabetes model mice with reduced β-cell mass. This technological innovation of organ imaging can be used to investigate morphological changes in vascular structures during transplantation, regeneration and diabetes development.

Towards a theory of PACS deployment: an integrative PACS maturity framework.

PubMed

van de Wetering, Rogier; Batenburg, Ronald

2014-06-01

Owing to large financial investments that go along with the picture archiving and communication system (PACS) deployments and inconsistent PACS performance evaluations, there is a pressing need for a better understanding of the implications of PACS deployment in hospitals. We claim that there is a gap in the research field, both theoretically and empirically, to explain the success of the PACS deployment and maturity in hospitals. Theoretical principles are relevant to the PACS performance; maturity and alignment are reviewed from a system and complexity perspective. A conceptual model to explain the PACS performance and a set of testable hypotheses are then developed. Then, structural equation modeling (SEM), i.e. causal modeling, is applied to validate the model and hypotheses based on a research sample of 64 hospitals that use PACS, i.e. 70 % of all hospitals in the Netherlands. Outcomes of the SEM analyses substantiate that the measurements of all constructs are reliable and valid. The PACS alignment-modeled as a higher-order construct of five complementary organizational dimensions and maturity levels-has a significant positive impact on the PACS performance. This result is robust and stable for various sub-samples and segments. This paper presents a conceptual model that explains how alignment in deploying PACS in hospitals is positively related to the perceived performance of PACS. The conceptual model is extended with tools as checklists to systematically identify the improvement areas for hospitals in the PACS domain. The holistic approach towards PACS alignment and maturity provides a framework for clinical practice.

Structural basis of fluorescence quenching in caspase activatable-GFP

PubMed Central

Nicholls, Samantha B; Hardy, Jeanne A

2013-01-01

Apoptosis is critical for organismal homeostasis and a wide variety of diseases. Caspases are the ultimate executors of the apoptotic programmed cell death pathway. As caspases play such a central role in apoptosis, there is significant demand for technologies to monitor caspase function. We recently developed a caspase activatable-GFP (CA-GFP) reporter. CA-GFP is unique due to its “dark” state, where chromophore maturation of the GFP is inhibited by the presence of a C-terminal peptide. Here we show that chromophore maturation is prevented because CA-GFP does not fold into the robust β-barrel of GFP until the peptide has been cleaved by active caspase. Both CA-GFP and GFP1-10, a split form of GFP lacking the 11th strand, have similar secondary structure, different from mature GFP. A similar susceptibility to proteolytic digestion indicates that this shared structure is not the robust, fully formed GFP β-barrel. We have developed a model that suggests that as CA-GFP is translated in vivo it follows the same folding path as wild-type GFP; however, the presence of the appended peptide does not allow CA-GFP to form the barrel of the fully matured GFP. CA-GFP is therefore held in a “pro-folding” intermediate state until the peptide is released, allowing it to continue folding into the mature barrel geometry. This new understanding of the structural basis of the dark state of the CA-GFP reporter will enable manipulation of this mechanism in the development of reporter systems for any number of cellular processes involving proteases and potentially other enzymes. PMID:23139158

Retrovirus maturation-an extraordinary structural transformation.

PubMed

Mattei, Simone; Schur, Florian Km; Briggs, John Ag

2016-06-01

Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Ecosystem development of Haizhou Bay Ecological Restoration Area from 2003 to 2013

NASA Astrophysics Data System (ADS)

Wang, Teng; Li, Yunkai; Xie, Bin; Zhang, Hu; Zhang, Shuo

2017-12-01

Two Ecopath mass-balance models were implemented for evaluating the structure and function of Haizhou Bay Ecological Restoration Area ecosystem using 14 ecological indicators in two distinctive years (2003 and 2013). The results showed that the size of HZERA ecosystem became larger as total biomass was increased in last decade, especially in primary producer and zooplankton groups. Total system throughput increased from 7496.00 t km-2 yr-1 to 9547.54 t km-2 yr-1. The P/R (production/respiration) ratio decreased over the decade. Finn's cycling index and Finn's mean path length increased over the decade. No keystone species (KS) occurred during ten years; however, evidences of top-down control in 2003 and 2013 models were demonstrated by high KS value belonging to Lophius litulon group in food web. Drawing upon Odum's theory of ecosystem maturity, the structured, web-like ecosystem of 2013 model had developed into a highly mature system compared with that of 2003 model.

Structural Maturation of HIV-1 Reverse Transcriptase—A Metamorphic Solution to Genomic Instability

PubMed Central

London, Robert E.

2016-01-01

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT)—a critical enzyme of the viral life cycle—undergoes a complex maturation process, required so that a pair of p66 precursor proteins can develop conformationally along different pathways, one evolving to form active polymerase and ribonuclease H (RH) domains, while the second forms a non-functional polymerase and a proteolyzed RH domain. These parallel maturation pathways rely on the structural ambiguity of a metamorphic polymerase domain, for which the sequence–structure relationship is not unique. Recent nuclear magnetic resonance (NMR) studies utilizing selective labeling techniques, and structural characterization of the p66 monomer precursor have provided important insights into the details of this maturation pathway, revealing many aspects of the three major steps involved: (1) domain rearrangement; (2) dimerization; and (3) subunit-selective RH domain proteolysis. This review summarizes the major structural changes that occur during the maturation process. We also highlight how mutations, often viewed within the context of the mature RT heterodimer, can exert a major influence on maturation and dimerization. It is further suggested that several steps in the RT maturation pathway may provide attractive targets for drug development. PMID:27690082

Peculiarities of convection and oil maturation in 3D porous medium structure.

NASA Astrophysics Data System (ADS)

Yurie Khachay, Professor; Mindubaev, Mansur

2017-04-01

An important estimation of oil source thickness productivity is to study the thermal influences of magmatic intrusions on the maturation of the organic matter. The heterogeneity of permeability distribution of the reservoir rock and respectively the convection structure provide temperature heterogeneity and different degree of maturity for the oil source material. A numerical algorithm for solving the problem of developed convection in two-dimensional and three-dimensional models of the porous medium, which consists of a system of Darcy equations, heat conduction with convection term and the continuity equation, is developed. Because of the effective values of the coefficients of thermal conductivity, heat capacity, viscosity and permeability of the medium depend from the temperature; the system of equations is nonlinear. For solution we used the dimensionless system of coordinates. For numerical solution we used the longitudinal cross-implicit scheme. The coordinates step for the 3D model had been used constant and equal to H/20, where H=1- dimensionless thickness of porous medium layer. As it is shown from the variants of numerical solution, by the stationary regime of developed convection because of the temperature heterogeneous distribution in the sedimentary reservoir the formation of oil source matter different degree of maturity is possible. That result is very significant for estimation of reservoirs oil-bearing The work was fulfilled by supporting of the Fund of UB RAS, project 1518532. Reference 1. Yurie Khachay and Mansur Mindubaev, 2016, Effect of convective transport in porous media on the conductions of organic matter maturation and generation of hydrocarbons in trap rocks complexes, Energy Procedia. 74 pp.79-83.

Growth Control and Disease Mechanisms in Computational Embryogeny

NASA Technical Reports Server (NTRS)

Shapiro, Andrew A.; Yogev, Or; Antonsson, Erik K.

2008-01-01

This paper presents novel approach to applying growth control and diseases mechanisms in computational embryogeny. Our method, which mimics fundamental processes from biology, enables individuals to reach maturity in a controlled process through a stochastic environment. Three different mechanisms were implemented; disease mechanisms, gene suppression, and thermodynamic balancing. This approach was integrated as part of a structural evolutionary model. The model evolved continuum 3-D structures which support an external load. By using these mechanisms we were able to evolve individuals that reached a fixed size limit through the growth process. The growth process was an integral part of the complete development process. The size of the individuals was determined purely by the evolutionary process where different individuals matured to different sizes. Individuals which evolved with these characteristics have been found to be very robust for supporting a wide range of external loads.

Changes in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophy

PubMed Central

Clelland, Allyson Kara; Bales, Alexandra Beatrice E.; Sleeman, Judith Elizabeth

2012-01-01

It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins (snRNPs): essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intranuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modelling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that subnuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intranuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA. PMID:22393244

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

PubMed

Wahlin, Karl J; Maruotti, Julien A; Sripathi, Srinivasa R; Ball, John; Angueyra, Juan M; Kim, Catherine; Grebe, Rhonda; Li, Wei; Jones, Bryan W; Zack, Donald J

2017-04-10

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro.

Monotone Approximation for a Nonlinear Size and Class Age Structured Epidemic Model

DTIC Science & Technology

2006-02-22

information if it does not display a currently valid OMB control number. 1. REPORT DATE 22 FEB 2006 2. REPORT TYPE 3. DATES COVERED 00-00-2006 to 00...follows from standard results, given the fact that they are all linear problems with local boundary conditions for Sinko-Streifer type systems. We...model, J. Franklin Inst., 297 (1974), 325-333. [14] K. E. Howard, A size and maturity structured model of cell dwarfism exhibiting chaotic be- havior

Enhancing Racial Self-Understanding through Structured Learning and Reflective Experiences

ERIC Educational Resources Information Center

Quaye, Stephen John; Baxter Magolda, Marcia B.

2007-01-01

Intercultural maturity and the learning partnerships model are offered as frameworks for understanding the intersection of students' developmental levels and readiness for cross-racial interactions, and for assisting educators in promoting racial self-understanding. A case study is used to illustrate the usefulness of the model in supporting…

Four types of interference competition and their impacts on the ecology and evolution of size-structured populations and communities.

PubMed

Zhang, Lai; Andersen, Ken H; Dieckmann, Ulf; Brännström, Åke

2015-09-07

We investigate how four types of interference competition - which alternatively affect foraging, metabolism, survival, and reproduction - impact the ecology and evolution of size-structured populations. Even though all four types of interference competition reduce population biomass, interference competition at intermediate intensity sometimes significantly increases the abundance of adult individuals and the population׳s reproduction rate. We find that foraging and metabolic interference evolutionarily favor smaller maturation size when interference is weak and larger maturation size when interference is strong. The evolutionary response to survival interference and reproductive interference is always larger maturation size. We also investigate how the four types of interference competition impact the evolutionary dynamics and resultant diversity and trophic structure of size-structured communities. Like other types of trait-mediated competition, all four types of interference competition can induce disruptive selection and thus promote initial diversification. Even though foraging interference and reproductive interference are more potent in promoting initial diversification, they catalyze the formation of diverse communities with complex trophic structure only at high levels of interference intensity. By contrast, survival interference does so already at intermediate levels, while reproductive interference can only support relatively smaller communities with simpler trophic structure. Taken together, our results show how the type and intensity of interference competition jointly affect coexistence patterns in structured population models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Junctophilin-2 is necessary for T-tubule maturation during mouse heart development

PubMed Central

Reynolds, Julia O.; Chiang, David Y.; Wang, Wei; Beavers, David L.; Dixit, Sayali S.; Skapura, Darlene G.; Landstrom, Andrew P.; Song, Long-Sheng; Ackerman, Michael J.; Wehrens, Xander H.T.

2013-01-01

Aims Transverse tubules (TTs) provide the basic subcellular structures that facilitate excitation–contraction (EC) coupling, the essential process that underlies normal cardiac contractility. Previous studies have shown that TTs develop within the first few weeks of life in mammals but the molecular determinants of this development have remained elusive. This study aims to elucidate the role of junctophilin-2 (JPH2), a junctional membrane complex protein, in the maturation of TTs in cardiomyocytes. Methods and results Using a novel cardiac-specific short-hairpin-RNA-mediated JPH2 knockdown mouse model (Mus musculus; αMHC-shJPH2), we assessed the effects of the loss of JPH2 on the maturation of the ventricular TT structure. Between embryonic day (E) 10.5 and postnatal day (P) 10, JPH2 mRNA and protein levels were reduced by >70% in αMHC-shJPH2 mice. At P8 and P10, knockdown of JPH2 significantly inhibited the maturation of TTs, while expression levels of other genes implicated in TT development remained mostly unchanged. At the same time, intracellular Ca2+ handling was disrupted in ventricular myocytes from αMHC- shJPH2 mice, which developed heart failure by P10 marked by reduced ejection fraction, ventricular dilation, and premature death. In contrast, JPH2 transgenic mice exhibited accelerated TT maturation by P8. Conclusion Our findings suggest that JPH2 is necessary for TT maturation during postnatal cardiac development in mice. In particular, JPH2 may be critical in anchoring the invaginating sarcolemma to the sarcoplasmic reticulum, thereby enabling the maturation of the TT network. PMID:23715556

Earth and ocean modeling

NASA Technical Reports Server (NTRS)

Knezovich, F. M.

1976-01-01

A modular structured system of computer programs is presented utilizing earth and ocean dynamical data keyed to finitely defined parameters. The model is an assemblage of mathematical algorithms with an inherent capability of maturation with progressive improvements in observational data frequencies, accuracies and scopes. The Eom in its present state is a first-order approach to a geophysical model of the earth's dynamics.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.

PubMed

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio; Nakano, Atsushi

2017-12-12

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

PubMed Central

Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio

2017-01-01

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy. PMID:29231167

Faith Maturity and Mental Well-Being: A Longitudinal Study of Indian American Followers of a Guru Tradition.

PubMed

Pandya, Samta P

2018-05-05

This article is based on a longitudinal study of Indian Americans devoted to a guru tradition, aiming to explore how faith contributes to their mental well-being. Respondent sample size at phase 1 (2003-2004) was 1872 and at phase 2 (2013-2014) was 1764. Two scales were used to measure faith maturity and well-being. Results showed that phase 2 well-being scores of the devotees were higher, influenced by faith maturity and engagement regularity, thereby corroborating the faith-religiosity-well-being link, further reinforced by the structural equation model. Faith emerges as critical variable in working with this cohort and planning interventions towards promoting their well-being.

Novel Insights in Mammalian Catalase Heme Maturation: Effect of NO and Thioredoxin-1

PubMed Central

Chakravarti, Ritu; Gupta, Karishma; Majors, Alana; Ruple, Lisa; Aronica, Mark; Stuehr, Dennis J.

2016-01-01

Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. The NO inhibition in catalase heme incorporation was associated with defective oligomerization of catalase, such that inactive catalase monomers and dimers accumulated in place of the mature tetrameric enzyme. We also found that GAPDH plays a key role in mediating these NO effects on the structure and activity of catalase. Moreover, the NO sensitivity of catalase maturation could be altered up or down by manipulating the cellular expression level or activity of thioredoxin-1, a known protein-SNO denitrosylase enzyme. In a mouse model of allergic inflammatory asthma, we found that lungs from allergen-challenged mice contained a greater percentage of dimeric catalase relative to tetrameric catalase in the unchallenged control, suggesting that the mechanisms described here are in play in the allergic asthma model. Together, our study shows how maturation of active catalase can be influenced by NO, S-nitrosylated GAPDH, and thioredoxin-1, and how maturation may become compromised in inflammatory conditions such as asthma. PMID:25659933

Novel insights in mammalian catalase heme maturation: effect of NO and thioredoxin-1.

PubMed

Chakravarti, Ritu; Gupta, Karishma; Majors, Alana; Ruple, Lisa; Aronica, Mark; Stuehr, Dennis J

2015-05-01

Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. The NO inhibition in catalase heme incorporation was associated with defective oligomerization of catalase, such that inactive catalase monomers and dimers accumulated in place of the mature tetrameric enzyme. We also found that GAPDH plays a key role in mediating these NO effects on the structure and activity of catalase. Moreover, the NO sensitivity of catalase maturation could be altered up or down by manipulating the cellular expression level or activity of thioredoxin-1, a known protein-SNO denitrosylase enzyme. In a mouse model of allergic inflammatory asthma, we found that lungs from allergen-challenged mice contained a greater percentage of dimeric catalase relative to tetrameric catalase in the unchallenged control, suggesting that the mechanisms described here are in play in the allergic asthma model. Together, our study shows how maturation of active catalase can be influenced by NO, S-nitrosylated GAPDH, and thioredoxin-1, and how maturation may become compromised in inflammatory conditions such as asthma. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational Aeroelastic Modeling of Airframes and TurboMachinery: Progress and Challenges

NASA Technical Reports Server (NTRS)

Bartels, R. E.; Sayma, A. I.

2006-01-01

Computational analyses such as computational fluid dynamics and computational structural dynamics have made major advances toward maturity as engineering tools. Computational aeroelasticity is the integration of these disciplines. As computational aeroelasticity matures it too finds an increasing role in the design and analysis of aerospace vehicles. This paper presents a survey of the current state of computational aeroelasticity with a discussion of recent research, success and continuing challenges in its progressive integration into multidisciplinary aerospace design. This paper approaches computational aeroelasticity from the perspective of the two main areas of application: airframe and turbomachinery design. An overview will be presented of the different prediction methods used for each field of application. Differing levels of nonlinear modeling will be discussed with insight into accuracy versus complexity and computational requirements. Subjects will include current advanced methods (linear and nonlinear), nonlinear flow models, use of order reduction techniques and future trends in incorporating structural nonlinearity. Examples in which computational aeroelasticity is currently being integrated into the design of airframes and turbomachinery will be presented.

Integrated exploration workflow in the south Middle Magdalena Valley (Colombia)

NASA Astrophysics Data System (ADS)

Moretti, Isabelle; Charry, German Rodriguez; Morales, Marcela Mayorga; Mondragon, Juan Carlos

2010-03-01

The HC exploration is presently active in the southern part of the Middle Magdalena Valley but only moderate size discoveries have been made up to date. The majority of these discoveries are at shallow depth in the Tertiary section. The structures located in the Valley are faulted anticlines charged by lateral migration from the Cretaceous source rocks that are assumed to be present and mature eastward below the main thrusts and the Guaduas Syncline. Upper Cretaceous reservoirs have also been positively tested. To reduce the risks linked to the exploration of deeper structures below the western thrusts of the Eastern Cordillera, an integrated study was carried out. It includes the acquisition of new seismic data, the integration of all surface and subsurface data within a 3D-geomodel, a quality control of the structural model by restoration and a modeling of the petroleum system (presence and maturity of the Cretaceous source rocks, potential migration pathways). The various steps of this workflow will be presented as well as the main conclusions in term of source rock, deformation phases and timing of the thrust emplacement versus oil maturation and migration. Our data suggest (or confirm) The good potential of the Umir Fm as a source rock. The early (Paleogene) deformation of the Bituima Trigo fault area. The maturity gap within the Cretaceous source rock between the hangingwall and footwall of the Bituima fault that proves an initial offset of Cretaceous burial in the range of 4.5 km between the Upper Cretaceous series westward and the Lower Cretaceous ones eastward of this fault zone. The post Miocene weak reactivation as dextral strike slip of Cretaceous faults such as the San Juan de Rio Seco fault that corresponds to change in the Cretaceous thickness and therefore in the depth of the thrust decollement.

CryoEM structure of the mature dengue virus at 3.5-Å resolution

PubMed Central

Zhang, Xiaokang; Ge, Peng; Yu, Xuekui; Brannan, Jennifer M.; Bi, Guoqiang; Zhang, Qinfen; Schein, Stan; Zhou, Z. Hong

2012-01-01

Regulated by pH, membrane-anchored proteins E and M play a series of roles during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo electron microscopy at 3.5Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch was fastened at an earlier stage, during maturation at acid pH in the trans-Golgi network. At a later stage, to initiate infection in response to acid pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery. PMID:23241927

Structural and Maturational Covariance in Early Childhood Brain Development.

PubMed

Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

2017-03-01

Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lipase Maturation Factor 1 (Lmf1): Structure and Role in Lipase Folding and Assembly

PubMed Central

Ehrhardt, Nicole

2014-01-01

Purpose of review Lipase maturation factor 1 (LMF1) is a membrane-bound protein located in the endoplasmic reticulum (ER). It is essential to the folding and assembly (i.e., maturation) of a select group of lipases that include lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). The purpose of this review is to examine recent studies that have begun to elucidate the structure and function of LMF1, and to place it in the context of lipase folding and assembly. Recent findings Recent studies identified mutations in LMF1 that cause combined lipase deficiency and hypertriglyceridemia in humans. These mutations result in the truncation of a large, evolutionarily conserved domain called DUF1222, which is essential for interaction with lipases and their attainment of enzymatic activity. The structural complexity of LMF1 has been further characterized by solving its topology in the ER membrane. Recent studies indicate that in addition to LPL and HL, the maturation of EL is also dependent on LMF1. Based on its apparent specificity for dimeric lipases, LMF1 is proposed to play an essential role in the assembly and/or stabilization of head-to-tail lipase homodimers. Summary LMF1 functions in the maturation of a select group of secreted lipases that assemble into homodimers in the ER. These dimeric lipases include LPL, HL and EL, all of which contribute significantly to plasma triglyceride and HDL cholesterol levels in human populations. Future studies involving genetically engineered mouse models will be required to fully elucidate the role of LMF1 in normal physiology and disease. PMID:20224398

The Variation of Planetary Surfaces' Structure and Size Distribution with Depth

NASA Astrophysics Data System (ADS)

Charalambous, C. A.; Pike, W. T.

2014-12-01

The particle, rock and boulder size distribution of a planetary surface bring important implications not only to crucial aspects of future missions but also to the better understanding of planetary and earth sciences. By exploiting a novel statistical model, the evolution of particle fragmentation phenomena can be understood in terms of a descriptive maturity index, a measure of the number of fragmentation events that have produced the soil. This statistical model, which is mathematically constructed via fundamental physical principles, has been validated by terrestrial mineral grinding data and impact experiments. Applying the model to planetary surfaces, the number of fragmentation events is determined by production function curves that quantify the degree of impact cratering. The model quantifies the variation of the maturity index of the regolith with depth, with a high maturity index at the surface decreasing to a low index corresponding to the megaregolith of a blocky population and fractured bedrock. The measured lunar and martian particle size distributions at the surface is well matched by the model over several orders of magnitude. The continuous transition invoked by the model can be furthermore synthesised to provide temporal and spatial visualisations of the internal architecture of the Martian and Lunar regolith. Finally, the model is applied to the risk assessment and success criteria of future mission landings as well as drilling on planetary surfaces. The solutions to a variety of planetary fragmentation related problems can be found via exact mathematical foundations or through simulations using the particle population provided by the model's maturation.

Intellectual, Psychosocial, and Moral Development in College: Four Major Theories. Revised.

ERIC Educational Resources Information Center

Kurfiss, Joanne

Four models are discussed with which to view students, educational goals, and learning environments. Each of the four theories emphasizes a unique aspect of the total development process. Piaget's model describes the development of structures and processes which characterize mature logical thinking. Perry provides a closer look at students'…

Kinematic Cosmology & a new ``Steady State'' Model of Continued Creation

NASA Astrophysics Data System (ADS)

Wegener, Mogens

2006-03-01

Only a new "steady state" model justifies the observations of fully mature galaxies at ever increasing distances. The basic idea behind the world model presented here, which is a synthesis of the cosmologies of Parmenides and Herakleitos, is that the invariant structure of the infinite contents of a universe in flux may be depicted as a finite hyperbolic pseudo-sphere.

Engineering epithelial-stromal interactions in vitro for toxicology assessment.

PubMed

Belair, David G; Abbott, Barbara D

2017-05-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. Published by Elsevier B.V.

Engineering epithelial-stromal interactions in vitro for toxicology assessment

PubMed Central

Belair, David G.; Abbott, Barbara D.

2018-01-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. PMID:28285100

Non-stationary recruitment dynamics of rainbow smelt: the influence of environmental variables and variation in size structure and length-at-maturation

USGS Publications Warehouse

Feiner, Zachary S.; Bunnell, David B.; Hook, Tomas O.; Madenjian, Charles P.; Warner, David M.; Collingsworth, Paris D.

2015-01-01

Fish stock-recruitment dynamics may be difficult to elucidate because of nonstationary relationships resulting from shifting environmental conditions and fluctuations in important vital rates such as individual growth or maturation. The Great Lakes have experienced environmental stressors that may have changed population demographics and stock-recruitment relationships while causing the declines of several prey fish species, including rainbow smelt (Osmerus mordax). We investigated changes in the size and maturation of rainbow smelt in Lake Michigan and Lake Huron and recruitment dynamics of the Lake Michigan stock over the past four decades. Mean lengths and length-at-maturation of rainbow smelt generally declined over time in both lakes. To evaluate recruitment, we used both a Ricker model and a Kalman filter-random walk (KF-RW) model which incorporated nonstationarity in stock productivity by allowing the productivity term to vary over time. The KF-RW model explained nearly four times more variation in recruitment than the Ricker model, indicating the productivity of the Lake Michigan stock has increased. By accounting for this nonstationarity, we were able identify significant variations in stock productivity, evaluate its importance to rainbow smelt recruitment, and speculate on potential environmental causes for the shift. Our results suggest that investigating mechanisms driving nonstationary shifts in stock-recruit relationships can provide valuable insights into temporal variation in fish population dynamics.

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution

NASA Astrophysics Data System (ADS)

Schur, Florian K. M.; Hagen, Wim J. H.; Rumlová, Michaela; Ruml, Tomáš; Müller, Barbara; Kräusslich, Hans-Georg; Briggs, John A. G.

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all α-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.

Natural language acquisition in large scale neural semantic networks

NASA Astrophysics Data System (ADS)

Ealey, Douglas

This thesis puts forward the view that a purely signal- based approach to natural language processing is both plausible and desirable. By questioning the veracity of symbolic representations of meaning, it argues for a unified, non-symbolic model of knowledge representation that is both biologically plausible and, potentially, highly efficient. Processes to generate a grounded, neural form of this model-dubbed the semantic filter-are discussed. The combined effects of local neural organisation, coincident with perceptual maturation, are used to hypothesise its nature. This theoretical model is then validated in light of a number of fundamental neurological constraints and milestones. The mechanisms of semantic and episodic development that the model predicts are then used to explain linguistic properties, such as propositions and verbs, syntax and scripting. To mimic the growth of locally densely connected structures upon an unbounded neural substrate, a system is developed that can grow arbitrarily large, data- dependant structures composed of individual self- organising neural networks. The maturational nature of the data used results in a structure in which the perception of concepts is refined by the networks, but demarcated by subsequent structure. As a consequence, the overall structure shows significant memory and computational benefits, as predicted by the cognitive and neural models. Furthermore, the localised nature of the neural architecture also avoids the increasing error sensitivity and redundancy of traditional systems as the training domain grows. The semantic and episodic filters have been demonstrated to perform as well, or better, than more specialist networks, whilst using significantly larger vocabularies, more complex sentence forms and more natural corpora.

Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change☆

PubMed Central

Pandurangan, Arun Prasad; Shakeel, Shabih; Butcher, Sarah Jane; Topf, Maya

2014-01-01

Fitting of atomic components into electron cryo-microscopy (cryoEM) density maps is routinely used to understand the structure and function of macromolecular machines. Many fitting methods have been developed, but a standard protocol for successful fitting and assessment of fitted models has yet to be agreed upon among the experts in the field. Here, we created and tested a protocol that highlights important issues related to homology modelling, density map segmentation, rigid and flexible fitting, as well as the assessment of fits. As part of it, we use two different flexible fitting methods (Flex-EM and iMODfit) and demonstrate how combining the analysis of multiple fits and model assessment could result in an improved model. The protocol is applied to the case of the mature and empty capsids of Coxsackievirus A7 (CAV7) by flexibly fitting homology models into the corresponding cryoEM density maps at 8.2 and 6.1 Å resolution. As a result, and due to the improved homology models (derived from recently solved crystal structures of a close homolog – EV71 capsid – in mature and empty forms), the final models present an improvement over previously published models. In close agreement with the capsid expansion observed in the EV71 structures, the new CAV7 models reveal that the expansion is accompanied by ∼5° counterclockwise rotation of the asymmetric unit, predominantly contributed by the capsid protein VP1. The protocol could be applied not only to viral capsids but also to many other complexes characterised by a combination of atomic structure modelling and cryoEM density fitting. PMID:24333899

Thermal maturation and petroleum source rocks in Forest City and Salina basins, mid-continent, U. S. A

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

Newell, K.D.; Watney, W.L.; Hatch, J.R.

1986-05-01

Shales in the Middle Ordovician Simpson Group are probably the source rocks for a geochemically distinct group of lower pristane and low phytane oils produced along the axis of the Forest City basin, a shallow cratonic Paleozoic basin. These oils, termed Ordovician-type oils, occur in some fields in the southern portion of the adjacent Salina basin. Maturation modeling by time-temperature index (TTI) calculations indicate that maturation of both basins was minimal during the early Paleozoic. The rate of maturation significantly increased during the Pennsylvanian because of rapid regional subsidence in response to the downwarping of the nearby Anadarko basin. Whenmore » estimated thicknesses of eroded Pennsylvanian, Permian, and Cretaceous strata are considered, both basins remain relatively shallow, with maximum basement burial probably not exceeding 2 km. According to maturation modeling and regional structure mapping, the axes of both basins should contain Simpson rocks in the early stages of oil generation. The probability of finding commercial accumulations of Ordovician-type oil along the northwest-southeast trending axis of the Salina basin will decrease in a northwestward direction because of (1) westward thinning of the Simpson Group, and (2) lesser maturation due to lower geothermal gradients and shallower paleoburial depths. The optimum localities for finding fields of Ordovician-type oil in the southern Salina basin will be in down-plunge closures on anticlines that have drainage areas near the basin axis.« less

Purification and structural determination of an inhibitor of starfish oocyte maturation from a Bacillus species.

PubMed Central

Toraya, T; Maoka, T; Tsuji, H; Kobayashi, M

1995-01-01

Inhibitors of bacterial origins of starfish oocyte maturation were sought to obtain biologically active substances which act on either hormonal signal transduction or cell cycle regulation. An oocyte maturation-inhibiting substance found in culture fluid of a Bacillus species was purified to homogeneity. This substance possessed the nature of a detergent and specifically inhibited 1-methyladenine-induced oocyte maturation (50% inhibitory concentration, 3.3 microM) but not dithiothreitol-induced maturation. Its total structure was established to be the lactone of 3-hydroxy-13-methyltetradecanoyl-Glu-Leu-Leu-Val-Asp-Leu -Leu through COOH of the carboxy-terminal Leu. This structure is identical to surfactin, although although the configuration of the substance's amino acid residues has not yet been determined. Surfactin was shown to be identical with this substance in its inhibitory effect on starfish oocyte maturation as well as its chromatographic and electrophoretic properties. Therefore, it was concluded that the oocyte maturation-inhibiting substance produced by a Bacillus species is surfactin. PMID:7646018

Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies.

PubMed

Nelson, Bryce; Adams, Jarrett; Kuglstatter, Andreas; Li, Zhijian; Harris, Seth F; Liu, Yang; Bohini, Sandya; Ma, Han; Klumpp, Klaus; Gao, Junjun; Sidhu, Sachdev S

2018-07-06

Hepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop in order to guide affinity maturation of two distinct antibodies by phage display. Affinity maturation of antibodies using phage display has proven to be critical to therapeutic antibody development and typically involves modification of the paratope for increased affinity, improved specificity, enhanced stability or a combination of these traits. One antibody was engineered for increased affinity for human CD81 large extracellular loop that equated to increased efficacy, while the second antibody was engineered for cross-reactivity with cynomolgus CD81 to facilitate animal model testing. The use of structures to guide affinity maturation library design demonstrates the utility of combining structural analysis with phage display technologies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recovery of Red Fluorescent Protein Chromophore Maturation Deficiency through Rational Design

PubMed Central

Moore, Matthew M.; Oteng-Pabi, Samuel K.; Pandelieva, Antonia T.; Mayo, Stephen L.; Chica, Roberto A.

2012-01-01

Red fluorescent proteins (RFPs) derived from organisms in the class Anthozoa have found widespread application as imaging tools in biological research. For most imaging experiments, RFPs that mature quickly to the red chromophore and produce little or no green chromophore are most useful. In this study, we used rational design to convert a yellow fluorescent mPlum mutant to a red-emitting RFP without reverting any of the mutations causing the maturation deficiency and without altering the red chromophore’s covalent structure. We also created an optimized mPlum mutant (mPlum-E16P) that matures almost exclusively to the red chromophore. Analysis of the structure/function relationships in these proteins revealed two structural characteristics that are important for efficient red chromophore maturation in DsRed-derived RFPs. The first is the presence of a lysine residue at position 70 that is able to interact directly with the chromophore. The second is an absence of non-bonding interactions limiting the conformational flexibility at the peptide backbone that is oxidized during red chromophore formation. Satisfying or improving these structural features in other maturation-deficient RFPs may result in RFPs with faster and more complete maturation to the red chromophore. PMID:23285050

Chemical structures and characteristics of animal manures and composts during composting and assessment of maturity indices

PubMed Central

Huang, Jieying; Yu, Zixuan; Gao, Hongjian; Yan, Xiaoming; Chang, Jiang; Wang, Chengming; Hu, Jingwei

2017-01-01

Changes in physicochemical characteristics, chemical structures and maturity of swine, cattle and chicken manures and composts during 70-day composting without addition of bulking agents were investigated. Physicochemical characteristics were measured by routine analyses and chemical structures by solid-state 13C NMR and FT-IR. Three manures were of distinct properties. Their changes in physicochemical characteristics, chemical structures, and maturity were different not only from each other but also from those with addition of bulking agents during composting. Aromaticity in chicken manure composts decreased at first, and then increased whereas that in cattle and swine manure composts increased. Enhanced ammonia volatilization occurred without addition of bulking agents. NMR structural information indicated that cattle and chicken composts were relatively stable at day 36 and 56, respectively, but swine manure composts were not mature up to day 70. Finally, the days required for three manures to reach the threshold values of different maturity indices were different. PMID:28604783

Geological evolution of the North Sea: a dynamic 3D model including petroleum system elements

NASA Astrophysics Data System (ADS)

Sabine, Heim; Rüdiger, Lutz; Dirk, Kaufmann; Lutz, Reinhardt

2013-04-01

This study investigates the sedimentary basin evolution of the German North Sea with a focus on petroleum generation, migration and accumulation. The study is conducted within the framework of the project "Geoscientific Potential of the German North Sea (GPDN)", a joint project of federal (BGR, BSH) and state authorities (LBEG) with partners from industry and scientific institutions. Based on the structural model of the "Geotektonischer Atlas 3D" (GTA3D, LBEG), this dynamic 3D model contains additionally the northwestern part ("Entenschnabel" area) of the German North Sea. Geological information, e.g. lithostratigraphy, facies and structural data, provided by industry, was taken from published research projects, or literature data such as the Southern Permian Basin Atlas (SPBA; Doornenbal et al., 2010). Numerical modeling was carried out for a sedimentary succession containing 17 stratigraphic layers and several sublayers, representing the sedimentary deposition from the Devonian until Present. Structural details have been considered in terms of simplified faults and salt structures, as well as main erosion and salt movement events. Lithology, facies and the boundary conditions e.g. heat flow, paleo water-depth and sediment water interface temperature were assigned. The system calibration is based on geochemical and petrological data, such as maturity of organic matter (VRr) and present day temperature. Due to the maturity of the sedimentary organic matter Carboniferous layers are the major source rocks for gas generation. Main reservoir rocks are the Rotliegend sandstones, furthermore, sandstones of the Lower Triassic and Jurassic can serve as reservoir rocks in areas where the Zechstein salts are absent. The model provides information on the temperature and maturity distribution within the main source rock layers as well as information of potential hydrocarbon generation based on kinetic data for gas liberation. Finally, this dynamic 3D model offers a first interpretation of the current data base and an estimation of the structural- and burial evolution of the German North Sea area, including information on the petroleum system elements. It includes information about possible migration pathways, oil and gas accumulations, as well as the type of generated hydrocarbons and non-hydrocarbons. References: Doornenbal, J.C. and Stevenson, A.G. (editors), 2010. Petroleum Geological Atlas of the Southern Permian Basin Area. EAGE Publications b.v. (Houten).

Deficits in morphofunctional maturation of hippocampal mossy fiber synapses in a mouse model of intellectual disability.

PubMed

Lanore, Frederic; Labrousse, Virginie F; Szabo, Zsolt; Normand, Elisabeth; Blanchet, Christophe; Mulle, Christophe

2012-12-05

The grik2 gene, coding for the kainate receptor subunit GluK2 (formerly GluR6), is associated with autism spectrum disorders and intellectual disability. Here, we tested the hypothesis that GluK2 could play a role in the appropriate maturation of synaptic circuits involved in learning and memory. We show that both the functional and morphological maturation of hippocampal mossy fiber to CA3 pyramidal cell (mf-CA3) synapses is delayed in mice deficient for the GluK2 subunit (GluK2⁻/⁻). In GluK2⁻/⁻ mice this deficit is manifested by a transient reduction in the amplitude of AMPA-EPSCs at a critical time point of postnatal development, whereas the NMDA component is spared. By combining multiple probability peak fluctuation analysis and immunohistochemistry, we have provided evidence that the decreased amplitude reflects a decrease in the quantal size per mf-CA3 synapse and in the number of active synaptic sites. Furthermore, we analyzed the time course of structural maturation of CA3 synapses by confocal imaging of YFP-expressing cells followed by tridimensional (3D) anatomical reconstruction of thorny excrescences and presynaptic boutons. We show that major changes in synaptic structures occur subsequently to the sharp increase in synaptic transmission, and more importantly that the course of structural maturation of synaptic elements is impaired in GluK2⁻/⁻ mice. This study highlights how a mutation in a gene linked to intellectual disability in the human may lead to a transient reduction of synaptic strength during postnatal development, impacting on the proper formation of neural circuits linked to memory.

Structural Insights into High Density Lipoprotein: Old Models and New Facts

PubMed Central

Gogonea, Valentin

2016-01-01

The physiological link between circulating high density lipoprotein (HDL) levels and cardiovascular disease is well-documented, albeit its intricacies are not well-understood. An improved appreciation of HDL function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein's molecular structure, its formation, and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport. This review focuses on summarizing recent developments in the field of lipid free apoA-I and HDL structure, with emphasis on new insights revealed by newly published nascent and spherical HDL models constructed by combining low resolution structures obtained from small angle neutron scattering (SANS) with contrast variation and geometrical constraints derived from hydrogen–deuterium exchange (HDX), crosslinking mass spectrometry, electron microscopy, Förster resonance energy transfer, and electron spin resonance. Recently published low resolution structures of nascent and spherical HDL obtained from SANS with contrast variation and isotopic labeling of apolipoprotein A-I (apoA-I) will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches. The new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins. The review will discuss the merits of newly proposed SANS based all atom models for nascent and spherical HDL, and compare them with accepted models. Finally, naturally occurring and bioengineered mutations in apoA-I, and their impact on HDL phenotype, are reviewed and discuss together with new therapeutics employed for restoring HDL function. PMID:26793109

Dynamic and Geometric Analyses of Nudaurelia capensis ωVirus Maturation Reveal the Energy Landscape of Particle Transitions

PubMed Central

Tang, Jinghua; Kearney, Bradley M.; Wang, Qiu; Doerschuk, Peter C.; Baker, Timothy S.; Johnson, John E.

2014-01-01

Quasi-equivalent viruses that infect animals and bacteria require a maturation process in which particles transition from initially assembled procapsids to infectious virions. Nudaurelia capensis ω virus (NωV) is a T=4, eukaryotic, ssRNA virus that has proved to be an excellent model system for studying the mechanisms of viral maturation. Structures of NωV procapsids (diam. = 480 Å), a maturation intermediate (410 Å), and the mature virion (410 Å) were determined by electron cryo-microscopy and three-dimensional image reconstruction (cryoEM). The cryoEM density for each particle type was analyzed with a recently developed Maximum Likelihood Variance (MLV) method for characterizing microstates occupied in the ensemble of particles used for the reconstructions. The procapsid and the mature capsid had overall low variance (i.e. uniform particle populations) while the maturation intermediate (that had not undergone post-assembly autocatalytic cleavage) had roughly 2-4 times the variance of the first two particles. Without maturation cleavage the particles assume a variety of microstates, as the frustrated subunits cannot reach a minimum energy configuration. Geometric analyses of subunit coordinates provided a quantitative description of the particle reorganization during maturation. Superposition of the four quasi-equivalent subunits in the procapsid had an average root mean square deviation (RMSD) of 3Å while the mature particle had an RMSD of 11Å, showing that the subunits differentiate from near equivalent environments in the procapsid to strikingly non-equivalent environments during maturation. Autocatalytic cleavage is clearly required for the reorganized mature particle to reach the minimum energy state required for stability and infectivity. PMID:24591180

Dynamic and geometric analyses of Nudaurelia capensis ω virus maturation reveal the energy landscape of particle transitions.

PubMed

Tang, Jinghua; Kearney, Bradley M; Wang, Qiu; Doerschuk, Peter C; Baker, Timothy S; Johnson, John E

2014-04-01

Quasi-equivalent viruses that infect animals and bacteria require a maturation process in which particles transition from initially assembled procapsids to infectious virions. Nudaurelia capensis ω virus (NωV) is a T = 4, eukaryotic, single-stranded ribonucleic acid virus that has proved to be an excellent model system for studying the mechanisms of viral maturation. Structures of NωV procapsids (diameter = 480 Å), a maturation intermediate (410 Å), and the mature virion (410 Å) were determined by electron cryo-microscopy and three-dimensional image reconstruction (cryoEM). The cryoEM density for each particle type was analyzed with a recently developed maximum likelihood variance (MLV) method for characterizing microstates occupied in the ensemble of particles used for the reconstructions. The procapsid and the mature capsid had overall low variance (i.e., uniform particle populations) while the maturation intermediate (that had not undergone post-assembly autocatalytic cleavage) had roughly two to four times the variance of the first two particles. Without maturation cleavage, the particles assume a variety of microstates, as the frustrated subunits cannot reach a minimum energy configuration. Geometric analyses of subunit coordinates provided a quantitative description of the particle reorganization during maturation. Superposition of the four quasi-equivalent subunits in the procapsid had an average root mean square deviation (RMSD) of 3 Å while the mature particle had an RMSD of 11 Å, showing that the subunits differentiate from near equivalent environments in the procapsid to strikingly non-equivalent environments during maturation. Autocatalytic cleavage is clearly required for the reorganized mature particle to reach the minimum energy state required for stability and infectivity. Copyright © 2014 John Wiley & Sons, Ltd.

Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development

PubMed Central

2013-01-01

Introduction Notochordal cells (NCs) pattern aneural and avascular intervertebral discs (IVDs), and their disappearance, is associated with onset of IVD degeneration. This study induced and characterized the maturation of nucleus pulposus (NP) tissue from a gelatinous NC-rich structure to a matrix-rich structure populated by small NP cells using dynamic pressurization in an ex vivo culture model, and also identified soluble factors from NCs with therapeutic potential. Methods Porcine NC-rich NP tissue was cultured and loaded with hydrostatic pressure (0.5 to 2 MPa at 0.1 Hz for 2 hours) either Daily, for 1 Dose, or Control (no pressurization) groups for up to eight days. Cell phenotype and tissue maturation was characterized with measurements of cell viability, cytomorphology, nitric oxide, metabolic activity, matrix composition, gene expression, and proteomics. Results Daily pressurization induced transition of NCs to small NP cells with 73.8%, 44%, and 28% NCs for Control, 1 Dose and Daily groups, respectively (P < 0.0002) and no relevant cell death. Dynamic loading matured NP tissue by significantly increasing metabolic activity and accumulating Safranin-O-stained matrix. Load-induced maturation was also apparent from the significantly decreased glycolytic, cytoskeletal (Vimentin) and stress-inducible (HSP70) proteins assessed with proteomics. Loading increased the production of bioactive proteins Sonic Hedgehog (SHH) and Noggin, and maintained Semaphorin3A (Sema3A). Discussion NP tissue maturation was induced from dynamic hydrostatic pressurization in a controlled ex vivo environment without influence from systemic effects or surrounding structures. NCs transitioned into small nonvacuolated NP cells probably via differentiation as evidenced by high cell viability, lack of nitric oxide and downregulation of stress-inducible and cytoskeletal proteins. SHH, Sema3A, and Noggin, which have patterning and neurovascular-inhibiting properties, were produced in both notochordal and matured porcine NP. Results therefore provide an important piece of evidence suggesting the transition of NCs to small NP cells is a natural part of aging and not the initiation of degeneration. Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain. PMID:24427812

Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development.

PubMed

Purmessur, Devina; Guterl, Clare C; Cho, Samuel K; Cornejo, Marisa C; Lam, Ying W; Ballif, Bryan A; Laudier, James C Iatridis; Iatridis, James C

2013-01-01

Notochordal cells (NCs) pattern aneural and avascular intervertebral discs (IVDs), and their disappearance, is associated with onset of IVD degeneration. This study induced and characterized the maturation of nucleus pulposus (NP) tissue from a gelatinous NC-rich structure to a matrix-rich structure populated by small NP cells using dynamic pressurization in an ex vivo culture model, and also identified soluble factors from NCs with therapeutic potential. Porcine NC-rich NP tissue was cultured and loaded with hydrostatic pressure (0.5 to 2 MPa at 0.1 Hz for 2 hours) either Daily, for 1 Dose, or Control (no pressurization) groups for up to eight days. Cell phenotype and tissue maturation was characterized with measurements of cell viability, cytomorphology, nitric oxide, metabolic activity, matrix composition, gene expression, and proteomics. Daily pressurization induced transition of NCs to small NP cells with 73.8%, 44%, and 28% NCs for Control, 1 Dose and Daily groups, respectively (P < 0.0002) and no relevant cell death. Dynamic loading matured NP tissue by significantly increasing metabolic activity and accumulating Safranin-O-stained matrix. Load-induced maturation was also apparent from the significantly decreased glycolytic, cytoskeletal (Vimentin) and stress-inducible (HSP70) proteins assessed with proteomics. Loading increased the production of bioactive proteins Sonic Hedgehog (SHH) and Noggin, and maintained Semaphorin3A (Sema3A). NP tissue maturation was induced from dynamic hydrostatic pressurization in a controlled ex vivo environment without influence from systemic effects or surrounding structures. NCs transitioned into small nonvacuolated NP cells probably via differentiation as evidenced by high cell viability, lack of nitric oxide and downregulation of stress-inducible and cytoskeletal proteins. SHH, Sema3A, and Noggin, which have patterning and neurovascular-inhibiting properties, were produced in both notochordal and matured porcine NP. Results therefore provide an important piece of evidence suggesting the transition of NCs to small NP cells is a natural part of aging and not the initiation of degeneration. Bioactive candidates identified from young porcine IVDs may be isolated and harnessed for therapies to target discogenic back pain.

Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

PubMed Central

Moussa, Mira; Carrel, Jean-Pierre; Scherrer, Susanne; Cattani-Lorente, Maria; Wiskott, Anselm; Durual, Stéphane

2015-01-01

Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP) and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8). Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3%) and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%). These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

Structural and functional insights into the HIV-1 maturation inhibitor binding pocket.

PubMed

Waki, Kayoko; Durell, Stewart R; Soheilian, Ferri; Nagashima, Kunio; Butler, Scott L; Freed, Eric O

2012-01-01

Processing of the Gag precursor protein by the viral protease during particle release triggers virion maturation, an essential step in the virus replication cycle. The first-in-class HIV-1 maturation inhibitor dimethylsuccinyl betulinic acid [PA-457 or bevirimat (BVM)] blocks HIV-1 maturation by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. A structurally distinct molecule, PF-46396, was recently reported to have a similar mode of action to that of BVM. Because of the structural dissimilarity between BVM and PF-46396, we hypothesized that the two compounds might interact differentially with the putative maturation inhibitor-binding pocket in Gag. To test this hypothesis, PF-46396 resistance was selected for in vitro. Resistance mutations were identified in three regions of Gag: around the CA-SP1 cleavage site where BVM resistance maps, at CA amino acid 201, and in the CA major homology region (MHR). The MHR mutants are profoundly PF-46396-dependent in Gag assembly and release and virus replication. The severe defect exhibited by the inhibitor-dependent MHR mutants in the absence of the compound is also corrected by a second-site compensatory change far downstream in SP1, suggesting structural and functional cross-talk between the HIV-1 CA MHR and SP1. When PF-46396 and BVM were both present in infected cells they exhibited mutually antagonistic behavior. Together, these results identify Gag residues that line the maturation inhibitor-binding pocket and suggest that BVM and PF-46396 interact differentially with this putative pocket. These findings provide novel insights into the structure-function relationship between the CA MHR and SP1, two domains of Gag that are critical to both assembly and maturation. The highly conserved nature of the MHR across all orthoretroviridae suggests that these findings will be broadly relevant to retroviral assembly. Finally, the results presented here provide a framework for increased structural understanding of HIV-1 maturation inhibitor activity.

Structural and functional maturation of rat gastrointestinal barrier with thyroxine

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

Israel, E.J.; Pang, K.Y.; Harmatz, P.R.

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed in rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activitymore » of treated animals (T) was 1.5-2 times less than that of controls (C), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased, while the K/sub a/ remained the same, demonstrating the functional maturation of the MVM. In conclusion, thryoid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.« less

78 FR 22941 - Sidump'r Trailer Company, Inc., Grant of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... performance requirements. Finite element modeling is a mature science and appropriately accurate for modeling... interpretation letter to Jason Backs (CPS Trailers, May 28, 1998). \\3\\ Finite element analysis can be used as a... FMVSS No. 224 that the guard-like structure can serve as a rear impact guard.\\2\\ Sidump'r used a finite...

Constructing stage-structured matrix population models from life tables: comparison of methods

PubMed Central

Diaz-Lopez, Jasmin

2017-01-01

A matrix population model is a convenient tool for summarizing per capita survival and reproduction rates (collectively vital rates) of a population and can be used for calculating an asymptotic finite population growth rate (λ) and generation time. These two pieces of information can be used for determining the status of a threatened species. The use of stage-structured population models has increased in recent years, and the vital rates in such models are often estimated using a life table analysis. However, potential bias introduced when converting age-structured vital rates estimated from a life table into parameters for a stage-structured population model has not been assessed comprehensively. The objective of this study was to investigate the performance of methods for such conversions using simulated life histories of organisms. The underlying models incorporate various types of life history and true population growth rates of varying levels. The performance was measured by comparing differences in λ and the generation time calculated using the Euler-Lotka equation, age-structured population matrices, and several stage-structured population matrices that were obtained by applying different conversion methods. The results show that the discretization of age introduces only small bias in λ or generation time. Similarly, assuming a fixed age of maturation at the mean age of maturation does not introduce much bias. However, aggregating age-specific survival rates into a stage-specific survival rate and estimating a stage-transition rate can introduce substantial bias depending on the organism’s life history type and the true values of λ. In order to aggregate survival rates, the use of the weighted arithmetic mean was the most robust method for estimating λ. Here, the weights are given by survivorship curve after discounting with λ. To estimate a stage-transition rate, matching the proportion of individuals transitioning, with λ used for discounting the rate, was the best approach. However, stage-structured models performed poorly in estimating generation time, regardless of the methods used for constructing the models. Based on the results, we recommend using an age-structured matrix population model or the Euler-Lotka equation for calculating λ and generation time when life table data are available. Then, these age-structured vital rates can be converted into a stage-structured model for further analyses. PMID:29085763

Constructing stage-structured matrix population models from life tables: comparison of methods.

PubMed

Fujiwara, Masami; Diaz-Lopez, Jasmin

2017-01-01

A matrix population model is a convenient tool for summarizing per capita survival and reproduction rates (collectively vital rates) of a population and can be used for calculating an asymptotic finite population growth rate ( λ ) and generation time. These two pieces of information can be used for determining the status of a threatened species. The use of stage-structured population models has increased in recent years, and the vital rates in such models are often estimated using a life table analysis. However, potential bias introduced when converting age-structured vital rates estimated from a life table into parameters for a stage-structured population model has not been assessed comprehensively. The objective of this study was to investigate the performance of methods for such conversions using simulated life histories of organisms. The underlying models incorporate various types of life history and true population growth rates of varying levels. The performance was measured by comparing differences in λ and the generation time calculated using the Euler-Lotka equation, age-structured population matrices, and several stage-structured population matrices that were obtained by applying different conversion methods. The results show that the discretization of age introduces only small bias in λ or generation time. Similarly, assuming a fixed age of maturation at the mean age of maturation does not introduce much bias. However, aggregating age-specific survival rates into a stage-specific survival rate and estimating a stage-transition rate can introduce substantial bias depending on the organism's life history type and the true values of λ . In order to aggregate survival rates, the use of the weighted arithmetic mean was the most robust method for estimating λ . Here, the weights are given by survivorship curve after discounting with λ . To estimate a stage-transition rate, matching the proportion of individuals transitioning, with λ used for discounting the rate, was the best approach. However, stage-structured models performed poorly in estimating generation time, regardless of the methods used for constructing the models. Based on the results, we recommend using an age-structured matrix population model or the Euler-Lotka equation for calculating λ and generation time when life table data are available. Then, these age-structured vital rates can be converted into a stage-structured model for further analyses.

Extinction threshold for spatial forest dynamics with height structure.

PubMed

Garcia-Domingo, Josep L; Saldaña, Joan

2011-05-07

We present a pair-approximation model for spatial forest dynamics defined on a regular lattice. The model assumes three possible states for a lattice site: empty (gap site), occupied by an immature tree, and occupied by a mature tree, and considers three nonlinearities in the dynamics associated to the processes of light interference, gap expansion, and recruitment. We obtain an expression of the basic reproduction number R(0) which, in contrast to the one obtained under the mean-field approach, uses information about the spatial arrangement of individuals close to extinction. Moreover, we analyze the corresponding survival-extinction transition of the forest and the spatial correlations among gaps, immature and mature trees close to this critical point. Predictions of the pair-approximation model are compared with those of a cellular automaton. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stimulated Emission Depletion Nanoscopy Reveals Time-Course of Human Immunodeficiency Virus Proteolytic Maturation.

PubMed

Hanne, Janina; Göttfert, Fabian; Schimer, Jiří; Anders-Össwein, Maria; Konvalinka, Jan; Engelhardt, Johann; Müller, Barbara; Hell, Stefan W; Kräusslich, Hans-Georg

2016-09-27

Concomitant with human immunodeficiency virus type 1 (HIV-1) budding from a host cell, cleavage of the structural Gag polyproteins by the viral protease (PR) triggers complete remodeling of virion architecture. This maturation process is essential for virus infectivity. Electron tomography provided structures of immature and mature HIV-1 with a diameter of 120-140 nm, but information about the sequence and dynamics of structural rearrangements is lacking. Here, we employed super-resolution STED (stimulated emission depletion) fluorescence nanoscopy of HIV-1 carrying labeled Gag to visualize the virion architecture. The incomplete Gag lattice of immature virions was clearly distinguishable from the condensed distribution of mature protein subunits. Synchronized activation of PR within purified particles by photocleavage of a caged PR inhibitor enabled time-resolved in situ observation of the induction of proteolysis and maturation by super-resolution microscopy. This study shows the rearrangement of subviral structures in a super-resolution light microscope over time, outwitting phototoxicity and fluorophore bleaching through synchronization of a biological process by an optical switch.

Effect of covering composting piles with mature compost on ammonia emission and microbial community structure of composting process.

PubMed

Maeda, Koki; Morioka, Riki; Osada, Takashi

2009-01-01

To control ammonia (NH(3)) volatilization from the dairy cattle (Bos taurus) manure composting process, a compost pile was covered with mature compost and the gas emissions evaluated using the dynamic chamber system. The peak of NH(3) volatilization observed immediately after piling up of the compost was reduced from 196 to 62 mg/m(3) by covering the compost pile with mature compost. The accumulation of NH(4)-N to the covered mature compost was also observed. Covering and mixing the compost with mature compost had no effect on the microbial community structure. However, over time the microbial community structure changed because of a decrease in easily degradable organic compounds in the compost piles. The availability of volatile fatty acids (VFA) was considered to be important for microbial community structure in the compost. After the VFA had disappeared, the NO(3)-N concentration increased and the cellulose degrading bacteria such as Cytophaga increased in number.

Crystal structure of an HIV assembly and maturation switch

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

Wagner, Jonathan M.; Zadrozny, Kaneil K.; Chrustowicz, Jakub

Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysismore » during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.« less

Testing Crites' Model of Career Maturity: A Hierarchical Strategy.

ERIC Educational Resources Information Center

Wallbrown, Fred H.; And Others

1986-01-01

Investigated the construct validity of Crites' model of career maturity and the Career Maturity Inventory (CMI). Results from a nationwide sample of adolescents, using hierarchical factor analytic methodology, indicated confirmatory support for the multidimensionality of Crites' model of career maturity, and the construct validity of the CMI as a…

The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

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

Li, Long; Lok, Shee-Mei; Yu, I-Mei

2008-09-17

Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide {beta}-barrel structure covers the fusion loop in E, preventingmore » fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.« less

Can we set a global threshold age to define mature forests?

PubMed

Martin, Philip; Jung, Martin; Brearley, Francis Q; Ribbons, Relena R; Lines, Emily R; Jacob, Aerin L

2016-01-01

Globally, mature forests appear to be increasing in biomass density (BD). There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1) how climate and forest age control global forest BD and (2) whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost-effectiveness of different methods for determining whether forests should be classified as mature.

Clay minerals and metal oxides strongly influence the structure of alkane-degrading microbial communities during soil maturation.

PubMed

Steinbach, Annelie; Schulz, Stefanie; Giebler, Julia; Schulz, Stephan; Pronk, Geertje J; Kögel-Knabner, Ingrid; Harms, Hauke; Wick, Lukas Y; Schloter, Michael

2015-07-01

Clay minerals, charcoal and metal oxides are essential parts of the soil matrix and strongly influence the formation of biogeochemical interfaces in soil. We investigated the role of these parental materials for the development of functional microbial guilds using the example of alkane-degrading bacteria harbouring the alkane monooxygenase gene (alkB) in artificial mixtures composed of different minerals and charcoal, sterile manure and a microbial inoculum extracted from an agricultural soil. We followed changes in abundance and community structure of alkane-degrading microbial communities after 3 and 12 months of soil maturation and in response to a subsequent 2-week plant litter addition. During maturation we observed an overall increasing divergence in community composition. The impact of metal oxides on alkane-degrading community structure increased during soil maturation, whereas the charcoal impact decreased from 3 to 12 months. Among the clay minerals illite influenced the community structure of alkB-harbouring bacteria significantly, but not montmorillonite. The litter application induced strong community shifts in soils, maturated for 12 months, towards functional guilds typical for younger maturation stages pointing to a resilience of the alkane-degradation function potentially fostered by an extant 'seed bank'.

Clay minerals and metal oxides strongly influence the structure of alkane-degrading microbial communities during soil maturation

PubMed Central

Steinbach, Annelie; Schulz, Stefanie; Giebler, Julia; Schulz, Stephan; Pronk, Geertje J; Kögel-Knabner, Ingrid; Harms, Hauke; Wick, Lukas Y; Schloter, Michael

2015-01-01

Clay minerals, charcoal and metal oxides are essential parts of the soil matrix and strongly influence the formation of biogeochemical interfaces in soil. We investigated the role of these parental materials for the development of functional microbial guilds using the example of alkane-degrading bacteria harbouring the alkane monooxygenase gene (alkB) in artificial mixtures composed of different minerals and charcoal, sterile manure and a microbial inoculum extracted from an agricultural soil. We followed changes in abundance and community structure of alkane-degrading microbial communities after 3 and 12 months of soil maturation and in response to a subsequent 2-week plant litter addition. During maturation we observed an overall increasing divergence in community composition. The impact of metal oxides on alkane-degrading community structure increased during soil maturation, whereas the charcoal impact decreased from 3 to 12 months. Among the clay minerals illite influenced the community structure of alkB-harbouring bacteria significantly, but not montmorillonite. The litter application induced strong community shifts in soils, maturated for 12 months, towards functional guilds typical for younger maturation stages pointing to a resilience of the alkane-degradation function potentially fostered by an extant ‘seed bank'. PMID:25535940

Tectonothermal modeling of hydrocarbon maturation, Central Maracaibo Basin, Venezuela

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

Manske, M.C.

1996-08-01

The petroliferous Maracaibo Basin of northwestern Venezuela and extreme eastern Colombia has evolved through a complex geologic history. Deciphering the tectonic and thermal evolution is essential in the prediction of hydrocarbon maturation (timing) within the basin. Individual wells in two areas of the central basin, Blocks III and V, have been modeled to predict timing of hydrocarbon generation within the source Upper Cretaceous La Luna Formation, as well as within interbedded shales of the Lower-Middle Eocene Misoa Formation reservoir sandstones. Tectonic evolution, including burial and uplift (erosional) history, has been constrained with available well data. The initial extensional thermal regimemore » of the basin has been approximated with a Mackenzie-type thermal model, and the following compressional stage of basin development by applying a foreland basin model. Corrected Bottom Hole Temperature (BHT) measurements; from wells in the central basin, along with thermal conductivity measurements of rock samples from the entire sedimentary sequence, resulted in the estimation of present day heat flow. An understanding of the basin`s heat flow, then, allowed extrapolation of geothermal gradients through time. The relation of geothermal gradients and overpressure within the Upper Cretaceous hydrocarbon-generating La Luna Formation and thick Colon Formation shales was also taken into account. Maturation modeling by both the conventional Time-Temperature Index (TTI) and kinetic Transformation Ratio (TR) methods predicts the timing of hydrocarbon maturation in the potential source units of these two wells. These modeling results are constrained by vitrinite reflectance and illite/smectite clay dehydration data, and show general agreement. These results also have importance regarding the timing of structural formation and hydrocarbon migration into Misoa reservoirs.« less

Dynamic HypA zinc site is essential for acid viability and proper urease maturation in Helicobacter pylori.

PubMed

Johnson, Ryan C; Hu, Heidi Q; Merrell, D Scott; Maroney, Michael J

2015-04-01

Helicobacter pylori requires urease activity in order to survive in the acid environment of the human stomach. Urease is regulated in part by nickelation, a process that requires the HypA protein, which is a putative nickel metallochaperone that is generally associated with hydrogenase maturation. However, in H. pylori, HypA plays a dual role. In addition to an N-terminal nickel binding site, HypA proteins also contain a structural zinc site that is coordinated by two rigorously conserved CXXC sequences, which in H. pylori are flanked by His residues. These structural Zn sites are known to be dynamic, converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in the presence of Ni(ii) ions. In this study, mutant strains of H. pylori that express zinc site variants of the HypA protein are used to show that the structural changes in the zinc site are important for the acid viability of the bacterium, and that a reduction in acid viability in these variants can be traced in large measure to deficient urease activity. This in turn leads to a model that connects the Zn(Cys)4 coordination to urease maturation.

Analysis of an age structured model for tick populations subject to seasonal effects

NASA Astrophysics Data System (ADS)

Liu, Kaihui; Lou, Yijun; Wu, Jianhong

2017-08-01

We investigate an age-structured hyperbolic equation model by allowing the birth and death functions to be density dependent and periodic in time with the consideration of seasonal effects. By studying the integral form solution of this general hyperbolic equation obtained through the method of integration along characteristics, we give a detailed proof of the uniqueness and existence of the solution in light of the contraction mapping theorem. With additional biologically natural assumptions, using the tick population growth as a motivating example, we derive an age-structured model with time-dependent periodic maturation delays, which is quite different from the existing population models with time-independent maturation delays. For this periodic differential system with seasonal delays, the basic reproduction number R0 is defined as the spectral radius of the next generation operator. Then, we show the tick population tends to die out when R0 < 1 while remains persistent if R0 > 1. When there is no intra-specific competition among immature individuals due to the sufficient availability of immature tick hosts, the global stability of the positive periodic state for the whole model system of four delay differential equations can be obtained with the observation that a scalar subsystem for the adult stage size can be decoupled. The challenge for the proof of such a global stability result can be overcome by introducing a new phase space, based on which, a periodic solution semiflow can be defined which is eventually strongly monotone and strictly subhomogeneous.

A Functional Interplay between Human Immunodeficiency Virus Type 1 Protease Residues 77 and 93 Involved in Differential Regulation of Precursor Autoprocessing and Mature Protease Activity

PubMed Central

Counts, Christopher J.; Ho, P. Shing; Donlin, Maureen J.; Tavis, John E.; Chen, Chaoping

2015-01-01

HIV-1 protease (PR) is a viral enzyme vital to the production of infectious virions. It is initially synthesized as part of the Gag-Pol polyprotein precursor in the infected cell. The free mature PR is liberated as a result of precursor autoprocessing upon virion release. We previously described a model system to examine autoprocessing in transfected mammalian cells. Here, we report that a covariance analysis of miniprecursor (p6*-PR) sequences derived from drug naïve patients identified a series of amino acid pairs that vary together across independent viral isolates. These covariance pairs were used to build the first topology map of the miniprecursor that suggests high levels of interaction between the p6* peptide and the mature PR. Additionally, several PR-PR covariance pairs are located far from each other (>12 Å Cα to Cα) relative to their positions in the mature PR structure. Biochemical characterization of one such covariance pair (77–93) revealed that each residue shows distinct preference for one of three alkyl amino acids (V, I, and L) and that a polar or charged amino acid at either of these two positions abolishes precursor autoprocessing. The most commonly observed 77V is preferred by the most commonly observed 93I, but the 77I variant is preferred by other 93 variances (L, V, or M) in supporting precursor autoprocessing. Furthermore, the 77I93V covariant enhanced precursor autoprocessing and Gag polyprotein processing but decreased the mature PR activity. Therefore, both covariance and biochemical analyses support a functional association between residues 77 and 93, which are spatially distant from each other in the mature PR structure. Our data also suggests that these covariance pairs differentially regulate precursor autoprocessing and the mature protease activity. PMID:25893662

Chemical and nanometer-scale structure of kerogen and its change during thermal maturation investigated by advanced solid-state 13C NMR spectroscopy

USGS Publications Warehouse

Mao, J.; Fang, X.; Lan, Y.; Schimmelmann, A.; Mastalerz, Maria; Xu, L.; Schmidt-Rohr, K.

2010-01-01

We have used advanced and quantitative solid-state nuclear magnetic resonance (NMR) techniques to investigate structural changes in a series of type II kerogen samples from the New Albany Shale across a range of maturity (vitrinite reflectance R0 from 0.29% to 1.27%). Specific functional groups such as CH3, CH2, alkyl CH, aromatic CH, aromatic C-O, and other nonprotonated aromatics, as well as "oil prone" and "gas prone" carbons, have been quantified by 13C NMR; atomic H/C and O/C ratios calculated from the NMR data agree with elemental analysis. Relationships between NMR structural parameters and vitrinite reflectance, a proxy for thermal maturity, were evaluated. The aromatic cluster size is probed in terms of the fraction of aromatic carbons that are protonated (???30%) and the average distance of aromatic C from the nearest protons in long-range H-C dephasing, both of which do not increase much with maturation, in spite of a great increase in aromaticity. The aromatic clusters in the most mature sample consist of ???30 carbons, and of ???20 carbons in the least mature samples. Proof of many links between alkyl chains and aromatic rings is provided by short-range and long-range 1H-13C correlation NMR. The alkyl segments provide most H in the samples; even at a carbon aromaticity of 83%, the fraction of aromatic H is only 38%. While aromaticity increases with thermal maturity, most other NMR structural parameters, including the aromatic C-O fractions, decrease. Aromaticity is confirmed as an excellent NMR structural parameter for assessing thermal maturity. In this series of samples, thermal maturation mostly increases aromaticity by reducing the length of the alkyl chains attached to the aromatic cores, not by pronounced growth of the size of the fused aromatic ring clusters. ?? 2010 Elsevier Ltd. All rights reserved.

Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements

DOE PAGES

Weck, Philippe F.; Kim, Eunja; Wang, Yifeng; ...

2017-08-01

Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematicallymore » compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.« less

Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements.

PubMed

Weck, Philippe F; Kim, Eunja; Wang, Yifeng; Kruichak, Jessica N; Mills, Melissa M; Matteo, Edward N; Pellenq, Roland J-M

2017-08-01

Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematically compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.

Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements

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

Weck, Philippe F.; Kim, Eunja; Wang, Yifeng

Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematicallymore » compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.« less

Parent Relationships, Emotion Regulation, Psychosocial Maturity and College Student Alcohol Use Problems

ERIC Educational Resources Information Center

Fischer, Judith L.; Forthun, Larry F.; Pidcock, Boyd W.; Dowd, Duane A.

2007-01-01

This study tested associations between problems in parent-youth relationships and problems with alcohol use among college students (N = 1592) using structural equation modeling. Hypotheses were that relationships between both substance-specific parenting factors (parental drinking) and non-substance-specific parenting factors (parental intrusive…

Effects of Interdisciplinary Education on Technology-Driven Application Design

ERIC Educational Resources Information Center

Tafa, Z.; Rakocevic, G.; Mihailovic, D.; Milutinovic, V.

2011-01-01

This paper describes the structure and the underlying rationale of a new course dedicated to capability maturity model integration (CMMI)-directed design of wireless sensor networks (WSNs)-based biomedical applications that stresses: 1) engineering-, medico-engineering-, and informatics-related issues; 2) design for general- and special-purpose…

Customer-Provider Strategic Alignment: A Maturity Model

NASA Astrophysics Data System (ADS)

Luftman, Jerry; Brown, Carol V.; Balaji, S.

This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

NASA Astrophysics Data System (ADS)

Buglione, Luigi

During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

Effects of posttreatment skeletal maturity measured with the cervical vertebral maturation method on incisor alignment relapse.

PubMed

Fudalej, Piotr; Rothe, Laura E; Bollen, Anne-Marie

2008-08-01

Our aim was to test the hypothesis that relapse of incisor alignment is associated with skeletal maturity at the end of treatment, as assessed with the cervical vertebral maturation (CVM) method. This was a case-control study with information from the postretention database at the University of Washington. Mandibular incisor irregularity (II) at least 10 years out of retention (T3) was used to define the subjects (II >6 mm, relapse group) and the controls (II <3.5 mm, stable group). The following model measurements were made: II at pretreatment (T1), II at posttreatment (T2), and intercanine width at T1 and T2. On cephalograms taken T2, the CVM status was determined. Logistic regression analyses were used to determine the association between relapse and CVM status after treatment. The models were adjusted for potentially confounding variables (II at pretreatment and posttreatment, intercanine width change during treatment, sex, age at T2, and treatment alternatives). No association between CVM stage at T2 and relapse was found (P = 0.89). Both groups had similar distributions of the CVM stages (P >0.05). Pretreatment II and postretention time were found to be correlated with long-term incisor stability (P = 0.007 and 0.034, respectively). Sex was not related to relapse (P = 0.33). Maturity of craniofacial structures at the end of treatment evaluated with the CVM method is not associated with long-term stability of incisor alignment.

Integration of Posttranscriptional Gene Networks into Metabolic Adaptation and Biofilm Maturation in Candida albicans

PubMed Central

Harrison, Paul F.; Lo, Tricia L.; Quenault, Tara; Dagley, Michael J.; Bellousoff, Matthew; Powell, David R.; Beilharz, Traude H.; Traven, Ana

2015-01-01

The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are incompletely defined. For example, metabolic change is a major feature that distinguishes community growth of C. albicans in biofilms compared to suspension cultures, but how metabolic adaptation is functionally interfaced with the structural and gene regulatory changes that drive biofilm maturation remains to be fully understood. We show here that the RNA binding protein Puf3 regulates a posttranscriptional mRNA network in C. albicans that impacts on mitochondrial biogenesis, and provide the first functional data suggesting evolutionary rewiring of posttranscriptional gene regulation between the model yeast Saccharomyces cerevisiae and C. albicans. A proportion of the Puf3 mRNA network is differentially expressed in biofilms, and by using a mutant in the mRNA deadenylase CCR4 (the enzyme recruited to mRNAs by Puf3 to control transcript stability) we show that posttranscriptional regulation is important for mitochondrial regulation in biofilms. Inactivation of CCR4 or dis-regulation of mitochondrial activity led to altered biofilm structure and over-production of extracellular matrix material. The extracellular matrix is critical for antifungal resistance and immune evasion, and yet of all biofilm maturation pathways extracellular matrix biogenesis is the least understood. We propose a model in which the hypoxic biofilm environment is sensed by regulators such as Ccr4 to orchestrate metabolic adaptation, as well as the regulation of extracellular matrix production by impacting on the expression of matrix-related cell wall genes. Therefore metabolic changes in biofilms might be intimately linked to a key biofilm maturation mechanism that ultimately results in untreatable fungal disease. PMID:26474309

BASIN ANALYSIS AND PETROLEUM SYSTEM CHARACTERIZATION AND MODELING, INTERIOR SALT BASINS, CENTRAL AND EASTERN GULF OF MEXICO

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

Ernest A. Mancini; Donald A. Goddard; Ronald K. Zimmerman

2005-05-10

The principal research effort for Year 2 of the project has been data compilation and the determination of the burial and thermal maturation histories of the North Louisiana Salt Basin and basin modeling and petroleum system identification. In the first nine (9) months of Year 2, the research focus was on the determination of the burial and thermal maturation histories, and during the remainder of the year the emphasis has basin modeling and petroleum system identification. Existing information on the North Louisiana Salt Basin has been evaluated, an electronic database has been developed, regional cross sections have been prepared, structuremore » and isopach maps have been constructed, and burial history, thermal maturation history and hydrocarbon expulsion profiles have been prepared. Seismic data, cross sections, subsurface maps and related profiles have been used in evaluating the tectonic, depositional, burial and thermal maturation histories of the basin. Oil and gas reservoirs have been found to be associated with salt-supported anticlinal and domal features (salt pillows, turtle structures and piercement domes); with normal faulting associated with the northern basin margin and listric down-to-the-basin faults (state-line fault complex) and faulted salt features; and with combination structural and stratigraphic features (Sabine and Monroe Uplifts) and monoclinal features with lithologic variations. Petroleum reservoirs are mainly Upper Jurassic and Lower Cretaceous fluvial-deltaic sandstone facies and Lower Cretaceous and Upper Cretaceous shoreline, marine bar and shallow shelf sandstone facies. Cretaceous unconformities significantly contribute to the hydrocarbon trapping mechanism capacity in the North Louisiana Salt Basin. The chief petroleum source rock in this basin is Upper Jurassic Smackover lime mudstone beds. The generation of hydrocarbons from Smackover lime mudstone was initiated during the Early Cretaceous and continued into the Tertiary. Hydrocarbon expulsion commenced during the Early Cretaceous and continued into the Tertiary with peak expulsion occurring mainly during the Late Cretaceous.« less

Trophic flow structure of a neotropical estuary in northeastern Brazil and the comparison of ecosystem model indicators of estuaries

NASA Astrophysics Data System (ADS)

Lira, Alex; Angelini, Ronaldo; Le Loc'h, François; Ménard, Frédéric; Lacerda, Carlos; Frédou, Thierry; Lucena Frédou, Flávia

2018-06-01

We developed an Ecopath model for the Estuary of Sirinhaém River (SIR), a small-sized system surrounded by mangroves, subject to high impact, mainly by the sugar cane and other farming industries in order to describe the food web structure and trophic interactions. In addition, we compared our findings with those of 20 available Ecopath estuarine models for tropical, subtropical and temperate regions, aiming to synthesize the knowledge on trophic dynamics and provide a comprehensive analysis of the structures and functioning of estuaries. Our model consisted of 25 compartments and its indicators were within the expected range for estuarine areas around the world. The average trophic transfer efficiency for the entire system was 11.8%, similar to the theoretical value of 10%. The Keystone Index and MTI (Mixed Trophic Impact) analysis indicated that the snook (Centropomus undecimalis and Centropomus parallelus) and jack (Caranx latus and Caranx hippos) are considered as key resources in the system, revealing their high impact in the food web. Both groups have a high ecological and commercial relevance, despite the unregulated fisheries. As result of the comparison of ecosystem model indicators in estuaries, differences in the ecosystem structure from the low latitude zones (tropical estuaries) to the high latitude zones (temperate system) were noticed. The structure of temperate and sub-tropical estuaries is based on high flows of detritus and export, while tropical systems have high biomass, respiration and consumption rates. Higher values of System Omnivory Index (SOI) and Overhead (SO) were observed in the tropical and subtropical estuaries, denoting a more complex food chain. Globally, none of the estuarine models were classified as fully mature ecosystems, although the tropical ecosystems were considered more mature than the subtropical and temperate ecosystems. This study is an important contribution to the trophic modeling of estuaries, which may also help the knowledge of the role of key ecosystem processes in SIR.

Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function.

PubMed

Herron, Todd J; Rocha, Andre Monteiro Da; Campbell, Katherine F; Ponce-Balbuena, Daniela; Willis, B Cicero; Guerrero-Serna, Guadalupe; Liu, Qinghua; Klos, Matt; Musa, Hassan; Zarzoso, Manuel; Bizy, Alexandra; Furness, Jamie; Anumonwo, Justus; Mironov, Sergey; Jalife, José

2016-04-01

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electric impulse propagation velocity and immature action potential profiles. Here, we have identified an optimal extracellular matrix for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal extracellular matrix combination have impulse propagation velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) and have mature cardiomyocyte action potential profiles, including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s; n=5 monolayers). In addition, the optimal extracellular matrix promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1, and connexin43) and myofilament markers (cardiac troponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase activation prevented structural maturation. Maturation of human stem cell-derived cardiomyocyte monolayers is achieved in a 1-week period by plating cardiomyocytes on PDMS (polydimethylsiloxane) coverslips rather than on conventional 2-dimensional cell culture formats, such as glass coverslips or plastic dishes. Activation of integrin signaling and focal adhesion kinase is essential for significant maturation of human cardiac monolayers. © 2016 American Heart Association, Inc.

Learning-based prediction of gestational age from ultrasound images of the fetal brain.

PubMed

Namburete, Ana I L; Stebbing, Richard V; Kemp, Bryn; Yaqub, Mohammad; Papageorghiou, Aris T; Alison Noble, J

2015-04-01

We propose an automated framework for predicting gestational age (GA) and neurodevelopmental maturation of a fetus based on 3D ultrasound (US) brain image appearance. Our method capitalizes on age-related sonographic image patterns in conjunction with clinical measurements to develop, for the first time, a predictive age model which improves on the GA-prediction potential of US images. The framework benefits from a manifold surface representation of the fetal head which delineates the inner skull boundary and serves as a common coordinate system based on cranial position. This allows for fast and efficient sampling of anatomically-corresponding brain regions to achieve like-for-like structural comparison of different developmental stages. We develop bespoke features which capture neurosonographic patterns in 3D images, and using a regression forest classifier, we characterize structural brain development both spatially and temporally to capture the natural variation existing in a healthy population (N=447) over an age range of active brain maturation (18-34weeks). On a routine clinical dataset (N=187) our age prediction results strongly correlate with true GA (r=0.98,accurate within±6.10days), confirming the link between maturational progression and neurosonographic activity observable across gestation. Our model also outperforms current clinical methods by ±4.57 days in the third trimester-a period complicated by biological variations in the fetal population. Through feature selection, the model successfully identified the most age-discriminating anatomies over this age range as being the Sylvian fissure, cingulate, and callosal sulci. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Subcellular localization of calcium and Ca-ATPase activity during nuclear maturation in Bufo arenarum oocytes.

PubMed

Ramos, Inés; Cisint, Susana B; Crespo, Claudia A; Medina, Marcela F; Fernández, Silvia N

2009-08-01

The localization of calcium and Ca-ATPase activity in Bufo arenarum oocytes was investigated by ultracytochemical techniques during progesterone-induced nuclear maturation, under in vitro conditions. No Ca2+ deposits were detected in either control oocytes or progesterone-treated ones for 1-2 h. At the time when nuclear migration started, electron dense deposits of Ca2+ were visible in vesicles, endoplasmic reticulum cisternae and in the space between the annulate lamellae membranes. Furthermore, Ca-ATPase activity was also detected in these membrane structures. As maturation progressed, the cation deposits were observed in the cytomembrane structures, which underwent an important reorganization and redistribution. Thus, they moved from the subcortex and became located predominantly in the oocyte cortex area when nuclear maturation ended. Ca2+ stores were observed in vesicles surrounding or between the cortical granules, which are aligned close to the plasma membrane. The positive Ca-ATPase reaction in these membrane structures could indicate that the calcium deposit is an ATP-dependent process. Our results suggest that during oocyte maturation calcium would be stored in membrane structures where it remains available for release at the time of fertilization. Data obtained under our experimental conditions indicate that calcium from the extracellular medium would be important for the oocyte maturation process.

Structure of cellulose microfibrils in mature cotton fibres.

PubMed

Martínez-Sanz, Marta; Pettolino, Filomena; Flanagan, Bernadine; Gidley, Michael J; Gilbert, Elliot P

2017-11-01

The structure of cellulose microfibrils in mature cotton fibres from three varieties - Gossypium hirsutum, G. barbadense and G. arboreum - has been investigated by a multi-technique approach combining small angle scattering techniques with spectroscopy and diffraction. Cellulose microfibrils present a Iβ-rich crystalline structure with limited surface disorder. Small angle scattering (SAXS and SANS) data have been successfully fitted using a core-shell model and the results obtained indicate that the cellulose microfibrils, formed by the association of 2-3 elementary fibrils, are composed of a ca. 2nm impermeable crystalline core, surrounded by a partially hydrated paracrystalline shell, with overall cross-sections of ca. 3.6-4.7nm. Different low levels of cell wall matrix components have a strong impact on the microfibril architecture and enable moisture penetration upon hydration. Furthermore, the higher amounts of non-cellulosic components in G. barbadense result in a less dense packing of cellulose microfibrils and increased solvent accessibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

Basin Analysis and Petroleum System Characterization and Modeling, Interior Salt Basins, Central and Eastern Gulf of Mexico

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

Ernest A. Mancini; Paul Aharon; Donald A. Goddard

2006-05-26

The principal research effort for Phase 1 (Concept Development) of the project has been data compilation; determination of the tectonic, depositional, burial, and thermal maturation histories of the North Louisiana Salt Basin; basin modeling (geohistory, thermal maturation, hydrocarbon expulsion); petroleum system identification; comparative basin evaluation; and resource assessment. Existing information on the North Louisiana Salt Basin has been evaluated, an electronic database has been developed, and regional cross sections have been prepared. Structure, isopach and formation lithology maps have been constructed, and burial history, thermal maturation history, and hydrocarbon expulsion profiles have been prepared. Seismic data, cross sections, subsurface mapsmore » and burial history, thermal maturation history, and hydrocarbon expulsion profiles have been used in evaluating the tectonic, depositional, burial and thermal maturation histories of the basin. Oil and gas reservoirs have been found to be associated with salt-supported anticlinal and domal features (salt pillows, turtle structures and piercement domes); with normal faulting associated with the northern basin margin and listric down-to-the-basin faults (state-line fault complex) and faulted salt features; and with combination structural and stratigraphic features (Sabine and Monroe Uplifts) and monoclinal features with lithologic variations. Petroleum reservoirs include Upper Jurassic and Cretaceous fluvial-deltaic sandstone facies; shoreline, marine bar and shallow shelf sandstone facies; and carbonate shoal, shelf and reef facies. Cretaceous unconformities significantly contribute to the hydrocarbon trapping mechanism capacity in the North Louisiana Salt Basin. The chief petroleum source rock in this basin is Upper Jurassic Smackover lime mudstone beds. The generation of hydrocarbons from Smackover lime mudstone was initiated during the Early Cretaceous and continued into the Tertiary. Hydrocarbon expulsion commenced during the Early Cretaceous and continued into the Tertiary with peak expulsion occurring during the Early to Late Cretaceous. The geohistory of the North Louisiana Salt Basin is comparable to the Mississippi Interior Salt Basin with the major difference being the elevated heat flow the strata in the North Louisiana Salt Basin experienced in the Cretaceous due primarily to reactivation of upward movement, igneous activity, and erosion associated with the Monroe and Sabine Uplifts. Potential undiscovered reservoirs in the North Louisiana Salt Basin are Triassic Eagle Mills sandstone and deeply buried Upper Jurassic sandstone and limestone. Potential underdeveloped reservoirs include Lower Cretaceous sandstone and limestone and Upper Cretaceous sandstone.« less

Maturity Models of Healthcare Information Systems and Technologies: a Literature Review.

PubMed

Carvalho, João Vidal; Rocha, Álvaro; Abreu, António

2016-06-01

The maturity models are instruments to facilitate organizational management, including the management of its information systems function. These instruments are used also in hospitals. The objective of this article is to identify and compare the maturity models for management of information systems and technologies (IST) in healthcare. For each maturity model, it is identified the methodology of development and validation, as well as the scope, stages and their characteristics by dimensions or influence factors. This study resulted in the need to develop a maturity model based on a holistic approach. It will include a comprehensive set of influencing factors to reach all areas and subsystems of health care organizations.

Social support and youth physical activity: the role of provider and type.

PubMed

Beets, Michael W; Vogel, Randy; Forlaw, Loretta; Pitetti, Kenneth H; Cardinal, Bradley J

2006-01-01

To examine provider and type variation in social support (SS) for activity. Three hundred sixty-three fifth to eighth-grade students completed a questionnaire assessing self-reported activity and social support (SS) from 3 providers: mom, dad, and peers. Important covariates of activity were included in the analysis: age, BMI, sex, and maturation. Structural equation modeling indicated peers, transportation, and praise affected activity levels. Boys reported greater SS than girls did. Maturation, age, and BMI exhibited unique affects on SS. Increasing positive feedback, transportation to places to be active, and peer support may prove advantageous in improving activity levels in this age-group.

Long-range dependence and multifractality in the term structure of LIBOR interest rates

NASA Astrophysics Data System (ADS)

Cajueiro, Daniel O.; Tabak, Benjamin M.

2007-01-01

In this paper we present evidence of long-range dependence in LIBOR interest rates. We study a data set from 2000 to 2005, for six different currencies and various maturities. Empirical results suggest that the degree of long-range dependence decreases with maturity, with the exception of interest rates on Japanese Yen and on Indonesian Rupiah. Furthermore, interest rates have a multifractal nature and the degree of multifractality is much stronger for Indonesia (emerging market). These findings suggest that interest rates derivatives should take these features into account. Furthermore, fixed income risk and portfolio management should incorporate long-range dependence in the modeling of interest rates.

Effects of simulated weightlessness on mammalian development. Part 1: Development of clinostat for mammalian tissue culture and use in studies on meiotic maturation of mouse oocytes

NASA Technical Reports Server (NTRS)

Wolegemuth, D. J.; Grills, G. S.

1984-01-01

The effects of weightlessness on three aspects of mammalian reproduction: oocyte development, fertilization, and early embryogenesis was studied. Zero-gravity conditions within the laboratory by construction of a clinostat designed to support in vitro tissue culture were simulated and the effects of simulated weightlessness on meiotic maturation in mammalian oocytes using mouse as the model system were studied. The timing and frequency of germinal vesicule breakdown and polar body extrusion, and the structural and numerical properties of meiotic chromosomes at Metaphase and Metaphase of meiosis are assessed.

In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

PubMed

Martin, J T; Gullbrand, S E; Kim, D H; Ikuta, K; Pfeifer, C G; Ashinsky, B G; Smith, L J; Elliott, D M; Smith, H E; Mauck, R L

2017-11-17

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

Naturally Engineered Maturation of Cardiomyocytes

PubMed Central

Scuderi, Gaetano J.; Butcher, Jonathan

2017-01-01

Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte maturation. This information can then be utilized to develop natural engineering approaches that can emulate this fetal microenvironment and thus make prominent progress in pluripotent stem cell-derived maturity toward a more clinically relevant model for cardiac regeneration. PMID:28529939

Post-natal molecular adaptations in anteromedial and posterolateral bundles of the ovine anterior cruciate ligament: one structure with two parts or two distinct ligaments?

PubMed

Huebner, Kyla D; O'Brien, Etienne J O; Heard, Bryan J; Chung, May; Achari, Yamini; Shrive, Nigel G; Frank, Cyril B

2012-01-01

The human anterior cruciate ligament (ACL) is a composite structure of two anatomically distinct bundles: an anteromedial (AM) and posterolateral (PL) bundles. Tendons are often used as autografts for surgical reconstruction of ACL following severe injury. However, despite successful surgical reconstruction, some people experience re-rupture and later development of osteoarthritis. Understanding the structure and molecular makeup of normal ACL is essential for its optimal replacement. Reportedly the two bundles display different tensions throughout joint motion and may be fundamentally different. This study assessed the similarities and differences in ultrastructure and molecular composition of the AM and PL bundles to test the hypothesis that the two bundles of the ACL develop unique characteristics with maturation. ACLs from nine mature and six immature sheep were compared. The bundles were examined for mRNA and protein levels of collagen types I, III, V, and VI, and two proteoglycans. The fibril diameter composition of the two bundles was examined with transmission electron microscopy. Maturation does alter the molecular and structural composition of the two bundles of ACL. Although the PL band appears to mature slower than the AM band, no significant differences were detected between the bundles in the mature animals. We thus reject our hypothesis that the two ACL bundles are distinct. The two anatomically distinct bundles of the sheep ACL can be considered as two parts of one structure at maturity and material that would result in a structure of similar functionality can be used to replace each ACL bundle in the sheep.

Surgical option for the correction of Peyronie's disease: an autologous tissue-engineered endothelialized graft.

PubMed

Imbeault, Annie; Bernard, Geneviève; Ouellet, Gabrielle; Bouhout, Sara; Carrier, Serge; Bolduc, Stéphane

2011-11-01

Surgical treatment is indicated in severe cases of Peyronie's disease. Incision of the plaque with subsequent graft material implantation is the option of choice. Ideal graft tissue is not yet available. To evaluate the use of an autologous tissue-engineered endothelialized graft by the self-assembly method, for tunica albuginea (TA) reconstruction in Peyronie's disease. Two TA models were created. Human fibroblasts were isolated from a skin biopsy and cultured in vitro until formation of fibroblast sheets. After 4 weeks of maturation, human umbilical vein endothelial cells (HUVEC) were seeded on fibroblasts sheets and wrapped around a tubular support to form a cylinder of about 10 layers. After 21 days of tube maturation, HUVEC were seeded into the lumen of the fibroblast tubes for the endothelialized tunica albuginea (ETA). No HUVEC were seeded into the lumen for the TA model. Both constructs were placed under perfusion in a bioreactor for 1 week. Histology, immunohistochemistry, and burst pressure were performed to characterize mature tubular graft. Animal manipulations were also performed to demonstrate the impact of endothelial cells in vivo. Histology showed uniform multilayered fibroblasts. Extracellular matrix, produced entirely by fibroblasts, presented a good staining for collagen 1. Some elastin fibers were also present. For the TA model, anti-human von Willebrand antibody revealed the endothelial cells forming capillary-like structures. TA model reached a burst pressure of 584 mm Hg and ETA model obtained a burst pressure of 719 mm Hg. This tissue-engineered endothelialized tubular graft is structurally similar to normal TA and presents an adequate mechanical resistance. The self-assembly method used and the autologous property of this model could represent an advantage comparatively to other available grafts. Further evaluation including functional testing will be necessary to characterize in vivo implantation and behavior of the graft. © 2011 International Society for Sexual Medicine.

A Curriculum Proposal for the Development of Maturity in Students.

ERIC Educational Resources Information Center

Jelinek, James John

Development of the mature person is a necessary theme for educational design in contemporary society. A structured definition of the term "maturity" is needed which can be applied to the design of educational experience. The author suggests that there are six criteria of maturity: intelligence, responsiblity, articulation, empathy, sexuality, and…

Asymmetry of intronic pre-miRNA structures in functional RISC assembly

PubMed Central

Lin, Shi-Lung; Chang, Donald; Ying, Shao-Yao

2006-01-01

The two oligonucleotide strands of a siRNA duplex are functionally asymmetric in assembling the RNAi effector, RNA-induced gene silencing complex (RISC). Based on this asymmetric RISC assembly model in vitro, formation of a microRNA (miRNA) and complementary miRNA (miRNA*) duplex was proposed to be an essential step for the assembly of miRNA-associated RISC (miRISC). We observed here that a strong structural bias exists in the selection of a mature miRNA strand for RISC assembly in zebrafish using an intronic miRNA-like vector to target EGFP mRNA for regulation. The position of the stemloop in a precursor miRNA (pre-miRNA) was involved in the determination of miRNA–miRNA* asymmetry of the pre-miRNA stemarm, leading to different miRNA maturation during miRISC assembly. These findings suggest that the miRISC assembly is likely different from the RISC assembly model of siRNA in zebrafish, providing the first in vivo evidence for asymmetric miRISC assembly. PMID:16005165

Critical review on the mechanisms of maturation stress generation in trees

PubMed Central

Clair, Bruno

2016-01-01

Trees control their posture by generating asymmetric mechanical stress around the periphery of the trunk or branches. This stress is produced in wood during the maturation of the cell wall. When the need for reaction is high, it is accompanied by strong changes in cell organization and composition called reaction wood, namely compression wood in gymnosperms and tension wood in angiosperms. The process by which stress is generated in the cell wall during its formation is not yet known, and various hypothetical mechanisms have been proposed in the literature. Here we aim at discriminating between these models. First, we summarize current knowledge about reaction wood structure, state and behaviour relevant to the understanding of maturation stress generation. Then, the mechanisms proposed in the literature are listed and discussed in order to identify which can be rejected based on their inconsistency with current knowledge at the frontier between plant science and mechanical engineering. PMID:27605169

Craniofacial morphology, dental occlusion, tooth eruption, and dental maturity in boys of short stature with or without growth hormone deficiency.

PubMed

Kjellberg, H; Beiring, M; Albertsson Wikland, K

2000-10-01

The aim of this project was to study the craniofacial morphology, dental occlusion, dental maturation and tooth eruption in short-statured boys with growth hormone secretion ranging from low to high. The measurements from lateral and posteroanterior cephalograms, orthopantomograms and plaster models were used. Almost all linear measurements of the facial structures were significantly smaller. A disproportionate growth in the cranial base structures as well as in the jaws resulted in facial retrognathia, a proportionately smaller posterior than anterior facial height, and a steep vertical inclination of the mandible. Dental crowding was more common and the overbite was small. Dental maturity and tooth eruption were delayed 1.2 and 1.3 yr, respectively. No significant differences between the idiopathic short-statured and the growth hormone-deficient group in any of the above-mentioned variables were found. It can be concluded that although most of the cephalometric variables measured differed significantly from the average, the facial appearance of the boys is not conspicuous and is of minor clinical importance. However, the short-statured boys might be in greater need of orthodontic treatment due to the higher percentage of dental crowding.

Basin deconstruction-construction: Seeking thermal-tectonic consistency through the integration of geochemical thermal indicators and seismic fault mechanical stratigraphy ​- Example from Faras Field, North Western Desert, Egypt

NASA Astrophysics Data System (ADS)

Pigott, John D.; Abouelresh, Mohamed O.

2016-02-01

To construct a model of a sedimentary basin's thermal tectonic history is first to deconstruct it: taking apart its geological elements, searching for its initial conditions, and then to reassemble the elements in the temporal order that the basin is assumed to have evolved. Two inherent difficulties implicit to the analysis are that most organic thermal indicators are cumulative, irreversible and a function of both temperature and time and the non-uniqueness of crustal strain histories which complicates tectonic interpretations. If the initial conditions (e.g. starting maturity of the reactants and initial crustal temperature) can be specified and the boundary conditions incrementally designated from changes in the lithospheric heat engine owing to stratigraphic structural constraints, then the number of pathways for the temporal evolution of a basin is greatly reduced. For this investigation, model input uncertainties are reduced through seeking a solution that iteratively integrates the geologically constrained tectonic subsidence, geochemically constrained thermal indicators, and geophysically constrained fault mechanical stratigraphy. The Faras oilfield in the Abu Gharadig Basin, North Western Desert, Egypt, provides an investigative example of such a basin's deconstructive procedure. Multiple episodes of crustal extension and shortening are apparent in the tectonic subsidence analyses which are constrained from the fault mechanical stratigraphy interpreted from reflection seismic profiles. The model was iterated with different thermal boundary conditions until outputs best fit the geochemical observations. In so doing, the thermal iterations demonstrate that general relationship that basin heat flow increases decrease vertical model maturity gradients, increases in surface temperatures shift vertical maturity gradients linearly to higher values, increases in sediment conductivities lower vertical maturities with depth, and the addition of ;ghost; layers (those layers removed) prior to the erosional event increase maturities beneath, and conversely. These integrated constraints upon the basin evolution model indicate that the principal source rocks, Khatatba and the lowest part of the Alam El Bueib formations, entered the oil window at approximately 95 Ma and the gas window at approximately 25 Ma. The upper part of the Alam El Bueib Formation is within the oil window at the present day. Establishing initial and boundary value conditions for a basin's thermal evolution when geovalidated by the integration of seismic fault mechanical stratigraphy, tectonic subsidence analysis, and organic geochemical maturity indicators provides a powerful tool for optimizing petroleum exploration in both mature and frontier basins.

Default risk modeling beyond the first-passage approximation: extended Black-Cox model.

PubMed

Katz, Yuri A; Shokhirev, Nikolai V

2010-07-01

We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm's ability to avoid default even if company's liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company's default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity.

A Maturity Model for Assessing the Use of ICT in School Education

ERIC Educational Resources Information Center

Solar, Mauricio; Sabattin, Jorge; Parada, Victor

2013-01-01

This article describes an ICT-based and capability-driven model for assessing ICT in education capabilities and maturity of schools. The proposed model, called ICTE-MM (ICT in School Education Maturity Model), has three elements supporting educational processes: information criteria, ICT resources, and leverage domains. Changing the traditional…

Constructing service-oriented architecture adoption maturity matrix using Kano model

NASA Astrophysics Data System (ADS)

Hamzah, Mohd Hamdi Irwan; Baharom, Fauziah; Mohd, Haslina

2017-10-01

Commonly, organizations adopted Service-Oriented Architecture (SOA) because it can provide a flexible reconfiguration and can reduce the development time and cost. In order to guide the SOA adoption, previous industry and academia have constructed SOA maturity model. However, there is a limited number of works on how to construct the matrix in the previous SOA maturity model. Therefore, this study is going to provide a method that can be used in order to construct the matrix in the SOA maturity model. This study adapts Kano Model to construct the cross evaluation matrix focused on SOA adoption IT and business benefits. This study found that Kano Model can provide a suitable and appropriate method for constructing the cross evaluation matrix in SOA maturity model. Kano model also can be used to plot, organize and better represent the evaluation dimension for evaluating the SOA adoption.

In vivo investigation of tissue-engineered periosteum for the repair of allogeneic critical size bone defects in rabbits.

PubMed

Zhao, Lin; Zhao, Junli; Yu, Jiajia; Sun, Rui; Zhang, Xiaofeng; Hu, Shuhua

2017-04-01

The aim of the study was to evaluate the efficacy of tissue-engineered periosteum (TEP) in repairing allogenic bone defects in the long term. TEP was biofabricated with osteoinduced rabbit bone marrow mesenchymal stem cells and porcine small intestinal submucosa (SIS). A total of 24 critical sized defects were created bilaterally in radii of 12 New Zealand White rabbits. TEP/SIS was implanted into the defect site. Bone defect repair was evaluated with radiographic and histological examination at 4, 8 and 12 weeks. Bone defects were structurally reconstructed in the TEP group with mature cortical bone and medullary canals, however this was not observed in the SIS group at 12 weeks. The TEP approach can effectively restore allogenic critical sized defects, and achieve maturity of long-bone structure in 12 weeks in rabbit models.

Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation

PubMed Central

Grabrucker, Andreas M; Knight, Mary J; Proepper, Christian; Bockmann, Juergen; Joubert, Marisa; Rowan, Magali; Nienhaus, G UIrich; Garner, Craig C; Bowie, Jim U; Kreutz, Michael R; Gundelfinger, Eckart D; Boeckers, Tobias M

2011-01-01

Neuronal morphology and number of synapses is not static, but can change in response to a variety of factors, a process called synaptic plasticity. These structural and molecular changes are believed to represent the basis for learning and memory, thereby underling both the developmental and activity-dependent remodelling of excitatory synapses. Here, we report that Zn2+ ions, which are highly enriched within the postsynaptic density (PSD), are able to influence the recruitment of ProSAP/Shank proteins to PSDs in a family member-specific manner during the course of synaptogenesis and synapse maturation. Through selectively overexpressing each family member at excitatory postsynapses and comparing this to shRNA-mediated knockdown, we could demonstrate that only the overexpression of zinc-sensitive ProSAP1/Shank2 or ProSAP2/Shank3 leads to increased synapse density, although all of them cause a decrease upon knockdown. Furthermore, depletion of synaptic Zn2+ along with the knockdown of zinc-insensitive Shank1 causes the rapid disintegration of PSDs and the loss of several postsynaptic molecules including Homer1, PSD-95 and NMDA receptors. These findings lead to the model that the concerted action of ProSAP/Shank and Zn2+ is essential for the structural integrity of PSDs and moreover that it is an important element of synapse formation, maturation and structural plasticity. PMID:21217644

[Natural succession of vegetation in Tiantong National Forest Park, Zhejiang Province of East China: a simulation study].

PubMed

Lü, Na; Ni, Jian

2013-01-01

By using spatially explicit landscape model (LANDIS 6.0 PRO), and parameterized this model with the long-term research and observation data of Tiantong National Station of Forest Eco-system Observation and Research, this paper simulated the natural succession of evergreen broad-leaved forest in Tiantong National Forest park, Zhejiang Province in the future 500 years, analyzed the spatial distribution and age structure of dominant species and major landscapes, and explored the succession pattern of the evergreen broad-leaved forest. In the park, the species alternation mostly occurred before the stage of evergreen broad-leaved forest. Pinus massoniana, Quercus fabric, and Liquidambar formosana occupied a large proportion during the early succession, but gradually disappeared with the succession process. Schima superba and Castanopsis fargesii took the main advantage in late succession, and developed to the climax community. Under the conditions without disturbances, the community was mainly composed of young forests in the early succession, and of mature or over-mature forests in the late succession, implying the insufficient regeneration ability of the community. LANDIS model could be used for simulating the landscape dynamics of evergreen broad-leaved forest in eastern China. In the future research, both the model structure and the model parameters should be improved, according to the complexity and diversity of subtropical evergreen broad-leaved forest.

An unexpected twist in viral capsid maturation

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

Gertsman, Ilya; Gan, Lu; Guttman, Miklos

2009-04-14

Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsidmore » structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.« less

Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?

PubMed

Mychasiuk, Richelle; Metz, Gerlinde A S

2016-11-01

Adolescence is defined as the gradual period of transition between childhood and adulthood that is characterized by significant brain maturation, growth spurts, sexual maturation, and heightened social interaction. Although originally believed to be a uniquely human aspect of development, rodent and non-human primates demonstrate maturational patterns that distinctly support an adolescent stage. As epigenetic processes are essential for development and differentiation, but also transpire in mature cells in response to environmental influences, they are an important aspect of adolescent brain maturation. The purpose of this review article was to examine epigenetic programming in animal models of brain maturation during adolescence. The discussion focuses on animal models to examine three main concepts; epigenetic processes involved in normal adolescent brain maturation, the influence of fetal programming on adolescent brain development and the epigenome, and finally, postnatal experiences such as exercise and drugs that modify epigenetic processes important for adolescent brain maturation. This corollary emphasizes the utility of animal models to further our understanding of complex processes such as epigenetic regulation and brain development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Carbohydrate and lipid spectroscopic molecular structures of different alfalfa hay and their relationship with nutrient availability in ruminants

PubMed Central

Yari, Mojtaba; Valizadeh, Reza; Nnaserian, Abbas Ali; Jonker, Arjan; Yu, Peiqiang

2017-01-01

Objective This study was conducted to determine molecular structures related to carbohydrates and lipid in alfalfa hay cut at early bud, late bud and early flower and in the afternoon and next morning using Fourier transform infrared spectroscopy (FT/IR) and to determine their relationship with alfalfa hay nutrient profile and availability in ruminants. Methods Chemical composition analysis, carbohydrate fractionation, in situ ruminal degradability, and DVE/OEB model were used to measure nutrient profile and availability of alfalfa hay. Univariate analysis, hierarchical cluster analysis (CLA) and principal components analysis (PCA) were conducted to identify FT/IR spectra differences. Results The FT/IR non-structural carbohydrate (NSCHO) to total carbohydrates and NSCHO to structural carbohydrate ratios decreased (p<0.05), while lignin to NSCHO and lipid CH3 symmetric to CH2 symmetric ratios increased with advancing maturity (p<0.05). The FT/IR spectra related to structural carbohydrates, lignin and lipids were distinguished for alfalfa hay at three maturities by PCA and CLA, while FT/IR molecular structures related to carbohydrates and lipids were similar between alfalfa hay cut in the morning and afternoon when analyzed by PCA and CLA analysis. Positive correlations were found for FT/IR NSCHO to total carbohydrate and NSCHO to structural carbohydrate ratios with non-fiber carbohydrate (by wet chemistry), ruminal fast and intermediately degradable carbohydrate fractions and total ruminal degradability of carbohydrates and predicted intestinal nutrient availability in dairy cows (r≥0.60; p<0.05) whereas FT/IR lignin to NSCHO and CH3 to CH2 symmetric stretching ratio had negative correlation with predicted ruminal and intestinal nutrient availability of alfalfa hay in dairy cows (r≥−0.60; p<0.05). Conclusion FT/IR carbohydrate and lipid molecular structures in alfalfa hay changed with advancing maturity from early bud to early flower, but not during the day, and these molecular structures correlated with predicted nutrient supply of alfalfa hay in ruminants. PMID:28335093

Small-Angle and Ultrasmall-Angle Neutron Scattering (SANS/USANS) Study of New Albany Shale: A Treatise on Microporosity

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

Bahadur, Jitendra; Radlinski, Andrzej P.; Melnichenko, Yuri B.

We applied small-angle neutron scattering (SANS) and ultrasmall-angle neutron scattering (USANS) techniques to study the microstructure of several New Albany shales of different maturity. It has been established that the total porosity decreases with maturity and increases somewhat for post-mature samples. A new method of SANS data analysis was developed, which allows the extraction of information about the size range and number density of micropores from the relatively flat scattering intensity observed in the limit of the large scattering vector Q. Macropores and significant number of mesopores are surface fractals, and their structure can be described in terms of themore » polydisperse spheres (PDSP) model. The model-independent Porod invariant method was employed to estimate total porosity, and the results were compared with the PDSP model results. It has been demonstrated that independent evaluation of incoherent background is crucial for accurate interpretation of the scattering data in the limit of large Q-values. Moreover, pore volumes estimated by the N 2 and CO 2 adsorption, as well as via the mercury intrusion technique, have been compared with those measured by SANS/USANS, and possible reasons for the observed discrepancies are discussed.« less

Small-Angle and Ultrasmall-Angle Neutron Scattering (SANS/USANS) Study of New Albany Shale: A Treatise on Microporosity

DOE PAGES

Bahadur, Jitendra; Radlinski, Andrzej P.; Melnichenko, Yuri B.; ...

2014-12-17

We applied small-angle neutron scattering (SANS) and ultrasmall-angle neutron scattering (USANS) techniques to study the microstructure of several New Albany shales of different maturity. It has been established that the total porosity decreases with maturity and increases somewhat for post-mature samples. A new method of SANS data analysis was developed, which allows the extraction of information about the size range and number density of micropores from the relatively flat scattering intensity observed in the limit of the large scattering vector Q. Macropores and significant number of mesopores are surface fractals, and their structure can be described in terms of themore » polydisperse spheres (PDSP) model. The model-independent Porod invariant method was employed to estimate total porosity, and the results were compared with the PDSP model results. It has been demonstrated that independent evaluation of incoherent background is crucial for accurate interpretation of the scattering data in the limit of large Q-values. Moreover, pore volumes estimated by the N 2 and CO 2 adsorption, as well as via the mercury intrusion technique, have been compared with those measured by SANS/USANS, and possible reasons for the observed discrepancies are discussed.« less

The convergence of maturational change and structural covariance in human cortical networks.

PubMed

Alexander-Bloch, Aaron; Raznahan, Armin; Bullmore, Ed; Giedd, Jay

2013-02-13

Large-scale covariance of cortical thickness or volume in distributed brain regions has been consistently reported by human neuroimaging studies. The mechanism of this population covariance of regional cortical anatomy has been hypothetically related to synchronized maturational changes in anatomically connected neuronal populations. Brain regions that grow together, i.e., increase or decrease in volume at the same rate over the course of years in the same individual, are thus expected to demonstrate strong structural covariance or anatomical connectivity across individuals. To test this prediction, we used a structural MRI dataset on healthy young people (N = 108; aged 9-22 years at enrollment), comprising 3-6 longitudinal scans on each participant over 6-12 years of follow-up. At each of 360 regional nodes, and for each participant, we estimated the following: (1) the cortical thickness in the median scan and (2) the linear rate of change in cortical thickness over years of serial scanning. We constructed structural and maturational association matrices and networks from these measurements. Both structural and maturational networks shared similar global and nodal topological properties, as well as mesoscopic features including a modular community structure, a relatively small number of highly connected hub regions, and a bias toward short distance connections. Using resting-state functional magnetic resonance imaging data on a subset of the sample (N = 32), we also demonstrated that functional connectivity and network organization was somewhat predictable by structural/maturational networks but demonstrated a stronger bias toward short distance connections and greater topological segregation. Brain structural covariance networks are likely to reflect synchronized developmental change in distributed cortical regions.

RNA secondary structures of the bacteriophage phi6 packaging regions.

PubMed

Pirttimaa, M J; Bamford, D H

2000-06-01

Bacteriophage phi6 genome consists of three segments of double-stranded RNA. During maturation, single-stranded copies of these segments are packaged into preformed polymerase complex particles. Only phi6 RNA is packaged, and each particle contains only one copy of each segment. An in vitro packaging and replication assay has been developed for phi6, and the packaging signals (pac sites) have been mapped to the 5' ends of the RNA segments. In this study, we propose secondary structure models for the pac sites of phi6 single-stranded RNA segments. Our models accommodate data from structure-specific chemical modifications, free energy minimizations, and phylogenetic comparisons. Previously reported pac site deletion studies are also discussed. Each pac site possesses a unique architecture, that, however, contains common structural elements.

School Performance, Status Relations, and the Structure of Sentiment: Bringing the Teacher Back In.

ERIC Educational Resources Information Center

Alexander, Karl L; And Others

1987-01-01

Teachers' social origins influence their reactions to students. Low-status and minority students experience difficulties in the classrooms of high-status teachers. Outcomes of these relationships are that the students are seen as less mature and less is expected of them. A model of teacher-pupil background congruence is proposed. (Author/VM)

Chemical vapor deposition modeling for high temperature materials

NASA Technical Reports Server (NTRS)

Gokoglu, Suleyman A.

1992-01-01

The formalism for the accurate modeling of chemical vapor deposition (CVD) processes has matured based on the well established principles of transport phenomena and chemical kinetics in the gas phase and on surfaces. The utility and limitations of such models are discussed in practical applications for high temperature structural materials. Attention is drawn to the complexities and uncertainties in chemical kinetics. Traditional approaches based on only equilibrium thermochemistry and/or transport phenomena are defended as useful tools, within their validity, for engineering purposes. The role of modeling is discussed within the context of establishing the link between CVD process parameters and material microstructures/properties. It is argued that CVD modeling is an essential part of designing CVD equipment and controlling/optimizing CVD processes for the production and/or coating of high performance structural materials.

People Capability Maturity Model. SM.

DTIC Science & Technology

1995-09-01

People Capability Maturity Model SM .^^^^_ -——’ Bill Curtis William E. ] Sally Mille] Hefley r Accesion For t NTIS DTIC...People CMM The P-CMM adapts the architecture and the maturity framework underlying the CMM for use with people-related improvement issues. The CMM...focuses on helping organizations improve their software development processes. By adapting the maturity framework and the CMM architecture

Analysis of the 918th Contracting Battalion and 410th Contracting Support Brigade Utilizing the Contract Management Maturity Model

DTIC Science & Technology

2015-12-01

organizational structure of Army contracting and the changes to that organization under the MICC 2025 plan. We then describe the organizations where we... organizational change . Portal: Libraries and the Academy, 4(3), 345–361. McFall, T. (2015). 918th CBN/MICC-FC organizational overview [PowerPoint slides...Installation Contracting Command (MICC) are undergoing a significant change in structure known as MICC 2025. In order to gauge the effectiveness of this

Configuration Management Process Assessment Strategy

NASA Technical Reports Server (NTRS)

Henry, Thad

2014-01-01

Purpose: To propose a strategy for assessing the development and effectiveness of configuration management systems within Programs, Projects, and Design Activities performed by technical organizations and their supporting development contractors. Scope: Various entities CM Systems will be assessed dependent on Project Scope (DDT&E), Support Services and Acquisition Agreements. Approach: Model based structured against assessing organizations CM requirements including best practices maturity criteria. The model is tailored to the entity being assessed dependent on their CM system. The assessment approach provides objective feedback to Engineering and Project Management of the observed CM system maturity state versus the ideal state of the configuration management processes and outcomes(system). center dot Identifies strengths and risks versus audit gotcha's (findings/observations). center dot Used "recursively and iteratively" throughout program lifecycle at select points of need. (Typical assessments timing is Post PDR/Post CDR) center dot Ideal state criteria and maturity targets are reviewed with the assessed entity prior to an assessment (Tailoring) and is dependent on the assessed phase of the CM system. center dot Supports exit success criteria for Preliminary and Critical Design Reviews. center dot Gives a comprehensive CM system assessment which ultimately supports configuration verification activities.*

Mechanical factors direct mouse aortic remodelling during early maturation

PubMed Central

Le, Victoria P.; Cheng, Jeffrey K.; Kim, Jungsil; Staiculescu, Marius C.; Ficker, Shawn W.; Sheth, Saahil C.; Bhayani, Siddharth A.; Mecham, Robert P.; Yanagisawa, Hiromi; Wagenseil, Jessica E.

2015-01-01

Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin (Eln+/−) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression (Fbln5−/−). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies. PMID:25652465

Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52/55k

PubMed Central

Condezo, Gabriela N.; Marabini, Roberto; Ayora, Silvia; Carazo, José M.; Alba, Raúl; Chillón, Miguel

2015-01-01

ABSTRACT Adenovirus is one of the most complex icosahedral, nonenveloped viruses. Even after its structure was solved at near-atomic resolution by both cryo-electron microscopy and X-ray crystallography, the location of minor coat proteins is still a subject of debate. The elaborated capsid architecture is the product of a correspondingly complex assembly process, about which many aspects remain unknown. Genome encapsidation involves the concerted action of five virus proteins, and proteolytic processing by the virus protease is needed to prime the virion for sequential uncoating. Protein L1 52/55k is required for packaging, and multiple cleavages by the maturation protease facilitate its release from the nascent virion. Light-density particles are routinely produced in adenovirus infections and are thought to represent assembly intermediates. Here, we present the molecular and structural characterization of two different types of human adenovirus light particles produced by a mutant with delayed packaging. We show that these particles lack core polypeptide V but do not lack the density corresponding to this protein in the X-ray structure, thereby adding support to the adenovirus cryo-electron microscopy model. The two types of light particles present different degrees of proteolytic processing. Their structures provide the first glimpse of the organization of L1 52/55k protein inside the capsid shell and of how this organization changes upon partial maturation. Immature, full-length L1 52/55k is poised beneath the vertices to engage the virus genome. Upon proteolytic processing, L1 52/55k disengages from the capsid shell, facilitating genome release during uncoating. IMPORTANCE Adenoviruses have been extensively characterized as experimental systems in molecular biology, as human pathogens, and as therapeutic vectors. However, a clear picture of many aspects of their basic biology is still lacking. Two of these aspects are the location of minor coat proteins in the capsid and the molecular details of capsid assembly. Here, we provide evidence supporting one of the two current models for capsid architecture. We also show for the first time the location of the packaging protein L1 52/55k in particles lacking the virus genome and how this location changes during maturation. Our results contribute to clarifying standing questions in adenovirus capsid architecture and provide new details on the role of L1 52/55k protein in assembly. PMID:26178997

Structure and composition of vegetation along an elevational gradient in Puerto Rico.

Treesearch

W.A. Gould; G. Gonzalez; G. Carrero Rivera

2006-01-01

Question: What are the composition, conservation status, and structural and environmental characteristics of eight mature tropical forest plant communities that occur along an elevational gradient. Location: Northeastern Puerto Rico. Methods: We quantified the species composition, diversity, conservation status, and ecological attributes of eight mature tropical forest...

Game Maturity Model for Health Care.

PubMed

de Boer, Jan C; Adriani, Paul; van Houwelingen, Jan Willem; Geerts, A

2016-04-01

This article introduces the Game Maturity Model for the healthcare industry as an extension to the general Game Maturity Model and describes the usage by two case studies of applied health games. The Game Maturity Model for healthcare provides a practical and value-adding method to assess existing games and to determine strategic considerations for application of applied health games. Our forecast is that within 5 years the use and development of applied games will have a role in our daily lives and the way we organize health care that will be similar to the role social media has today.

Mature students' experiences of undergraduate nurse education programmes: the Irish experience.

PubMed

O'Brien, Frances; Keogh, Brian; Neenan, Kathleen

2009-08-01

In recent years mature students have been encouraged into nurse education for the valuable qualities they are known to possess, along with their ability to assist in providing a sustainable solution to the current health care crisis. Unfortunately corresponding resources and support structures have not accompanied this widening of access and mature students are expected to fit into structures that already exist, structures that were formulated with eighteen year olds in mind. This qualitative study explores the experiences of mature students in nurse education. Three discipline specific focus group interviews were used as a means of gathering data from 28 mature students. Data were analysed using thematic content analysis as described by Burnard [Burnard, P., 1991. A method of analysing interview transcripts in qualitative research. Nurse Education Today 11, 461-466]. Findings revealed that students continue to struggle with the academic component of the course. They also found it difficult to balance the home and university divide. Greater challenges were identified by female participants as they maintained their previous roles. Males on the other hand were provided with greater freedom to pursue their studies. There is a need for curricular changes to be implemented in order to provide a greater flexibility and supportive experience for mature students. Further research is advocated in this area.

Age, maturation, and population structure of the Humboldt squid Dosidicus gigas off the Peruvian Exclusive Economic Zones

NASA Astrophysics Data System (ADS)

Liu, Bilin; Chen, Xinjun; Chen, Yong; Tian, Siquan; Li, Jianhua; Fang, Zhou; Yang, Mingxia

2013-01-01

Age, maturation and population structure of the Humboldt squid Dosidicus gigas were studied based on random sampling of the Chinese jigging fishery off the Peruvian Exclusive Economic Zones (EEZ) during 2008-2010. Estimated ages ranged from 144 to 633 days, confirming that the squid is a short-lived species with longevity no longer than 2 years. Occurrence of mature females and hatching in each month indicated that Humboldt squid spawned year-round. Back-calculated hatching dates for the samples were from January 22nd, 2008 to April 22nd, 2010 with a peak between January and March. Two size-based and two hatching date-based populations could be defined from mantle length (ML) at maturity and back-calculated hatching dates, respectively. Females matured at a larger size than males, and there was a significant difference in ML at maturity between the two hatching groups ( P <0.05). The waters adjacent to 11°S off the Peruvian EEZ may be a potential spawning ground. This study shows the complexity of the population structure and large variability in key life history parameters in the Humboldt squid off the Peruvian EEZ, which should be considered in the assessment and management of this important resource.

Molecular cloning, sequence analysis and homology modeling of the first caudata amphibian antifreeze-like protein in axolotl (Ambystoma mexicanum).

PubMed

Zhang, Songyan; Gao, Jiuxiang; Lu, Yiling; Cai, Shasha; Qiao, Xue; Wang, Yipeng; Yu, Haining

2013-08-01

Antifreeze proteins (AFPs) refer to a class of polypeptides that are produced by certain vertebrates, plants, fungi, and bacteria and which permit their survival in subzero environments. In this study, we report the molecular cloning, sequence analysis and three-dimensional structure of the axolotl antifreeze-like protein (AFLP) by homology modeling of the first caudate amphibian AFLP. We constructed a full-length spleen cDNA library of axolotl (Ambystoma mexicanum). An EST having highest similarity (∼42%) with freeze-responsive liver protein Li16 from Rana sylvatica was identified, and the full-length cDNA was subsequently obtained by RACE-PCR. The axolotl antifreeze-like protein sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 93 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein were 10128.6 Da and 8.97, respectively. The molecular characterization of this gene and its deduced protein were further performed by detailed bioinformatics analysis. The three-dimensional structure of current AFLP was predicted by homology modeling, and the conserved residues required for functionality were identified. The homology model constructed could be of use for effective drug design. This is the first report of an antifreeze-like protein identified from a caudate amphibian.

The effect of seasonal harvesting on stage-structured population models.

PubMed

Tang, Sanyi; Chen, Lansun

2004-04-01

In most models of population dynamics, increases in population due to birth are assumed to be time-independent, but many species reproduce only during a single period of the year. We propose an exploited single-species model with stage structure for the dynamics in a fish population for which births occur in a single pulse once per time period. Since birth pulse populations are often characterized with a discrete time dynamical system determined by its Poincaré map, we explore the consequences of harvest timing to equilibrium population sizes under seasonal dependence and obtain threshold conditions for their stability, and show that the timing of harvesting has a strong impact on the persistence of the fish population, on the volume of mature fish stock and on the maximum annual-sustainable yield. Moreover, our results imply that the population can sustain much higher harvest rates if the mature fish is removed as early in the season (after the birth pulse) as possible. Further, the effects of harvesting effort and harvest timing on the dynamical complexity are also investigated. Bifurcation diagrams are constructed with the birth rate (or harvesting effort or harvest timing) as the bifurcation parameter, and these are observed to display rich structure, including chaotic bands with periodic windows, pitch-fork and tangent bifurcations, non-unique dynamics (meaning that several attractors coexist) and attractor crisis. This suggests that birth pulse, in effect, provides a natural period or cyclicity that makes the dynamical behavior more complex.

Subsurface temperature as a passkey for exploration of mature basins: Hot anticlines - A key to discovery?

USGS Publications Warehouse

Merriam, D.F.

2004-01-01

Temperature anomalies associated with oil-producing structures in the US Midcontinent and similar cratonic areas probably can be used reliably as a passkey for petroleum exploration in mature areas, and thus the concept of hot anticlines could be a key to discovery. Analysis of accumulated data during the past several decades allows a definition of the problem of hot anticlines. A possible solution for migration and entrapment of petroleum can be explained by the Roberts temperature differential model and the Walters fluid-flow paradigm. In fact, if the Roberts model is valid, higher shallow temperatures, temperature gradients, or heat flow could indicate the entrapment of hydrocarbons at depth. The recognition and promotion of shallow "hotspots" as an exploration key is not new and was proposed years ago by Haas and Hoffmann, Kappelmeyer, and as recently as 1986 by Blackwell.

System Maturity and Architecture Assessment Methods, Processes, and Tools

DTIC Science & Technology

2012-03-02

Deshmukh , and M. Sarfaraz. Development of Systems Engineering Maturity Models and Management Tools. Systems Engineering Research Center Final Technical...Ramirez- Marquez, D. Nowicki, A. Deshmukh , and M. Sarfaraz. Development of Systems Engineering Maturity Models and Management Tools. Systems Engineering

Guidelines for Applying the Capability Maturity Model Analysis to Connected and Automated Vehicle Deployment

DOT National Transportation Integrated Search

2017-11-23

The Federal Highway Administration (FHWA) has adapted the Transportation Systems Management and Operations (TSMO) Capability Maturity Model (CMM) to describe the operational maturity of Infrastructure Owner-Operator (IOO) agencies across a range of i...

Monitoring stand structure in mature coastal Douglas-fir forests: effect of plot size.

Treesearch

Andrew Gray

2003-01-01

National and regional interest in the distribution and trends of forest habitat structure and diversity have placed demands on forest inventories for accurate stand-level data. a primary need in the coastal Pacific Northwest of the United States is information on the extent and rate of development of mature forest structure. The objective of this study was to evaluate...

The structure of mononuclear phagocytes differentiating in vivo. III. The effect of particulate foreign substances.

PubMed

Goldner, R D; Adams, D O

1977-11-01

The response of mononuclear phagocytes to three inert particles--barium sulfate, talc, and thorium dioxide--was studied by correlated light and electron microscopy. All three particles induced maturation of the mononuclear phagocytes, which proceeded to the stage of the mature macrophage and required 7 to 9 days. Once established, maturation persisted as long as 45 days, as did the inert particles. The resultant lesions, dense aggregates of mature macrophages, were termed mature granulomas. The resultant maturation differed from that produced by digestible bacteria in tempo and extent but not in pattern.

Analysis of ecological thresholds in a temperate forest undergoing dieback

PubMed Central

Newton, Adrian C.; Cantarello, Elena; Evans, Paul M.

2017-01-01

Positive feedbacks in drivers of degradation can cause threshold responses in natural ecosystems. Though threshold responses have received much attention in studies of aquatic ecosystems, they have been neglected in terrestrial systems, such as forests, where the long time-scales required for monitoring have impeded research. In this study we explored the role of positive feedbacks in a temperate forest that has been monitored for 50 years and is undergoing dieback, largely as a result of death of the canopy dominant species (Fagus sylvatica, beech). Statistical analyses showed strong non-linear losses in basal area for some plots, while others showed relatively gradual change. Beech seedling density was positively related to canopy openness, but a similar relationship was not observed for saplings, suggesting a feedback whereby mortality in areas with high canopy openness was elevated. We combined this observation with empirical data on size- and growth-mediated mortality of trees to produce an individual-based model of forest dynamics. We used this model to simulate changes in the structure of the forest over 100 years under scenarios with different juvenile and mature mortality probabilities, as well as a positive feedback between seedling and mature tree mortality. This model produced declines in forest basal area when critical juvenile and mature mortality probabilities were exceeded. Feedbacks in juvenile mortality caused a greater reduction in basal area relative to scenarios with no feedback. Non-linear, concave declines of basal area occurred only when mature tree mortality was 3–5 times higher than rates observed in the field. Our results indicate that the longevity of trees may help to buffer forests against environmental change and that the maintenance of old, large trees may aid the resilience of forest stands. In addition, our work suggests that dieback of forests may be avoidable providing pressures on mature and juvenile trees do not pass critical thresholds. PMID:29240842

A Maturity Model: Does It Provide a Path for Online Course Design?

ERIC Educational Resources Information Center

Neuhauser, Charlotte

2004-01-01

Maturity models are successfully used by organizations attempting to improve their processes, products, and delivery. As more faculty include online course design and teaching, a maturity model of online course design may serve as a tool in planning and assessing their courses for improvement based on best practices. This article presents such a…

Retroviral proteases and their roles in virion maturation.

PubMed

Konvalinka, Jan; Kräusslich, Hans-Georg; Müller, Barbara

2015-05-01

Proteolytic processing of viral polyproteins is essential for retrovirus infectivity. Retroviral proteases (PR) become activated during or after assembly of the immature, non-infectious virion. They cleave viral polyproteins at specific sites, inducing major structural rearrangements termed maturation. Maturation converts retroviral enzymes into their functional form, transforms the immature shell into a metastable state primed for early replication events, and enhances viral entry competence. Not only cleavage at all PR recognition sites, but also an ordered sequence of cleavages is crucial. Proteolysis is tightly regulated, but the triggering mechanisms and kinetics and pathway of morphological transitions remain enigmatic. Here, we outline PR structures and substrate specificities focusing on HIV PR as a therapeutic target. We discuss design and clinical success of HIV PR inhibitors, as well as resistance development towards these drugs. Finally, we summarize data elucidating the role of proteolysis in maturation and highlight unsolved questions regarding retroviral maturation. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of New Cationic N,N-Dimethyl[70]fulleropyrrolidinium Iodide Derivatives as Potent HIV-1 Maturation Inhibitors.

PubMed

Castro, Edison; Martinez, Zachary S; Seong, Chang-Soo; Cabrera-Espinoza, Andrea; Ruiz, Mauro; Hernandez Garcia, Andrea; Valdez, Federico; Llano, Manuel; Echegoyen, Luis

2016-12-22

HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% of HIV-1 infectivity at low micromolar concentrations. Analysis of the HIV-1 life cycle indicated that these compounds inhibit viral maturation by impairing Gag and Gag-Pol processing. Importantly, fullerene derivatives 2a-c did not inhibit in vitro PR activity and strongly interacted with HIV immature capsid protein in pull-down experiments. Furthermore, these compounds potently blocked infectivity of viruses harboring mutant PR that are resistant to multiple PR inhibitors or mutant Gag proteins that confer resistance to the maturation inhibitor Bevirimat. Collectively, our studies indicate fullerene derivatives 2a-c as potent and novel HIV-1 maturation inhibitors.

Effect of Thermal Maturation on n-alkanes and Kerogen in Preserved Organic Matter: Implications for Paleoenvironment Biomarkers

NASA Astrophysics Data System (ADS)

Craven, O. D.; Longbottom, T. L.; Hockaday, W. C.; Blackaby, E.

2017-12-01

Understanding the effects of maturity on biomarkers is vital in assessing biomarker reliability in mature sediments. It is well known for n-alkanes that increased maturity shortens chain lengths and decreases the odd over even preference however, the amount of change in these variables has not been determined for different maturities and types of preserved organic matter. For this reason, it is difficult to judge the trustworthiness of even lightly matured samples for paleoenvironment reconstruction. Another complication is the difficulty of accurately determining maturity as many maturity indicators are error-prone or not appropriate at low maturities. Using hydrous pyrolysis, we artificially matured black shale samples with type I (lacustrine) and type II (marine) kerogen to measure changes in n-alkane length and odd over even preference. Whole rock samples underwent hydrous pyrolysis for 72 hours, at 250 °C, 300 °C, 325 °C, 350 °C, and 375 °C to cover a wide maturity range. From the immature and artificially matured samples, the bitumen was extracted and the saturate fraction was separated using column chromatography. The saturate fraction was analyzed for n-alkanes using gas chromatography-mass spectroscopy. Kerogen structural changes were also measured using solid-state 13C NMR to relate changes in n-alkane biomarkers to changes in kerogen structure. Results show that for type I bitumen the n-alkanes did not change at low maturities considered premature in terms of oil generation (<325 °C). The NMR spectra of the type I kerogen support the lack of change, at low maturities no changes in the aliphatic portion (Fal) were observed, however, after 325 °C Fal decreased with increasing maturity. The loss of Fal indicates kerogen contributing hydrocarbons to bitumen that cause changes in n-alkane measurements. The type II kerogen's Fal also decreased with increasing maturity, but unlike the type I kerogen Fal loss started at low maturities. The differences between the matured type I and II organic matter indicate that organic matter type affects when n-alkane measurements change due to maturity. Additionally, the kerogen carbonyl functional group (FaC) decreases greatly from immature to low maturities, leveling off between 300 °C and 325 °C, allowing FaC to be a tool for determining low maturities.

Stem-Cell-Derived Cardiomyocytes Grow Up: Start Young and Train Harder.

PubMed

Maxwell, Joshua T; Xu, Chunhui

2018-06-01

Engineering cardiac tissue that accurately recapitulates adult myocardium is critical for advancing disease modeling, drug screening, and regenerative medicine. Ronaldson-Bouchard et al. report a new strategy for generating cardiac tissues from stem-cell-derived cardiomyocytes that reach a maturation level closer to human adult cardiac structure and function. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.

PubMed

Tresoldi, Claudia; Bianchi, Elena; Pellegata, Alessandro Filippo; Dubini, Gabriele; Mantero, Sara

2017-08-01

The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.

Population structure and the evolution of sexual size dimorphism and sex ratios in an insular population of Florida box turtles (Terrapene carolina bauri)

USGS Publications Warehouse

Dodd, C.K.

1997-01-01

Hypotheses in the chelonian literature suggest that in species with sexual size dimorphism, the smaller sex will mature at a smaller size and a younger age than the larger sex, sex ratios should be biased in favor of the earlier maturing sex, and deviations from a 1:1 sex ratio result from maturation of the smaller sex at a younger age. I tested these hypotheses using data collected from 1991 to 1995 on an insular (Egmont Key) population of Florida box turtles, Terrapene carolina bauri. Contrary to predictions, the earlier maturing sex (males) grew to larger sizes than the late maturing sex. Males were significantly larger than females in mean carapace length but not mean body mass. Sex ratios were not balanced, favoring the earlier maturing sex (1.6 males:1 female), but the sex-ratio imbalance did not result from faster maturation of the smaller sex. The imbalance in the sex ratio in Egmont Key's box turtles is not the result of sampling biases; it may result from nest placement. Size-class structure and sex ratios can provide valuable insights into the status and trends of populations of long-lived turtles.

X-ray Structure of the Mature Ectodomain of Phogrin

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

Noguera, M. E.; Primo, M.; Jakoncic, J.

2014-11-26

Phogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure–function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Likewise to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold:more » a sheet of four antiparallel β-strands packed against two α-helices. Furthermore, sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.« less

Roles of density-dependent growth and life history evolution in accounting for fisheries-induced trait changes.

PubMed

Eikeset, Anne Maria; Dunlop, Erin S; Heino, Mikko; Storvik, Geir; Stenseth, Nils C; Dieckmann, Ulf

2016-12-27

The relative roles of density dependence and life history evolution in contributing to rapid fisheries-induced trait changes remain debated. In the 1930s, northeast Arctic cod (Gadus morhua), currently the world's largest cod stock, experienced a shift from a traditional spawning-ground fishery to an industrial trawl fishery with elevated exploitation in the stock's feeding grounds. Since then, age and length at maturation have declined dramatically, a trend paralleled in other exploited stocks worldwide. These trends can be explained by demographic truncation of the population's age structure, phenotypic plasticity in maturation arising through density-dependent growth, fisheries-induced evolution favoring faster-growing or earlier-maturing fish, or a combination of these processes. Here, we use a multitrait eco-evolutionary model to assess the capacity of these processes to reproduce 74 y of historical data on age and length at maturation in northeast Arctic cod, while mimicking the stock's historical harvesting regime. Our results show that model predictions critically depend on the assumed density dependence of growth: when this is weak, life history evolution might be necessary to prevent stock collapse, whereas when a stronger density dependence estimated from recent data is used, the role of evolution in explaining fisheries-induced trait changes is diminished. Our integrative analysis of density-dependent growth, multitrait evolution, and stock-specific time series data underscores the importance of jointly considering evolutionary and ecological processes, enabling a more comprehensive perspective on empirically observed stock dynamics than previous studies could provide.

Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year.

PubMed

Provenzale, James M; Liang, Luxia; DeLong, David; White, Leonard E

2007-08-01

The purpose of this study was to use diffusion-weighted and diffusion tensor imaging to investigate the status of cerebral white matter (WM) at term gestation and the rate of WM maturation throughout the first year of life in healthy infants. Fifty-three children (35 boys) ranging in age from 1.5 weeks premature to 51.5 weeks (mean age, 22.9 weeks) underwent conventional MRI, diffusion imaging in three directions (b = 1,000 s/mm2), and diffusion tensor imaging with gradient encoding in six directions, all on a 1.5-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in three deep WM structures (posterior limb of internal capsule, genu, and splenium of corpus callosum) and two peripheral WM regions (associational WM underlying prefrontal and posterior parietal cortex) with a standard region of interest (44 +/- 4 cm2). ADC and FA were expressed as a percentage of corresponding values measured in a group of healthy young adults. Mean ADC and FA values for deep and peripheral WM were plotted against gestational age normalized to term. The data were fit best with a broken-line linear regression model with a breakpoint at 100 days. ADC and FA values at term were estimated according to the intercept of the initial linear period (before day 100) with day 0. The slope of the linear fits was used to determine the rate of WM maturation in both the early and the late (after day 100) periods. Multivariate analysis of variance tests were used to compare deep and peripheral WM structures at term and at representative early and late ages (days 30 and 200) and to compare rates of ADC and FA maturation in early and late periods within the first year. At term, peripheral WM was less mature than deep WM according to results of extrapolation of ADC and FA values in the first 100 days of life to day 0 (p < 0.01). Mean ADC and FA value (percentage of mean adult value) for peripheral WM were 1.32 x 10(-3) mm2/s (163%) and 0.16 (32%), respectively, and 1.09 x 10(-3) mm2/s (143%) and 0.36 (54%), respectively, for deep WM. On day 30 and day 200, estimated mean ADC and FA continued to show greater diffusion (higher ADC) and less anisotropy (lower FA value) in peripheral WM (p <0.01). During the first year of postnatal life, both ADC and FA matured at higher rates before postnatal day 100 compared with a later time. Differences were observed in rates of maturation in the first 100 days when rates of decrease in ADC and increase in FA were compared between peripheral WM and deep WM; however, the maturational trends differed whether ADC or FA was examined. The early rate of ADC decrease (maturation) was twice as great for peripheral WM than for deep WM (p < 0.01) unexpectedly, but the opposite pattern was observed for FA. The early rate of FA increase (maturation) was approximately one half as great for peripheral WM as for deep WM (p = 0.01). Throughout the rest of the first year, no differences were observed in the rates of change in either index between peripheral WM and deep WM. At term, both ADC and FA differ significantly in peripheral WM and deep WM, deep WM structures being more mature. Both deep WM and peripheral WM mature more rapidly during approximately the first 3 months in comparison with the rest of the first year. Unexpected differences in early (first 100 days) rates of maturation assessed with diffusion-weighted (ADC) and diffusion tensor (FA) imaging suggest that these two techniques may be sensitive to different aspects of WM maturation in the early perinatal period.

Default risk modeling beyond the first-passage approximation: Extended Black-Cox model

NASA Astrophysics Data System (ADS)

Katz, Yuri A.; Shokhirev, Nikolai V.

2010-07-01

We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm’s ability to avoid default even if company’s liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company’s default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity.

Neonatal lungs: maturational changes in lung resistivity spectra.

PubMed

Brown, B H; Primhak, R A; Smallwood, R H; Milnes, P; Narracott, A J; Jackson, M J

2002-09-01

The electrical resistivity of lung tissue can be related to the structure and composition of the tissue and also to the air content. Electrical impedance tomographic measurements have been used on 155 normal children over the first three years of life and 25 pre-term infants, to determine the absolute resistivity of lung tissue as a function of frequency. The results show consistent changes with increasing age in both lung tissue resistivity (5.8 ohm m at birth to 20.9 ohm m at 3 years of age) and in the changes of resistivity with frequency (Cole parameter ratio R/S=0.41 at birth and 0.84 at 3 years of age). Comparison with a lung model showed that the measurements are consistent with maturational changes in the number and size of alveoli, the extracapillary blood volume and the size of the extracapillary vessels. However, the results show that the process of maturation is not complete at the age of three years.

Critical review on the mechanisms of maturation stress generation in trees.

PubMed

Alméras, Tancrède; Clair, Bruno

2016-09-01

Trees control their posture by generating asymmetric mechanical stress around the periphery of the trunk or branches. This stress is produced in wood during the maturation of the cell wall. When the need for reaction is high, it is accompanied by strong changes in cell organization and composition called reaction wood, namely compression wood in gymnosperms and tension wood in angiosperms. The process by which stress is generated in the cell wall during its formation is not yet known, and various hypothetical mechanisms have been proposed in the literature. Here we aim at discriminating between these models. First, we summarize current knowledge about reaction wood structure, state and behaviour relevant to the understanding of maturation stress generation. Then, the mechanisms proposed in the literature are listed and discussed in order to identify which can be rejected based on their inconsistency with current knowledge at the frontier between plant science and mechanical engineering. © 2016 The Author(s).

Identifying a New Mechanism of HIV Core Formation | Center for Cancer Research

Cancer.gov

During the maturation of human immunodeficiency virus 1 (HIV-1), viral particles transition from a noninfectious form to an infectious one, and this conversion requires the cleavage of the HIV-1 Gag polyprotein. Gag is made up of three structural proteins—matrix (MA), capsid (CA), and nucleocapsid (NC)—connected by linkers. MA anchors Gag in the membrane, CA surrounds the HIV-1 core, and NC packages the viral RNA within the core. Current models of the development of HIV-1 suggest that when CA is cleaved from Gag it dissociates from the membrane and moves into the virus interior before nucleating, in a concentration-dependent manner, into the core, which is the last step in virus maturation. The core is thought to grow from its narrow end stopping only when it reaches the opposite side of the virus membrane. Since blocking the formation of infectious viral particles is an important therapeutic strategy, it is critical to understand the detailed mechanism of core maturation.

Predictive Capability Maturity Model (PCMM).

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

Swiler, Laura Painton; Knupp, Patrick Michael; Urbina, Angel

2010-10-01

Predictive Capability Maturity Model (PCMM) is a communication tool that must include a dicussion of the supporting evidence. PCMM is a tool for managing risk in the use of modeling and simulation. PCMM is in the service of organizing evidence to help tell the modeling and simulation (M&S) story. PCMM table describes what activities within each element are undertaken at each of the levels of maturity. Target levels of maturity can be established based on the intended application. The assessment is to inform what level has been achieved compared to the desired level, to help prioritize the VU activities &more » to allocate resources.« less

Maturity Model for Advancing Smart Grid Interoperability

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

Knight, Mark; Widergren, Steven E.; Mater, J.

2013-10-28

Abstract—Interoperability is about the properties of devices and systems to connect and work properly. Advancing interoperability eases integration and maintenance of the resulting interconnection. This leads to faster integration, lower labor and component costs, predictability of projects and the resulting performance, and evolutionary paths for upgrade. When specifications are shared and standardized, competition and novel solutions can bring new value streams to the community of stakeholders involved. Advancing interoperability involves reaching agreement for how things join at their interfaces. The quality of the agreements and the alignment of parties involved in the agreement present challenges that are best met withmore » process improvement techniques. The GridWise® Architecture Council (GWAC) sponsored by the United States Department of Energy is supporting an effort to use concepts from capability maturity models used in the software industry to advance interoperability of smart grid technology. An interoperability maturity model has been drafted and experience is being gained through trials on various types of projects and community efforts. This paper describes the value and objectives of maturity models, the nature of the interoperability maturity model and how it compares with other maturity models, and experiences gained with its use.« less

A novel enteric neuron-glia coculture system reveals the role of glia in neuronal development.

PubMed

Le Berre-Scoul, Catherine; Chevalier, Julien; Oleynikova, Elena; Cossais, François; Talon, Sophie; Neunlist, Michel; Boudin, Hélène

2017-01-15

Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown. To examine the role of EGCs in the formation of the neuronal network, we developed a novel neuron-enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs. We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic- and glial cell line-derived neurotrophic factor-dependent pathways. Using a novel and valuable culture model to study enteric neuron-glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation. In the nervous system, the formation of neuronal circuitry results from a complex and coordinated action of intrinsic and extrinsic factors. In the CNS, extrinsic mediators derived from astrocytes have been shown to play a key role in neuronal maturation, including dendritic shaping, axon guidance and synaptogenesis. In the enteric nervous system (ENS), the potential role of enteric glial cells (EGCs) in the maturation of developing enteric neuronal circuit is currently unknown. A major obstacle in addressing this question is the difficulty in obtaining a valuable experimental model in which enteric neurons could be isolated and maintained without EGCs. We adapted a cell culture method previously developed for CNS neurons to establish a neuron-enriched primary culture from embryonic rat intestine which was cultured in indirect coculture with EGCs. We demonstrated that enteric neurons grown in such conditions showed several structural, phenotypic and functional hallmarks of proper development and maturation. However, when neurons were grown without EGCs, the complexity of the axonal arbour and the density of synapses were markedly reduced, suggesting that glial-derived factors contribute strongly to the formation of the neuronal circuitry. We found that these effects played by EGCs were mediated in part through purinergic P2Y 1 receptor- and glial cell line-derived neurotrophic factor-dependent pathways. Using a novel and valuable culture model to study enteric neuron-glia interactions, our study identified EGCs as a key cellular actor required for neuronal network maturation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

A novel enteric neuron–glia coculture system reveals the role of glia in neuronal development

PubMed Central

Le Berre‐Scoul, Catherine; Chevalier, Julien; Oleynikova, Elena; Cossais, François; Talon, Sophie; Neunlist, Michel

2016-01-01

Key points Unlike astrocytes in the brain, the potential role of enteric glial cells (EGCs) in the formation of the enteric neuronal circuit is currently unknown.To examine the role of EGCs in the formation of the neuronal network, we developed a novel neuron‐enriched culture model from embryonic rat intestine grown in indirect coculture with EGCs.We found that EGCs shape axonal complexity and synapse density in enteric neurons, through purinergic‐ and glial cell line‐derived neurotrophic factor‐dependent pathways.Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor regulating neuronal network maturation. Abstract In the nervous system, the formation of neuronal circuitry results from a complex and coordinated action of intrinsic and extrinsic factors. In the CNS, extrinsic mediators derived from astrocytes have been shown to play a key role in neuronal maturation, including dendritic shaping, axon guidance and synaptogenesis. In the enteric nervous system (ENS), the potential role of enteric glial cells (EGCs) in the maturation of developing enteric neuronal circuit is currently unknown. A major obstacle in addressing this question is the difficulty in obtaining a valuable experimental model in which enteric neurons could be isolated and maintained without EGCs. We adapted a cell culture method previously developed for CNS neurons to establish a neuron‐enriched primary culture from embryonic rat intestine which was cultured in indirect coculture with EGCs. We demonstrated that enteric neurons grown in such conditions showed several structural, phenotypic and functional hallmarks of proper development and maturation. However, when neurons were grown without EGCs, the complexity of the axonal arbour and the density of synapses were markedly reduced, suggesting that glial‐derived factors contribute strongly to the formation of the neuronal circuitry. We found that these effects played by EGCs were mediated in part through purinergic P2Y1 receptor‐ and glial cell line‐derived neurotrophic factor‐dependent pathways. Using a novel and valuable culture model to study enteric neuron–glia interactions, our study identified EGCs as a key cellular actor required for neuronal network maturation. PMID:27436013

Volumetric analysis of medial temporal lobe structures in brain development from childhood to adolescence.

PubMed

Hu, Shiyan; Pruessner, Jens C; Coupé, Pierrick; Collins, D Louis

2013-07-01

Puberty is an important stage of development as a child's sexual and physical characteristics mature because of hormonal changes. To better understand puberty-related effects on brain development, we investigated the magnetic resonance imaging (MRI) data of 306 subjects from 4 to 18 years of age. Subjects were grouped into before and during puberty groups according to their sexual maturity levels measured by the puberty scores. An appearance model-based automatic segmentation method with patch-based local refinement was employed to segment the MRI data and extract the volumes of medial temporal lobe (MTL) structures including the amygdala (AG), the hippocampus (HC), the entorhinal/perirhinal cortex (EPC), and the parahippocampal cortex (PHC). Our analysis showed age-related volumetric changes for the AG, HC, right EPC, and left PHC but only before puberty. After onset of puberty, these volumetric changes then correlate more with sexual maturity level, as measured by the puberty score. When normalized for brain volume, the volumes of the right HC decrease for boys; the volumes of the left HC increase for girls; and the volumes of the left and right PHC decrease for boys. These findings suggest that the rising levels of testosterone in boys and estrogen in girls might have opposite effects, especially for the HC and the PHC. Our findings on sex-specific and sexual maturity-related volumes may be useful in better understanding the MTL developmental differences and related learning, memory, and emotion differences between boys and girls during puberty. Copyright © 2013 Elsevier Inc. All rights reserved.

ADP-ribosylation Factor 6 (ARF6) Bidirectionally Regulates Dendritic Spine Formation Depending on Neuronal Maturation and Activity*

PubMed Central

Kim, Yoonju; Lee, Sang-Eun; Park, Joohyun; Kim, Minhyung; Lee, Boyoon; Hwang, Daehee; Chang, Sunghoe

2015-01-01

Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. PMID:25605715

Capability 9.4 Servicing

NASA Technical Reports Server (NTRS)

Moe, Rud

2005-01-01

This paper presents viewgraphs on capability structure 9.4 servicing. The topics include: 1) Servicing Description; 2) Benefits of Servicing; 3) Drivers & Assumptions for Servicing; 4) Capability Breakdown Structure 9.4 Servicing; 5) Roadmap for Servicing; 6) 9.4 Servicing Critical Gaps; 7) Capability 9.4 Servicing; 8) Capability 9.4.1 Inspection; 9) State-of-the-Art /Maturity Level /Capabilities for 9.4.1 Inspection; 10) Capability 9.4.2 Diagnostics; 11) State-of-the-Art/Maturity Level /Capabilities for 9.4.2 Diagnostics; 12) Capability 9.4.3 Perform Planned Maintenance; 13) State-of-the-Art /Maturity Level /Capabilities for 9.4.3 Perform Planned Maintenance; 14) Capability 9.4.4 Perform Unplanned Repair; 15) State-of-the-Art /Maturity Level /Capabilities for 9.4.4 Perform Unplanned Repair; 16) Capability 9.4.5 Install Upgrade; 17) Capability 9.4.5 Install Upgrade; 18) State-of-the-Art /Maturity Level /Capabilities for 9.4.5 Install Upgrade; 19) Capability 9.4.6 Planning, Logistics, Training; and 20) State-of-the-Art /Maturity Level /Capabilities for 9.4.6 Planning, Logistics, & Training;

Structure and Uncoating of Immature Adenovirus

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

Perez-Berna, A.J.; Mangel, W.; Marabini, R.

2009-09-18

Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particlesmore » as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.« less

A Developmental Model of Intercultural Maturity

ERIC Educational Resources Information Center

King, Patricia M.; Baxter Magolda, Marcia B.

2005-01-01

This article focuses on the development of intercultural maturity, which is frequently cited as a desired collegiate outcome. We position our work on intercultural maturity in the context of a holistic approach to human development using Kegan's (1994) model as a foundation and relating this outcome to other collegiate learning outcomes. We…

New constraints on Neogene uplift of the northern Colorado Plateau

NASA Astrophysics Data System (ADS)

Van Wijk, J. W.; Raschilla, R.

2013-12-01

The Late Cretaceous Uinta Basin is located in northeastern Utah within the northern most portion of the Colorado Plateau. The basin's uplift and subsidence history and thermal evolution have impacted the maturity of source beds in the Parachute Creek Member of the Green River Formation. Using measured data of the petroleum system of the Uinta Basin, we were able to constrain timing and amplitude of uplift of the northern Colorado Plateau. We used sixty wells in a basin modeling study of the Uinta Basin's thermal structure, tectonic history and petroleum system. The wells reached into basement, and four wells provided vitrinite reflectance measurements. Vitrinite reflectance is a measurement of the percentage of reflected light from a polished vitrinite sample. The percentage of reflected light is related to the temperature conditions the sample experienced during burial, and vitrinite reflectance is a maturity indicator that covers a broad temperature range from diagenesis through the latest stages of catagenesis and records the maximum temperature a rock experiences during its burial history All models were calibrated to measured data, including vitrinite reflectance and transformation ratios from Rock-Eval pyrolysis. The models predict that the heat flow ranges from 65 mW/m2 to 45 mW/m2 from south to north in the study area. Additionally, model calibration provides a means for estimating the amount of uplift and erosion in the Uinta Basin. Uplift predicted for the Uinta Basin ranges from ~2050 m to ~2200 m and started in the Late Miocene. Our models also predicted the maturity of the rich oil shales of the Parachute Creek Member.

White Matter Maturation Supports the Development of Reasoning Ability Through its Influence on Processing Speed

PubMed Central

Ferrer, E.; Whitaker, K.J.; Steele, J.; Green, C.T.; Wendelken, C.; Bunge, S.A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability. PMID:24118718

Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation

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

Lokareddy, Ravi K.; Sankhala, Rajeshwer S.; Roy, Ankoor

Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid’) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinitymore » for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging’ is a DNA-dependent symmetrization of portal protein.« less

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

PubMed Central

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio

2018-01-01

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. PMID:29504938

Structure and Assembly of Intracellular Mature Vaccinia Virus: Thin-Section Analyses

PubMed Central

Griffiths, Gareth; Roos, Norbert; Schleich, Sybille; Locker, Jacomine Krijnse

2001-01-01

In the preceding study (see accompanying paper), we showed by a variety of different techniques that intracellular mature vaccinia virus (vaccinia IMV) is unexpectedly complex in its structural organization and that this complexity also extends to the underlying viral core, which is highly folded. With that analysis as a foundation, we now present different thin-section electron microscopy approaches for analyzing the IMV and the processes by which it is assembled in infected HeLa cells. We focus on conventional epoxy resin thin sections as well as cryosections to describe key intermediates in the assembly process. We took advantage of streptolysin O's ability to selectively permeabilize the plasma membrane of infected cells to improve membrane contrast, and we used antibodies against bone fide integral membrane proteins of the virus to unequivocally identify membrane profiles in thin sections. All of the images presented here can be rationalized with respect to the model put forward for the assembly of the IMV in the accompanying paper. PMID:11602745

Acoustic and Petrophysical Evolution of Organic-Rich Chalk Following Maturation Induced by Unconfined Pyrolysis

NASA Astrophysics Data System (ADS)

Shitrit, Omri; Hatzor, Yossef H.; Feinstein, Shimon; Vinegar, Harold J.

2017-12-01

Thermal maturation is known to influence the rock physics of organic-rich rocks. While most studies were performed on low-porosity organic-rich shales, here we examine the effect of thermal maturation on a high-porosity organic-rich chalk. We compare the physical properties of native state immature rock with the properties at two pyrolysis-simulated maturity levels: early-mature and over-mature. We further evaluate the applicability of results from unconfined pyrolysis experiments to naturally matured rock properties. Special attention is dedicated to the elastic properties of the organic phase and the influence of bitumen and kerogen contents. Rock physics is studied based on confined petrophysical measurements of porosity, density and permeability, and measurements of bedding-normal acoustic velocities at estimated field stresses. Geochemical parameters like total organic carbon (TOC), bitumen content and thermal maturation indicators are used to monitor variations in density and volume fraction of each phase. We find that porosity increases significantly upon pyrolysis and that P wave velocity decreases in accordance. Solids density versus TOC relationships indicate that the kerogen increases its density from 1.43 to 1.49 g/cc at the immature and early-mature stages to 2.98 g/cc at the over-mature stage. This density value is unusually high, although increase in S wave velocity and backscatter SEM images of the over-mature samples verify that the over-mature kerogen is significantly denser and stiffer. Using the petrophysical and acoustic properties, the elastic moduli of the rock are estimated by two Hashin-Shtrikman (HS)-based models: "HS + BAM" and "HS kerogen." The "HS + BAM" model is calibrated to the post-pyrolysis measurements to describe the mechanical effect of the unconfined pyrolysis on the rock. The absence of compaction in the pyrolysis process causes the post-pyrolysis samples to be extremely porous. The "HS kerogen" model, which simulates a kerogen-supported matrix, depicts a compacted version of the matrix and is believed to be more representative of a naturally matured rock. Rock physics analysis using the "HS kerogen" model indicates strong mechanical dominance of porosity and organic content, and only small maturity-associated effects.

Genetic subpopulation structuring and its implications in a mature eastern white pine stand

Treesearch

Samuel E. Nijensohn; Paul G. Schaberg; Gary J. Hawley; Donald H. DeHayes; Donald H. DeHayes

2005-01-01

We examined patterns of genetic structuring within a mature eastern white pine (Pinus strobus L.) forest, using geographic information system (GIS)-based data and maps that combined genetic (isozyme analysis of 46 loci) and other tree-specific information (e.g., size, growth, age, and location) for 220 trees in Jericho, Vermont. Interconnections between genotypic...

Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease*

PubMed Central

Packer, Nicolle H.; Schulz, Benjamin L.

2016-01-01

The glycoproteome remains severely understudied because of significant analytical challenges associated with glycoproteomics, the system-wide analysis of intact glycopeptides. This review introduces important structural aspects of protein N-glycosylation and summarizes the latest technological developments and applications in LC-MS/MS-based qualitative and quantitative N-glycoproteomics. These maturing technologies provide unique structural insights into the N-glycoproteome and its synthesis and regulation by complementing existing methods in glycoscience. Modern glycoproteomics is now sufficiently mature to initiate efforts to capture the molecular complexity displayed by the N-glycoproteome, opening exciting opportunities to increase our understanding of the functional roles of protein N-glycosylation in human health and disease. PMID:26929216

Protein Modelling: What Happened to the “Protein Structure Gap”?

PubMed Central

Schwede, Torsten

2013-01-01

Computational modeling and prediction of three-dimensional macromolecular structures and complexes from their sequence has been a long standing vision in structural biology as it holds the promise to bypass part of the laborious process of experimental structure solution. Over the last two decades, a paradigm shift has occurred: starting from a situation where the “structure knowledge gap” between the huge number of protein sequences and small number of known structures has hampered the widespread use of structure-based approaches in life science research, today some form of structural information – either experimental or computational – is available for the majority of amino acids encoded by common model organism genomes. Template based homology modeling techniques have matured to a point where they are now routinely used to complement experimental techniques. With the scientific focus of interest moving towards larger macromolecular complexes and dynamic networks of interactions, the integration of computational modeling methods with low-resolution experimental techniques allows studying large and complex molecular machines. Computational modeling and prediction techniques are still facing a number of challenges which hamper the more widespread use by the non-expert scientist. For example, it is often difficult to convey the underlying assumptions of a computational technique, as well as the expected accuracy and structural variability of a specific model. However, these aspects are crucial to understand the limitations of a model, and to decide which interpretations and conclusions can be supported. PMID:24010712

Estimating latent time of maturation and survival costs of reproduction in continuous time from capture-recapture data

USGS Publications Warehouse

Ergon, T.; Yoccoz, N.G.; Nichols, J.D.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.

2009-01-01

In many species, age or time of maturation and survival costs of reproduction may vary substantially within and among populations. We present a capture-mark-recapture model to estimate the latent individual trait distribution of time of maturation (or other irreversible transitions) as well as survival differences associated with the two states (representing costs of reproduction). Maturation can take place at any point in continuous time, and mortality hazard rates for each reproductive state may vary according to continuous functions over time. Although we explicitly model individual heterogeneity in age/time of maturation, we make the simplifying assumption that death hazard rates do not vary among individuals within groups of animals. However, the estimates of the maturation distribution are fairly robust against individual heterogeneity in survival as long as there is no individual level correlation between mortality hazards and latent time of maturation. We apply the model to biweekly capture?recapture data of overwintering field voles (Microtus agrestis) in cyclically fluctuating populations to estimate time of maturation and survival costs of reproduction. Results show that onset of seasonal reproduction is particularly late and survival costs of reproduction are particularly large in declining populations.

“And Yet It Was a Blessing”: The Case for Existential Maturity

PubMed Central

Reddy, Neha; Hauser, Joshua; Sonnenfeld, Sarah B.

2017-01-01

Abstract We are interested in the kind of well-being that can occur as a person approaches death; we call it “existential maturity.” We describe a conceptual model of this state that we felt was realized in an individual case, illustrating the state by describing the case. Our goal is to articulate a generalizable, working model of existential maturity in concepts and terms taken from fundamentals of psychodynamic theory. We hope that a recognizable case and a model-based way of thinking about what was going on can both help guide care that fosters existential maturity and stimulate more theoretical modeling of the state. PMID:28128674

A Molecular Approach Designed to Limit the Replication of Mature DENV2 in Host Cells.

PubMed

Raheel, Ummar; Jamal, Muhsin; Zaidi, Najam Us Sahar Sadaf

2015-09-01

Dengue virus (DENV) is an arthropod-borne virus, which belongs to the Flaviviridae family, and completes its life cycle in two hosts: humans and mosquitoes. For DENV maturation, the surface pre-membrane (prM) protein is cleaved to form a mature membrane protein (M) by furin, which is a cellular enzyme subsequently releasing the mature virus from the host dendritic cell. The objective of the current study was to inhibit mature DENV isotype 2 (DENV2) by RNA-interference in a Vero-81 cell line. Mature DENV2 was propagated in and isolated from U937 cells expressing dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin. Maturation of DENV2 was confirmed by Western blot analysis, where virus stock lacking prM was considered mature. Inhibition studies were carried out by transfection of Vero-81 cells with six synthetic siRNAs along with a control siRNA. Reduction in cellular DENV2 was observed also by focus-reduction assay, immunofluorescence assay (IFA), and real-time quantitative polymerase chain reaction (RT-qPCR). Cells transfected with DENV2SsiRNA2, which was targeting the structural region M of mature DENV2, was able to reduce DENV2 titer by up to 85% in focus reduction assays. A significant reduction in mature DENV2 RNA load was observed by RT-qPCR, confirming the previous findings. IFA also revealed reduced levels of cellular DENV2. These results demonstrated that mature DENV2 can be effectively inhibited by synthetic siRNA targeting the structural region of the genome. Mature DENV2 can be successfully inhibited by siRNAs, and specifically high knock-down efficiency is observed by siRNAs against M region of mature DENV2. This study shows that M represents a potential target for RNAi based inhibitory approaches.

Optmization and Fabrication Studies in the Development of Structurally Integrated Thermal Protection System Technology

NASA Technical Reports Server (NTRS)

Stephens, Craig A.

2009-01-01

NASA HYP M&S is pursuing the development of SITPS: 1) Working with HYP MDAO to formulate methodology to incorporate SITPS into hypersonic vehicle design trades. 2) SITPS-0 to SITPS-1 (FY10): a) Manufacturing development and weight reduction (5.8 to 3.1 lb(sub m)/sq ft); b) Structural testing to mature SITPS model. 3) SITPS-2 (FY11): a) Focus on panel closeout, panel-to-panel load transfer, and panel curvature. 4) Extend fabrication technology to include alternate cores and insulations (FY12).

Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

PubMed Central

LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

2012-01-01

Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

Cortical plasticity and preserved function in early blindness

PubMed Central

Renier, Laurent; De Volder, Anne G.; Rauschecker, Josef P.

2013-01-01

The “neural Darwinism” theory predicts that when one sensory modality is lacking, as in congenital blindness, the target structures are taken over by the afferent inputs from other senses that will promote and control their functional maturation (Edelman, 1993). This view receives support from both cross-modal plasticity experiments in animal models and functional imaging studies in man, which are presented here. PMID:23453908

Long-term effects of different forest regeneration methods on mature forest birds

Treesearch

Roger W. Perry; Julianna M.A. Jenkins; Ronald E. Thill; Frank R. Thompson

2018-01-01

Changes in forest structure that result from silviculture, including timber harvest, can positively or negatively affect bird species that use forests. Because many bird species associated with mature forests are facing population declines, managers need to know how timber harvesting affects species of birds that rely on mature trees or forests for breeding, foraging,...

The skeletal maturation status estimated by statistical shape analysis: axial images of Japanese cervical vertebra.

PubMed

Shin, S M; Kim, Y-I; Choi, Y-S; Yamaguchi, T; Maki, K; Cho, B-H; Park, S-B

2015-01-01

To evaluate axial cervical vertebral (ACV) shape quantitatively and to build a prediction model for skeletal maturation level using statistical shape analysis for Japanese individuals. The sample included 24 female and 19 male patients with hand-wrist radiographs and CBCT images. Through generalized Procrustes analysis and principal components (PCs) analysis, the meaningful PCs were extracted from each ACV shape and analysed for the estimation regression model. Each ACV shape had meaningful PCs, except for the second axial cervical vertebra. Based on these models, the smallest prediction intervals (PIs) were from the combination of the shape space PCs, age and gender. Overall, the PIs of the male group were smaller than those of the female group. There was no significant correlation between centroid size as a size factor and skeletal maturation level. Our findings suggest that the ACV maturation method, which was applied by statistical shape analysis, could confirm information about skeletal maturation in Japanese individuals as an available quantifier of skeletal maturation and could be as useful a quantitative method as the skeletal maturation index.

The skeletal maturation status estimated by statistical shape analysis: axial images of Japanese cervical vertebra

PubMed Central

Shin, S M; Choi, Y-S; Yamaguchi, T; Maki, K; Cho, B-H; Park, S-B

2015-01-01

Objectives: To evaluate axial cervical vertebral (ACV) shape quantitatively and to build a prediction model for skeletal maturation level using statistical shape analysis for Japanese individuals. Methods: The sample included 24 female and 19 male patients with hand–wrist radiographs and CBCT images. Through generalized Procrustes analysis and principal components (PCs) analysis, the meaningful PCs were extracted from each ACV shape and analysed for the estimation regression model. Results: Each ACV shape had meaningful PCs, except for the second axial cervical vertebra. Based on these models, the smallest prediction intervals (PIs) were from the combination of the shape space PCs, age and gender. Overall, the PIs of the male group were smaller than those of the female group. There was no significant correlation between centroid size as a size factor and skeletal maturation level. Conclusions: Our findings suggest that the ACV maturation method, which was applied by statistical shape analysis, could confirm information about skeletal maturation in Japanese individuals as an available quantifier of skeletal maturation and could be as useful a quantitative method as the skeletal maturation index. PMID:25411713

In situ structures of the genome and genome-delivery apparatus in a single-stranded RNA virus.

PubMed

Dai, Xinghong; Li, Zhihai; Lai, Mason; Shu, Sara; Du, Yushen; Zhou, Z Hong; Sun, Ren

2017-01-05

Packaging of the genome into a protein capsid and its subsequent delivery into a host cell are two fundamental processes in the life cycle of a virus. Unlike double-stranded DNA viruses, which pump their genome into a preformed capsid, single-stranded RNA (ssRNA) viruses, such as bacteriophage MS2, co-assemble their capsid with the genome; however, the structural basis of this co-assembly is poorly understood. MS2 infects Escherichia coli via the host 'sex pilus' (F-pilus); it was the first fully sequenced organism and is a model system for studies of translational gene regulation, RNA-protein interactions, and RNA virus assembly. Its positive-sense ssRNA genome of 3,569 bases is enclosed in a capsid with one maturation protein monomer and 89 coat protein dimers arranged in a T = 3 icosahedral lattice. The maturation protein is responsible for attaching the virus to an F-pilus and delivering the viral genome into the host during infection, but how the genome is organized and delivered is not known. Here we describe the MS2 structure at 3.6 Å resolution, determined by electron-counting cryo-electron microscopy (cryoEM) and asymmetric reconstruction. We traced approximately 80% of the backbone of the viral genome, built atomic models for 16 RNA stem-loops, and identified three conserved motifs of RNA-coat protein interactions among 15 of these stem-loops with diverse sequences. The stem-loop at the 3' end of the genome interacts extensively with the maturation protein, which, with just a six-helix bundle and a six-stranded β-sheet, forms a genome-delivery apparatus and joins 89 coat protein dimers to form a capsid. This atomic description of genome-capsid interactions in a spherical ssRNA virus provides insight into genome delivery via the host sex pilus and mechanisms underlying ssRNA-capsid co-assembly, and inspires speculation about the links between nucleoprotein complexes and the origins of viruses.

Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility.

PubMed

Ollero, M; Gil-Guzman, E; Lopez, M C; Sharma, R K; Agarwal, A; Larson, K; Evenson, D; Thomas, A J; Alvarez, J G

2001-09-01

Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.

Cellular and molecular maturation in fetal and adult ovine calcaneal tendons

PubMed Central

Russo, Valentina; Mauro, Annunziata; Martelli, Alessandra; Di Giacinto, Oriana; Di Marcantonio, Lisa; Nardinocchi, Delia; Berardinelli, Paolo; Barboni, Barbara

2015-01-01

Processes of development during fetal life profoundly transform tendons from a plastic tissue into a highly differentiated structure, characterised by a very low ability to regenerate after injury in adulthood. Sheep tendon is frequently used as a translational model to investigate cell-based regenerative approaches. However, in contrast to other species, analytical and comparative baseline studies on the normal developmental maturation of sheep tendons from fetal through to adult life are not currently available. Thus, a detailed morphological and biochemical study was designed to characterise tissue maturation during mid- (2 months of pregnancy: 14 cm of length) and late fetal (4 months: 40 cm of length) life, through to adulthood. The results confirm that ovine tendon morphology undergoes profound transformations during this period. Endotenon was more developed in fetal tendons than in adult tissues, and its cell phenotype changed through tendon maturation. Indeed, groups of large rounded cells laying on smaller and more compacted ones expressing osteocalcin, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were identified exclusively in fetal mid-stage tissues, and not in late fetal or adult tendons. VEGF, NGF as well as blood vessels and nerve fibers showed decreased expression during tendon development. Moreover, the endotenon of mid- and late fetuses contained identifiable cells that expressed several pluripotent stem cell markers [Telomerase Reverse Transcriptase (TERT), SRY Determining Region Y Box-2 (SOX2), Nanog Homeobox (NANOG) and Octamer Binding Transcription Factor-4A (OCT-4A)]. These cells were not identifiable in adult specimens. Ovine tendon development was also accompanied by morphological modifications to cell nuclei, and a progressive decrease in cellularity, proliferation index and expression of connexins 43 and 32. Tendon maturation was similarly characterised by modulation of several other gene expression profiles, including Collagen type I, Collagen type III, Scleraxis B, Tenomodulin, Trombospondin 4 and Osteocalcin. These gene profiles underwent a dramatic reduction in adult tissues. Transforming growth factor-1 expression (involved in collagen synthesis) underwent a similar decrease. In conclusion, these morphological studies carried out on sheep tendons at different stages of development and aging offer normal structural and molecular baseline data to allow accurate evaluation of data from subsequent interventional studies investigating tendon healing and regeneration in ovine experimental models. PMID:25546075

Composition, structure, and dynamics of a mature, unmanaged, pine-dominated old-field stand in southeastern Arkansas

Treesearch

Don C. Bragg; Eric Heitzman

2009-01-01

This study describes the composition and structure of a mature, second-growthPinus taeda (Loblolly Pine) and Pinus echinata (Shortleaf Pine)-dominatedold-field stand. Now owned by the University of Arkansas, this 22.5-ha parcel justoutside of the city of Monticello, AR, has been protected as a de facto natural area

Size increment of jumbo flying squid Dosidicus gigas mature females in Peruvian waters, 1989-2004

NASA Astrophysics Data System (ADS)

Argüelles, Juan; Tafur, Ricardo; Taipe, Anatolio; Villegas, Piero; Keyl, Friedeman; Dominguez, Noel; Salazar, Martín

2008-10-01

Changes in population structure of the jumbo flying squid Dosidicus gigas in Peruvian waters were studied based on size-at-maturity from 1989 to 2004. From 1989 to 1999, mature squid belonging to the medium-sized group prevailed, but from 2001 on, mature squids were larger. This change is not related to the changes in sea surface temperature and we hypothesized that it was caused by the population increase of mesopelagic fishes as prey.

7 CFR 29.1085 - Width.

Code of Federal Regulations, 2010 CFR

2010-01-01

....) Elements Degrees Maturity Immature Unripe Mature Ripe Mellow. Leaf structure Tight Close Firm Open Body... Type 92) § 29.1085 Width. The relative breadth of a tobacco leaf expressed in relation to its length...

7 CFR 29.1085 - Width.

Code of Federal Regulations, 2013 CFR

2013-01-01

....) Elements Degrees Maturity Immature Unripe Mature Ripe Mellow. Leaf structure Tight Close Firm Open Body... Type 92) § 29.1085 Width. The relative breadth of a tobacco leaf expressed in relation to its length...

7 CFR 29.1085 - Width.

Code of Federal Regulations, 2011 CFR

2011-01-01

....) Elements Degrees Maturity Immature Unripe Mature Ripe Mellow. Leaf structure Tight Close Firm Open Body... Type 92) § 29.1085 Width. The relative breadth of a tobacco leaf expressed in relation to its length...

7 CFR 29.1085 - Width.

Code of Federal Regulations, 2014 CFR

2014-01-01

....) Elements Degrees Maturity Immature Unripe Mature Ripe Mellow. Leaf structure Tight Close Firm Open Body... Type 92) § 29.1085 Width. The relative breadth of a tobacco leaf expressed in relation to its length...

7 CFR 29.1085 - Width.

Code of Federal Regulations, 2012 CFR

2012-01-01

....) Elements Degrees Maturity Immature Unripe Mature Ripe Mellow. Leaf structure Tight Close Firm Open Body... Type 92) § 29.1085 Width. The relative breadth of a tobacco leaf expressed in relation to its length...

Quantifying model-structure- and parameter-driven uncertainties in spring wheat phenology prediction with Bayesian analysis

DOE PAGES

Alderman, Phillip D.; Stanfill, Bryan

2016-10-06

Recent international efforts have brought renewed emphasis on the comparison of different agricultural systems models. Thus far, analysis of model-ensemble simulated results has not clearly differentiated between ensemble prediction uncertainties due to model structural differences per se and those due to parameter value uncertainties. Additionally, despite increasing use of Bayesian parameter estimation approaches with field-scale crop models, inadequate attention has been given to the full posterior distributions for estimated parameters. The objectives of this study were to quantify the impact of parameter value uncertainty on prediction uncertainty for modeling spring wheat phenology using Bayesian analysis and to assess the relativemore » contributions of model-structure-driven and parameter-value-driven uncertainty to overall prediction uncertainty. This study used a random walk Metropolis algorithm to estimate parameters for 30 spring wheat genotypes using nine phenology models based on multi-location trial data for days to heading and days to maturity. Across all cases, parameter-driven uncertainty accounted for between 19 and 52% of predictive uncertainty, while model-structure-driven uncertainty accounted for between 12 and 64%. Here, this study demonstrated the importance of quantifying both model-structure- and parameter-value-driven uncertainty when assessing overall prediction uncertainty in modeling spring wheat phenology. More generally, Bayesian parameter estimation provided a useful framework for quantifying and analyzing sources of prediction uncertainty.« less

Social induction of maturation and sex determination in a coral reef fish.

PubMed Central

Hobbs, Jean-Paul A.; Munday, Philip L.; Jones, Geoffrey P.

2004-01-01

Labile maturation and sex determination should be advantageous where the probability of finding a mating partner is unpredictable. Here we tested the hypothesis that the presence of a potential mating partner induces maturation and sex determination in a coral-dwelling fish, Gobiodon erythrospilus. In natural populations at Lizard Island (Great Barrier Reef), single individuals were less likely to be mature than paired individuals and they matured at a larger size, indicating plasticity in the timing of maturation. By manipulating group structure we demonstrated that both the timing of maturation and the sex of maturing individuals are socially controlled. Single juveniles did not mature, but maturation was rapidly induced by the presence of an adult partner. In addition, sex determination was found to be labile, with juveniles maturing into the opposite sex of the partner encountered. To our knowledge, this is the first experimental demonstration of social induction of maturation in conjunction with labile sex determination at maturation in vertebrates. This flexibility enables individuals to maximize their reproductive success in an environment where the timing of mate acquisition and the sex of their future partner are unpredictable. PMID:15475329

A pediatric brain structure atlas from T1-weighted MR images

NASA Astrophysics Data System (ADS)

Shan, Zuyao Y.; Parra, Carlos; Ji, Qing; Ogg, Robert J.; Zhang, Yong; Laningham, Fred H.; Reddick, Wilburn E.

2006-03-01

In this paper, we have developed a digital atlas of the pediatric human brain. Human brain atlases, used to visualize spatially complex structures of the brain, are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1 weighted MR data set of a 9 year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. Higher curvature surfaces were simplified with more reference points; lower curvature surfaces, with fewer. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/BrainAtlas) can be used to plan treatment, to conduct knowledge and modeldriven segmentation, and to analyze the shapes of brain structures in pediatric patients.

[Sex difference of functional and structural alterations in the myocardium of rats with hypothyroidism].

PubMed

Khara, M R; Pavlovych, S I; Mykhaĭliuk, V M

2013-01-01

In experiments on sexually mature rats we studied specific cholinergic regulations of the heart and the degree of its structural damage in hypothyroidism, depending on gender and hormone-productive activity of the gonads. Hypothyroidism in sexually mature males and females was modelled with mercazolil intragastric administration (75 mg/kg) daily during 15 days. We also studied the intensity of bradycardia, which occurred in response to electrical stimulation of vagus nerve and intravenous acetylcholine administration. The degree of structural heart damage was assessed by the percentage of damaged cardiomyocytes in the ventricles of myocardium. It was found that one of the mechanisms of bradycardia in merkazolil-induced hypothyroidism is an increase of the sensitivity of sinus node cholinergic receptors and release of more quanta of acetylcholine from stimulated nerves vagus endings, what was more intense in females. The intensity of bradycardia in hypothyroidism was more significant in gonadectomized animals than in individuals with preserved gonads. The mechanisms of its occurrence in males consist of release of greater amount of acetylcholine from the endings of the nerves vagus, and in females it was the result of significant increase of the sensitivity of sinus node cholinergic receptors. Regardless of the gonads activity, structural damage of the myocardium in merkazolil-induced hypothyroidism was more intensive in female rats.

Spine Formation and Maturation in the Developing Rat Auditory Cortex

PubMed Central

Schachtele, Scott J.; Losh, Joe; Dailey, Michael E.; Green, Steven H.

2013-01-01

The rat auditory cortex is organized as a tonotopic map of sound frequency. This map is broadly tuned at birth and is refined during the first 3 weeks postnatal. The structural correlates underlying tonotopic map maturation and reorganization during development are poorly understood. We employed fluorescent dye ballistic labeling (“DiOlistics”) alone, or in conjunction with immunohistochemistry, to quantify synaptogenesis in the auditory cortex of normal hearing rats. We show that the developmental appearance of dendritic protrusions, which include both immature filopodia and mature spines, on layers 2/3, 4, and 5 pyramidal and layer 4 spiny nonpyramidal neurons occurs in three phases: slow addition of dendritic protrusions from postnatal day 4 (P4) to P9, rapid addition of dendritic protrusions from P9 to P19, and a final phase where mature protrusion density is achieved (>P21). Next, we combined DiOlistics with immunohistochemical labeling of bassoon, a presynaptic scaffolding protein, as a novel method to categorize dendritic protrusions as either filopodia or mature spines in cortex fixed in vivo. Using this method we observed an increase in the spine-to-filopodium ratio from P9–P16, indicating a period of rapid spine maturation. Previous studies report mature spines as being shorter in length compared to filopodia. We similarly observed a reduction in protrusion length between P9 and P16, corroborating our immunohistochemical spine maturation data. These studies show that dendritic protrusion formation and spine maturation occur rapidly at a time previously shown to correspond to auditory cortical tonotopic map refinement (P11–P14), providing a structural correlate of physiological maturation. PMID:21800311

The art of maturity modeling. Part 2. Alternative models and sensitivity analysis

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

Waples, D.W.; Suizu, Masahiro; Kamata, Hiromi

1992-01-01

The sensitivity of exploration decisions to variations in several input parameters for maturity modeling was examined for the MITI Rumoi well, Hokkaido, Japan. Decisions were almost completely insensitive to uncertainties about formation age and erosional removal across some unconformities, but were more sensitive to changes in removal during unconformities which occurred near maximum paleotemperatures. Exploration decisions were not very sensitive to the choice of a particular kinetic model for hydrocarbon generation. Uncertainties in kerogen type and the kinetics of different kerogen types are more serious than differences among the various kinetic models. Results of modeling using the TTI method weremore » unsatisfactory. Thermal history and timing and amount of hydrocarbon generation estimated or calculated using the TTI method were greatly different from those obtained using a purely kinetic model. The authors strongly recommend use of the kinetic R{sub o} method instead of the TTI method. If they had lacked measured R{sub o} data, subsurface temperature data, or both, their confidence in the modeling results would have been sharply reduced. Conceptual models for predicting heat flow and thermal conductivity are simply too weak at present to allow one to carry out highly meaningful modeling unless the input is constrained by measured data. Maturity modeling therefore requires the use of more, not fewer, measured temperature and maturity data. The use of sensitivity analysis in maturity modeling is very important for understanding the geologic system, for knowing what level of confidence to place on the results, and for determining what new types of data would be most necessary to improve confidence. Sensitivity analysis can be carried out easily using a rapid, interactive maturity-modeling program.« less

The evolution of human phenotypic plasticity: age and nutritional status at maturity.

PubMed

Gage, Timothy B

2003-08-01

Several evolutionary optimal models of human plasticity in age and nutritional status at reproductive maturation are proposed and their dynamics examined. These models differ from previously published models because fertility is not assumed to be a function of body size or nutritional status. Further, the models are based on explicitly human demographic patterns, that is, model human life-tables, model human fertility tables, and, a nutrient flow-based model of maternal nutritional status. Infant survival (instead of fertility as in previous models) is assumed to be a function of maternal nutritional status. Two basic models are examined. In the first the cost of reproduction is assumed to be a constant proportion of total nutrient flow. In the second the cost of reproduction is constant for each birth. The constant proportion model predicts a negative slope of age and nutritional status at maturation. The constant cost per birth model predicts a positive slope of age and nutritional status at maturation. Either model can account for the secular decline in menarche observed over the last several centuries in Europe. A search of the growth literature failed to find definitive empirical documentation of human phenotypic plasticity in age and nutritional status at maturation. Most research strategies confound genetics with phenotypic plasticity. The one study that reports secular trends suggests a marginally insignificant, but positive slope. This view tends to support the constant cost per birth model.

Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

PubMed

Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

2018-04-12

Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Individual heterogeneity in growth and age at sexual maturity: A gamma process analysis of capture–mark–recapture data

USGS Publications Warehouse

Link, William; Hesed, Kyle Miller

2015-01-01

Knowledge of organisms’ growth rates and ages at sexual maturity is important for conservation efforts and a wide variety of studies in ecology and evolutionary biology. However, these life history parameters may be difficult to obtain from natural populations: individuals encountered may be of unknown age, information on age at sexual maturity may be uncertain and interval-censored, and growth data may include both individual heterogeneity and measurement errors. We analyzed mark–recapture data for Red-backed Salamanders (Plethodon cinereus) to compare sex-specific growth rates and ages at sexual maturity. Aging of individuals was made possible by the use of a von Bertalanffy model of growth, complemented with models for interval-censored and imperfect observations at sexual maturation. Individual heterogeneity in growth was modeled through the use of Gamma processes. Our analysis indicates that female P. cinereus mature earlier and grow more quickly than males, growing to nearly identical asymptotic size distributions as males.

Maturity method demonstration : final report.

DOT National Transportation Integrated Search

2003-07-01

The concrete maturity method is a quality control/quality assurance tool that can be used to assist contractors and transportation officials in producing cost-efficient, durable concrete structures. This report documents the findings of an investigat...

The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation

PubMed Central

Hom, Jennifer R.; Quintanilla, Rodrigo A.; Hoffman, David L.; Karen L., de Mesy Bentley; Molkentin, Jeffery D.; Sheu, Shey-Shing; Porter, George A.

2011-01-01

SUMMARY Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myocyte differentiation (measured by counting Z-bands). Furthermore, myocyte differentiation was inhibited and enhanced with oxidant and antioxidant treatment, respectively, suggesting that redox signaling pathways lie downstream of mitochondria to regulate cardiac myocyte differentiation. PMID:21920313

Roles of density-dependent growth and life history evolution in accounting for fisheries-induced trait changes

PubMed Central

Eikeset, Anne Maria; Dunlop, Erin S.; Heino, Mikko; Storvik, Geir; Stenseth, Nils C.; Dieckmann, Ulf

2016-01-01

The relative roles of density dependence and life history evolution in contributing to rapid fisheries-induced trait changes remain debated. In the 1930s, northeast Arctic cod (Gadus morhua), currently the world’s largest cod stock, experienced a shift from a traditional spawning-ground fishery to an industrial trawl fishery with elevated exploitation in the stock’s feeding grounds. Since then, age and length at maturation have declined dramatically, a trend paralleled in other exploited stocks worldwide. These trends can be explained by demographic truncation of the population’s age structure, phenotypic plasticity in maturation arising through density-dependent growth, fisheries-induced evolution favoring faster-growing or earlier-maturing fish, or a combination of these processes. Here, we use a multitrait eco-evolutionary model to assess the capacity of these processes to reproduce 74 y of historical data on age and length at maturation in northeast Arctic cod, while mimicking the stock’s historical harvesting regime. Our results show that model predictions critically depend on the assumed density dependence of growth: when this is weak, life history evolution might be necessary to prevent stock collapse, whereas when a stronger density dependence estimated from recent data is used, the role of evolution in explaining fisheries-induced trait changes is diminished. Our integrative analysis of density-dependent growth, multitrait evolution, and stock-specific time series data underscores the importance of jointly considering evolutionary and ecological processes, enabling a more comprehensive perspective on empirically observed stock dynamics than previous studies could provide. PMID:27940913

Thermal history of sedimentary basins, maturation indices, and kinetics of oil and gas generation

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

Tissot, B.P.; Pelet, R.; Ungerer, P.

1987-12-01

Temperature is the most sensitive parameter in hydrocarbon generation. Thus, reconstruction of temperature history is essential when evaluating petroleum prospects. No measurable parameter can be directly converted to paleotemperature. Maturation indices such as vitrinite reflectance, T/sub max/ from Rock-Eval pyrolysis, spore coloration, Thermal Alteration Index (TAI), or concentration of biological markers offer an indirect approach. All these indices are a function of the thermal history through rather complex kinetics, frequently influenced by the type of organic matter. Their significance and validity are reviewed. Besides the problems of identification (e.g. vitrinite) and interlaboratory calibration, it is important to simultaneously interpret kerogenmore » type and maturation and to avoid difficult conversions from one index to another. Geodynamic models, where structural and thermal histories are connected, are another approach to temperature reconstruction which could be calibrated against the present distribution of temperature and the present value of maturation indices. Kinetics of kerogen decomposition controls the amount and composition of hydrocarbons generated. An empirical time-temperature index (TTI), originally introduced by Lopatin, does not allow such a quantitative evaluation. Due to several limitations (no provision for different types of kerogen and different rates of reactions, poor calibration on vitrinite reflectance), it is of limited interest unless one has no access to a desk-top computer. Kinetic models, based on a specific calibration made on actual source rock samples, can simulate the evolution of all types of organic matter and can provide a quantitative evaluation of oil and gas generated. 29 figures.« less

A Quantitative Assessment of the Structure and Functions of a Mature Bottomland Hardwood Community: The Iatt Creek Ecosystem Site

Treesearch

Calvin E. Meier; John A. Stanturf; Emile S. Gardiner; Paul B. Hamel; Melvin L. Warren

1999-01-01

We report our efforts, initiated in 1995, to quantify ecological processes and functions in a relatively undisturbed, mature hardwood forest. The 320-ha site is located in central Louisiana on the upper reaches of Iatt Creek, an anastomosing minor stream bottom. The forest is a mature sweetgum (Liquidambar styraciflua L.)-cherrybark oak (

Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNA

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

Zhang, Jun; McCann, Kathleen L.; Qiu, Chen

Numerous factors direct eukaryotic ribosome biogenesis, and defects in a single ribosome assembly factor may be lethal or produce tissue-specific human ribosomopathies. Pre-ribosomal RNAs (pre-rRNAs) must be processed stepwise and at the correct subcellular locations to produce the mature rRNAs. Nop9 is a conserved small ribosomal subunit biogenesis factor, essential in yeast. Here we report a 2.1-Å crystal structure of Nop9 and a small-angle X-ray-scattering model of a Nop9:RNA complex that reveals a ‘C’-shaped fold formed from 11 Pumilio repeats. We show that Nop9 recognizes sequence and structural features of the 20S pre-rRNA near the cleavage site of the nuclease,more » Nob1. We further demonstrate that Nop9 inhibits Nob1 cleavage, the final processing step to produce mature small ribosomal subunit 18S rRNA. Together, our results suggest that Nop9 is critical for timely cleavage of the 20S pre-rRNA. Moreover, the Nop9 structure exemplifies a new class of Pumilio repeat proteins.« less

The Roles of Family B and D DNA Polymerases in Thermococcus Species 9°N Okazaki Fragment Maturation*

PubMed Central

Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F.

2015-01-01

During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. PMID:25814667

A modern regional geological analysis of Venezuela - lessons from a major new world oil province on exploration in mature areas

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

Daly, M.; Audemard, F.; Valdes, G.

1993-09-01

Venezuela has produced some 44 billion bbl of oil since the early part of the century. As such, it represents one of the world's major oil producers and a mature petroleum province. However, major tracts of Venezuela's sedimentary basins remain underexplored and large discoveries are still being made in new and old reservoir systems. A regional geological analysis of Venezuela, focusing on basin evolution and sequence stratigraphy and incorporating data from the three national oil companies, is presented. The analysis presents a regionally consistent tectonostratigraphic model capable of explaining the evolution of the Mesozoic and Cenozoic basins of Venezuela andmore » placing the major reservoir facies in their regional tectonic and sequence stratigraphic context. Four regional cross sections describe the stratigraphic and structural model. The model recognizes a Jurassic rifting event and inversion, succeeded by an Early Cretaceous passive margin. In western Venezuela, the Early Cretaceous passive subsidence is enhanced locally by extension related to the Colombian active margin. Venezuela experienced a major change in the Campanian with the initial collision of the Caribbean arc, recorded by foreland structuring and widespread stratigraphic changes. From the Campanian onward, the tectonostratigraphic evolution can be modeled in terms of a progressive southeast-directed arc-continent collision and the migration of the associated foredeep and rift basins. Within the tectonic framework, the major sequence stratigraphic units are identified and the reservoir distribution interpreted. This model provides a strong predictive tool to extrapolate reservoir systems into Venezuela's underexplored areas and to readdress its traditional areas.« less

Pea Border Cell Maturation and Release Involve Complex Cell Wall Structural Dynamics1[OPEN

PubMed Central

2017-01-01

The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases, though, plant cells are programmed to detach, and root cap-derived border cells are examples of this. Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we undertook a systematic, detailed analysis of pea (Pisum sativum) root tip cell walls. Our study included immunocarbohydrate microarray profiling, monosaccharide composition determination, Fourier-transformed infrared microspectroscopy, quantitative reverse transcription-PCR of cell wall biosynthetic genes, analysis of hydrolytic activities, transmission electron microscopy, and immunolocalization of cell wall components. Using this integrated glycobiology approach, we identified multiple novel modes of cell wall structural and compositional rearrangement during root cap growth and the release of border cells. Our findings provide a new level of detail about border cell maturation and enable us to develop a model of the separation process. We propose that loss of adhesion by the dissolution of homogalacturonan in the middle lamellae is augmented by an active biophysical process of cell curvature driven by the polarized distribution of xyloglucan and extensin epitopes. PMID:28400496

Capsid expansion mechanism of bacteriophage T7 revealed by multistate atomic models derived from cryo-EM reconstructions

PubMed Central

Guo, Fei; Liu, Zheng; Fang, Ping-An; Zhang, Qinfen; Wright, Elena T.; Wu, Weimin; Zhang, Ci; Vago, Frank; Ren, Yue; Jakana, Joanita; Chiu, Wah; Serwer, Philip; Jiang, Wen

2014-01-01

Many dsDNA viruses first assemble a DNA-free procapsid, using a scaffolding protein-dependent process. The procapsid, then, undergoes dramatic conformational maturation while packaging DNA. For bacteriophage T7 we report the following four single-particle cryo-EM 3D reconstructions and the derived atomic models: procapsid (4.6-Å resolution), an early-stage DNA packaging intermediate (3.5 Å), a later-stage packaging intermediate (6.6 Å), and the final infectious phage (3.6 Å). In the procapsid, the N terminus of the major capsid protein, gp10, has a six-turn helix at the inner surface of the shell, where each skewed hexamer of gp10 interacts with two scaffolding proteins. With the exit of scaffolding proteins during maturation the gp10 N-terminal helix unfolds and swings through the capsid shell to the outer surface. The refolded N-terminal region has a hairpin that forms a novel noncovalent, joint-like, intercapsomeric interaction with a pocket formed during shell expansion. These large conformational changes also result in a new noncovalent, intracapsomeric topological linking. Both interactions further stabilize the capsids by interlocking all pentameric and hexameric capsomeres in both DNA packaging intermediate and phage. Although the final phage shell has nearly identical structure to the shell of the DNA-free intermediate, surprisingly we found that the icosahedral faces of the phage are slightly (∼4 Å) contracted relative to the faces of the intermediate, despite the internal pressure from the densely packaged DNA genome. These structures provide a basis for understanding the capsid maturation process during DNA packaging that is essential for large numbers of dsDNA viruses. PMID:25313071

The influences of family environment on personality traits.

PubMed

Nakao, K; Takaishi, J; Tatsuta, K; Katayama, H; Iwase, M; Yorifuji, K; Takeda, M

2000-02-01

In order to clarify the influences of family environment on the development of personality traits, 150 children (104 males and 46 females, mean age 13.2 +/- 2.4 years) who had been interviewed at the Child Guidance Clinic in Osaka were investigated. From 13 behavioral characteristics (activity, talkativeness, sociability, social skills, rule-keeping, will, aggression, emotional control, imagination, anxiety, maturity, intelligence, and neuroticism), factor analysis identified three personality traits: extraversion, maturity, and intellect. The effects of family environment (maternal and paternal participation in child rearing before and after 4years of age, child-rearing style, parental relationship, sibling relationship, number of siblings, birth order, and socioeconomic status) on these personality traits were examined based on a structural equation model. The results found, first, that extraversion was negatively associated with overprotection/interference and with maternal participation in child rearing. Maturity correlated with high socioeconomic status, appropriate child-rearing style, and paternal participation in child rearing. Intellect was related to high socioeconomic status and maternal participation in child rearing. Second, path analysis with selected variables revealed that 8% of variance in extraversion, 14% in maturity, and 10% in intellect was due to family environment. Third, children with high introversion or high intellect had stronger influences from family environment than did those with high extraversion or low intellect.

Sex differences in thickness, and folding developments throughout the cortex.

PubMed

Mutlu, A Kadir; Schneider, Maude; Debbané, Martin; Badoud, Deborah; Eliez, Stephan; Schaer, Marie

2013-11-15

While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females. Copyright © 2013 Elsevier Inc. All rights reserved.

Species area relationships in mediterranean-climate plant communities

USGS Publications Warehouse

Keeley, Jon E.; Fotheringham, C.J.

2003-01-01

Aim To determine the best-fit model of species–area relationships for Mediterranean-type plant communities and evaluate how community structure affects these species–area models.Location Data were collected from California shrublands and woodlands and compared with literature reports for other Mediterranean-climate regions.Methods The number of species was recorded from 1, 100 and 1000 m2 nested plots. Best fit to the power model or exponential model was determined by comparing adjusted r2 values from the least squares regression, pattern of residuals, homoscedasticity across scales, and semi-log slopes at 1–100 m2 and 100–1000 m2. Dominance–diversity curves were tested for fit to the lognormal model, MacArthur's broken stick model, and the geometric and harmonic series.Results Early successional Western Australia and California shrublands represented the extremes and provide an interesting contrast as the exponential model was the best fit for the former, and the power model for the latter, despite similar total species richness. We hypothesize that structural differences in these communities account for the different species–area curves and are tied to patterns of dominance, equitability and life form distribution. Dominance–diversity relationships for Western Australian heathlands exhibited a close fit to MacArthur's broken stick model, indicating more equitable distribution of species. In contrast, Californian shrublands, both postfire and mature stands, were best fit by the geometric model indicating strong dominance and many minor subordinate species. These regions differ in life form distribution, with annuals being a major component of diversity in early successional Californian shrublands although they are largely lacking in mature stands. Both young and old Australian heathlands are dominated by perennials, and annuals are largely absent. Inherent in all of these ecosystems is cyclical disequilibrium caused by periodic fires. The potential for community reassembly is greater in Californian shrublands where only a quarter of the flora resprout, whereas three quarters resprout in Australian heathlands.Other Californian vegetation types sampled include coniferous forests, oak savannas and desert scrub, and demonstrate that different community structures may lead to a similar species–area relationship. Dominance–diversity relationships for coniferous forests closely follow a geometric model whereas associated oak savannas show a close fit to the lognormal model. However, for both communities, species–area curves fit a power model. The primary driver appears to be the presence of annuals. Desert scrub communities illustrate dramatic changes in both species diversity and dominance–diversity relationships in high and low rainfall years, because of the disappearance of annuals in drought years.Main conclusions Species–area curves for immature shrublands in California and the majority of Mediterranean plant communities fit a power function model. Exceptions that fit the exponential model are not because of sampling error or scaling effects, rather structural differences in these communities provide plausible explanations. The exponential species–area model may arise in more than one way. In the highly diverse Australian heathlands it results from a rapid increase in species richness at small scales. In mature California shrublands it results from very depauperate richness at the community scale. In both instances the exponential model is tied to a preponderance of perennials and paucity of annuals. For communities fit by a power model, coefficients z and log c exhibit a number of significant correlations with other diversity parameters, suggesting that they have some predictive value in ecological communities.

Genotype x environmental interaction for mature size and rate of maturing for Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte infected fescue.

PubMed

Sandelin, B A; Brown, A H; Brown, M A; Johnson, Z B; Kellogg, D W; Stelzleni, A M

2002-12-01

Mature weight and rate of maturing were estimated in 177 Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte-infected tall fescue over a 4-yr period to evaluate genotype x environment interactions. Data were collected every 28 d until cows were approximately 18 mo of age and then at prebreeding, postcalving, and weaning of calf. All cows with weight data to at least 42 mo of age were included in the analysis. Mature weight and rate of maturing were estimated using the three-parameter growth curve model described by Brody (1945). Data were pooled over year and analyzed by the general linear model procedure of SAS. Included in the models for mature weight and rate of maturing were the independent variables of genotype, environment, and genotype x environment interaction. There was a genotype x environment interaction (P < 0.01) for mature body weight (BW) but not for rate of maturing. Angus cows grazing fescue pastures had greater (P < 0.01) mean mature BW than Angus x Brahman cows grazing bermudagrass (611 +/- 17 vs 546 +/- 16 kg). Angus x Brahman cows grazing bermudagrass had lower (P < 0.05) mean mature BW than Brahman x Angus cows grazing bermudagrass or endophyte-infected fescue and Brahman cows grazing bermudagrass (546 +/- 16 vs 624 +/- 19, 614 +/- 22 and 598 +/- 20 kg, respectively). Brahman cows grazing endophyte-infected fescue had smaller (P < 0.05) mean mature BW than all genotype x forage combinations except for Angus x Brahman cows grazing bermudagrass. Angus cows had a smaller (P < 0.05) mean rate of maturing than Angus x Brahman and Brahman x Angus cows (0.039 +/- 0.002 vs 0.054 +/- 0.002 and 0.049 +/- 0.002%/mo, respectively), respectively, and Angus x Brahman cows had a larger (P < 0.05) mean rate of maturing than Brahman x Angus and Brahman cows (0.054 +/- 0.002 vs 0.049 +/- 0.002 and 0.041 +/- 0.002 %/mo, respectively). There was a direct breed x forage interaction (P < 0.05) for mature BW. These data suggest that the choice of breed type is important in maintaining a crossbreeding program, in that mature BW and rate of maturing are critical to the matching of animal requirements to available production resources.

Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.

PubMed

Bedore, Jake; Martyn, Amanda C; Li, Anson K C; Dolinar, Eric A; McDonald, Ian S; Coupland, Stuart G; Prado, Vania F; Prado, Marco A; Hill, Kathleen A

2015-01-01

Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina. A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5) deletion of VAChT (VAChTSix3-Cre-flox/flox) and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses. This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

α-Actinin-2 Mediates Spine Morphology and Assembly of the Post-Synaptic Density in Hippocampal Neurons

PubMed Central

Hodges, Jennifer L.; Vilchez, Samuel Martin; Asmussen, Hannelore; Whitmore, Leanna A.; Horwitz, Alan Rick

2014-01-01

Dendritic spines are micron-sized protrusions that constitute the primary post-synaptic sites of excitatory neurotransmission in the brain. Spines mature from a filopodia-like protrusion into a mushroom-shaped morphology with a post-synaptic density (PSD) at its tip. Modulation of the actin cytoskeleton drives these morphological changes as well as the spine dynamics that underlie learning and memory. Several PSD molecules respond to glutamate receptor activation and relay signals to the underlying actin cytoskeleton to regulate the structural changes in spine and PSD morphology. α-Actinin-2 is an actin filament cross-linker, which localizes to dendritic spines, enriched within the post-synaptic density, and implicated in actin organization. We show that loss of α-actinin-2 in rat hippocampal neurons creates an increased density of immature, filopodia-like protrusions that fail to mature into a mushroom-shaped spine during development. α-Actinin-2 knockdown also prevents the recruitment and stabilization of the PSD in the spine, resulting in failure of synapse formation, and an inability to structurally respond to chemical stimulation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. The Ca2+-insensitive EF-hand motif in α-actinin-2 is necessary for the molecule's function in regulating spine morphology and PSD assembly, since exchanging it for the similar but Ca2+-sensitive domain from α-actinin-4, another α-actinin isoform, inhibits its function. Furthermore, when the Ca2+-insensitive domain from α-actinin-2 is inserted into α-actinin-4 and expressed in neurons, it creates mature spines. These observations support a model whereby α-actinin-2, partially through its Ca2+-insensitive EF-hand motif, nucleates PSD formation via F-actin organization and modulates spine maturation to mediate synaptogenesis. PMID:25007055

Effect of sialic acid loss on dendritic cell maturation

PubMed Central

Crespo, Hélio J; Guadalupe Cabral, M; Teixeira, Alexandra V; Lau, Joseph T Y; Trindade, Hélder; Videira, Paula A

2009-01-01

Sialic acids are key structural determinants and contribute to the functionality of a number of immune cell receptors. Previously, we demonstrated that differentiation of human dendritic cells (DCs) is accompanied by an increased expression of sialylated cell surface structures, putatively through the activity of the ST3Gal.I and ST6Gal.I sialyltransferases. Furthermore, DC endocytosis was reduced upon removal of the cell surface sialic acid residues by neuraminidase. In the present work, we evaluate the contribution of the sialic acid modifications in DC maturation. We demonstrate that neuraminidase-treated human DCs have increased expression of major histocompatibility complex (MHC) and costimulatory molecules, increased gene expression of specific cytokines and induce a higher proliferative response of T lymphocytes. Together, the data suggest that clearance of cell surface sialic acids contributes to the development of a T helper type 1 proinflammatory response. This postulate is supported by mouse models, where elevated MHC class II and increased maturation of specific DC subsets were observed in DCs harvested from ST3Gal.I−/− and ST6Gal.I−/− mice. Moreover, important qualitative differences, particularly in the extent of reduced endocytosis and in the peripheral distribution of DC subsets, existed between the ST3Gal.I−/− and ST6Gal.I−/− strains. Together, the data strongly suggest not only a role of cell surface sialic acid modifications in maturation and functionality of DCs, but also that the sialic acid linkages created by different sialyltransferases are functionally distinct. Consequently, with particular relevance to DC-based therapies, cell surface sialylation, mediated by individual sialyltransferases, can influence the immunogenicity of DCs upon antigen loading. PMID:19740323

Graphene Sheet-Induced Global Maturation of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.

PubMed

Wang, Jiaxian; Cui, Chang; Nan, Haiyan; Yu, Yuanfang; Xiao, Yini; Poon, Ellen; Yang, Gang; Wang, Xijie; Wang, Chenchen; Li, Lingsong; Boheler, Kenneth Richard; Ma, Xu; Cheng, Xin; Ni, Zhenhua; Chen, Minglong

2017-08-09

Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, or physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate, which is a biocompatible and superconductive material. The hiPSCs lines were successfully maintained on the graphene sheets and were able to differentiate into functional cardiomyocytes. This strategy markedly increased the myofibril ultrastructural organization, elevated the conduction velocity, and enhanced both the Ca 2+ handling and electrophysiological properties in the absence of electrical stimulation. On the graphene substrate, the expression of connexin 43 increased along with the conduction velocity. Interestingly, the bone morphogenetic proteins signaling was also significantly activated during early cardiogenesis, confirmed by RNA sequencing analysis. Here, we reasoned that graphene substrate as a conductive biomimetic surface could facilitate the intrinsic electrical propagation, mimicking the microenvironment of the native heart, to further promote the global maturation of hiPSC-CMs. Our findings highlight the capability of electrically active substrates to influence cardiomyocyte development. We believe that application of graphene sheets will be useful for simple, fast, and scalable maturation of regenerated cardiomyocytes.

Wireless Concrete Strength Monitoring of Wind Turbine Foundations.

PubMed

Perry, Marcus; Fusiek, Grzegorz; Niewczas, Pawel; Rubert, Tim; McAlorum, Jack

2017-12-16

Wind turbine foundations are typically cast in place, leaving the concrete to mature under environmental conditions that vary in time and space. As a result, there is uncertainty around the concrete's initial performance, and this can encourage both costly over-design and inaccurate prognoses of structural health. Here, we demonstrate the field application of a dense, wireless thermocouple network to monitor the strength development of an onshore, reinforced-concrete wind turbine foundation. Up-to-date methods in fly ash concrete strength and maturity modelling are used to estimate the distribution and evolution of foundation strength over 29 days of curing. Strength estimates are verified by core samples, extracted from the foundation base. In addition, an artificial neural network, trained using temperature data, is exploited to demonstrate that distributed concrete strengths can be estimated for foundations using only sparse thermocouple data. Our techniques provide a practical alternative to computational models, and could assist site operators in making more informed decisions about foundation design, construction, operation and maintenance.

Wireless Concrete Strength Monitoring of Wind Turbine Foundations

PubMed Central

Niewczas, Pawel; Rubert, Tim

2017-01-01

Wind turbine foundations are typically cast in place, leaving the concrete to mature under environmental conditions that vary in time and space. As a result, there is uncertainty around the concrete’s initial performance, and this can encourage both costly over-design and inaccurate prognoses of structural health. Here, we demonstrate the field application of a dense, wireless thermocouple network to monitor the strength development of an onshore, reinforced-concrete wind turbine foundation. Up-to-date methods in fly ash concrete strength and maturity modelling are used to estimate the distribution and evolution of foundation strength over 29 days of curing. Strength estimates are verified by core samples, extracted from the foundation base. In addition, an artificial neural network, trained using temperature data, is exploited to demonstrate that distributed concrete strengths can be estimated for foundations using only sparse thermocouple data. Our techniques provide a practical alternative to computational models, and could assist site operators in making more informed decisions about foundation design, construction, operation and maintenance. PMID:29258176

Adipose tissue-organotypic culture system as a promising model for studying adipose tissue biology and regeneration

PubMed Central

Uchihashi, Kazuyoshi; Aoki, Shigehisa; Sonoda, Emiko; Yamasaki, Fumio; Piao, Meihua; Ootani, Akifumi; Yonemitsu, Nobuhisa; Sugihara, Hajime

2009-01-01

Adipose tissue consists of mature adipocytes, preadipocytes and mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. We have recently developed “adipose tissue-organotypic culture system” that maintains unilocular structure, proliferative ability and functions of mature adipocytes for a long term, using three-dimensional collagen gel culture of the tissue fragments. In this system, both preadipocytes and MSCs regenerate actively at the peripheral zone of the fragments. Our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome. Thus, it seems to be a promising model for investigating adipose tissue biology and regeneration. In this article, we introduce adipose tissue-organotypic culture, and propose two theories regarding the mechanism of tissue regeneration that occurs specifically at peripheral zone of tissue fragments in vitro. PMID:19794899

An Environmental Management Maturity Model of Construction Programs Using the AHP-Entropy Approach.

PubMed

Bai, Libiao; Wang, Hailing; Huang, Ning; Du, Qiang; Huang, Youdan

2018-06-23

The accelerating process of urbanization in China has led to considerable opportunities for the development of construction projects, however, environmental issues have become an important constraint on the implementation of these projects. To quantitatively describe the environmental management capabilities of such projects, this paper proposes a 2-dimensional Environmental Management Maturity Model of Construction Program (EMMMCP) based on an analysis of existing projects, group management theory and a management maturity model. In this model, a synergetic process was included to compensate for the lack of consideration of synergies in previous studies, and it was involved in the construction of the first dimension, i.e., the environmental management index system. The second dimension, i.e., the maturity level of environment management, was then constructed by redefining the hierarchical characteristics of construction program (CP) environmental management maturity. Additionally, a mathematical solution to this proposed model was derived via the Analytic Hierarchy Process (AHP)-entropy approach. To verify the effectiveness and feasibility of this proposed model, a computational experiment was conducted, and the results show that this approach could not only measure the individual levels of different processes, but also achieve the most important objective of providing a reference for stakeholders when making decisions on the environmental management of construction program, which reflects this model is reasonable for evaluating the level of environmental management maturity in CP. To our knowledge, this paper is the first study to evaluate the environmental management maturity levels of CP, which would fill the gap between project program management and environmental management and provide a reference for relevant management personnel to enhance their environmental management capabilities.

The synergistic use of models and observations: understanding the mechanisms behind observed biomass dynamics at 14 Amazonian field sites and the implications for future biomass change

NASA Astrophysics Data System (ADS)

Levine, N. M.; Galbraith, D.; Christoffersen, B. J.; Imbuzeiro, H. A.; Restrepo-Coupe, N.; Malhi, Y.; Saleska, S. R.; Costa, M. H.; Phillips, O.; Andrade, A.; Moorcroft, P. R.

2011-12-01

The Amazonian rainforests play a vital role in global water, energy and carbon cycling. The sensitivity of this system to natural and anthropogenic disturbances therefore has important implications for the global climate. Some global models have predicted large-scale forest dieback and the savannization of Amazonia over the next century [Meehl et al., 2007]. While several studies have demonstrated the sensitivity of dynamic global vegetation models to changes in temperature, precipitation, and dry season length [e.g. Galbraith et al., 2010; Good et al., 2011], the ability of these models to accurately reproduce ecosystem dynamics of present-day transitional or low biomass tropical forests has not been demonstrated. A model-data intercomparison was conducted with four state-of-the-art terrestrial ecosystem models to evaluate the ability of these models to accurately represent structure, function, and long-term biomass dynamics over a range of Amazonian ecosystems. Each modeling group conducted a series of simulations for 14 sites including mature forest, transitional forest, savannah, and agricultural/pasture sites. All models were run using standard physical parameters and the same initialization procedure. Model results were compared against forest inventory and dendrometer data in addition to flux tower measurements. While the models compared well against field observations for the mature forest sites, significant differences were observed between predicted and measured ecosystem structure and dynamics for the transitional forest and savannah sites. The length of the dry season and soil sand content were good predictors of model performance. In addition, for the big leaf models, model performance was highest for sites dominated by late successional trees and lowest for sites with predominantly early and mid-successional trees. This study provides insight into tropical forest function and sensitivity to environmental conditions that will aid in predictions of the response of the Amazonian rainforest to future anthropogenically induced changes.

Static aeroelastic analysis of wings using Euler/Navier-Stokes equations coupled with improved wing-box finite element structures

NASA Technical Reports Server (NTRS)

Guruswamy, Guru P.; MacMurdy, Dale E.; Kapania, Rakesh K.

1994-01-01

Strong interactions between flow about an aircraft wing and the wing structure can result in aeroelastic phenomena which significantly impact aircraft performance. Time-accurate methods for solving the unsteady Navier-Stokes equations have matured to the point where reliable results can be obtained with reasonable computational costs for complex non-linear flows with shock waves, vortices and separations. The ability to combine such a flow solver with a general finite element structural model is key to an aeroelastic analysis in these flows. Earlier work involved time-accurate integration of modal structural models based on plate elements. A finite element model was developed to handle three-dimensional wing boxes, and incorporated into the flow solver without the need for modal analysis. Static condensation is performed on the structural model to reduce the structural degrees of freedom for the aeroelastic analysis. Direct incorporation of the finite element wing-box structural model with the flow solver requires finding adequate methods for transferring aerodynamic pressures to the structural grid and returning deflections to the aerodynamic grid. Several schemes were explored for handling the grid-to-grid transfer of information. The complex, built-up nature of the wing-box complicated this transfer. Aeroelastic calculations for a sample wing in transonic flow comparing various simple transfer schemes are presented and discussed.

Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies.

PubMed

Davenport, Thaddeus M; Gorman, Jason; Joyce, M Gordon; Zhou, Tongqing; Soto, Cinque; Guttman, Miklos; Moquin, Stephanie; Yang, Yongping; Zhang, Baoshan; Doria-Rose, Nicole A; Hu, Shiu-Lok; Mascola, John R; Kwong, Peter D; Lee, Kelly K

2016-08-02

Antibody somatic hypermutation (SHM) and affinity maturation enhance antigen recognition by modifying antibody paratope structure to improve its complementarity with the target epitope. SHM-induced changes in paratope dynamics may also contribute to antibody maturation, but direct evidence of this is limited. Here, we examine two classes of HIV-1 broadly neutralizing antibodies (bNAbs) for SHM-induced changes in structure and dynamics, and delineate the effects of these changes on interactions with the HIV-1 envelope glycoprotein (Env). In combination with new and existing structures of unmutated and affinity matured antibody Fab fragments, we used hydrogen/deuterium exchange with mass spectrometry to directly measure Fab structural dynamics. Changes in antibody structure and dynamics were positioned to improve complementarity with Env, with changes in dynamics primarily observed at the paratope peripheries. We conclude that SHM optimizes paratope complementarity to conserved HIV-1 epitopes and restricts the mobility of paratope-peripheral residues to minimize clashes with variable features on HIV-1 Env. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Socioanalytic Model of Maturity

ERIC Educational Resources Information Center

Hogan, Robert; Roberts, Brent W.

2004-01-01

K0 describes a point of view on maturity that departs from earlier treatments in two ways. First, it rejects the popular assumption from humanistic psychology that maturity is a function of self-actualization and stipulates that maturity is related to certain performance capacities--namely, the ability to form lasting relationships and to achieve…

Toward a Concept of Psychosocial Maturity.

ERIC Educational Resources Information Center

Greenberger, Ellen; Sorensen, Aage B.

The first in a series of related reports (see TM 000 775), this paper attempts to define a concept of psychosocial maturity which would be appropriate as a comprehensive educational goal. Biological, sociological, psychological and temporal formulations of maturity are discussed and compared. Am interdisciplinary model of maturity is evolved which…

The Lys-Asp-Tyr Triad within the Mite Allergen Der p 1 Propeptide Is a Critical Structural Element for the pH-Dependent Initiation of the Protease Maturation.

PubMed

Chevigné, Andy; Campizi, Vincenzo; Szpakowska, Martyna; Bourry, David; Dumez, Marie-Eve; Martins, José C; Matagne, André; Galleni, Moreno; Jacquet, Alain

2017-05-20

The major house dust mite allergen, Der p 1, is a papain-like cysteine protease expressed as an inactive precursor, proDer p 1, carrying an N-terminal propeptide with a unique structure. The maturation of the zymogen into an enzymatically-active form of Der p 1 is a multistep autocatalytic process initiated under acidic conditions through conformational changes of the propeptide, leading to the loss of its inhibitory ability and its subsequent gradual cleavage. The aims of this study were to characterize the residues present in the Der p 1 propeptide involved in the initiation of the zymogen maturation process, but also to assess the impact of acidic pH on the propeptide structure, the activity of Der p 1 and the fate of the propeptide. Using various complementary enzymatic and structural approaches, we demonstrated that a structural triad K17p-D51p-Y19p within the N-terminal domain of the propeptide is essential for its stabilization and the sensing of pH changes. Particularly, the protonation of D51p under acidic conditions unfolds the propeptide through disruption of the K17p-D51p salt bridge, reduces its inhibition capacity and unmasks the buried residues K17p and Y19p constituting the first maturation cleavage site of the zymogen. Our results also evidenced that this triad acts in a cooperative manner with other propeptide pH-responsive elements, including residues E56p and E80p, to promote the propeptide unfolding and/or to facilitate its proteolysis. Furthermore, we showed that acidic conditions modify Der p 1 proteolytic specificity and confirmed that the formation of the first intermediate represents the limiting step of the in vitro Der p 1 maturation process. Altogether, our results provide new insights into the early events of the mechanism of proDer p 1 maturation and identify a unique structural triad acting as a stabilizing and a pH-sensing regulatory element.

Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate

DOE PAGES

Cao, Hongnan; Tan, Kemin; Wang, Fengbin; ...

2016-04-29

CalE6 from Micromonospora echinospora is a (pyridoxal 50 phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. Here, we report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis andmore » holoenzyme maturation.« less

Simulation of electron transport in quantum well devices

NASA Technical Reports Server (NTRS)

Miller, D. R.; Gullapalli, K. K.; Reddy, V. R.; Neikirk, D. P.

1992-01-01

Double barrier resonant tunneling diodes (DBRTD) have received much attention as possible terahertz devices. Despite impressive experimental results, the specifics of the device physics (i.e., how the electrons propagate through the structure) are only qualitatively understood. Therefore, better transport models are warranted if this technology is to mature. In this paper, the Lattice Wigner function is used to explain the important transport issues associated with DBRTD device behavior.

Know the Network, Knit the Network: Applying SNA to N2C2 Maturity Model Experiments

DTIC Science & Technology

2010-06-01

Networks (COINS) 2009. Procedia - Social and Behavioral Sciences (2009). Snijders, Tom A.B., Christian E. G. Steglich and Michael Schweinberger...8217 patterning that create social structures. As an interdisciplinary behavioural science specialty, SNA defends that social actors are interdependent...production of social science data involve a process of interpretation. To carry out such interpretation robustly it is understood that it is imperative to

Time in tortoiseshell: a bomb radiocarbon-validated chronology in sea turtle scutes.

PubMed

Van Houtan, Kyle S; Andrews, Allen H; Jones, T Todd; Murakawa, Shawn K K; Hagemann, Molly E

2016-01-13

Some of the most basic questions of sea turtle life history are also the most elusive. Many uncertainties surround lifespan, growth rates, maturity and spatial structure, yet these are critical factors in assessing population status. Here we examine the keratinized hard tissues of the hawksbill (Eretmochelys imbricata) carapace and use bomb radiocarbon dating to estimate growth and maturity. Scutes have an established dietary record, yet the large keratin deposits of hawksbills evoke a reliable chronology. We sectioned, polished and imaged posterior marginal scutes from 36 individual hawksbills representing all life stages, several Pacific populations and spanning eight decades. We counted the apparent growth lines, microsampled along growth contours and calibrated Δ(14)C values to reference coral series. We fit von Bertalanffy growth function (VBGF) models to the results, producing a range of age estimates for each turtle. We find Hawaii hawksbills deposit eight growth lines annually (range 5-14), with model ensembles producing a somatic growth parameter (k) of 0.13 (range 0.1-0.2) and first breeding at 29 years (range 23-36). Recent bomb radiocarbon values also suggest declining trophic status. Together, our results may reflect long-term changes in the benthic community structure of Hawaii reefs, and possibly shed light on the critical population status for Hawaii hawksbills. © 2016 The Author(s).

Time in tortoiseshell: a bomb radiocarbon-validated chronology in sea turtle scutes

PubMed Central

Van Houtan, Kyle S.; Andrews, Allen H.; Jones, T. Todd; Murakawa, Shawn K. K.; Hagemann, Molly E.

2016-01-01

Some of the most basic questions of sea turtle life history are also the most elusive. Many uncertainties surround lifespan, growth rates, maturity and spatial structure, yet these are critical factors in assessing population status. Here we examine the keratinized hard tissues of the hawksbill (Eretmochelys imbricata) carapace and use bomb radiocarbon dating to estimate growth and maturity. Scutes have an established dietary record, yet the large keratin deposits of hawksbills evoke a reliable chronology. We sectioned, polished and imaged posterior marginal scutes from 36 individual hawksbills representing all life stages, several Pacific populations and spanning eight decades. We counted the apparent growth lines, microsampled along growth contours and calibrated Δ14C values to reference coral series. We fit von Bertalanffy growth function (VBGF) models to the results, producing a range of age estimates for each turtle. We find Hawaii hawksbills deposit eight growth lines annually (range 5–14), with model ensembles producing a somatic growth parameter (k) of 0.13 (range 0.1–0.2) and first breeding at 29 years (range 23–36). Recent bomb radiocarbon values also suggest declining trophic status. Together, our results may reflect long-term changes in the benthic community structure of Hawaii reefs, and possibly shed light on the critical population status for Hawaii hawksbills. PMID:26740617

BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.

PubMed

Goldie, Belinda J; Barnett, Michelle M; Cairns, Murray J

2014-01-01

The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. (2000) using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled.

Skeletal maturity determination from hand radiograph by model-based analysis

NASA Astrophysics Data System (ADS)

Vogelsang, Frank; Kohnen, Michael; Schneider, Hansgerd; Weiler, Frank; Kilbinger, Markus W.; Wein, Berthold B.; Guenther, Rolf W.

2000-06-01

Derived from a model based segmentation algorithm for hand radiographs proposed in our former work we now present a method to determine skeletal maturity by an automated analysis of regions of interest (ROI). These ROIs including the epiphyseal and carpal bones, which are most important for skeletal maturity determination, can be extracted out of the radiograph by knowledge based algorithms.

A Quality Framework for Continuous Improvement of e-Learning: The e-Learning Maturity Model

ERIC Educational Resources Information Center

Marshall, Stephen

2010-01-01

The E-Learning Maturity Model (eMM) is a quality improvement framework designed to help institutional leaders assess their institution's e-learning maturity. This paper reviews the eMM, drawing on examples of assessments conducted in New Zealand, Australia, the UK and the USA to show how it helps institutional leaders assess and compare their…

Biocultural approach of the association between maturity and physical activity in youth.

PubMed

Werneck, André O; Silva, Danilo R; Collings, Paul J; Fernandes, Rômulo A; Ronque, Enio R V; Coelho-E-Silva, Manuel J; Sardinha, Luís B; Cyrino, Edilson S

2017-11-13

To test the biocultural model through direct and indirect associations between biological maturation, adiposity, cardiorespiratory fitness, feelings of sadness, social relationships, and physical activity in adolescents. This was a cross-sectional study conducted with 1,152 Brazilian adolescents aged between 10 and 17 years. Somatic maturation was estimated through Mirwald's method (peak height velocity). Physical activity was assessed through Baecke questionnaire (occupational, leisure, and sport contexts). Body mass index, body fat (sum of skinfolds), cardiorespiratory fitness (20-m shuttle run test), self-perceptions of social relationship, and frequency of sadness feelings were obtained for statistical modeling. Somatic maturation is directly related to sport practice and leisure time physical activity only among girls (β=0.12, p<0.05 and β=0.09, respectively, p<0.05). Moreover, biological (adiposity and cardiorespiratory fitness), psychological (sadness), and social (satisfaction with social relationships) variables mediated the association between maturity and physical activity in boys and for occupational physical activity in girls. In general, models presented good fit coefficients. Biocultural model presents good fit and emotional/biological factors mediate part of the relationship between somatic maturation and physical activity. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Approaches to Process Performance Modeling: A Summary from the SEI Series of Workshops on CMMI High Maturity Measurement and Analysis

DTIC Science & Technology

2010-01-01

Soporte de Modelos Sistémicos: Aplicación al Sector de Desarrollo de Software de Argentina,” Tesis de PhD, Universidad Tecnológica Nacional-Facultad...with New Results 31  2.3  Other Simulation Approaches 37  Conceptual Planning , Execution, and Operation of Combat Fire Support Effectiveness: A...Figure 29:  Functional Structure of Multiple Regression Model 80  Figure 30:  TSP Quality Plan One 85  Figure 31:  TSP Quality Plan Two 85  Figure

Can Structural MRI Indices of Cerebral Integrity Track Cognitive Trends in Executive Control Function During Normal Maturation and Adulthood?

PubMed Central

Kochunov, Peter; Robin, Don A.; Royall, Don R.; Coyle, Thomas; Lancaster, Jack; Kochunov, Valeria; Schlosser, Anita E.; Fox, Peter T.

2009-01-01

We explored the relationship between structural neuroimaging-based indices of cerebral integrity and executive control function (ECF) in two groups of healthy subjects: A maturing group (33 subjects; 19–29 years) and a senescing group (38 adults; 30–90 years). ECF was assessed using the Executive Interview (EXIT) battery. Cortical indices of cerebral integrity included GM thickness, intergyral span, and sulcal span, each measured for five cortical regions per hemisphere. Subcortical indices included fractional anisotropy (FA), measured using track-based-spatial-statistics (TBSS), and the volume of T2-hyperintense WM (HWM). In the maturing group, no significant relationships between neuroanatomical changes and ECF were found; however, there were hints that late-term maturation of cerebral WM influenced variability in ECF. In the senescing group, the decline in ECF corresponded to atrophic changes in cerebral WM (sulcal and intergyral span) primarily in the superior frontal and anterior cingulate regions. A large fraction of the variability in ECF (62%) can be explained by variability in the structural indices from these two regions. PMID:19067326

Axial cervical vertebrae-based multivariate regression model for the estimation of skeletal-maturation status.

PubMed

Yang, Y-M; Lee, J; Kim, Y-I; Cho, B-H; Park, S-B

2014-08-01

This study aimed to determine the viability of using axial cervical vertebrae (ACV) as biological indicators of skeletal maturation and to build models that estimate ossification level with improved explanatory power over models based only on chronological age. The study population comprised 74 female and 47 male patients with available hand-wrist radiographs and cone-beam computed tomography images. Generalized Procrustes analysis was used to analyze the shape, size, and form of the ACV regions of interest. The variabilities of these factors were analyzed by principal component analysis. Skeletal maturation was then estimated using a multiple regression model. Separate models were developed for male and female participants. For the female estimation model, the adjusted R(2) explained 84.8% of the variability of the Sempé maturation level (SML), representing a 7.9% increase in SML explanatory power over that using chronological age alone (76.9%). For the male estimation model, the adjusted R(2) was over 90%, representing a 1.7% increase relative to the reference model. The simplest possible ACV morphometric information provided a statistically significant explanation of the portion of skeletal-maturation variability not dependent on chronological age. These results verify that ACV is a strong biological indicator of ossification status. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The developmental morphology of a "periosteal" ligament insertion: growth and maturation of the tibial insertion of the rabbit medial collateral ligament.

PubMed

Matyas, J R; Bodie, D; Andersen, M; Frank, C B

1990-05-01

The structural properties of ligament insertions change dramatically during growth and maturation, but little is known about their developmental anatomy. This study describes and quantifies changes in the gross and microscopic anatomy of the tibial insertion of the rabbit medial collateral ligament (MCL) during development and at skeletal maturity. Eighty animals were used for growth and descriptive studies. From this group, 27 animals, ranging in age from 1 to 24 months, were injected with fluorescent bone markers and their tibial insertions were processed undecalcified for histology. Sections were examined by polarized light and fluorescence microscopy to identify matrix and cells and to quantify mineral formation. Results showed that animals achieved histological skeletal maturity between 9 and 12 months of age. Body weights were a poor index of skeletal maturity. The tibial insertion was composed of five tissue layers, which changed proportions during growth and maturation. In immature animals, MCL fibers entered the periosteum; in older animals, MCL fibers were cemented to the tibia by advancing mineral. The tibial attachment of the MCL was thus transferred from the periosteum to the cortex during growth, suggesting that the term "periosteal insertion" is imprecise in adults. The hypothesis is put forward that these structural changes account for the reported increase in tensile failure of this insertion near skeletal maturity.

The roles of identity formation and moral identity in college student mental health, health-risk behaviors, and psychological well-being.

PubMed

Hardy, Sam A; Francis, Stephen W; Zamboanga, Byron L; Kim, Su Yeong; Anderson, Spencer G; Forthun, Larry F

2013-04-01

This study examined the roles of identity formation and moral identity in predicting college student mental health (anxiety and depressive symptoms), health-risk behaviors (hazardous alcohol use and sexual risk taking), and psychological well-being (self-esteem and meaning). The sample comprised 9,500 college students (aged 18-25 years, mean = 19.78, standard deviation = 1.61; 73% female; 62% European American), from 31 different universities, who completed an online self-report survey. Structural equation models found that identity maturity (commitment making and identity synthesis) predicted 5 of the health outcomes (except sexual risk taking), and moral identity predicted all of the health outcomes. In most cases identity maturity and moral identity also interacted in predicting mental health and psychological well-being, but not health-risk behaviors. The maturity and specific contents of identity may both play unique and often interactive roles in predicting college student health. Thus, college student health might be bolstered by helping them establish appropriate identity commitments. © 2012 Wiley Periodicals, Inc.

Ossification score is a better indicator of maturity related changes in eating quality than animal age.

PubMed

Bonny, S P F; Pethick, D W; Legrand, I; Wierzbicki, J; Allen, P; Farmer, L J; Polkinghorne, R J; Hocquette, J-F; Gardner, G E

2016-04-01

Ossification score and animal age are both used as proxies for maturity-related collagen crosslinking and consequently decreases in beef tenderness. Ossification score is strongly influenced by the hormonal status of the animal and may therefore better reflect physiological maturity and consequently eating quality. As part of a broader cross-European study, local consumers scored 18 different muscle types cooked in three ways from 482 carcasses with ages ranging from 590 to 6135 days and ossification scores ranging from 110 to 590. The data were studied across three different maturity ranges; the complete range of maturities, a lesser range and a more mature range. The lesser maturity group consisted of carcasses having either an ossification score of 200 or less or an age of 987 days or less with the remainder in the greater maturity group. The three different maturity ranges were analysed separately with a linear mixed effects model. Across all the data, and for the greater maturity group, animal age had a greater magnitude of effect on eating quality than ossification score. This is likely due to a loss of sensitivity in mature carcasses where ossification approached and even reached the maximum value. In contrast, age had no relationship with eating quality for the lesser maturity group, leaving ossification score as the more appropriate measure. Therefore ossification score is more appropriate for most commercial beef carcasses, however it is inadequate for carcasses with greater maturity such as cull cows. Both measures may therefore be required in models to predict eating quality over populations with a wide range in maturity.

Evolution of Structural Empowerment: Moving From Shared to Professional Governance.

PubMed

Clavelle, Joanne T; Porter O'Grady, Tim; Weston, Marla J; Verran, Joyce A

2016-06-01

The aim of this study is to describe the maturation of the concept of shared governance to professional governance as a framework for structural empowerment. An analysis of the literature and concept clarification of structural empowerment and shared governance demonstrate that the concept and attributes of shared governance have evolved toward professional governance. A comprehensive, deductive literature review and concept clarification of structural empowerment, shared governance, and related constructs was completed. The concept and practice of shared governance has matured to a concept of professional governance with the attributes of accountability, professional obligation, collateral relationships, and effective decision-making.

CMMI Version 1.2 and Beyond Systems and Software Technology Conference

DTIC Science & Technology

2008-04-29

Presentation • “Extreme Programming (XP), Six Sigma, & CMMI: How They Can Work Together” • “CMMI V1.2 Model Changes” Presentation 5 CMMI Update: V1.2 and...Level 4 Reported Maturity Level 5 Reported Country Number of Appraisals Maturity Level 1 Reported Maturity Level 2 Reported Maturity Level 3...Reported Maturity Level 4 Reported Maturity Level 5 Reported Argentina 26 No Yes Yes Yes Yes Malaysia 29 No Yes Yes No Yes Australia 26 Yes Yes

Evaluation of methods to estimate lake herring spawner abundance in Lake Superior

USGS Publications Warehouse

Yule, D.L.; Stockwell, J.D.; Cholwek, G.A.; Evrard, L.M.; Schram, S.; Seider, M.; Symbal, M.

2006-01-01

Historically, commercial fishers harvested Lake Superior lake herring Coregonus artedi for their flesh, but recently operators have targeted lake herring for roe. Because no surveys have estimated spawning female abundance, direct estimates of fishing mortality are lacking. The primary objective of this study was to determine the feasibility of using acoustic techniques in combination with midwater trawling to estimate spawning female lake herring densities in a Lake Superior statistical grid (i.e., a 10′ latitude × 10′ longitude area over which annual commercial harvest statistics are compiled). Midwater trawling showed that mature female lake herring were largely pelagic during the night in late November, accounting for 94.5% of all fish caught exceeding 250 mm total length. When calculating acoustic estimates of mature female lake herring, we excluded backscattering from smaller pelagic fishes like immature lake herring and rainbow smelt Osmerus mordax by applying an empirically derived threshold of −35.6 dB. We estimated the average density of mature females in statistical grid 1409 at 13.3 fish/ha and the total number of spawning females at 227,600 (95% confidence interval = 172,500–282,700). Using information on mature female densities, size structure, and fecundity, we estimate that females deposited 3.027 billion (109) eggs in grid 1409 (95% confidence interval = 2.356–3.778 billion). The relative estimation error of the mature female density estimate derived using a geostatistical model—based approach was low (12.3%), suggesting that the employed method was robust. Fishing mortality rates of all mature females and their eggs were estimated at 2.3% and 3.8%, respectively. The techniques described for enumerating spawning female lake herring could be used to develop a more accurate stock–recruitment model for Lake Superior lake herring.

Effects of structural heterogeneity on frictional heating from biomarker thermal maturity analysis of the Muddy Mountain thrust, Nevada, USA

NASA Astrophysics Data System (ADS)

Coffey, G. L.; Savage, H. M.; Polissar, P. J.; Rowe, C. D.

2017-12-01

Faults are generally heterogeneous along-strike, with changes in thickness and structural complexity that should influence coseismic slip. However, observational limitations (e.g. limited outcrop or borehole samples) can obscure this complexity. Here we investigate the heterogeneity of frictional heating determined from biomarker thermal maturity and microstructural observations along a well-exposed fault to understand whether coseismic stress and frictional heating are related to structural complexity. We focus on the Muddy Mountain thrust, Nevada, a Sevier-age structure that has continuous exposure of its fault core and considerable structural variability for up to 50 m, to explore the distribution of earthquake slip and temperature rise along strike. We present new biomarker thermal maturity results that capture the heating history of fault rocks. Biomarkers are organic molecules produced by living organisms and preserved in the rock record. During heating, their structure is altered systematically with increasing time and temperature. Preliminary results show significant variability in thermal maturity along-strike at the Muddy Mountain thrust, suggesting differences in coseismic temperature rise on the meter- scale. Temperatures upwards of 500°C were generated in the principal slip zone at some locations, while in others, no significant temperature rise occurred. These results demonstrate that stress or slip heterogeneity occurred along the Muddy Mountain thrust at the meter-scale and considerable along-strike complexity existed, highlighting the importance of careful interpretation of whole-fault behavior from observations at a single point on a fault.

Modeling timelines for translational science in cancer; the impact of technological maturation

PubMed Central

McNamee, Laura M.; Ledley, Fred D.

2017-01-01

This work examines translational science in cancer based on theories of innovation that posit a relationship between the maturation of technologies and their capacity to generate successful products. We examined the growth of technologies associated with 138 anticancer drugs using an analytical model that identifies the point of initiation of exponential growth and the point at which growth slows as the technology becomes established. Approval of targeted and biological products corresponded with technological maturation, with first approval averaging 14 years after the established point and 44 years after initiation of associated technologies. The lag in cancer drug approvals after the increases in cancer funding and dramatic scientific advances of the 1970s thus reflects predictable timelines of technology maturation. Analytical models of technological maturation may be used for technological forecasting to guide more efficient translation of scientific discoveries into cures. PMID:28346525

Risking it for Love: Romantic Relationships and Early Pubertal Development Confer Risk for later Disruptive Behavior Disorders in African-American Girls Receiving Psychiatric Care

PubMed Central

Rodriguez, Erin M.; Nichols, Sara; Emerson, Erin; Donenberg, Geri R.

2014-01-01

Disruptive behavior problems (DBP) represent a growing concern for young women (e.g., Snyder & Sickmund, 2006), but gender-specific investigations have been traditionally underrepresented in this area. The purpose of this study is to examine the associations among gender-relevant risk factors for DBP among 217 African American girls in psychiatric care. African American girls, 12–16 years old (M=14.6; SD=1.2), and their primary female caregivers (N=254) were recruited from outpatient mental health clinics and reported on girls’ DBP, heterosexual dating experiences (romantic and sexual), peer relationships, pubertal development, and self-silencing at baseline, 6-, and 12-months. Structural Equation Modeling examined evidence for full versus mediated (via self-silencing) models and the structural relationships (direct and indirect) among key study variables. Results suggest that the full model was a significantly better fit than the mediated model as indicated by a Chi-squared difference test (p < .01). In the full model, direct effects of greater romantic dating experiences and lower quality peer relationships at baseline predicted DBP at 12-months. Sexual dating experiences were more strongly linked with DBP at 12-months for early maturing compared to average or later maturing girls. Indirect effects analyses suggested that girls’ suppression of relational needs, assessed through a measure of self-silencing, explained the association between peer relationships and DBP. Findings highlight the importance of the relational context for girls’ DBP, with treatment implications supporting relationship-based models of care, early intervention, and skill building around negotiating needs with peers and partners. PMID:24748499

Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.

PubMed

Murgatroyd, Christopher; Pirrie, Lisa; Tran, Fanny; Smith, Terry K; Westwood, Nicholas J; Adamson, Catherine S

2016-09-15

HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they target the Gag protein, specifically by inhibiting CA-SP1 proteolytic cleavage. The lack of high-resolution structural information of the CA-SP1 target in Gag has hindered our understanding of the inhibitor-binding pocket and maturation inhibitor mode of action. Therefore, we utilized analogues of the maturation inhibitor PF-46396 as chemical tools to determine the chemical components of PF-46396 that contribute to antiviral activity and Gag binding and the relationship between these essential properties. This is the first study to report structure-activity relationships of the maturation inhibitor PF-46396. PF-46396 is chemically distinct from betulinic acid-derived maturation inhibitors; therefore, our data provide a foundation of knowledge that will aid our understanding of how structurally distinct maturation inhibitors act by similar modes of action. Copyright © 2016 Murgatroyd et al.

Human prorenin structure sheds light on a novel mechanism of its autoinhibition and on its non-proteolytic activation by the (pro)renin receptor.

PubMed

Morales, Renaud; Watier, Yves; Böcskei, Zsolt

2012-08-03

Antibodies and prorenin mutants have long been used to structurally characterize prorenin, the inactive proenzyme form of renin. They were designed on the basis of homology models built using other aspartyl protease proenzyme structures since no structure was available for prorenin. Here, we present the first X-ray structure of a prorenin. The current structure of prorenin reveals that, in this zymogene, the active site of renin is blocked by the N-terminal residues of the mature version of the renin molecule, which are, in turn, covered by an Ω-shaped prosegment. This prevents access of substrates to the active site. The departure of the prosegment on activation induces an important global conformational change in the mature renin molecule with respect to prorenin: similar to other related enzymes such as pepsin or gastricsin, the segment that constitutes the N-terminal β-strand in renin is displaced from the renin active site by about 180° straight into the position that corresponds to the N-terminal β-strand of the prorenin prosegment. This way, the renin active site will become completely exposed and capable of carrying out its catalytic functions. A unique inactivation mechanism is also revealed, which does not make use of a lysine against the catalytic aspartates, probably in order to facilitate pH-independent activation [e.g., by the (pro)renin receptor]. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mature Thunderstorm Cloud-Top Structure and Dynamics: A Three-Dimensional Numerical Simulation Study.

NASA Astrophysics Data System (ADS)

Schlesinger, Robert E.

1984-05-01

An anelastic three-dimensional model is used to investigate the effects of vertical wind shear regime on cloud-top structure and internal properties of mature isolated midlatitude thunderstorms. Four comparative experiments, designated A through D, are performed with varying shear profiles in otherwise identical initializations. Cases A-C assume strong shear, differing only in the veering of the low-level hodograph: moderate in A, strong in B and none in C. Weak shear, everywhere 40% as great as in C, is assumed in case D.The strong-shear cases A-C show moderately vigorous quasi-steady mature updrafts with strong midlevel mesovortex couplets, and marked anvil elongation along the net vertical shear vector. Differences are modest, especially at cloud top, though with low-level hodograph curvature the updraft is enhanced and skewed toward the cyclonic right flank. The weak-shear case D shows a weaker and less persistent mature updraft than A-C, along with weaker midlevel rotation and a much more newly circular anvil.In the strong-shear experiments, the cloud top considerably resembles geostationary satellite observations of tornadic storms (Negri, 1982), even though the model storm interiors lack the significant low-level mesocyclone and very strong concentrated updraft typical of observed tornadic storms. Both model and observations show a persistent cloud-top temperature pattern featuring a cold area slightly upshear of the cloud summit, with a warm area downshear in the absence of a local height minimum, though in the model the thermal couplet is smaller-scale with lower amplitude and lacks the well-developed `V' shape seen in the observations. The thermal couplet is also present with weak shear, but is only about half as strong, largely due to a much weaker cold area.Several dynamic features of the cloud-top thermal couplet are revealed by backward and forward parcel trajectory analyses for Case B: 1) The cold and warm areas at cloud top result from ascent and descent, respectively, of stratospheric air from upshear. 2) Only slightly below cloud top, shallow downward extensions of the warm and cold areas consist of air that originates from downshear in the lower troposphere, traverses' the updraft core and overshoots the tropopause. 3) Strong turbulent mixing between these contrasting airflow branches takes place astride the cloud top. 4) Parcels intercepting the cold region subside subsequently into the warm region. 5) The perturbation vertical pressure gradient force is an important factor in the trajectories.

MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

PubMed

Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

2014-12-03

The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

MET Receptor Tyrosine Kinase Controls Dendritic Complexity, Spine Morphogenesis, and Glutamatergic Synapse Maturation in the Hippocampus

PubMed Central

Lu, Zhongming; Levitt, Pat

2014-01-01

The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. PMID:25471559

Overview of Heatshield for Extreme Entry Environment Technology (HEEET)

NASA Technical Reports Server (NTRS)

Driver, David M.; Ellerby, Donald T.; Gasch, Matthew J.; Mahzari, Milad; Milos, Frank S.; Nishioka, Owen S.; Stackpoole, Margaret M.; Venkatapathy, Ethiraj; Young, Zion W.; Gage, Peter J.;

Testing models of female reproductive migratory behaviour and population structure in the Caribbean hawksbill turtle, Eretmochelys imbricata, with mtDNA sequences.

PubMed

Bass, A L; Good, D A; Bjorndal, K A; Richardson, J I; Hillis, Z M; Horrocks, J A; Bowen, B W

1996-06-01

Information on the reproductive behaviour and population structure of female hawksbill turtles, Eretmochelys imbricata, is necessary to define conservation priorities for this highly endangered species. Two hypotheses to explain female nest site choice, natal homing and social facilitation, were tested by analyzing mtDNA control region sequences of 103 individuals from seven nesting colonies in the Caribbean and western Atlantic. Under the social facilitation model, newly mature females follow older females to a nesting location, and subsequently use this site for future nesting. This model generates an expectation that female lineages will be homogenized among regional nesting colonies. Contrary to expectations of the social facilitation model, mtDNA lineages were highly structured among western Atlantic nesting colonies. These analyses identified at least 6 female breeding stocks in the Caribbean and western Atlantic and support a natal homing model for recruitment of breeding females. Reproductive populations are effectively isolated over ecological time scales, and recovery plans for this species should include protection at the level of individual nesting colonies.

An siRNA-based method for efficient silencing of gene expression in mature brown adipocytes.

PubMed

Isidor, Marie S; Winther, Sally; Basse, Astrid L; Petersen, M Christine H; Cannon, Barbara; Nedergaard, Jan; Hansen, Jacob B

2016-01-01

Brown adipose tissue is a promising therapeutic target for opposing obesity, glucose intolerance and insulin resistance. The ability to modulate gene expression in mature brown adipocytes is important to understand brown adipocyte function and delineate novel regulatory mechanisms of non-shivering thermogenesis. The aim of this study was to optimize a lipofection-based small interfering RNA (siRNA) transfection protocol for efficient silencing of gene expression in mature brown adipocytes. We determined that a critical parameter was to deliver the siRNA to mature adipocytes by reverse transfection, i.e. transfection of non-adherent cells. Using this protocol, we effectively knocked down both high- and low-abundance transcripts in a model of mature brown adipocytes (WT-1) as well as in primary mature mouse brown adipocytes. A functional consequence of the knockdown was confirmed by an attenuated increase in uncoupled respiration (thermogenesis) in response to β-adrenergic stimulation of mature WT-1 brown adipocytes transfected with uncoupling protein 1 siRNA. Efficient gene silencing was also obtained in various mouse and human white adipocyte models (3T3-L1, primary mouse white adipocytes, hMADS) with the ability to undergo "browning." In summary, we report an easy and versatile reverse siRNA transfection protocol to achieve specific silencing of gene expression in various models of mature brown and browning-competent white adipocytes, including primary cells.

Scrub-Successional Bird Community Dynamics in Young and Mature Pine-Wiregrass Savannahs

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

Krementz, D.G.; Christie, J.S.

2001-01-01

We investigated how management for habitat conditions to support the endangered red-cockaded woodpecker effects the biodiversity of the breeding bird community associated with those habitats. Habitat is created by thinning, burning and mid-story control of hardwoods in mature longleaf stands. In addition, similar habitat structurally can be found in recently harvested areas. We tested the hypothesis that diversity and abundance, as well as survival and reproduction would be greater in mature stands. However, mature stands used for recruitment always had fewer species (36/31) than recently harvested areas (54/55). All species that occurred in recruitment stands also occurred in mature stands.more » No differences in survival rates were found between mature and recent cuts for Bachman's sparrow and indigo bunting.« less

Does implied volatility of currency futures option imply volatility of exchange rates?

NASA Astrophysics Data System (ADS)

Wang, Alan T.

2007-02-01

By investigating currency futures options, this paper provides an alternative economic implication for the result reported by Stein [Overreactions in the options market, Journal of Finance 44 (1989) 1011-1023] that long-maturity options tend to overreact to changes in the implied volatility of short-maturity options. When a GARCH process is assumed for exchange rates, a continuous-time relationship is developed. We provide evidence that implied volatilities may not be the simple average of future expected volatilities. By comparing the term-structure relationship of implied volatilities with the process of the underlying exchange rates, we find that long-maturity options are more consistent with the exchange rates process. In sum, short-maturity options overreact to the dynamics of underlying assets rather than long-maturity options overreacting to short-maturity options.

Root architecture simulation improves the inference from seedling root phenotyping towards mature root systems

PubMed Central

Zhao, Jiangsan; Rewald, Boris; Leitner, Daniel; Nagel, Kerstin A.; Nakhforoosh, Alireza

2017-01-01

Abstract Root phenotyping provides trait information for plant breeding. A shortcoming of high-throughput root phenotyping is the limitation to seedling plants and failure to make inferences on mature root systems. We suggest root system architecture (RSA) models to predict mature root traits and overcome the inference problem. Sixteen pea genotypes were phenotyped in (i) seedling (Petri dishes) and (ii) mature (sand-filled columns) root phenotyping platforms. The RSA model RootBox was parameterized with seedling traits to simulate the fully developed root systems. Measured and modelled root length, first-order lateral number, and root distribution were compared to determine key traits for model-based prediction. No direct relationship in root traits (tap, lateral length, interbranch distance) was evident between phenotyping systems. RootBox significantly improved the inference over phenotyping platforms. Seedling plant tap and lateral root elongation rates and interbranch distance were sufficient model parameters to predict genotype ranking in total root length with an RSpearman of 0.83. Parameterization including uneven lateral spacing via a scaling function substantially improved the prediction of architectures underlying the differently sized root systems. We conclude that RSA models can solve the inference problem of seedling root phenotyping. RSA models should be included in the phenotyping pipeline to provide reliable information on mature root systems to breeding research. PMID:28168270

Demonstrating the improvement of predictive maturity of a computational model

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

Hemez, Francois M; Unal, Cetin; Atamturktur, Huriye S

2010-01-01

We demonstrate an improvement of predictive capability brought to a non-linear material model using a combination of test data, sensitivity analysis, uncertainty quantification, and calibration. A model that captures increasingly complicated phenomena, such as plasticity, temperature and strain rate effects, is analyzed. Predictive maturity is defined, here, as the accuracy of the model to predict multiple Hopkinson bar experiments. A statistical discrepancy quantifies the systematic disagreement (bias) between measurements and predictions. Our hypothesis is that improving the predictive capability of a model should translate into better agreement between measurements and predictions. This agreement, in turn, should lead to a smallermore » discrepancy. We have recently proposed to use discrepancy and coverage, that is, the extent to which the physical experiments used for calibration populate the regime of applicability of the model, as basis to define a Predictive Maturity Index (PMI). It was shown that predictive maturity could be improved when additional physical tests are made available to increase coverage of the regime of applicability. This contribution illustrates how the PMI changes as 'better' physics are implemented in the model. The application is the non-linear Preston-Tonks-Wallace (PTW) strength model applied to Beryllium metal. We demonstrate that our framework tracks the evolution of maturity of the PTW model. Robustness of the PMI with respect to the selection of coefficients needed in its definition is also studied.« less

Geospatial Information System Capability Maturity Models

DOT National Transportation Integrated Search

2017-06-01

To explore how State departments of transportation (DOTs) evaluate geospatial tool applications and services within their own agencies, particularly their experiences using capability maturity models (CMMs) such as the Urban and Regional Information ...

Basement-driven strike-slip deformation involving a salt-stock canopy system

NASA Astrophysics Data System (ADS)

Dooley, Tim; Jackson, Martin; Hudec, Mike

2016-04-01

NW-striking basement-involved strike-slip zones have been reported or inferred from the northern Gulf of Mexico (GoM). This interpretation is uncertain, because the effects of strike-slip deformation are commonly difficult to recognize in cross sections. Recognition is doubly difficult if the strike-slip zone passes through a diapir field that complicates deformation, and an associated salt canopy that partially decouples shallow deformation from deep deformation. We use physical models to explore the effects of strike-slip deformation above and below a salt-stock canopy system. Canopies of varying maturity grew from a series of 14 feeders/diapirs located on and off the axis of a dextral basement fault. Strike-slip deformation styles in the overburden vary significantly depending on: (1) the location of the diapirs with respect to the basement fault trace, and; (2) the continuity of the canopy system. On-axis diapirs (where the diapirs lie directly above the basement fault) are typically strongly deformed and pinched shut at depth to form sharp S-shapes, whereas their shallow deformation style is that of a open-S-shaped pop-up structure in a restraining bend. The narrow diapir stem acts as a shear zone at depth. Pull-apart structures form between diapirs that are arranged in a right-stepping array tangental to the basement fault trace. These grade along strike into narrow negative flower structures. Off-axis diapirs (diapirs laterally offset from the basement fault but close enough to participate in the deformation) form zones of distributed deformation in the form of arrays of oblique faults (R shears) that converge along strike onto the narrower deformation zones associated with on-axis diapirs. Above an immature, or patchy, canopy system the strike-slip structures closely match sub canopy structures, with the exception of wrench fold formation where the supracanopy roof is thin. In contrast, the surface structures above a mature canopy system consist of a broad zone of PDZ-parallel faults and high-angle wrench folds, strongly decoupled from the subcanopy structure. The exception to this is where there are gaps (windows) in the canopy, allowing coupling to the deeper deformation field. In this mature canopy open-S planforms are muted as deformation is spread over a broader area of coalesced salt sheets, except at the canopy edge and where the supracanopy roof is thin. Supracanopy structures are also influenced by the sutures between the individual salt sheets. Results from this set of analog models are potentially useful as predictive tools to understand the origin and geometry of structures in areas where subsurface data is scarce or data quality is poor.

Structural Basis for Specificity of Propeptide-Enzyme Interaction in Barley C1A Cysteine Peptidases

PubMed Central

Cambra, Inés; Hernández, David; Diaz, Isabel; Martinez, Manuel

2012-01-01

C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes place by proteolysis cleaving off the inhibitory propeptide. The inhibitory capacity of propeptides from barley cathepsin L and B-like peptidases towards commercial and barley cathepsins has been characterized. Differences in selectivity have been found for propeptides from L-cathepsins against their cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional structures suggests that most propeptide inhibitory properties can be explained from the interaction between the propeptide and the mature cathepsin structures. Their potential use as biotechnological tools is discussed. PMID:22615948

Microfluidic assay of the deformability of primitive erythroblasts.

PubMed

Zhou, Sitong; Huang, Yu-Shan; Kingsley, Paul D; Cyr, Kathryn H; Palis, James; Wan, Jiandi

2017-09-01

Primitive erythroblasts (precursors of red blood cells) enter vascular circulation during the embryonic period and mature while circulating. As a result, primitive erythroblasts constantly experience significant hemodynamic shear stress. Shear-induced deformation of primitive erythroblasts however, is poorly studied. In this work, we examined the deformability of primitive erythroblasts at physiologically relevant flow conditions in microfluidic channels and identified the regulatory roles of the maturation stage of primitive erythroblasts and cytoskeletal protein 4.1 R in shear-induced cell deformation. The results showed that the maturation stage affected the deformability of primitive erythroblasts significantly and that primitive erythroblasts at later maturational stages exhibited a better deformability due to a matured cytoskeletal structure in the cell membrane.

Predicting the Timing of Maturational Spurts in Skeletal Age

PubMed Central

Nahhas, Ramzi W.; Sherwood, Richard J.; Chumlea, Wm. Cameron; Towne, Bradford; Duren, Dana L.

2014-01-01

Measures of maturity provide windows into the timing and tempo of childhood growth and maturation. Delayed maturation in a single child, or systemically in a population, can result from either genetic or environmental factors. In terms of the skeleton, delayed maturation may result in short stature or indicate another underlying issue. Thus, prediction of the timing of a maturational spurt is often desirable in order to determine the likelihood that a child will catch up to their chronological age peers. Serial data from the Fels Longitudinal Study were used to predict future skeletal age conditional on current skeletal age and to predict the timing of maturational spurts. For children who were delayed relative to their chronological age peers, the like-lihood of catch-up maturation increased through the average age of onset of puberty and decreased prior to the average age of peak height velocity. For boys, the probability of an imminent maturational spurt was higher for those who were less mature. For girls aged 11 to 13 years, however, this probability was higher for those who were more mature, potentially indicating the presence of a skeletal maturation plateau between multiple spurts. The prediction model, available on the web, is most relevant to children of European ancestry living in the Midwestern US. Our model may also provide insight into the tempo of maturation for children in other populations, but must be applied with caution if those populations are known to have high burdens of environmental stressors not typical of the Midwestern US. Am J Phys Anthropol 150:68–75, 2013. PMID:23283666

The influence of sex steroids on structural brain maturation in adolescence.

PubMed

Koolschijn, P Cédric M P; Peper, Jiska S; Crone, Eveline A

2014-01-01

Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8-25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with luteinizing hormone, testosterone and estradiol, and pubertal stage based on self-reports. Our results indicate sex-specific differences in testosterone related influences on gray matter volumes of the anterior cingulate cortex after controlling for age effects. No significant associations between subcortical structures and sex hormones were found. Pubertal stage was not a stronger predictor than chronological age for brain anatomical differences. Our findings indicate that sex steroids are associated with cerebral gray matter morphology in a sex specific manner. These hormonal and morphological differences may explain in part differences in brain development between boys and girls.

Structure and activation of pro-activin A

PubMed Central

Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

2016-01-01

Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells

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

Lamb, Kristen; Lokesh, G.L.; Sherman, Michael

2010-10-25

Venezuelan equine encephalitis virus (VEEV) is a prototypical enveloped ssRNA virus of the family Togaviridae. To better understand alphavirus assembly, we analyzed newly formed nucleocapsid particles (termed pre-viral nucleocapsids) isolated from infected cells. These particles were intermediates along the virus assembly pathway, and ultimately bind membrane-associated viral glycoproteins to bud as mature infectious virus. Purified pre-viral nucleocapsids were spherical with a unimodal diameter distribution. The structure of one class of pre-viral nucleocapsids was determined with single particle reconstruction of cryo-electron microscopy images. These studies showed that pre-viral nucleocapsids assembled into an icosahedral structure with a capsid stoichiometry similar to themore » mature nucleocapsid. However, the individual capsomers were organized significantly differently within the pre-viral and mature nucleocapsids. The pre-viral nucleocapsid structure implies that nucleocapsids are highly plastic and undergo glycoprotein and/or lipid-driven rearrangements during virus self-assembly. This mechanism of self-assembly may be general for other enveloped viruses.« less

The roles of family B and D DNA polymerases in Thermococcus species 9°N Okazaki fragment maturation.

PubMed

Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F

2015-05-15

During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Maturation of high-density lipoproteins

PubMed Central

Shih, Amy Y.; Sligar, Stephen G.; Schulten, Klaus

2009-01-01

Human high-density lipoproteins (HDLs) are involved in the transport of cholesterol. The mechanism by which HDL assembles and functions is not well understood owing to a lack of structural information on circulating spherical HDL. Here, we report a series of molecular dynamics simulations that describe the maturation of discoidal HDL into spherical HDL upon incorporation of cholesterol ester as well as the resulting atomic level structure of a mature circulating spherical HDL particle. Sixty cholesterol ester molecules were added in a stepwise fashion to a discoidal HDL particle containing two apolipoproteins wrapped around a 160 dipalmitoylphosphatidylcholine lipid bilayer. The resulting matured particle, captured in a coarse-grained description, was then described in a consistent all-atom representation and analysed in chemical detail. The simulations show that maturation results from the formation of a highly dynamic hydrophobic core comprised of cholesterol ester surrounded by phospholipid and protein; the two apolipoprotein strands remain in a belt-like conformation as seen in the discoidal HDL particle, but with flexible N- and C-terminal helices and a central region stabilized by salt bridges. In the otherwise flexible lipoproteins, a less mobile central region provides an ideal location to bind lecithin cholesterol acyltransferase, the key enzyme that converts cholesterol to cholesterol ester during HDL maturation. PMID:19570799

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.

PubMed

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio; Gardoni, Fabrizio; Pisani, Antonio

2018-03-05

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a +/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. © 2018, Maltese et al.

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

Bray, R.; Lawrence, S.; Swart, R.

Namibia`s territorial waters occupy a large portion of West Africa`s continental shelf. The area to the 1,000 m isobath is comparable in size to the combined offshore areas of Gabon, Congo, Zaire, and Angola. Around half as much again lies in 1,000--2,500 m of water. The whole unlicensed part of this area will be open for bidding when the Third Licensing Round starts Oct. 1, 1998. Offshore Namibia is underexplored by drilling with only seven exploration wells drilled. Shell`s Kudu field represents a considerable gas resource with reserves of around 3 tcf and is presently the only commercial discovery.Namibia`s offshoremore » area holds enormous exploration potential. Good quality sandstone reservoirs are likely to be distributed widely, and a number of prospective structural and stratigraphic traps have been identified. The recognition of Cretaceous marine oil-prone source rocks combined with the results of new thermal history reconstruction and maturity modeling studies are particularly significant in assessment of the oil potential. The paper discusses resource development and structures, oil source potential, maturity, and hydrocarbon generation.« less

Equivalent circuit models for interpreting impedance perturbation spectroscopy data

NASA Astrophysics Data System (ADS)

Smith, R. Lowell

2004-07-01

As in-situ structural integrity monitoring disciplines mature, there is a growing need to process sensor/actuator data efficiently in real time. Although smaller, faster embedded processors will contribute to this, it is also important to develop straightforward, robust methods to reduce the overall computational burden for practical applications of interest. This paper addresses the use of equivalent circuit modeling techniques for inferring structure attributes monitored using impedance perturbation spectroscopy. In pioneering work about ten years ago significant progress was associated with the development of simple impedance models derived from the piezoelectric equations. Using mathematical modeling tools currently available from research in ultrasonics and impedance spectroscopy is expected to provide additional synergistic benefits. For purposes of structural health monitoring the objective is to use impedance spectroscopy data to infer the physical condition of structures to which small piezoelectric actuators are bonded. Features of interest include stiffness changes, mass loading, and damping or mechanical losses. Equivalent circuit models are typically simple enough to facilitate the development of practical analytical models of the actuator-structure interaction. This type of parametric structure model allows raw impedance/admittance data to be interpreted optimally using standard multiple, nonlinear regression analysis. One potential long-term outcome is the possibility of cataloging measured viscoelastic properties of the mechanical subsystems of interest as simple lists of attributes and their statistical uncertainties, whose evolution can be followed in time. Equivalent circuit models are well suited for addressing calibration and self-consistency issues such as temperature corrections, Poisson mode coupling, and distributed relaxation processes.

Capability Maturity Model (CMM) for Software Process Improvements

NASA Technical Reports Server (NTRS)

Ling, Robert Y.

2000-01-01

This slide presentation reviews the Avionic Systems Division's implementation of the Capability Maturity Model (CMM) for improvements in the software development process. The presentation reviews the process involved in implementing the model and the benefits of using CMM to improve the software development process.

Knowledge Management as an Indication of Organizational Maturity in Project Management: An Enhancement of the OPM3(c) Model

ERIC Educational Resources Information Center

Smith, Dedrick A.

2010-01-01

This dissertation reviews the knowledge management's role in organizational maturity in project management. It draws a direct linked between organizational maturity knowledge channels both informal and then formal and organizational project management maturity. The study uses a mixed method approach through online and telephone surveys that draws…

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents

PubMed Central

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K.

2015-01-01

Purpose To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: 1) peer influence links early pubertal timing to later sexual behavior and substance use, 2) early maturers engage in substance use on their own and then select substance-using friends, or 3) early maturers initiate sexual behaviors which leads them to substance-using peers. Methods The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age: 9–13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three timepoints including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Results Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. Conclusions The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. PMID:26003577

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

PubMed Central

Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

2018-01-01

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

A Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success

ERIC Educational Resources Information Center

Luong, Ming; Stevens, Jeff

2015-01-01

The Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success, a theoretical stages-of-growth model, explains long-term success in IT outsourcing relationships. Research showed the IT outsourcing relationship life cycle consists of four distinct, sequential stages: contract, transition, support, and partnership. The model was…

ALL OUR SONS: THE DEVELOPMENTAL NEUROBIOLOGY AND NEUROENDOCRINOLOGY OF BOYS AT RISK.

PubMed

Schore, Allan N

2017-01-01

Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain. I present interdisciplinary research which indicates that the stress-regulating circuits of the male brain mature more slowly than those of the female in the prenatal, perinatal, and postnatal critical periods, and that this differential structural maturation is reflected in normal gender differences in right-brain attachment functions. Due to this maturational delay, developing males also are more vulnerable over a longer period of time to stressors in the social environment (attachment trauma) and toxins in the physical environment (endocrine disruptors) that negatively impact right-brain development. In terms of differences in gender-related psychopathology, I describe the early developmental neuroendocrinological and neurobiological mechanisms that are involved in the increased vulnerability of males to autism, early onset schizophrenia, attention deficit hyperactivity disorder, and conduct disorders as well as the epigenetic mechanisms that can account for the recent widespread increase of these disorders in U.S. culture. I also offer a clinical formulation of early assessments of boys at risk, discuss the impact of early childcare on male psychopathogenesis, and end with a neurobiological model of optimal adult male socioemotional functions. © 2017 Michigan Association for Infant Mental Health.

Functional correlates of central white matter maturation in perinatal period in rabbits.

PubMed

Drobyshevsky, Alexander; Jiang, Rugang; Derrick, Matthew; Luo, Kehuan; Tan, Sidhartha

2014-11-01

Anisotropy indices derived from diffusion tensor imaging (DTI) are being increasingly used as biomarkers of central WM structural maturation, myelination and even functional development. Our hypothesis was that the rate of functional changes in central WM tracts directly reflects rate of changes in structural development as determined by DTI indices. We examined structural and functional development of four major central WM tracts with different maturational trajectories, including internal capsule (IC), corpus callosum (CC), fimbria hippocampi (FH) and anterior commissure (AC). Rabbits were chosen due to perinatal brain development being similar to humans, and four time points were studied: P1, P11, P18 and adults. Imaging parameters of structural maturation included fractional anisotropy (FA), mean and directional diffusivities derived from DTI, and T2 relaxation time. Axonal composition and degree of myelination were confirmed on electron microscopy. To assess functional maturation, conduction velocity was measured in myelinated and non-myelinated fibers by electrophysiological recordings of compound action potential in perfused brain slices. Diffusion indices and T2 relaxation time in rabbits followed a sigmoid curve during development similar to that for humans, with active changes even at premyelination stage. The shape of the developmental curve was different between the fiber tracts, with later onset but steeper rapid phase of development in IC and FH than in CC. The structural development was not directly related to myelination or to functional development. Functional properties in projection (IC) and limbic tracts (FH) matured earlier than in associative and commissural tracts (CC and AC). The rapid phase of changes in diffusion anisotropy and T2 relaxation time coincided with the development of functional responses and myelination in IC and FH between the second and third weeks of postnatal development in rabbits. In these two tracts, MRI indices could serve as surrogate markers of the early stage of myelination. However, the discordance between developmental change of diffusion indices, myelination and functional properties in CC and AC cautions against equating DTI index changes as biomarkers for myelination in all tracts. Copyright © 2014 Elsevier Inc. All rights reserved.

Maturation of Cortico-Subcortical Structural Networks-Segregation and Overlap of Medial Temporal and Fronto-Striatal Systems in Development.

PubMed

Walhovd, Kristine B; Tamnes, Christian K; Bjørnerud, Atle; Due-Tønnessen, Paulina; Holland, Dominic; Dale, Anders M; Fjell, Anders M

2015-07-01

The brain consists of partly segregated neural circuits within which structural convergence and functional integration occurs during development. The relationship of structural cortical and subcortical maturation is largely unknown. We aimed to study volumetric development of the hippocampus and basal ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes throughout the cortex. Longitudinal MRI data were obtained across a mean interval of 2.6 years in 85 participants with an age range of 8-19 years at study start. Left and right subcortical changes were related to cortical change vertex-wise in the ipsilateral hemisphere with general linear models with age, sex, interval between scans, and mean cortical volume change as covariates. Hippocampal-cortical change relationships centered on parts of the Papez circuit, including entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal, insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia-cortical change relationships were observed in mostly nonoverlapping and more anterior cortical areas, all including the anterior cingulate. Other patterns were unique to specific basal ganglia structures, including pre-, post-, and paracentral patterns relating to putamen change. In conclusion, patterns of cortico-subcortical development as assessed by morphometric analyses in part map out segregated neural circuits at the macrostructural level. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Structure-based affinity maturation of a chimeric anti-ricin antibody C4C13.

PubMed

Luo, Longlong; Luo, Qun; Guo, Leiming; Lv, Ming; Lin, Zhou; Geng, Jing; Li, Xinying; Li, Yan; Shen, Beifen; Qiao, Chunxia; Feng, Jiannan

2014-01-01

Ricin is a highly lethal toxin. Anti-ricin chimeric monoclonal antibody (mAb) C4C13 was prepared in our lab; however, its binding affinity was much weaker than that of the parent antibody 4C13. In this study, based on the computer-guided homology modeling and conformational optimization methods, the 3-D structure of C4C13 variable regions Fv was constructed and optimized. Using molecular docking and dynamics simulation methods, the 3-D complex structure of ricin and C4C13 Fv was obtained. Considering the orientation property, surface electrostatic distribution, residues chemical and physical character and intermolecular hydrogen bond, the binding mode and key residues were predicted. According to C4C13 Fv fragment and ricin complementary binding surface, electrostatic attraction periphery and van der Waals interaction interface, three mutants (i.e., M1 (N(H102)F, W(H103)Y); M2 (W(H103)Y) and M3 (R(L90)G)) were designed, in which M1 and M2 were predicted to possess higher antigen-binding activity than C4C13, while M3 was weaker. The relative affinity assays by ELISA showed that M1 and M2 mutations had higher affinity (9.6 and 18.3 nmol/L) than C4C13 (130 nmol/L) and M3 had weaker affinity (234.5 nmol/L) than C4C13. The results showed that the modeling complex structure of the antigen (ricin) and antibody (C4C13) is reasonable. Our work offered affinity maturated antibodies by site mutations, which were beneficial for valuable anti-ricin antibody design and preparation in future.

La protein and its associated small nuclear and nucleolar precursor RNAs.

PubMed

Maraia, Richard J; Intine, Robert V

2002-01-01

After transcription by RNA polymerase (pol) III, nascent Pol III transcripts pass through RNA processing, modification, and transport machineries as part of their posttranscriptional maturation process. The first factor to interact with Pol III transcripts is La protein, which binds principally via its conserved N-terminal domain (NTD), to the UUU-OH motif that results from transcription termination. This review includes a sequence Logo of the most conserved region of La and its refined modeling as an RNA recognition motif (RRM). La protects RNAs from 3' exonucleolytic digestion and also contributes to their nuclear retention. The variety of modifications found on La-associated RNAs is reviewed in detail and considered in the contexts of how La may bind the termini of structured RNAs without interfering with recognition by modification enzymes, and its ability to chaperone RNAs through multiple parts of their maturation pathways. The CTD of human La recognizes the 5' end region of nascent RNA in a manner that is sensitive to serine 366 phosphorylation. Although the CTD can control pre-tRNA cleavage by RNase P, a rate-limiting step in tRNASerUGA maturation, the extent to which it acts in the maturation pathway(s) of other transcripts is unknown but considered here. Evidence that a fraction of La resides in the nucleolus together with recent findings that several Pol III transcripts pass through the nucleolus is also reviewed. An imminent goal is to understand how the bipartite RNA binding, intracellular trafficking, and signal transduction activities of La are integrated with the maturation pathways of the various RNAs with which it associates.

Stepwise Organization of the β-Structure Identifies Key Regions Essential for the Propagation and Cytotoxicity of Insulin Amyloid Fibrils*

PubMed Central

Chatani, Eri; Imamura, Hiroshi; Yamamoto, Naoki; Kato, Minoru

2014-01-01

Amyloid fibrils are supramolecular assemblies, the deposition of which is associated with many serious diseases including Alzheimer, prion, and Huntington diseases. Several smaller aggregates such as oligomers and protofibrils have been proposed to play a role in early stages of the fibrillation process; however, little is known about how these species contribute to the formation of mature amyloid fibrils with a rigid cross-β structure. Here, we identified a new pathway for the formation of insulin amyloid fibrils at a high concentration of salt in which mature fibrils were formed in a stepwise manner via a prefibrillar intermediate: minute prefibrillar species initially accumulated, followed by the subsequent formation of thicker amyloid fibrils. Fourier transform infrared spectra suggested the sequential formation of two types of β-sheets with different strength hydrogen bonds, one of which was developed concomitantly with the mutual assembly of the prefibrillar intermediate to form mature fibrils. Interestingly, fibril propagation and cellular toxicity appeared only after the later step of structural organization, and a comparison of β-sheet regions between the prefibrillar intermediate and mature fibrils using proteolysis led to the proposal of specific regions essential for manifestation of these properties. PMID:24569992

Characteristics Associated with the Madden-Julian Oscillation at Manus Island

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

Deng, Liping; McFarlane, Sally A.; Flaherty, Julia E.

2013-05-15

Ground-based high temporal and vertical resolution datasets from 2002 to 2008 of observations at the Atmospheric Radiation Measurement (ARM) Tropical Western Pacific (TWP) site on Manus Island, Papua New Guinea are used to examine the evolution of clouds and rainfall associated with the MJO life cycle. A composite MJO event is developed based on the NOAA MJO Index 4 using 13 events. The analysis shows that the cloud evolution during the composited MJO life cycle depicts a two-phase structure consisting of a development phase and a mature phase. During the development phase, congestus is the most important cloud type; duringmore » the mature phase, deep convection is the dominant cloud type. Consistent with this two-phase structure, the heavy rainfall frequency also shows a two-peak structure during the MJO life cycle. Light rainfall does not show a clear relation to the MJO life cycle, but shows variability on shorter time scales. From the development phase to the mature phase, the MJO structure shifts from the Type I to Type II structure, showing a different phase relationship between convection and dynamic fields (or wave motion) in the development and mature phases. During the shift, mid-level clouds play an important role in moving moisture to the mid-troposphere and preparing the atmosphere for the following deep convection. The discharge-recharge theory explains some of observed features of the MJO evolution at the ARM TWP Manus Island site.« less

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study.

PubMed

Crum, William R; Sawiak, Stephen J; Chege, Winfred; Cooper, Jonathan D; Williams, Steven C R; Vernon, Anthony C

2017-07-01

Genetic and environmental risk factors for psychiatric disorders are suggested to disrupt the trajectory of brain maturation during adolescence, leading to the development of psychopathology in adulthood. Rodent models are powerful tools to dissect the specific effects of such risk factors on brain maturational profiles, particularly when combined with Magnetic Resonance Imaging (MRI; clinically comparable technology). We therefore investigated the effect of maternal immune activation (MIA), an epidemiological risk factor for adult-onset psychiatric disorders, on rat brain maturation using atlas and tensor-based morphometry analysis of longitudinal in vivo MR images. Exposure to MIA resulted in decreases in the volume of several cortical regions, the hippocampus, amygdala, striatum, nucleus accumbens and unexpectedly, the lateral ventricles, relative to controls. In contrast, the volumes of the thalamus, ventral mesencephalon, brain stem and major white matter tracts were larger, relative to controls. These volumetric changes were maximal between post-natal day 50 and 100 with no differences between the groups thereafter. These data are consistent with and extend prior studies of brain structure in MIA-exposed rodents. Apart from the ventricular findings, these data have robust face validity to clinical imaging findings reported in studies of individuals at high clinical risk for a psychiatric disorder. Further work is now required to address the relationship of these MRI changes to behavioral dysfunction and to establish thier cellular correlates. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Pea Border Cell Maturation and Release Involve Complex Cell Wall Structural Dynamics.

PubMed

Mravec, Jozef; Guo, Xiaoyuan; Hansen, Aleksander Riise; Schückel, Julia; Kračun, Stjepan Krešimir; Mikkelsen, Maria Dalgaard; Mouille, Grégory; Johansen, Ida Elisabeth; Ulvskov, Peter; Domozych, David S; Willats, William George Tycho

2017-06-01

The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases, though, plant cells are programmed to detach, and root cap-derived border cells are examples of this. Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we undertook a systematic, detailed analysis of pea ( Pisum sativum ) root tip cell walls. Our study included immunocarbohydrate microarray profiling, monosaccharide composition determination, Fourier-transformed infrared microspectroscopy, quantitative reverse transcription-PCR of cell wall biosynthetic genes, analysis of hydrolytic activities, transmission electron microscopy, and immunolocalization of cell wall components. Using this integrated glycobiology approach, we identified multiple novel modes of cell wall structural and compositional rearrangement during root cap growth and the release of border cells. Our findings provide a new level of detail about border cell maturation and enable us to develop a model of the separation process. We propose that loss of adhesion by the dissolution of homogalacturonan in the middle lamellae is augmented by an active biophysical process of cell curvature driven by the polarized distribution of xyloglucan and extensin epitopes. © 2017 American Society of Plant Biologists. All Rights Reserved.

A ruler protein in a complex for antiviral defense determines the length of small interfering CRISPR RNAs.

PubMed

Hatoum-Aslan, Asma; Samai, Poulami; Maniv, Inbal; Jiang, Wenyan; Marraffini, Luciano A

2013-09-27

Small RNAs undergo maturation events that precisely determine the length and structure required for their function. CRISPRs (clustered regularly interspaced short palindromic repeats) encode small RNAs (crRNAs) that together with CRISPR-associated (cas) genes constitute a sequence-specific prokaryotic immune system for anti-viral and anti-plasmid defense. crRNAs are subject to multiple processing events during their biogenesis, and little is known about the mechanism of the final maturation step. We show that in the Staphylococcus epidermidis type III CRISPR-Cas system, mature crRNAs are measured in a Cas10·Csm ribonucleoprotein complex to yield discrete lengths that differ by 6-nucleotide increments. We looked for mutants that impact this crRNA size pattern and found that an alanine substitution of a conserved aspartate residue of Csm3 eliminates the 6-nucleotide increments in the length of crRNAs. In vitro, recombinant Csm3 binds RNA molecules at multiple sites, producing gel-shift patterns that suggest that each protein binds 6 nucleotides of substrate. In vivo, changes in the levels of Csm3 modulate the crRNA size distribution without disrupting the 6-nucleotide periodicity. Our data support a model in which multiple Csm3 molecules within the Cas10·Csm complex bind the crRNA with a 6-nucleotide periodicity to function as a ruler that measures the extent of crRNA maturation.

Applications of the Wilkinson Model of Writing Maturity to College Writing.

ERIC Educational Resources Information Center

Sternglass, Marilyn

1982-01-01

Examines the four-category model developed by Andrew Wilkinson at the University of Essex (England) to assess growth in writing maturity. The four measures of development are stylistic, affective, cognitive, and moral. Each has several subcategories. Includes college student essays to illustrate the model. (HTH)

Longitudinal Study of Repeated Sprint Performance in Youth Soccer Players of Contrasting Skeletal Maturity Status

PubMed Central

Valente-dos-Santos, João; Coelho-e-Silva, Manuel J.; Severino, Vítor; Duarte, João; Martins, Raúl S.; Figueiredo, António J.; Seabra, André T.; Philippaerts, Renaat M.; Cumming, Sean P; Elferink-Gemser, Marije; Malina, Robert M.

2012-01-01

The purpose of the study was to evaluate the developmental changes in performance in a repeated-sprint ability (RSA) test in young soccer players of contrasting maturity status. A total of 83 regional level Portuguese youth soccer players, aged 11-13 years at baseline was assessed annually. Stature, body mass, 7x34.2-m sprint protocol (25-s active recovery), 20-m multi-stage continuous shuttle endurance run and counter-movement jump (CMJ) without the use of the arms were measured. Fat-free mass (FFM) was determined by age and gender-specific formulas. Developmental changes in total sprint time across ages were predicted using multilevel modeling. Corresponding measurements were performed on an independent cross-sectional subsample of 52 youth soccer players 11-17 years to evaluate the predictive model. CA, CA2, maturational status (SA-CA), body size (mass and stature), FFM, aerobic endurance, lower limb explosive strength and annual volume training significantly improved the statistical fit of the RSA multilevel model. In ‘late’ maturing athletes, the best model for predicting change in RSA was expressed by the following equation: 86.54 - 2.87 x CA + 0.05 x CA2 - 0.25 x FFM + 0.15 x body mass + 0.05 x stature - 0.05 x aerobic endurance - 0.09 x lower limb explosive strength - 0.01 x annual volume training. The best fitting models for players who were ‘on time’ and ‘early’ maturing were identical to the best model for late maturing players, less 0.64 seconds and 1.74 seconds, respectively. Multilevel modeling provided performance curves that permitted the prediction of individual RSA performance across adolescent years in regional level soccer players. Key pointsRepeated-sprint ability tests are a valuable sport-specific field test of sprint performance in youth soccer players. Here, the test had reasonable reliability and can be useful to trainers and coaches in the assessment of young athletes and in monitoring changes over time.The total sprint time of youth soccer players advanced in biological maturation improves more, on average, than that of players who are on time (average) and late in maturation. The performance difference between early and late maturing players is consistent after about 13 years of age.Multilevel modeling is a promising statistical technique for analyzing the development of functional capacity in a sport. It has the potential to provide useful information to assist trainers and coaches in evaluating and facilitating the development of individual players. PMID:24149342

Characterizing the structural maturity of fault zones using high-resolution earthquake locations.

NASA Astrophysics Data System (ADS)

Perrin, C.; Waldhauser, F.; Scholz, C. H.

2017-12-01

We use high-resolution earthquake locations to characterize the three-dimensional structure of active faults in California and how it evolves with fault structural maturity. We investigate the distribution of aftershocks of several recent large earthquakes that occurred on immature faults (i.e., slow moving and small cumulative displacement), such as the 1992 (Mw7.3) Landers and 1999 (Mw7.1) Hector Mine events, and earthquakes that occurred on mature faults, such as the 1984 (Mw6.2) Morgan Hill and 2004 (Mw6.0) Parkfield events. Unlike previous studies which typically estimated the width of fault zones from the distribution of earthquakes perpendicular to the surface fault trace, we resolve fault zone widths with respect to the 3D fault surface estimated from principal component analysis of local seismicity. We find that the zone of brittle deformation around the fault core is narrower along mature faults compared to immature faults. We observe a rapid fall off of the number of events at a distance range of 70 - 100 m from the main fault surface of mature faults (140-200 m fault zone width), and 200-300 m from the fault surface of immature faults (400-600 m fault zone width). These observations are in good agreement with fault zone widths estimated from guided waves trapped in low velocity damage zones. The total width of the active zone of deformation surrounding the main fault plane reach 1.2 km and 2-4 km for mature and immature faults, respectively. The wider zone of deformation presumably reflects the increased heterogeneity in the stress field along complex and discontinuous faults strands that make up immature faults. In contrast, narrower deformation zones tend to align with well-defined fault planes of mature faults where most of the deformation is concentrated. Our results are in line with previous studies suggesting that surface fault traces become smoother, and thus fault zones simpler, as cumulative fault slip increases.

Root architecture simulation improves the inference from seedling root phenotyping towards mature root systems.

PubMed

Zhao, Jiangsan; Bodner, Gernot; Rewald, Boris; Leitner, Daniel; Nagel, Kerstin A; Nakhforoosh, Alireza

2017-02-01

Root phenotyping provides trait information for plant breeding. A shortcoming of high-throughput root phenotyping is the limitation to seedling plants and failure to make inferences on mature root systems. We suggest root system architecture (RSA) models to predict mature root traits and overcome the inference problem. Sixteen pea genotypes were phenotyped in (i) seedling (Petri dishes) and (ii) mature (sand-filled columns) root phenotyping platforms. The RSA model RootBox was parameterized with seedling traits to simulate the fully developed root systems. Measured and modelled root length, first-order lateral number, and root distribution were compared to determine key traits for model-based prediction. No direct relationship in root traits (tap, lateral length, interbranch distance) was evident between phenotyping systems. RootBox significantly improved the inference over phenotyping platforms. Seedling plant tap and lateral root elongation rates and interbranch distance were sufficient model parameters to predict genotype ranking in total root length with an RSpearman of 0.83. Parameterization including uneven lateral spacing via a scaling function substantially improved the prediction of architectures underlying the differently sized root systems. We conclude that RSA models can solve the inference problem of seedling root phenotyping. RSA models should be included in the phenotyping pipeline to provide reliable information on mature root systems to breeding research. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix—A Comparative Analysis of Bioartificial Liver Microenvironments

PubMed Central

Wang, Bo; Jakus, Adam E.; Baptista, Pedro M.; Soker, Shay; Soto-Gutierrez, Alejandro; Abecassis, Michael M.; Shah, Ramille N.

2016-01-01

Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three-dimensional bioartificial microenvironments on function and maturation of hepatocyte-like cells differentiated from iPSCs and grown within an acellular, liver-derived extracellular matrix (ECM) scaffold. In parallel, we also compared a bioplotted poly-l-lactic acid (PLLA) scaffold that allows for cell growth in three dimensions and formation of cell-cell contacts but is infused with type I collagen (PLLA-collagen scaffold) alone as a “deconstructed” control scaffold with narrowed biological diversity. iPSC-derived hepatocytes cultured within both scaffolds remained viable, became polarized, and formed bile canaliculi-like structures; however, cells grown within ECM scaffolds had significantly higher P450 (CYP2C9, CYP3A4, CYP1A2) mRNA levels and metabolic enzyme activity compared with iPSC hepatocytes grown in either bioplotted PLLA collagen or Matrigel sandwich control culture. Additionally, the rate of albumin synthesis approached the level of primary cryopreserved hepatocytes with lower transcription of fetal-specific genes, α-fetoprotein and CYP3A7, compared with either PLLA-collagen scaffolds or sandwich culture. These studies show that two acellular, three-dimensional culture systems increase the function of iPSC-derived hepatocytes. However, scaffolds derived from ECM alone induced further hepatocyte maturation compared with bioplotted PLLA-collagen scaffolds. This effect is likely mediated by the complex composition of ECM scaffolds in contrast to bioplotted scaffolds, suggesting their utility for in vitro hepatocyte assays or drug discovery. Significance Through the use of novel technology to develop three-dimensional (3D) scaffolds, the present study demonstrated that hepatocyte-like cells derived via induced pluripotent stem cell (iPSC) technology mature on 3D extracellular matrix scaffolds as a result of 3D matrix structure and scaffold biology. The result is an improved hepatic phenotype with increased synthetic and catalytic potency, an improvement on the blunted phenotype of iPSC-derived hepatocytes, a critical limitation of iPSC technology. These findings provide insight into the influence of 3D microenvironments on the viability, proliferation, and function of iPSC hepatocytes to yield a more mature population of cells for cell toxicity studies and disease modeling. PMID:27421950

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

PubMed

Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

2005-10-01

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes

PubMed Central

White, Jennifer; Barro, Marietta V.; Makarenkova, Helen P.; Sanger, Joseph W.; Sanger, Jean M.

2014-01-01

It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, non-muscle myosin II, muscle myosin II, and α-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that non-muscle myosins II A and B are components of the Z-Bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-Bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. PMID:25125171

How does the body representation system develop in the human brain?

PubMed

Fontan, Aurelie; Cignetti, Fabien; Nazarian, Bruno; Anton, Jean-Luc; Vaugoyeau, Marianne; Assaiante, Christine

2017-04-01

Exploration of the body representation system (BRS) from kinaesthetic illusions in fMRI has revealed a complex network composed of sensorimotor and frontoparietal components. Here, we evaluated the degree of maturity of this network in children aged 7-11 years, and the extent to which structural factors account for network differences with adults. Brain activation following tendon vibration at 100Hz ('illusion') and 30Hz ('no illusion') were analysed using the two-stage random effects model, with or without white and grey matter covariates. The BRS was already well established in children as revealed by the contrast 'illusion' vs 'no illusion', although still immature in some aspects. This included a lower level of activation in primary somatosensory and posterior parietal regions, and the exclusive activation of the frontopolar cortex (FPC) in children compared to adults. The former differences were related to structure, while the latter difference reflected a functional strategy where the FPC may serve as the 'top' in top-down modulation of the activity of the other BRS regions to facilitate the establishment of body representations. Hence, the development of the BRS not only relies on structural maturation, but also involves the disengagement of an executive region not classically involved in body processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of Structural Covariance From Childhood to Adolescence: A Longitudinal Study in 22q11.2DS.

PubMed

Sandini, Corrado; Zöller, Daniela; Scariati, Elisa; Padula, Maria C; Schneider, Maude; Schaer, Marie; Van De Ville, Dimitri; Eliez, Stephan

2018-01-01

Background: Schizophrenia is currently considered a neurodevelopmental disorder of connectivity. Still few studies have investigated how brain networks develop in children and adolescents who are at risk for developing psychosis. 22q11.2 Deletion Syndrome (22q11DS) offers a unique opportunity to investigate the pathogenesis of schizophrenia from a neurodevelopmental perspective. Structural covariance (SC) is a powerful approach to explore morphometric relations between brain regions that can furthermore detect biomarkers of psychosis, both in 22q11DS and in the general population. Methods: Here we implement a state-of-the-art sliding-window approach to characterize maturation of SC network architecture in a large longitudinal cohort of patients with 22q11DS (110 with 221 visits) and healthy controls (117 with 211 visits). We furthermore propose a new clustering-based approach to group regions according to trajectories of structural connectivity maturation. We correlate measures of SC with development of working memory, a core executive function that is highly affected in both idiopathic psychosis and 22q11DS. Finally, in 22q11DS we explore correlations between SC dysconnectivity and severity of internalizing psychopathology. Results: In HCs network architecture underwent a quadratic developmental trajectory maturing up to mid-adolescence. Late-childhood maturation was particularly evident for fronto-parietal cortices, while Default-Mode-Network-related regions showed a more protracted linear development. Working memory performance was positively correlated with network segregation and fronto-parietal connectivity. In 22q11DS, we demonstrate aberrant maturation of SC with disturbed architecture selectively emerging during adolescence and correlating more severe internalizing psychopathology. Patients also presented a lack of typical network development during late-childhood, that was particularly prominent for frontal connectivity. Conclusions: Our results suggest that SC maturation may underlie critical cognitive development occurring during late-childhood in healthy controls. Aberrant trajectories of SC maturation may reflect core developmental features of 22q11DS, including disturbed cognitive maturation during childhood and predisposition to internalizing psychopathology and psychosis during adolescence.

Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity

PubMed Central

Groves, Maria AT; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

2014-01-01

In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics. PMID:24256948

Application of stochastic differential geometry to the term structure of interst rates in developed markets

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

Taranenko, Y.; Barnes, C.

1996-12-31

This paper deals with further developments of the new theory that applies stochastic differential geometry (SDG) to dynamics of interest rates. We examine mathematical constraints on the evolution of interest rate volatilities that arise from stochastic differential calculus under assumptions of an arbitrage free evolution of zero coupon bonds and developed markets (i.e., none of the party/factor can drive the whole market). The resulting new theory incorporates the Heath-Jarrow-Morton (HJM) model of interest rates and provides new equations for volatilities which makes the system of equations for interest rates and volatilities complete and self consistent. It results in much smallermore » amount of volatility data that should be guessed for the SDG model as compared to the HJM model. Limited analysis of the market volatility data suggests that the assumption of the developed market is violated around maturity of two years. Such maturities where the assumptions of the SDG model are violated are suggested to serve as boundaries at which volatilities should be specified independently from the model. Our numerical example with two boundaries (two years and five years) qualitatively resembles the market behavior. Under some conditions solutions of the SDG model become singular that may indicate market crashes. More detail comparison with the data is needed before the theory can be established or refuted.« less

Efficient Computation of Info-Gap Robustness for Finite Element Models

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

Stull, Christopher J.; Hemez, Francois M.; Williams, Brian J.

2012-07-05

A recent research effort at LANL proposed info-gap decision theory as a framework by which to measure the predictive maturity of numerical models. Info-gap theory explores the trade-offs between accuracy, that is, the extent to which predictions reproduce the physical measurements, and robustness, that is, the extent to which predictions are insensitive to modeling assumptions. Both accuracy and robustness are necessary to demonstrate predictive maturity. However, conducting an info-gap analysis can present a formidable challenge, from the standpoint of the required computational resources. This is because a robustness function requires the resolution of multiple optimization problems. This report offers anmore » alternative, adjoint methodology to assess the info-gap robustness of Ax = b-like numerical models solved for a solution x. Two situations that can arise in structural analysis and design are briefly described and contextualized within the info-gap decision theory framework. The treatments of the info-gap problems, using the adjoint methodology are outlined in detail, and the latter problem is solved for four separate finite element models. As compared to statistical sampling, the proposed methodology offers highly accurate approximations of info-gap robustness functions for the finite element models considered in the report, at a small fraction of the computational cost. It is noted that this report considers only linear systems; a natural follow-on study would extend the methodologies described herein to include nonlinear systems.« less

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

Graham, R.; Howe, S.; O`Leary, J.

The Piedemonte Llanero petroleum trend of the Cordillera Oriental in Colombia has proven to be one of the most prolific hydrocarbon provinces discovered in recent years. The Piedemonte Llanero is a fold and thrust belt of complex, multi-phase structuration and hydrocarbon generation. Following the discovery of the Cusiana and Cupiagua fields in the southern part of the trend, BP and its partners began exploration further to the northeast. Early seismic data showed the existence of two structural trends: the frontal (or basal) thrust trend, with structures similar to Cusiana; and the overthrust (or duplex) trend, with multiple imbricated structures. Improvedmore » quality seismic data defined the gross structures and allowed them to be successfully drilled, but did not give a constrained model for the kinematic evolution of the fold and thrust belt nor the petroleum play. This resulted in no clear predictive models for reservoir quality and hydrocarbon phase distribution in the undrilled parts of the trend. A wide variety of geological and geochemical analytical techniques including biostratigraphy, reservoir petrology, petroleum geochemistry, thermal maturity data, basin modelling and fluid inclusion studies were undertaken. These were iteratively integrated into the seismo-structural model to develop a constrained interpretation for the evolution of the Piedemonte Llanero petroleum system. This paper summarizes the current understanding of the structural evolution of the trend and the development of a major petroleum system. A companion paper details the reservoir petrography and petroleum geochemistry studies.« less

Molecular Characteristics of the Equine Periodontal Ligament

PubMed Central

Pöschke, Antje; Krähling, Bastian; Failing, Klaus; Staszyk, Carsten

2018-01-01

The equine periodontal ligament (PDL) is a fibrous connective tissue that covers the intra-alveolar parts of the tooth and anchors it to the alveolar bone—it, therefore, provides a similar function to a tendinous structure. While several studies have considered the formation and structure of tendons, there is insufficient information particularly on the molecular composition of the PDL. Especially for the equine PDL, there is limited knowledge concerning the expression of genes commonly regarded as typical for tendon tissue. In this study, the gene expression of, e.g., collagen type 1 alpha 1 (COL1), collagen type 3 alpha 1 (COL3), scleraxis (SCX), and fibrocartilage markers was examined in the functional mature equine PDL compared with immature and mature equine tendon tissue. PDL samples were obtained from incisor, premolar, and molar teeth from seven adult horses. Additionally, tendon samples were collected from four adult horses and five foals at different sampling locations. Analyses of gene expression were performed using real-time quantitative polymerase chain reaction (qRT-PCR). Significantly higher expression levels of COL1 and 3 were found in the mature equine PDL in comparison with mature tendon, indicating higher rates of collagen production and turnover in the mature equine PDL. The expression levels of SCX, a specific marker for tenogenic-differentiated cells, were on a similar level in functional mature PDL and in mature tendon tissue. Evidence of chondrogenic metaplasia, often found in tendon entheses or in pressurized regions of tendons, was not found in the mature equine PDL. The obtained results justify further experiments focused on the possible use of equine PDL cells for cell-based regenerative therapies. PMID:29376061

FT-IR and FT-Raman characterization of non-cellulosic polysaccharides fractions isolated from plant cell wall.

PubMed

Chylińska, Monika; Szymańska-Chargot, Monika; Zdunek, Artur

2016-12-10

The purpose of this work was to reveal the structural changes of cell wall polysaccharides' fractions during tomato fruit development by analysis of spectral data. Mature green and red ripe tomato fruit were taken into consideration. The FT-IR spectra of water soluble pectin (WSP), imidazole soluble pectin (ISP) and diluted alkali soluble pectin (DASP) contained bands typical for pectins. Whereas for KOH fraction spectra bands typical for hemicelluloses were present. The FT-IR spectra showed the drop down of esterification degree of WSP and ISP polysaccharides during maturation. The changes in polysaccharides structure revealed by spectra were the most visible in the case of pectic polysaccharides. The WSP and DASP fraction pectins molecules length were shortened during tomato maturation and ripening. Whereas the ISP fraction spectra analysis showed that this fraction contained rhamnogalacturonan I, but also for red ripe was rich in pectic galactan comparing with ISP fraction from mature green. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maturation of Shark Single-Domain (IgNAR) Antibodies: Evidence for Induced-Fit Binding

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

Stanfield, R.L.; Dooley, H.; Verdino, P.

2007-07-13

Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts withmore » antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.« less

Maturation of the Gag core decreases the stability of retroviral lipid membranes.

PubMed

Davidoff, Candice; Payne, Riley J; Willis, Sharon H; Doranz, Benjamin J; Rucker, Joseph B

2012-11-25

To better understand how detergents disrupt enveloped viruses, we monitored the biophysical stability of murine leukemia virus (MLV) virus-like particles (VLPs) against a panel of commonly used detergents using real-time biosensor measurements. Although exposure to many detergents, such as Triton X-100 and Empigen, results in lysis of VLP membranes, VLPs appeared resistant to complete membrane lysis by a significant number of detergents, including Tween 20, Tween 80, Lubrol, and Saponin. VLPs maintained their structural integrity after exposure to Tween 20 at concentrations up to 500-fold above its CMC. Remarkably, VLPs containing immature cores composed of unprocessed (uncleaved) Gag polyprotein were significantly more resistant to detergent lysis than VLPs with mature cores. Although the maturity of retroviral Gag is known to influence the stability of the protein core structure itself, our studies suggest that the maturity of the Gag core also influences the stability of the lipid bilayer surrounding the core. Copyright © 2012 Elsevier Inc. All rights reserved.

Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity.

PubMed

Steven, Alasdair C; Heymann, J Bernard; Cheng, Naiqian; Trus, Benes L; Conway, James F

2005-04-01

For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process -- maturation -- is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins -- major capsid protein, scaffolding protein, portal, protease and accessory protein -- that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy.

Maturation of the Gag core decreases the stability of retroviral lipid membranes

PubMed Central

Davidoff, Candice; Payne, Riley; Willis, Sharon H.; Doranz, Benjamin J.; Rucker, Joseph B.

2012-01-01

To better understand how detergents disrupt enveloped viruses, we monitored the biophysical stability of murine leukemia virus (MLV) virus-like particles (VLPs) against a panel of commonly used detergents using real-time biosensor measurements. Although exposure to many detergents, such as Triton X-100 and Empigen, results in lysis of VLP membranes, VLPs appeared resistant to complete membrane lysis by a significant number of detergents, including Tween 20, Tween 80, Lubrol, and Saponin. VLPs maintained their structural integrity after exposure to Tween 20 at concentrations up to 500-fold above its CMC. Remarkably, VLPs containing immature cores composed of unprocessed (uncleaved) Gag polyprotein were significantly more resistant to detergent lysis than VLPs with mature cores. Although the maturity of retroviral Gag is known to influence the stability of the protein core structure itself, our studies suggest that the maturity of the Gag core also influences the stability of the lipid bilayer surrounding the core. PMID:22995186

Temporal dynamics of leafy spurge (Euphorbia esula) and two species of flea beetle (Aphthona spp.) used as biological control agents

USGS Publications Warehouse

Larson, D.L.; Grace, J.B.

2004-01-01

The goal of this study was to evaluate the biological control program of leafy spurge {Euphorbia esula) in a large natural area, Theodore Roosevelt National Park, western North Dakota, USA. Aphthona lacertosa and Aphthona nigriscutis have been released at more than 1800 points in the 18,600-ha South Unit of the park beginning in 1989; most releases have occurred since 1994. We established permanent vegetation plots throughout the infested area of the park and determined stem counts and biomass of leafy spurge and abundance of the two flea beetle species at these plots each year from 1999 to 2001. Both biomass and stem counts declined over the 3 years of the study. Both species of flea beetle are well established within the park and have expanded into areas where they were not released. A. nigriscutis was more abundant than A. lacertosa in the grassland areas we surveyed but in all other habitats abundances were similar. Using structural equation models, only A. lacertosa could be shown to have a significant effect on counts of mature stems of leafy spurge. A. nigriscutis numbers were positively correlated with stem counts of mature stems. Previous year's stem counts had the greatest influence on change in stem counts over each 2-year time step examined with structural equation models.

Temporal dynamics of leafy spurge (Euphorbia esula) and two species of flea beetles (Aphthona spp.) used as biological control agents

USGS Publications Warehouse

Larson, D.L.; Grace, J.B.

2004-01-01

The goal of this study was to evaluate the biological control program of leafy spurge (Euphorbia esula) in a large natural area, Theodore Roosevelt National Park, western North Dakota, USA. Aphthona lacertosa and Aphthona nigriscutis have been released at more than 1800 points in the 18,600-ha South Unit of the park beginning in 1989; most releases have occurred since 1994. We established permanent vegetation plots throughout the infested area of the park and determined stem counts and biomass of leafy spurge and abundance of the two flea beetle species at these plots each year from 1999 to 2001. Both biomass and stem counts declined over the 3 years of the study. Both species of flea beetle are well established within the park and have expanded into areas where they were not released. A. nigriscutis was more abundant than A. lacertosa in the grassland areas we surveyed, but in all other habitats abundances were similar. Using structural equation models, only A. lacertosa could be shown to have a significant effect on counts of mature stems of leafy spurge. A. nigriscutis numbers were positively correlated with stem counts of mature stems. Previous year's stem counts had the greatest influence on change in stem counts over each 2-year time step examined with structural equation models.

Four RNA families with functional transient structures

PubMed Central

Zhu, Jing Yun A; Meyer, Irmtraud M

2015-01-01

Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5′ flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5′ UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here. PMID:25751035

Four RNA families with functional transient structures.

PubMed

Zhu, Jing Yun A; Meyer, Irmtraud M

2015-01-01

Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5' flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5' UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here.

Induced formation and maturation of acetylcholine receptor clusters in a defined 3D bio-artificial muscle.

PubMed

Wang, Lin; Shansky, Janet; Vandenburgh, Herman

2013-12-01

Dysfunction of the neuromuscular junction is involved in a wide range of muscular diseases. The development of neuromuscular junction through which skeletal muscle is innervated requires the functional modulation of acetylcholine receptor (AchR) clustering on myofibers. However, studies on AchR clustering in vitro are mostly done on monolayer muscle cell culture, which lacks a three-dimensional (3D) structure, a prominent limitation of the two-dimensional (2D) system. To enable a better understanding on the structure-function correlation underlying skeletal muscle innervation, a muscle system with a well-defined geometry mimicking the in vivo muscular setting is needed. Here, we report a 3D bio-artificial muscle (BAM) bioengineered from green fluorescent protein-transduced C3H murine myoblasts as a novel in vitro tissue-based model for muscle innervation studies. Our cell biological and molecular analysis showed that this BAM is structurally similar to in vivo muscle tissue and can reach the perinatal differentiation stage, higher than does 2D culture. Effective clustering and morphological maturation of AchRs on BAMs induced by agrin and laminin indicate the functional activity and plasticity of this BAM system toward innervation. Taken together, our results show that the BAM provides a favorable 3D environment that at least partially recapitulates real physiological skeletal muscle with regard to innervation. With a convenience of fabrication and manipulation, this 3D in vitro system offers a novel model for studying mechanisms underlying skeletal muscle innervation and testing therapeutic strategies for relevant nervous and muscular diseases.

Cytoskeletal and cellular adhesion proteins in zebrafish (Danio rerio) myogenesis.

PubMed

Costa, M L; Escaleira, R; Manasfi, M; de Souza, L F; Mermelstein, C S

2003-08-01

The current myogenesis and myofibrillogenesis model has been based mostly on in vitro cell culture studies, and, to a lesser extent, on in situ studies in avian and mammalian embryos. While the more isolated artificial conditions of cells in culture permitted careful structural analysis, the actual in situ cellular structures have not been described in detail because the embryos are more difficult to section and manipulate. To overcome these difficulties, we used the optically clear and easy to handle embryos of the zebrafish Danio rerio. We monitored the expression of cytoskeletal and cell-adhesion proteins (actin, myosin, desmin, alpha-actinin, troponin, titin, vimentin and vinculin) using immunofluorescence microscopy and video-enhanced, background-subtracted, differential interference contrast of 24- to 48-h zebrafish embryos. In the mature myotome, the mononucleated myoblasts displayed periodic striations for all sarcomeric proteins tested. The changes in desmin distribution from aggregates to perinuclear and striated forms, although following the same sequence, occurred much faster than in other models. All desmin-positive cells were also positive for myofibrillar proteins and striated, in contrast to that which occurs in cell cultures. Vimentin appeared to be striated in mature cells, while it is developmentally down-regulated in vitro. The whole connective tissue septum between the somites was positive for adhesion proteins such as vinculin, instead of the isolated adhesion plaques observed in cell cultures. The differences in the myogenesis of zebrafish in situ and in cell culture in vitro suggest that some of the previously observed structures and protein distributions in cultures could be methodological artifacts.

Perspectives for computational modeling of cell replacement for neurological disorders

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

Aimone, James B.; Weick, Jason P.

In mathematical modeling of anatomically-constrained neural networks we provide significant insights regarding the response of networks to neurological disorders or injury. Furthermore, a logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impactmore » circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

Perspectives for computational modeling of cell replacement for neurological disorders

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

Aimone, James B.; Weick, Jason P.

Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behaviormore » in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

[Local injection of exogenous nerve growth factor improves early bone maturation of implants].

PubMed

Yao, Yang; Du, Yu; Gu, Xia; Guang, Meng-Kai; Huang, Bo; Gong, Ping

2018-04-01

To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). NGF can shorten the period of bone maturation.

The AGU Data Management Maturity Model Initiative

NASA Astrophysics Data System (ADS)

Bates, J. J.

2015-12-01

In September 2014, the AGU Board of Directors approved two initiatives to help the Earth and space sciences community address the growing challenges accompanying the increasing size and complexity of data. These initiatives are: 1) Data Science Credentialing: development of a continuing education and professional certification program to help scientists in their careers and to meet growing responsibilities and requirements around data science; and 2) Data Management Maturity (DMM) Model: development and implementation of a data management maturity model to assess process maturity against best practices, and to identify opportunities in organizational data management processes. Each of these has been organized within AGU as an Editorial Board and both Boards have held kick off meetings. The DMM model Editorial Board will recommend strategies for adapting and deploying a DMM model to the Earth and space sciences create guidance documents to assist in its implementation, and provide input on a pilot appraisal process. This presentation will provide an overview of progress to date in the DMM model Editorial Board and plans for work to be done over the upcoming year.

Environmental drivers defining linkages among life-history traits: mechanistic insights from a semiterrestrial amphipod subjected to macroscale gradients.

PubMed

Gómez, Julio; Barboza, Francisco R; Defeo, Omar

2013-10-01

Determining the existence of interconnected responses among life-history traits and identifying underlying environmental drivers are recognized as key goals for understanding the basis of phenotypic variability. We studied potentially interconnected responses among senescence, fecundity, embryos size, weight of brooding females, size at maturity and sex ratio in a semiterrestrial amphipod affected by macroscale gradients in beach morphodynamics and salinity. To this end, multiple modelling processes based on generalized additive mixed models were used to deal with the spatio-temporal structure of the data obtained at 10 beaches during 22 months. Salinity was the only nexus among life-history traits, suggesting that this physiological stressor influences the energy balance of organisms. Different salinity scenarios determined shifts in the weight of brooding females and size at maturity, having consequences in the number and size of embryos which in turn affected sex determination and sex ratio at the population level. Our work highlights the importance of analysing field data to find the variables and potential mechanisms that define concerted responses among traits, therefore defining life-history strategies.

Connective Tissue Mineralization in Abcc6−/− Mice, a Model for Pseudoxanthoma Elasticum

PubMed Central

Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

Effects of stratospheric lapse rate on thunderstorm cloud-top structure in a three-dimensional numerical simulation. I - Some basic results of comparative experiments

NASA Technical Reports Server (NTRS)

Schlesinger, Robert E.

1988-01-01

The effects of stratospheric temperature lapse rate on cloud top height/temperature structure for strongly sheared, mature, isolated midlatitude thunderstorms are investigated by performing three different experiments with an anelastic, three-dimensional model: (1) with an assumed stratospheric lapse rate of 0 K/km (i.e., the isothermal case), (2) with 3 K/km, and (3) with -3 K/km (i.e., the case of inversion). Kinematic storm structure is very similar in all three cases, especially in the troposphere; a strong quasi-steady updraft evolves and splits into a dominant cyclonic overshooting right-mover and a weaker, anticyclonic left-mover that does not reach the tropopause.

Capability maturity models for offshore organisational management.

PubMed

Strutt, J E; Sharp, J V; Terry, E; Miles, R

2006-12-01

The goal setting regime imposed by the UK safety regulator has important implications for an organisation's ability to manage health and safety related risks. Existing approaches to safety assurance based on risk analysis and formal safety assessments are increasingly considered unlikely to create the step change improvement in safety to which the offshore industry aspires and alternative approaches are being considered. One approach, which addresses the important issue of organisational behaviour and which can be applied at a very early stage of design, is the capability maturity model (CMM). The paper describes the development of a design safety capability maturity model, outlining the key processes considered necessary to safety achievement, definition of maturity levels and scoring methods. The paper discusses how CMM is related to regulatory mechanisms and risk based decision making together with the potential of CMM to environmental risk management.

Personality and trait aggression profiles of male and female prison inmates.

PubMed

Falk, Örjan; Sfendla, Anis; Brändström, Sven; Anckarsäter, Henrik; Nilsson, Thomas; Kerekes, Nóra

2017-04-01

Gender specific personality profiles in association with the level of aggressive antisocial behavior in offenders have not been previously investigated. In the present study we analyzed data collected from 65 male and 50 female offenders using structured protocols regarding criminal history (by criminal register data), trait aggression (by the Life History of Aggression (LHA) questionnaire), and personality profiles (by the Temperament and Character Inventory (TCI)). Prison inmates differed significantly on several personality dimensions, most pronouncedly were they characterized with low character maturity (low scores in the Self-Directedness and Cooperativeness dimensions of TCI) when compared to gender and age matched controls of the general population. The majority of offenders scored distinctively high on trait aggression. There were moderate to strong associations between the personality dimensions and each of the subscales of LHA (Aggression, Self-directed Aggression and Antisocial behavior). These associations were stronger in the female offender sample. Trait aggression could be best explained by a model, which included male gender, younger age, high novelty seeking temperament and low character maturity. Our results suggest that therapies aiming at strengthening self-governance and increasing cooperativeness (focusing on character maturity) may alleviate aggressive antisocial behavior in offenders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Networking and rheology of concentrated clay suspensions "matured" in mineral medicinal water.

PubMed

Aguzzi, Carola; Sánchez-Espejo, Rita; Cerezo, Pilar; Machado, José; Bonferoni, Cristina; Rossi, Silvia; Salcedo, Inmaculada; Viseras, César

2013-09-10

This work studied the influence of "maturation" conditions (time and agitation) on aggregation states, gel structure and rheological behaviour of a special kind of pharmaceutical semisolid products made of concentrated clay suspensions in mineral medicinal water. Maturation of the samples was carried out in distilled and sulphated mineral medicinal water, both in static conditions (without agitation) and with manual stirring once a week, during a maximum period of three months. At the measured pH interval (7.5-8.0), three-dimensional band-type networks resulting from face/face contacts were predominant in the laminar (disc-like) clay suspensions, whereas the fibrous (rod-like) particles formed micro-aggregates by van der Waals attractions. The high concentration of solids in the studied systems greatly determined their behaviour. Rod-like sepiolite particles tend to align the major axis in aggregates promoted by low shearing maturation, whereas aggregates of disc-like smectite particles did not have a preferential orientation and their complete swelling required long maturation time, being independent of stirring. Maturation of both kinds of suspensions resulted in improved rheological properties. Laminar clay suspensions became more structured with time, independently from static or dynamic maturation conditions, whereas for fibrous clay periodic agitation was also required. Rheological properties of the studied systems have been related to aggregation states and networking mechanisms, depending on the type of clay minerals constituents. Physical stability of the suspensions was not impaired by the specific composition of the Graena medicinal water. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of selection for growth rate on relative growth in rabbits.

PubMed

Pascual, M; Pla, M; Blasco, A

2008-12-01

The effect of selection for growth rate on relative growth of the rabbit body components was studied. Animals from the 18th generation of a line selected for growth rate were compared with a contemporary control group formed with offspring of embryos that were frozen at the seventh generation of selection of the same line. A total of 313 animals were slaughtered at 4, 9, 13, 20, and 40 wk old. The offal, organs, tissues, and retail cuts were weighed, and several carcass linear measurements were recorded. Huxley's allometric equations relating the weights of the components with respect to BW were fitted. Butterfield's quadratic equations relating the degree of maturity of the components and the degree of maturity of BW were also fitted. In most of the components studied, both models lead to similar patterns of growth. Blood was isometric or early maturing and skin was late maturing or isometric depending on the use of Huxley's or Butterfield's model. Full gastrointestinal tract, liver, kidneys, thoracic viscera, and head were early maturing, and the chilled carcass and reference carcass were late maturing. The retail cuts of the reference carcass showed isometry (forelegs) or late maturing growth (breast and ribs, loin, hind legs, and abdominal walls). Dissectible fat of the carcass and meat of the hind leg had a late development, whereas bone of the hind leg was early maturing. Lumbar circumference length was later maturing than the carcass length and thigh length. Sex did not affect the relative growth of most of the components. Butterfield's model showed that males had an earlier development of full gastrointestinal tract and later growth of kidneys than females. No effect of selection on the relative growth of any of the components studied was found, leading to similar patterns of growth and similar carcass composition at a given degree of maturity after 11 generations of selection for growth rate.

Investigation into mechanical properties of bone and its main constituents

NASA Astrophysics Data System (ADS)

Evdokimenko, Ekaterina

Bone is a hierarchically structured natural composite material, consisting of organic phase (type-I collagen), inorganic phase (hydroxyapatite), and water. Studies of the two main bone constituents, utilizing controlled demineralization and deproteinization, can shed light on mineral-collagen interaction which makes bone such a unique biological material. This knowledge is necessary for computational analysis of bone structure to identify preferential sites in the collagen matrix and mineral network that degrade more easily. The main goal of this work is to develop a comprehensive picture of mechanical properties of bone and its main constituents. Following the Introduction, Chapter 2 presents an investigation of microstructure and compressive mechanical properties of bovine femur cortical bone carried out on completely demineralized, completely deproteinized, and untreated bone samples in three anatomical directions. Anisotropic nature of bone was clearly identified in all cases. Extra levels of porosity along with microstructural differences for the three directions were found to be the main sources of the anisotropy. In Chapter 3, a new theoretical model of cortical and trabecular bone as composite materials with hierarchical structure spanning from nanometer (collagen-mineral) level to millimeter (bone) level was developed. Compression testing was performed on untreated, demineralized, and deproteinized cortical and trabecular bovine femur bone samples to verify the model. The experimental data were compared with theoretical predictions; excellent agreement was found between the theory and experiments for all bone phases. Optical microscopy, scanning electron microscopy, and micro-computed tomography techniques were applied to characterize the structure of the samples at multiple length scales and provide further inputs for the modeling. Chapter 4 presents a comparative study of mechanical properties, microstructure, and porosity of mature and young bovine femur cortical bone. It was found that the amount of porosity decreases, while the microhardness increases with maturation. Osteoporotic degradation of trabecular bone elasticity, described in Chapter 5, was modeled using a cellular mechanics approach. Evolution equations for elastic modulus of bone in terms of those of mineral and protein trabeculae and in terms of demineralized and deproteinized bones were formulated and verified by the analysis of compressive properties of bovine femur trabecular bone.

Idiopathic precocious puberty in girls: Psychosexual development.

PubMed

Meyer-Bahlburg, H F; Ehrhardt, A A; Bell, J J; Cohen, S F; Healey, J M; Feldman, J F; Morishima, A; Baker, S W; New, M I

1985-08-01

A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.

Applying the High Reliability Health Care Maturity Model to Assess Hospital Performance: A VA Case Study.

PubMed

Sullivan, Jennifer L; Rivard, Peter E; Shin, Marlena H; Rosen, Amy K

2016-09-01

The lack of a tool for categorizing and differentiating hospitals according to their high reliability organization (HRO)-related characteristics has hindered progress toward implementing and sustaining evidence-based HRO practices. Hospitals would benefit both from an understanding of the organizational characteristics that support HRO practices and from knowledge about the steps necessary to achieve HRO status to reduce the risk of harm and improve outcomes. The High Reliability Health Care Maturity (HRHCM) model, a model for health care organizations' achievement of high reliability with zero patient harm, incorporates three major domains critical for promoting HROs-Leadership, Safety Culture, and Robust Process Improvement ®. A study was conducted to examine the content validity of the HRHCM model and evaluate whether it can differentiate hospitals' maturity levels for each of the model's components. Staff perceptions of patient safety at six US Department of Veterans Affairs (VA) hospitals were examined to determine whether all 14 HRHCM components were present and to characterize each hospital's level of organizational maturity. Twelve of the 14 components from the HRHCM model were detected; two additional characteristics emerged that are present in the HRO literature but not represented in the model-teamwork culture and system-focused tools for learning and improvement. Each hospital's level of organizational maturity could be characterized for 9 of the 14 components. The findings suggest the HRHCM model has good content validity and that there is differentiation between hospitals on model components. Additional research is needed to understand how these components can be used to build the infrastructure necessary for reaching high reliability.

NASA Experience with CMM and CMMI

NASA Technical Reports Server (NTRS)

Crumbley, Tim; Kelly, John C.

2010-01-01

This slide presentation reviews the experience NASA has had in using Capability Maturity Model (CMM) and Capability Maturity Model Integration (CMMI). In particular this presentation reviews the agency's experience within the software engineering discipline and the lessons learned and key impacts from using CMMI.

The influence of maturation, body size and physical self-perceptions on longitudinal changes in physical activity in adolescent girls.

PubMed

Fawkner, Samantha; Henretty, Joan; Knowles, Ann-Marie; Nevill, Alan; Niven, Ailsa

2014-01-01

The aim of this study was to adopt a longitudinal design to explore the direct effects of both absolute and relative maturation and changes in body size on physical activity, and explore if, and how, physical self-perceptions might mediate this effect. We recruited 208 girls (11.8 ± 0.4 years) at baseline. Data were collected at three subsequent time points, each 6 months apart. At 18 months, 119 girls remained in the study. At each time point, girls completed the Physical Activity Questionnaire for Children, the Pubertal Development Scale (from which, both a measure of relative and absolute maturation were defined) and the Physical Self-Perception Profile, and had physical size characteristics assessed. Multilevel modelling for physical activity indicated a significant negative effect of age, positive effect for physical condition and sport competence and positive association for relatively early maturers. Absolute maturation, body mass, waist circumference and sum of skinfolds did not significantly contribute to the model. Contrary to common hypotheses, relatively more mature girls may, in fact, be more active than their less mature peers. However, neither changes in absolute maturation nor physical size appear to directly influence changes in physical activity in adolescent girls.

Resolving model parameter values from carbon and nitrogen stock measurements in a wide range of tropical mature forests using nonlinear inversion and regression trees

Treesearch

Shuguang Liua; Pamela Anderson; Guoyi Zhoud; Boone Kauffman; Flint Hughes; David Schimel; Vicente Watson; Joseph Tosi

2008-01-01

Objectively assessing the performance of a model and deriving model parameter values from observations are critical and challenging in landscape to regional modeling. In this paper, we applied a nonlinear inversion technique to calibrate the ecosystem model CENTURY against carbon (C) and nitrogen (N) stock measurements collected from 39 mature tropical forest sites in...

Ergonomic sustainability based on the ergonomic maturity level measurement.

PubMed

Vidal, Mario Cesar; Guizze, Carmen Lucia Campos; Bonfatti, Renato José; Silva e Santos, Marcello

2012-01-01

This paper aims at the application of an ergonomic maturity model (EMM), in order to assess the ergonomic sustainability outreach of ergonomic actions. This proposition was motivated by the widespread sensation that the development of the discipline, its educational devices and related practices depends on the attitude of ergonomics practitioners rather than environmental macroergonomic conditions. Maturity modeling in this paper is undertaken as a tool for ergonomic practitioners. Thus, its foundations were uprooted from diverse fields: Clinic Psychology, Quality Management and Project Management. The paper brings about a detailled explanation of this ergonomic maturity tool. The empirical part is fulfilled by the examination - using the EMM - of four emblematic cases excerpted from our research lab ergonomic portfolio.

On the dimensionality of the stress-related growth scale: one, three, or seven factors?

PubMed

Roesch, Scott C; Rowley, Anthony A; Vaughn, Allison A

2004-06-01

We examined the factorial validity and dimensionality of the Stress-Related Growth Scale (SRGS; Park, Cohen, & Murch, 1996) using a large multiethnic sample (n = 1,070). Exploratory and confirmatory factor analyses suggested that a multidimensional representation of the SRGS fit better than a unidimensional representation. Specifically, we cross-validated both a 3-factor model and a 7-factor model using confirmatory factor analysis and were shown to be invariant across gender and ethnic groups. The 3-factor model was represented by global dimensions of growth that included rational/mature thinking, affective/emotional growth, and religious/spiritual growth. We replicated the 7-factor model of Armeli, Gunthert, and Cohen (2001) and it represented more specific components of growth such as Self-Understanding and Treatment of Others. However, some factors of the 7-factor model had questionable internal consistency and were strongly intercorrelated, suggesting redundancy. The findings support the notion that the factor structure of both the original 1-factor and revised 7-factor models are unstable and that the 3-factor model developed in this research has more reliable psychometric properties and structure.

Life History Attributes of Asian Carps in the Upper Mississippi River System

DTIC Science & Technology

2007-05-01

Mature ovary of a female silver carp. Each small white spherical structure is a mature egg 4 ERDC/TN ANSRP-07-1 May 2007 Silver carp in the...weight/fish weight), and fecundity (number of eggs per female ) of each silver and bighead carp were quantified. Diets of silver carp from the MMR also...through November, with gonads ranging from 1 to 13 percent of body weight. Females with mature ovaries (Figure 3) were present as early as age 2 years

Measurement invariance of big-five factors over the life span: ESEM tests of gender, age, plasticity, maturity, and la dolce vita effects.

PubMed

Marsh, Herbert W; Nagengast, Benjamin; Morin, Alexandre J S

2013-06-01

This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due in part to the overly restrictive assumptions of CFA models. Here we demonstrate that exploratory structural equation modeling (ESEM), an integration of CFA and exploratory factor analysis, overcomes these problems with the 15-item Big Five Inventory administered as part of the nationally representative British Household Panel Study (N = 14,021; age: 15-99 years, Mage = 47.1). ESEM fitted the data substantially better and resulted in much more differentiated (less correlated) factors than did CFA. Methodologically, we extended ESEM (introducing ESEM-within-CFA models and a hybrid of multiple groups and multiple indicators multiple causes models), evaluating full measurement invariance and latent mean differences over age, gender, and their interaction. Substantively the results showed that women had higher latent scores for all Big Five factors except for Openness and that these gender differences were consistent over the entire life span. Substantial nonlinear age effects led to the rejection of the plaster hypothesis and the maturity principle but did support a newly proposed la dolce vita effect in old age. In later years, individuals become happier (more agreeable and less neurotic), more self-content and self-centered (less extroverted and open), more laid back and satisfied with what they have (less conscientious, open, outgoing and extroverted), and less preoccupied with productivity. PsycINFO Database Record (c) 2013 APA, all rights reserved

The P-chain: relating sentence production and its disorders to comprehension and acquisition

PubMed Central

Dell, Gary S.; Chang, Franklin

2014-01-01

This article introduces the P-chain, an emerging framework for theory in psycholinguistics that unifies research on comprehension, production and acquisition. The framework proposes that language processing involves incremental prediction, which is carried out by the production system. Prediction necessarily leads to prediction error, which drives learning, including both adaptive adjustment to the mature language processing system as well as language acquisition. To illustrate the P-chain, we review the Dual-path model of sentence production, a connectionist model that explains structural priming in production and a number of facts about language acquisition. The potential of this and related models for explaining acquired and developmental disorders of sentence production is discussed. PMID:24324238

The P-chain: relating sentence production and its disorders to comprehension and acquisition.

PubMed

Dell, Gary S; Chang, Franklin

2014-01-01

This article introduces the P-chain, an emerging framework for theory in psycholinguistics that unifies research on comprehension, production and acquisition. The framework proposes that language processing involves incremental prediction, which is carried out by the production system. Prediction necessarily leads to prediction error, which drives learning, including both adaptive adjustment to the mature language processing system as well as language acquisition. To illustrate the P-chain, we review the Dual-path model of sentence production, a connectionist model that explains structural priming in production and a number of facts about language acquisition. The potential of this and related models for explaining acquired and developmental disorders of sentence production is discussed.

The effects of vortex structure and vortex translation on the tropical cyclone boundary layer wind field

NASA Astrophysics Data System (ADS)

Williams, Gabriel J.

2015-03-01

The effects of vortex translation and radial vortex structure in the distribution of boundary layer winds in the inner core of mature tropical cyclones are examined using a high-resolution slab model and a multilevel model. It is shown that the structure and magnitude of the wind field (and the corresponding secondary circulation) depends sensitively on the radial gradient of the gradient wind field above the boundary layer. Furthermore, it is shown that vortex translation creates low wave number asymmetries in the wind field that rotate anticyclonically with height. A budget analysis of the steady state wind field for both models was also performed in this study. Although the agradient force drives the evolution of the boundary layer wind field for both models, it is shown that the manner in which the boundary layer flow responds to this force differs between the two model representations. In particular, the inner core boundary layer flow in the slab model is dominated by the effects of horizontal advection and horizontal diffusion, leading to the development of shock structures in the model. Conversely, the inner core boundary layer flow in the multilevel model is primarily influenced by the effects of vertical advection and vertical diffusion, which eliminates shock structures in this model. These results further indicate that special care is required to ensure that qualitative applications from slab models are not unduly affected by the neglect of vertical advection. This article was corrected on 31 MAR 2015. See the end of the full text for details.

12 CFR Appendix B to Part 230 - Model Clauses and Sample Forms

Code of Federal Regulations, 2011 CFR

2011-01-01

... for Change in Terms (Section 230.5(a)) B-3—Model Clauses for Pre-Maturity Notices for Time Accounts... avoid imposition of a fee will increase to $___. B-3—Model Clauses for Pre-Maturity Notices for Time... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Model Clauses and Sample Forms B Appendix B to...

The development and use of a molecular model for soybean maturity groups

USDA-ARS?s Scientific Manuscript database

Achieving appropriate maturity in a target environment is essential to maximizing crop yield potential. In soybean [Glycine max (L.) Merr.], the time to maturity is largely dependent on developmental response to dark periods. Once the critical photoperiod is reached, flowering is initiated and rep...

Characterization of the post-translational modification of recombinant human BMP-15 mature protein

PubMed Central

Saito, Seiji; Yano, Keiichi; Sharma, Shweta; McMahon, Heather E.; Shimasaki, Shunichi

2008-01-01

Bone morphogenetic protein-15 (BMP-15) is an oocyte-secreted factor critical for the regulation of ovarian physiology. When recombinant human BMP-15 (rhBMP-15) produced in human embryonic kidney 293 cells was subjected to SDS-PAGE analysis, two mature protein forms corresponding to 16 kDa (P16) and 17 kDa (P17) were observed. Despite the physiological relevance and critical function of BMP-15 in female reproduction, little is known about the structure of rhBMP-15. Here, we have analyzed the structure of the rhBMP-15 mature proteins (P16 and P17) using state-of-the-art proteomics technology. Our findings are as follows: (1) the N-terminal amino acid of P16 and P17 is pyroglutamic acid; (2) the Ser residue at the sixth position of P16 is phosphorylated; (3) P17 is O-glycosylated at Thr10; and (4) the C-terminal amino acid of P16 and P17 is truncated. These findings are the first knowledge of the structure of rhBMP-15 mature protein toward understanding the molecular basis of BMP-15 function and could provide an important contribution to the rapidly progressing research area involving oocyte-specific growth factors in modulation of female fertility. PMID:18227435

Microbial diversity and interactions in subgingival biofilm communities.

PubMed

Diaz, Patricia I

2012-01-01

The human subgingival environment is a complex environmental niche where microorganisms from the three domains of life meet to form diverse biofilm communities that exist in close proximity to the host. Bacteria constitute the most abundant, diverse and ultimately well-studied component of these communities with about 500 bacterial taxa reported to occur in this niche. Cultivation and molecular approaches are revealing the breadth and depth of subgingival biofilm diversity as part of an effort to understand the subgingival microbiome, the collection of microorganisms that inhabit the gingival crevices. Although these investigations are constructing a pretty detailed taxonomical census of subgingival microbial communities, including inter-subject and temporal variability in community structure, as well as differences according to periodontal health status, we are still at the front steps in terms of understanding community function. Clinical studies that evaluate community structure need to be coupled with biologically relevant models that allow evaluation of the ecological determinants of subgingival biofilm maturation. Functional characteristics of subgingival biofilm communities that still need to be clarified include main metabolic processes that support microbial communities, identification of keystone species, microbial interactions and signaling events that lead to community maturation and the relationship of different communities with the host. This manuscript presents a summary of our current understanding of subgingival microbial diversity and an overview of experimental models used to dissect the functional characteristics of subgingival communities. Future coupling of 'omics'-based approaches with such models will facilitate a better understanding of subgingival ecology opening opportunities for community manipulation. Copyright © 2012 S. Karger AG, Basel.

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents.

PubMed

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K

2015-06-01

To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: (1) peer influence links early pubertal timing to later sexual behavior and substance use; (2) early maturers engage in substance use on their own and then select substance-using friends; or (3) early maturers initiate sexual behaviors which lead them to substance-using peers. The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age, 9-13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three time points including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy.

PubMed

Yang, Hee Seok; Ieronimakis, Nicholas; Tsui, Jonathan H; Kim, Hong Nam; Suh, Kahp-Yang; Reyes, Morayma; Kim, Deok-Ho

2014-02-01

Skeletal muscle is a highly organized tissue in which the extracellular matrix (ECM) is composed of highly-aligned cables of collagen with nanoscale feature sizes, and provides structural and functional support to muscle fibers. As such, the transplantation of disorganized tissues or the direct injection of cells into muscles for regenerative therapy often results in suboptimal functional improvement due to a failure to integrate with native tissue properly. Here, we present a simple method in which biodegradable, biomimetic substrates with precisely controlled nanotopography were fabricated using solvent-assisted capillary force lithography (CFL) and were able to induce the proper development and differentiation of primary mononucleated cells to form mature muscle patches. Cells cultured on these nanopatterned substrates were highly-aligned and elongated, and formed more mature myotubes as evidenced by up-regulated expression of the myogenic regulatory factors Myf5, MyoD and myogenin (MyoG). When transplanted into mdx mice models for Duchenne muscular dystrophy (DMD), the proposed muscle patches led to the formation of a significantly greater number of dystrophin-positive muscle fibers, indicating that dystrophin replacement and myogenesis is achievable in vivo with this approach. These results demonstrate the feasibility of utilizing biomimetic substrates not only as platforms for studying the influences of the ECM on skeletal muscle function and maturation, but also to create transplantable muscle cell patches for the treatment of chronic and acute muscle diseases or injuries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advanced Mirror Technology Development (AMTD) Project: 3.0 Year Status

NASA Technical Reports Server (NTRS)

Stahl, H. Philip

2015-01-01

Advanced Mirror Technology Development (AMTD) is a funded NASA Strategic Astrophysics Technology project. Begun in 2011, we are in Phase 2 of a multi-year effort. Our objective is to mature towards TRL6 critical technologies needed to produce 4-m or larger flight-qualified UVOIR mirrors by 2018 so that a viable astronomy mission can be considered by the 2020 Decadal Review. The developed technology must enable missions capable of both general astrophysics and ultra-high contrast observations of exoplanets. Just as JWST's architecture was driven by launch vehicle, a future UVOIR mission's architecture (monolithic, segmented or interferometric) will depend on capacities of future launch vehicles (and budget). Since we cannot predict the future, we must prepare for all potential futures. Therefore, we are pursuing multiple technology paths. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND result in a high-performance low-cost low-risk system. One of our key accomplishments is that we have derived engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicle and its inherent mass and volume constraints. Another key accomplishment is that we have matured our technology by building and testing hardware. To demonstrate stacked core technology, we built a 400 mm thick mirror. Currently, to demonstrate lateral scalability, we are manufacturing a 1.5 meter mirror. To assist in architecture trade studies, the Engineering team develops Structural, Thermal and Optical Performance (STOP) models of candidate mirror assembly systems including substrates, structures, and mechanisms. These models are validated by test of full- and subscale components in relevant thermo-vacuum environments. Specific analyses include: maximum mirror substrate size, first fundamental mode frequency (i.e., stiffness) and mass required to fabricate without quilting, survive launch, and achieve stable pointing and maximum thermal time constant.

Meteorological models for estimating phenology of corn

NASA Technical Reports Server (NTRS)

Daughtry, C. S. T.; Cochran, J. C.; Hollinger, S. E.

1984-01-01

Knowledge of when critical crop stages occur and how the environment affects them should provide useful information for crop management decisions and crop production models. Two sources of data were evaluated for predicting dates of silking and physiological maturity of corn (Zea mays L.). Initial evaluations were conducted using data of an adapted corn hybrid grown on a Typic Agriaquoll at the Purdue University Agronomy Farm. The second phase extended the analyses to large areas using data acquired by the Statistical Reporting Service of USDA for crop reporting districts (CRD) in Indiana and Iowa. Several thermal models were compared to calendar days for predicting dates of silking and physiological maturity. Mixed models which used a combination of thermal units to predict silking and days after silking to predict physiological maturity were also evaluated. At the Agronomy Farm the models were calibrated and tested on the same data. The thermal models were significantly less biased and more accurate than calendar days for predicting dates of silking. Differences among the thermal models were small. Significant improvements in both bias and accuracy were observed when the mixed models were used to predict dates of physiological maturity. The results indicate that statistical data for CRD can be used to evaluate models developed at agricultural experiment stations.

Study of cartilage and bone layers of the bearing surface of the equine metacarpophalangeal joint relative to different timescales of maturation.

PubMed

van der Harst, M R; van de Lest, C H A; Degroot, J; Kiers, G H; Brama, P A J; van Weeren, P R

2005-05-01

A detailed and comprehensive insight into the normal maturation process of the different tissues that make up functional units of the locomotor system such as joints is necessary to understand the influence of early training on musculoskeletal tissues. To study simultaneously the maturation process in the entire composite structure that makes up the bearing surface of a joint (cartilage, subchondral and trabecular bone) in terms of biochemical changes in the tissues of juvenile horses at 2 differently loaded sites of the metacarpophalangeal joint, compared to a group of mature horses. In all the structures described above developmental changes may follow a different timescale. Age-related changes in biochemical characteristics of the collagen part of the extracellular matrix (hydroxylysine, hydroxyproline, hydroxypyridinum crosslinks) of articular cartilage and of the underlying subchondral and trabecular bone were determined in a group of juvenile horses (n = 13) (Group 1, age 6 months-4 years) and compared to a group of mature horses (n = 30) (Group 2, >4 years). In both bony layers, bone mineral density, ash content and levels of individual minerals were determined. In cartilage, subchondral bone and trabecular bone, virtually all collagen parameters in juvenile horses were already at a similar (stable) level as in mature horses. In both bony layers, bone mineral density, ash- and calcium content were also stable in the mature horses, but continued to increase in the juvenile group. For magnesium there was a decrease in the juvenile animals, followed by a steady state in the mature horses. In horses age 6 months-4 years, the collagen network of all 3 layers within the joint has already attained a mature biochemical composition, but the mineral composition of both subchondral and trabecular bone continues to develop until approximately age 4 years. The disparity in maturation of the various extracellular matrix components of a joint can be assumed to have consequences for the capacity to sustain load and should hence be taken into account when training or racing young animals.

Aging, Maturation and Growth of Sauropodomorph Dinosaurs as Deduced from Growth Curves Using Long Bone Histological Data: An Assessment of Methodological Constraints and Solutions

PubMed Central

Griebeler, Eva Maria; Klein, Nicole; Sander, P. Martin

2013-01-01

Information on aging, maturation, and growth is important for understanding life histories of organisms. In extinct dinosaurs, such information can be derived from the histological growth record preserved in the mid-shaft cortex of long bones. Here, we construct growth models to estimate ages at death, ages at sexual maturity, ages at which individuals were fully-grown, and maximum growth rates from the growth record preserved in long bones of six sauropod dinosaur individuals (one indeterminate mamenchisaurid, two Apatosaurus sp., two indeterminate diplodocids, and one Camarasaurus sp.) and one basal sauropodomorph dinosaur individual (Plateosaurus engelhardti). Using these estimates, we establish allometries between body mass and each of these traits and compare these to extant taxa. Growth models considered for each dinosaur individual were the von Bertalanffy model, the Gompertz model, and the logistic model (LGM), all of which have inherently fixed inflection points, and the Chapman-Richards model in which the point is not fixed. We use the arithmetic mean of the age at the inflection point and of the age at which 90% of asymptotic mass is reached to assess respectively the age at sexual maturity or the age at onset of reproduction, because unambiguous indicators of maturity in Sauropodomorpha are lacking. According to an AIC-based model selection process, the LGM was the best model for our sauropodomorph sample. Allometries established are consistent with literature data on other Sauropodomorpha. All Sauropodomorpha reached full size within a time span similar to scaled-up modern mammalian megaherbivores and had similar maximum growth rates to scaled-up modern megaherbivores and ratites, but growth rates of Sauropodomorpha were lower than of an average mammal. Sauropodomorph ages at death probably were lower than that of average scaled-up ratites and megaherbivores. Sauropodomorpha were older at maturation than scaled-up ratites and average mammals, but younger than scaled-up megaherbivores. PMID:23840575

Aging, Maturation and Growth of Sauropodomorph Dinosaurs as Deduced from Growth Curves Using Long Bone Histological Data: An Assessment of Methodological Constraints and Solutions.

PubMed

Griebeler, Eva Maria; Klein, Nicole; Sander, P Martin

2013-01-01

Information on aging, maturation, and growth is important for understanding life histories of organisms. In extinct dinosaurs, such information can be derived from the histological growth record preserved in the mid-shaft cortex of long bones. Here, we construct growth models to estimate ages at death, ages at sexual maturity, ages at which individuals were fully-grown, and maximum growth rates from the growth record preserved in long bones of six sauropod dinosaur individuals (one indeterminate mamenchisaurid, two Apatosaurus sp., two indeterminate diplodocids, and one Camarasaurus sp.) and one basal sauropodomorph dinosaur individual (Plateosaurus engelhardti). Using these estimates, we establish allometries between body mass and each of these traits and compare these to extant taxa. Growth models considered for each dinosaur individual were the von Bertalanffy model, the Gompertz model, and the logistic model (LGM), all of which have inherently fixed inflection points, and the Chapman-Richards model in which the point is not fixed. We use the arithmetic mean of the age at the inflection point and of the age at which 90% of asymptotic mass is reached to assess respectively the age at sexual maturity or the age at onset of reproduction, because unambiguous indicators of maturity in Sauropodomorpha are lacking. According to an AIC-based model selection process, the LGM was the best model for our sauropodomorph sample. Allometries established are consistent with literature data on other Sauropodomorpha. All Sauropodomorpha reached full size within a time span similar to scaled-up modern mammalian megaherbivores and had similar maximum growth rates to scaled-up modern megaherbivores and ratites, but growth rates of Sauropodomorpha were lower than of an average mammal. Sauropodomorph ages at death probably were lower than that of average scaled-up ratites and megaherbivores. Sauropodomorpha were older at maturation than scaled-up ratites and average mammals, but younger than scaled-up megaherbivores.

Thermal maturation history of the Wilcox group (Paleocene-Eocene), Texas: Results of regional-scale multi-1D modeling

USGS Publications Warehouse

Rowan, E.L.; Warwick, Peter D.; Pitman, Janet K.; Kennan, Lorcan; Pindell, James; Rosen, Norman C.

2007-01-01

The thermal maturation history of the Paleocene-Eocene Wilcox Group has been reconstructed based on burial history models of 53 wells in the Texas coastal plain. This modeling study has been conducted in conjunction with a geologically based assessment of the oil and gas resources in Cenozoic strata of the Gulf of Mexico coastal plain and state waters. In the onshore Texas coastal plain, coals and organic-rich shales, predominantly of terrestrial origin, within the Wilcox Group are the primary source of oil (Wenger et al., 1994) as well as a source of gas. The Wilcox, however, is modeled as a single unit, without subdivision into source rock and non-source rock intervals.Generation of oil from Type III kerogen within the Wilcox Group is modeled using hydrous pyrolysis reaction kinetic parameters (Lewan, M.D., written communication, 2006). Gas generation from Type III kerogen is represented using calculated Ro values. The models are calibrated with bottom hole temperature (BHT), and vitrinite reflectance (Ro %) data for the Wilcox Group. Ro data from near-coastal sites have been selected to minimize the possible effects of uplift and erosion and then composited to give a regional Rodepth trend.Model calculations for the study area, the onshore Texas coastal plain, indicate that downdip portions of the basal Wilcox had reached sufficient thermal maturity to generate hydrocarbons by early Eocene (~50 Ma). This relatively early maturation is explained by rapid sediment accumulation in the early Tertiary combined with the reaction kinetic parameters used in the models. Thermal maturation increases through time with increasing burial depth and temperature, gradually moving the maturation front updip. At present day, hydrocarbon generation is complete in the downdip Wilcox within the study area but is currently ongoing in the updip portions of the formation.

Amelogenin-Ameloblastin Spatial Interaction around Maturing Enamel Rods.

PubMed

Mazumder, P; Prajapati, S; Bapat, R; Moradian-Oldak, J

2016-08-01

Amelogenin and ameloblastin are 2 extracellular matrix proteins that are essential for the proper development of enamel. We recently reported that amelogenin and ameloblastin colocalized during the secretory stage of enamel formation when nucleation of enamel crystallites occurs. Direct interactions between the 2 proteins have been also demonstrated in our in vitro studies. Here, we explore interactions between their fragments during enamel maturation. We applied in vivo immunofluorescence imaging, quantitative co-localization analysis, and a new FRET (fluorescence resonance energy transfer) technique to demonstrate ameloblastin and amelogenin interaction in the maturing mouse enamel. Using immunochemical analysis of protein samples extracted from 8-d-old (P8) first molars from mice as a model for maturation-stage enamel, we identified the ~17-kDa ameloblastin (Ambn-N) and the TRAP (tyrosine-rich amelogenin peptide) fragments. We used Ambn-N18 and Ambn-M300 antibodies raised against the N-terminal and C-terminal segments of ameloblastin, as well as Amel-FL and Amel-C19 antibodies against full-length recombinant mouse amelogenin (rM179) and C-terminal amelogenin, respectively. In transverse sections, co-localization images of N-terminal fragments of amelogenin and ameloblastin around the prism boundary revealed the "fish net" pattern of the enamel matrix. Using in vivo FRET microscopy, we further demonstrated spatial interactions between amelogenin and ameloblastin N-terminal fragments. In the maturing mouse enamel, the association of these residual protein fragments created a discontinuity between enamel rods, which we suggest is important for support and maintenance of enamel rods and eventual contribution to unique enamel mechanical properties. We present data that support cooperative functions of enamel matrix proteins in mediating the structural hierarchy of enamel and that contribute to our efforts to design and develop enamel biomimetic material. © International & American Associations for Dental Research 2016.

Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification

PubMed Central

Jeliazkov, Jeliazko R.; Sljoka, Adnan; Kuroda, Daisuke; Tsuchimura, Nobuyuki; Katoh, Naoki; Tsumoto, Kouhei; Gray, Jeffrey J.

2018-01-01

Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity. PMID:29545810

Fourier Transform Infrared Spectroscopic Imaging-Derived Collagen Content and Maturity Correlates with Stress in the Aortic Wall of Abdominal Aortic Aneurysm Patients.

PubMed

Cheheltani, Rabee; Pichamuthu, Joseph E; Rao, Jayashree; Weinbaum, Justin S; Kiani, Mohammad F; Vorp, David A; Pleshko, Nancy

2017-03-01

Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta characterized by severe disruption of the structural integrity of the aortic wall and its major molecular constituents. From the early stages of disease, elastin in the aorta becomes highly degraded and is replaced by collagen. Questions persist as to the contribution of collagen content, quality and maturity to the potential for rupture. Here, using our recently developed Fourier transform infrared imaging spectroscopy (FT-IRIS) method, we quantified collagen content and maturity in the wall of AAA tissues in pairs of specimens with different wall stresses. CT scans of AAAs from 12 patients were used to create finite element models to estimate stress in different regions of tissue. Each patient underwent elective repair of the AAA, and two segments of the AAA tissues from anatomic regions more proximal or distal with different wall stresses were evaluated by histology and FT-IRIS after excision. For each patient, collagen content was generally greater in the tissue location with lower wall stress, which corresponded to the more distal anatomic regions. The wall stress/collagen ratio was greater in the higher stress region compared to the lower stress region (1.01 ± 1.09 vs. 0.55 ± 0.084, p = 0.02). The higher stress region also corresponded to the location with reduced intraluminal thrombus thickness. Further, collagen maturity tended to decrease with increased collagen content (p = 0.068, R = 0.38). Together, these results suggest that an increase in less mature collagen content in AAA patients does not effectively compensate for the loss of elastin in the aortic wall, and results in a reduced capability to endure wall stresses.

Probiotics Can Induce Follicle Maturational Competence: The Danio rerio Case1

PubMed Central

Gioacchini, Giorgia; Giorgini, Elisabetta; Merrifield, Daniel L.; Hardiman, Gary; Borini, Andrea; Vaccari, Lisa; Carnevali, Oliana

2011-01-01

ABSTRACT In the present study, the effects of the probiotic Lactobacillus rhamnosus IMC 501 on the acquisition of oocyte maturational competence was examined in zebrafish (Danio rerio). L. rhamnosus administration induced the responsiveness of incompetent follicles (stage IIIa) to 17,20-dihydroxy-4-pregnen-3-one and their in vitro maturation. Acquisition of competence by the stage IIIa follicles was further validated by changes of lhr, mprb, inhbaa (activin betaA1), tgfb1, and gdf9 gene expression, which have recently emerged as key regulators of oocyte acquisition of maturational competence, and pou5f1 gene expression, which in other models has been shown to govern the establishment of developmental competence of oocytes. In addition, a DNA microarray experiment was conducted using the same follicles, and with relative gene ontology (GO) data analysis, the molecular effects of probiotic administration emerged. Molecular analysis using PCR-DGGE (denaturing gradient gel electrophoresis) approach, providing information about only the most abundant bacterial members of the microbial community, revealed that the probiotic was able to populate the gastrointestinal tract and modulate the microbial communities, causing a clear shift in them and specifically enhancing the presence of the lactic acid bacteria Streptococcus thermophilus. At the same time, PCR-DGGE analysis revealed that the probiotic was not directly associated with the ovaries. Finally, the effects of probiotic treatment on zebrafish follicle development were also analyzed by FPA (focal plane array) Fourier transform-infrared (FT-IR) imaging, a technique that provides the overall biochemical composition of samples. Changes were found above all in stage IIIa follicles from probiotic-exposed females; the modifications, observed in protein secondary structures as well as in hydration and in bands related to phosphate moieties, allowed us to hypothesize that probiotics act at this follicle stage, affecting the maturation phase. PMID:22088919

McDonnell Douglas Helicopter Company independent research and development: Preparing for the future

NASA Technical Reports Server (NTRS)

Haggerty, Allen C.

1988-01-01

During the 1970's and 80's, research has produced the technology that is seen in aircraft such as the LHX and future models. The technology is discussed that is reaching maturity and moving into the application stage of future programs. Technology is discussed in six major areas: advanced concepts, analysis techniques, structures, systems, simulation, and research and development facilities. The partnership of McDonnell Douglas Helicopter Co. and the government in developing these technologies is illustrated in several programs.

Ontogeny of vestibular compound action potentials in the domestic chicken

NASA Technical Reports Server (NTRS)

Jones, S. M.; Jones, T. A.

2000-01-01

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

PubMed Central

M. Jones, Sherri

2000-01-01

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of –0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately –25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6–P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 μV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ. PMID:11545229

Modelling phenolic and technological maturities of grapes by means of the multivariate relation between organoleptic and physicochemical properties.

PubMed

Meléndez, E; Ortiz, M C; Sarabia, L A; Íñiguez, M; Puras, P

2013-01-25

The ripeness of grapes at the harvest time is one of the most important parameters for obtaining high quality red wines. Traditionally the decision of harvesting is to be taken only after analysing sugar concentration, titratable acidity and pH of the grape juice (technological maturity). However, these parameters only provide information about the pulp ripeness and overlook the real degree of skins and seeds maturities (phenolic maturity). Both maturities, technological and phenolic, are not simultaneously reached, on the contrary they tend to separate depending on several factors: grape variety, cultivar, adverse weather conditions, soil, water availability and cultural practices. Besides, this divergence is increasing as a consequence of the climate change (larger quantities of CO(2), less rain, and higher temperatures). 247 samples collected in vineyards representative of the qualified designation of origin Rioja from 2007 to 2011 have been analysed. Samples contain the four grape varieties usual in the elaboration of Rioja wines ('tempranillo', 'garnacha', 'mazuelo' and 'graciano'). The present study is the first systematic investigation on the maturity of grapes that includes the organoleptic evaluation of the degree of grapes maturity (sugars/acidity maturity, aromatic maturity of the pulp, aromatic maturity of the skins and tannins maturity) together with the values of the physicochemical parameters (probable alcohol degree, total acidity, pH, malic acid, K, total index polyphenolics, anthocyans, absorbances at 420, 520 and 620 nm, colour index and tartaric acid) determined over the same samples. A varimax rotation of the latent variables of a PLS model between the physicochemical variables and the mean of four sensory variables allows identifying both maturities. Besides, the position of the samples in the first plane defines the effect that the different factors exert on both phenolic and technological maturities. Copyright © 2012 Elsevier B.V. All rights reserved.

Aerobic fitness, maturation, and training experience in youth basketball.

PubMed

Carvalho, Humberto M; Coelho-e-Silva, Manuel J; Eisenmann, Joey C; Malina, Robert M

2013-07-01

Relationships among chronological age (CA), maturation, training experience, and body dimensions with peak oxygen uptake (VO2max) were considered in male basketball players 14-16 y of age. Data for all players included maturity status estimated as percentage of predicted adult height attained at the time of the study (Khamis-Roche protocol), years of training, body dimensions, and VO2max (incremental maximal test on a treadmill). Proportional allometric models derived from stepwise regressions were used to incorporate either CA or maturity status and to incorporate years of formal training in basketball. Estimates for size exponents (95% CI) from the separate allometric models for VO2max were height 2.16 (1.23-3.09), body mass 0.65 (0.37-0.93), and fat-free mass 0.73 (0.46-1.02). Body dimensions explained 39% to 44% of variance. The independent variables in the proportional allometric models explained 47% to 60% of variance in VO2max. Estimated maturity status (11-16% of explained variance) and training experience (7-11% of explained variance) were significant predictors with either body mass or estimated fat-free mass (P ≤ .01) but not with height. Biological maturity status and training experience in basketball had a significant contribution to VO2max via body mass and fat-free fat mass and also had an independent positive relation with aerobic performance. The results highlight the importance of considering variation associated with biological maturation in aerobic performance of late-adolescent boys.

Evolutionistic or revolutionary paths? A PACS maturity model for strategic situational planning.

PubMed

van de Wetering, Rogier; Batenburg, Ronald; Lederman, Reeva

2010-07-01

While many hospitals are re-evaluating their current Picture Archiving and Communication System (PACS), few have a mature strategy for PACS deployment. Furthermore, strategies for implementation, strategic and situational planning methods for the evolution of PACS maturity are scarce in the scientific literature. Consequently, in this paper we propose a strategic planning method for PACS deployment. This method builds upon a PACS maturity model (PMM), based on the elaboration of the strategic alignment concept and the maturity growth path concept previously developed in the PACS domain. First, we review the literature on strategic planning for information systems and information technology and PACS maturity. Secondly, the PMM is extended by applying four different strategic perspectives of the Strategic Alignment Framework whereupon two types of growth paths (evolutionistic and revolutionary) are applied that focus on a roadmap for PMM. This roadmap builds a path to get from one level of maturity and evolve to the next. An extended method for PACS strategic planning is developed. This method defines eight distinctive strategies for PACS strategic situational planning that allow decision-makers in hospitals to decide which approach best suits their hospitals' current situation and future ambition and what in principle is needed to evolve through the different maturity levels. The proposed method allows hospitals to strategically plan for PACS maturation. It is situational in that the required investments and activities depend on the alignment between the hospital strategy and the selected growth path. The inclusion of both strategic alignment and maturity growth path concepts make the planning method rigorous, and provide a framework for further empirical research and clinical practice.

Visualisation of macropinosome maturation by the recruitment of sorting nexins.

PubMed

Kerr, Markus C; Lindsay, Margaret R; Luetterforst, Robert; Hamilton, Nicholas; Simpson, Fiona; Parton, Robert G; Gleeson, Paul A; Teasdale, Rohan D

2006-10-01

We report that phosphoinositol-binding sorting nexin 5 (SNX5) associates with newly formed macropinosomes induced by EGF stimulation. We used the recruitment of GFP-SNX5 to macropinosomes to track their maturation. Initially, GFP-SNX5 is sequestered to discrete subdomains of the macropinosome; these subdomains are subsequently incorporated into highly dynamic, often branched, tubular structures. Time-lapse videomicroscopy revealed the highly dynamic extension of SNX5-labelled tubules and their departure from the macropinosome body to follow predefined paths towards the perinuclear region of the cell, before fusing with early endosomal acceptor membranes. The extension and departure of these tubular structures occurs rapidly over 5-10 minutes and is dependent upon intact microtubules. As the tubular structures depart from the macropinosome there is a reduction in the surface area and an increase in tension of the limiting membrane of the macropinosome. In addition to the recruitment of SNX5 to the macropinosome, Rab5, SNX1 and EEA1 are also recruited by newly formed macropinosomes, followed by the accumulation of Rab7. SNX5 forms heterodimers with SNX1 and this interaction is required for endosome association of SNX5. We propose that the departure of SNX5-positive tubules represents a rapid mechanism of recycling components from macropinosomes thereby promoting their maturation into Rab7-positive structures. Collectively these findings provide a detailed real-time characterisation of the maturation process of the macropinocytic endosome.

Neocortical maturation during adolescence: change in neuronal soma dimension.

PubMed

Rabinowicz, Theodore; Petetot, Jean Macdonald-Comber; Khoury, Jane C; de Courten-Myers, Gabrielle M

2009-03-01

During adolescence, cognitive abilities increase robustly. To search for possible related structural alterations of the cerebral cortex, we measured neuronal soma dimension (NSD = width times height), cortical thickness and neuronal densities in different types of neocortex in post-mortem brains of five 12-16 and five 17-24 year-olds (each 2F, 3M). Using a generalized mixed model analysis, mean normalized NSD comparing the age groups shows layer-specific change for layer 2 (p < .0001) and age-related differences between categorized type of cortex: primary/primary association cortex (BA 1, 3, 4, and 44) shows a generalized increase; higher-order regions (BA 9, 21, 39, and 45) also show increase in layers 2 and 5 but decrease in layers 3, 4, and 6 while limbic/orbital cortex (BA 23, 24, and 47) undergoes minor decrease (BA 1, 3, 4, and 44 vs. BA 9, 21, 39, and 45: p = .036 and BA 1, 3, 4, and 44 vs. BA 23, 24, and 47: p = .004). These data imply the operation of cortical layer- and type-specific processes of growth and regression adding new evidence that the human brain matures during adolescence not only functionally but also structurally.

Finite element analysis (FEA) analysis of the preflex beam

NASA Astrophysics Data System (ADS)

Wan, Lijuan; Gao, Qilang

2017-10-01

The development of finite element analysis (FEA) has been relatively mature, and is one of the important means of structural analysis. This method changes the problem that the research of complex structure in the past needs to be done by a large number of experiments. Through the finite element method, the numerical simulation of the structure can be used to achieve a variety of static and dynamic simulation analysis of the mechanical problems, it is also convenient to study the parameters of the structural parameters. Combined with a certain number of experiments to verify the simulation model can be completed in the past all the needs of experimental research. The nonlinear finite element method is used to simulate the flexural behavior of the prestressed composite beams with corrugated steel webs. The finite element analysis is used to understand the mechanical properties of the structure under the action of bending load.

The structure of human tripeptidyl peptidase II as determined by a hybrid approach.

PubMed

Schönegge, Anne-Marie; Villa, Elizabeth; Förster, Friedrich; Hegerl, Reiner; Peters, Jürgen; Baumeister, Wolfgang; Rockel, Beate

2012-04-04

Tripeptidyl-peptidase II (TPPII) is a high molecular mass (∼5 MDa) serine protease, which is thought to act downstream of the 26S proteasome, cleaving peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has been determined to subnanometer resolution by cryoelectron microscopy and single-particle analysis. The complex is built from two strands forming a quasihelical structure harboring a complex system of inner cavities. HsTPPII particles exhibit some polymorphism resulting in complexes consisting of nine or of eight dimers per strand. To obtain deeper insights into the architecture and function of HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a comparative model of HsTPPII dimers and molecular dynamics flexible fitting. Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modeling growth from weaning to maturity in beef cattle breeds

USDA-ARS?s Scientific Manuscript database

To better understand growth trajectory and maturity differences between beef breeds, three models – Brody, spline, and quadratic – were fit to cow growth data, and resulting parameter estimates were evaluated for 3 breed categories – British, continental, and Brahman-influenced. The data were weight...

Black-Scholes finite difference modeling in forecasting of call warrant prices in Bursa Malaysia

NASA Astrophysics Data System (ADS)

Mansor, Nur Jariah; Jaffar, Maheran Mohd

2014-07-01

Call warrant is a type of structured warrant in Bursa Malaysia. It gives the holder the right to buy the underlying share at a specified price within a limited period of time. The issuer of the structured warrants usually uses European style to exercise the call warrant on the maturity date. Warrant is very similar to an option. Usually, practitioners of the financial field use Black-Scholes model to value the option. The Black-Scholes equation is hard to solve analytically. Therefore the finite difference approach is applied to approximate the value of the call warrant prices. The central in time and central in space scheme is produced to approximate the value of the call warrant prices. It allows the warrant holder to forecast the value of the call warrant prices before the expiry date.

Modeling the Multi-Body System Dynamics of a Flexible Solar Sail Spacecraft

NASA Technical Reports Server (NTRS)

Kim, Young; Stough, Robert; Whorton, Mark

2005-01-01

Solar sail propulsion systems enable a wide range of space missions that are not feasible with current propulsion technology. Hardware concepts and analytical methods have matured through ground development to the point that a flight validation mission is now realizable. Much attention has been given to modeling the structural dynamics of the constituent elements, but to date an integrated system level dynamics analysis has been lacking. Using a multi-body dynamics and control analysis tool called TREETOPS, the coupled dynamics of the sailcraft bus, sail membranes, flexible booms, and control system sensors and actuators of a representative solar sail spacecraft are investigated to assess system level dynamics and control issues. With this tool, scaling issues and parametric trade studies can be performed to study achievable performance, control authority requirements, and control/structure interaction assessments.

The structure and host entry of an invertebrate parvovirus.

PubMed

Meng, Geng; Zhang, Xinzheng; Plevka, Pavel; Yu, Qian; Tijssen, Peter; Rossmann, Michael G

2013-12-01

The 3.5-Å resolution X-ray crystal structure of mature cricket parvovirus (Acheta domesticus densovirus [AdDNV]) has been determined. Structural comparisons show that vertebrate and invertebrate parvoviruses have evolved independently, although there are common structural features among all parvovirus capsid proteins. It was shown that raising the temperature of the AdDNV particles caused a loss of their genomes. The structure of these emptied particles was determined by cryo-electron microscopy to 5.5-Å resolution, and the capsid structure was found to be the same as that for the full, mature virus except for the absence of the three ordered nucleotides observed in the crystal structure. The viral protein 1 (VP1) amino termini could be externalized without significant damage to the capsid. In vitro, this externalization of the VP1 amino termini is accompanied by the release of the viral genome.

The Structure and Host Entry of an Invertebrate Parvovirus

PubMed Central

Meng, Geng; Zhang, Xinzheng; Plevka, Pavel; Yu, Qian; Tijssen, Peter

2013-01-01

The 3.5-Å resolution X-ray crystal structure of mature cricket parvovirus (Acheta domesticus densovirus [AdDNV]) has been determined. Structural comparisons show that vertebrate and invertebrate parvoviruses have evolved independently, although there are common structural features among all parvovirus capsid proteins. It was shown that raising the temperature of the AdDNV particles caused a loss of their genomes. The structure of these emptied particles was determined by cryo-electron microscopy to 5.5-Å resolution, and the capsid structure was found to be the same as that for the full, mature virus except for the absence of the three ordered nucleotides observed in the crystal structure. The viral protein 1 (VP1) amino termini could be externalized without significant damage to the capsid. In vitro, this externalization of the VP1 amino termini is accompanied by the release of the viral genome. PMID:24027306

In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

PubMed

Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

2018-01-01

In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

Diazotrophic Community Structure and Function in Two Successional Stages of Biological Soil Crusts from the Colorado Plateau and Chihuahuan Desert

USGS Publications Warehouse

Yeager, C.M.; Kornosky, J.L.; Housman, D.C.; Grote, E.E.; Belnap, J.; Kuske, C.R.

2004-01-01

The objective of this study was to characterize the community structure and activity of N2-fixing microorganisms in mature and poorly developed biological soil crusts from both the Colorado Plateau and Chihuahuan Desert. Nitrogenase activity was approximately 10 and 2.5 times higher in mature crusts than in poorly developed crusts at the Colorado Plateau site and Chihuahuan Desert site, respectively. Analysis of nifH sequences by clone sequencing and the terminal restriction fragment length polymorphism technique indicated that the crust diazotrophic community was 80 to 90% heterocystous cyanobacteria most closely related to Nostoc spp. and that the composition of N2-fixing species did not vary significantly between the poorly developed and mature crusts at either site. In contrast, the abundance of nifH sequences was approximately 7.5 times greater (per microgram of total DNA) in mature crusts than in poorly developed crusts at a given site as measured by quantitative PCR. 16S rRNA gene clone sequencing and microscopic analysis of the cyanobacterial community within both crust types demonstrated a transition from a Microcoleus vaginatus-dominated, poorly developed crust to mature crusts harboring a greater percentage of Nostoc and Scytonema spp. We hypothesize that ecological factors, such as soil instability and water stress, may constrain the growth of N2-fixing microorganisms at our study sites and that the transition to a mature, nitrogen-producing crust initially requires bioengineering of the surface microenvironment by Microcoleus vaginatus.

Migration, Integration and Maturation of Photoreceptor Precursors Following Transplantation in the Mouse Retina

PubMed Central

Warre-Cornish, Katherine; Barber, Amanda C.; Sowden, Jane C.; Ali, Robin R.

2014-01-01

Retinal degeneration leading to loss of photoreceptors is a major cause of untreatable blindness. Recent research has yielded definitive evidence for restoration of vision following the transplantation of rod photoreceptors in murine models of blindness, while advances in stem cell biology have enabled the generation of transplantable photoreceptors from embryonic stem cells. Importantly, the amount of visual function restored is dependent upon the number of photoreceptors that migrate correctly into the recipient retina. The developmental stage of the donor cells is important for their ability to migrate; they must be immature photoreceptor precursors. Little is known about how and when donor cell migration, integration, and maturation occurs. Here, we have performed a comprehensive histological analysis of the 6-week period following rod transplantation in mice. Donor cells migrate predominately as single entities during the first week undergoing a stereotyped sequence of morphological changes in their translocation from the site of transplantation, through the interphotoreceptor matrix and into the recipient retina. This includes initial polarization toward the outer nuclear layer (ONL), followed by formation of an apical attachment and rudimentary segment during migration into the ONL. Strikingly, acquisition of a nuclear architecture typical of mature rods was accelerated compared with normal development and a feature of migrating cells. Once within the ONL, precursors formed synaptic-like structures and outer segments in accordance with normal maturation. The restoration of visual function mediated by transplanted photoreceptors correlated with the later expression of rod α-transducin, achieving maximal function by 5 weeks. PMID:24328605

A Ruler Protein in a Complex for Antiviral Defense Determines the Length of Small Interfering CRISPR RNAs

PubMed Central

Hatoum-Aslan, Asma; Samai, Poulami; Maniv, Inbal; Jiang, Wenyan; Marraffini, Luciano A.

2013-01-01

Small RNAs undergo maturation events that precisely determine the length and structure required for their function. CRISPRs (clustered regularly interspaced short palindromic repeats) encode small RNAs (crRNAs) that together with CRISPR-associated (cas) genes constitute a sequence-specific prokaryotic immune system for anti-viral and anti-plasmid defense. crRNAs are subject to multiple processing events during their biogenesis, and little is known about the mechanism of the final maturation step. We show that in the Staphylococcus epidermidis type III CRISPR-Cas system, mature crRNAs are measured in a Cas10·Csm ribonucleoprotein complex to yield discrete lengths that differ by 6-nucleotide increments. We looked for mutants that impact this crRNA size pattern and found that an alanine substitution of a conserved aspartate residue of Csm3 eliminates the 6-nucleotide increments in the length of crRNAs. In vitro, recombinant Csm3 binds RNA molecules at multiple sites, producing gel-shift patterns that suggest that each protein binds 6 nucleotides of substrate. In vivo, changes in the levels of Csm3 modulate the crRNA size distribution without disrupting the 6-nucleotide periodicity. Our data support a model in which multiple Csm3 molecules within the Cas10·Csm complex bind the crRNA with a 6-nucleotide periodicity to function as a ruler that measures the extent of crRNA maturation. PMID:23935102

Proteomic analysis of 'Zaosu' pear (Pyrus bretschneideri Rehd.) and its early-maturing bud sport.

PubMed

Liu, Xueting; Zhai, Rui; Feng, Wenting; Zhang, Shiwei; Wang, Zhigang; Qiu, Zonghao; Zhang, Junke; Ma, Fengwang; Xu, Lingfei

2014-07-01

Maturation of fruits involves a series of physiological, biochemical, and organoleptic changes that eventually make fleshy fruits attractive, palatable, and nutritional. In order to understand the mature mechanism of the early-maturing bud sport of 'Zaosu' pear, we analyzed the differences of proteome expression between the both pears in different mature stages by the methods of a combination of two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Seventy-five differential expressed protein spots (p<0.05) were obtained between 'Zaosu' pear and its early-maturing bud sport, but only sixty-eight were demonstratively identified in the database of NCBI and uniprot. The majority of proteins were linked to metabolism, energy, stress response/defense and cell structure. Additionally, our data confirmed an increase of proteins related to cell-wall modification, oxidative stress and pentose phosphate metabolism and a decrease of proteins related to photosynthesis and glycolysis during the development process of both pears, but all these proteins increased or decreased faster in the early-maturing bud sport. This comparative analysis between both pears showed that these proteins were closely associated with maturation and could provide more detailed characteristics of the maturation process of both pears. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Seasonal dynamics of radial growth and stem water deficit in co-occurring saplings and mature conifers under drought: Canopy density affects water stress experienced by saplings

NASA Astrophysics Data System (ADS)

Oberhuber, Walter

2017-04-01

Size-mediated climate sensitivity of trees will affect forest structure, composition and productivity under a warmer and drier climate. Therefore, the influence of tree size (saplings vs. mature trees) and site conditions on radial stem growth and stem water deficit of Picea abies (dry-mesic site; canopy cover [CC]: 70 %) and Pinus sylvestris (xeric site; CC: 30 %) were evaluated in a drought-prone inner Alpine environment (c. 750 m a.s.l.). Stem radius variations (SRVs) of saplings (mean stem diameter [SDM]: 2.3 cm) and co-occurring mature trees (SDM: 24 cm) were continuously recorded by dendrometers during two years (n = 6 - 8 individuals per species and size class). Growth-detrended SRVs (SSRV), which represent reversible shrinkage and swelling of tissues outside the cambium and contribute most to stem water storage capacity, were calculated by removing the Gompertz-modeled daily growth from SRVs. Dendrometer records revealed that irrespective of tree size, radial growth in Pinus sylvestris occurred in April-May, whereas the main growing period of Picea abies was April-June and May-June in saplings and mature trees, respectively. Growth-detrended SRVs were approximately twice as large in Pinus sylvestris compared to Picea abies indicating more intense exploitation of stem water reserves at the xeric site. Linear relationships between SSRVs of mature trees vs. saplings and climate-SSRV relationships revealed greater use of stem water reserves by mature Picea abies compared to saplings. This suggests that the strikingly depressed radial growth of Picea abies saplings was primarily caused by reduced carbon availability beneath the dense canopy. In contrast, a tree size effect on the seasonal dynamics of radial growth, stem water deficit and climate-SSRV relationships was mostly lacking in Pinus sylvestris, indicating comparable water status in mature trees and saplings under an open canopy. Results of this study provide evidence that development of a buffered microclimate under dense canopy mitigates water stress experienced by saplings and favors tree recruitment at drought-prone sites. This study was funded by the Austrian Science Fund (FWF): P25643-B16 "Carbon allocation and growth of Scots pine".

Notch3 is required for arterial identity and maturation of vascular smooth muscle cells

PubMed Central

Domenga, Valérie; Fardoux, Peggy; Lacombe, Pierre; Monet, Marie; Maciazek, Jacqueline; Krebs, Luke T.; Klonjkowski, Bernard; Berrou, Eliane; Mericskay, Matthias; Li, Zhen; Tournier-Lasserve, Elisabeth; Gridley, Thomas; Joutel, Anne

2004-01-01

Formation of a fully functional artery proceeds through a multistep process. Here we show that Notch3 is required to generate functional arteries in mice by regulating arterial differentiation and maturation of vascular smooth muscle cells (vSMC). In adult Notch3–/– mice distal arteries exhibit structural defects and arterial myogenic responses are defective. The postnatal maturation stage of vSMC is deficient in Notch3–/– mice. We further show that Notch3 is required for arterial specification of vSMC but not of endothelial cells. Our data reveal Notch3 to be the first cell-autonomous regulator of arterial differentiation and maturation of vSMC. PMID:15545631

Characterising the proximal patellar tendon attachment and its relationship to skeletal maturity in adolescent ballet dancers

PubMed Central

Rudavsky, Aliza; Cook, Jillianne; Magnusson, Stig Peter; Kjaer, Michael; Docking, Sean

2017-01-01

Summary Background It is unknown how and when the proximal attachment of the patellar tendon matures; puberty may be key in ensuring normal tendon formation. The aim of this study was to investigate the features of the proximal patellar tendon attachment at different stages of skeletal maturity, to help gain an understanding of how and when the tendon attachment matures. Methods Sixty adolescent elite ballet students (ages 11–18) and eight mature adults participated. Peak height velocity (PHV) estimated skeletal maturity. Ultrasound tissue characterisation (UTC) scan was taken of the left knee and analysed for stability of echopattern. An image-based grading scale for greyscale ultrasound was developed to describe the tendon appearance. Anterior-posterior thickness was measured at the inferior pole of the patella, 1 and 2 centimetres distally. Outcomes were compared with skeletal maturity. Results Mid-portion patellar tendon thickness increased with skeletal maturity (p=0.001 at 1 cm and p=0.007 at 2 cm). There was more variance in structural appearance (greyscale classification and UTC echopattern) in pre and peri-PHV participants. Tendon attachment one-year post PHV appeared similar to mature tendons. Conclusions Early adolescence was associated with highly variable tendon appearance, whereas the tendon appeared mature after PHV. Adolescence may be a critical time for the formation of normal tendon attachment. Level of evidence IIb individual cohort study. PMID:29264342

Spiritual Maturation and Religious Behaviors in Christian University Students

ERIC Educational Resources Information Center

Welch, Ronald D.; Mellberg, Kimberlee

2008-01-01

Spiritual maturation processes of internalization and questing were assessed at a Christian university to determine their relationship to year in school and certain religious behaviors. This was a first step toward the development of a new model of Christian higher education that will intentionally facilitate spiritual maturation. A group of 179…

An Analysis of Career Maturity among Korean Youths Using Latent Growth Modeling

ERIC Educational Resources Information Center

Bae, Sung-Man

2017-01-01

This study examined the developmental trajectories of career maturity among Korean youths between late adolescence and mid-20s, and explored how career-counseling experiences, academic achievement, household income, parental involvement, and gender affected their career maturity. We used the 2,362 Youth Panel data collected between 2008-2014 by…

Induced maturation of human immunodeficiency virus.

PubMed

Mattei, Simone; Anders, Maria; Konvalinka, Jan; Kräusslich, Hans-Georg; Briggs, John A G; Müller, Barbara

2014-12-01

HIV-1 assembles at the plasma membrane of virus-producing cells as an immature, noninfectious particle. Processing of the Gag and Gag-Pol polyproteins by the viral protease (PR) activates the viral enzymes and results in dramatic structural rearrangements within the virion--termed maturation--that are a prerequisite for infectivity. Despite its fundamental importance for viral replication, little is currently known about the regulation of proteolysis and about the dynamics and structural intermediates of maturation. This is due mainly to the fact that HIV-1 release and maturation occur asynchronously both at the level of individual cells and at the level of particle release from a single cell. Here, we report a method to synchronize HIV-1 proteolysis in vitro based on protease inhibitor (PI) washout from purified immature virions, thereby temporally uncoupling virus assembly and maturation. Drug washout resulted in the induction of proteolysis with cleavage efficiencies correlating with the off-rate of the respective PR-PI complex. Proteolysis of Gag was nearly complete and yielded the correct products with an optimal half-life (t(1/2)) of ~5 h, but viral infectivity was not recovered. Failure to gain infectivity following PI washout may be explained by the observed formation of aberrant viral capsids and/or by pronounced defects in processing of the reverse transcriptase (RT) heterodimer associated with a lack of RT activity. Based on our results, we hypothesize that both the polyprotein processing dynamics and the tight temporal coupling of immature particle assembly and PR activation are essential for correct polyprotein processing and morphological maturation and thus for HIV-1 infectivity. Cleavage of the Gag and Gag-Pol HIV-1 polyproteins into their functional subunits by the viral protease activates the viral enzymes and causes major structural rearrangements essential for HIV-1 infectivity. This proteolytic maturation occurs concomitant with virus release, and investigation of its dynamics is hampered by the fact that virus populations in tissue culture contain particles at all stages of assembly and maturation. Here, we developed an inhibitor washout strategy to synchronize activation of protease in wild-type virus. We demonstrated that nearly complete Gag processing and resolution of the immature virus architecture are accomplished under optimized conditions. Nevertheless, most of the resulting particles displayed irregular morphologies, Gag-Pol processing was not faithfully reconstituted, and infectivity was not recovered. These data show that HIV-1 maturation is sensitive to the dynamics of processing and also that a tight temporal link between virus assembly and PR activation is required for correct polyprotein processing. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Fracturing alliance allows economical production of massive diatomite oil reserves: A case study

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

Klins, M.A.; Stewart, D.W.; Pferdehirt, D.J.

1996-01-01

As North American oilfield operations mature, there is a perceptible loosening of the autocratic ties between oil companies and contractors. They are being replaced by alliances or partnerships designed to minimize cost while improving profitability of the companies involved. This paper evaluates a mature alliance, its implementation, structure, and results.

Social Justice and Faith Maturity: Exploring Whether Religious Beliefs Impact Civic Engagement

ERIC Educational Resources Information Center

Kozlowski, Christine; Ferrari, Joseph R.; Odahl, Charlynn

2014-01-01

The current study compared perceptions by college students (n = 304; M age=19.75 years old) enrolled at an urban and diverse Roman Catholic university on self-report measures of faith/belief structures, social justice, and community service attitudes. Survey results indicated that both horizontal and vertical faith maturity perceptions…

Effect of sexual maturation on thermal stability, viscoelastic properties, and texture of rainbow trout, Oncorhynchus mykiss, fillets

USDA-ARS?s Scientific Manuscript database

The nutrient and energy demand of sexual maturation in many fish cultivars causes structural change to key contractile proteins and thereby, affects fillet firmness. Thermal denaturation and viscoelastic properties of white muscle from diploid (2N; fertile) and triploid (3N; sterile) female rainbow...

Characteristics of gaps and natural regeneration in mature longleaf pine flatwoods ecosystems

Treesearch

Jennifer L. Gagnon; Eric J. Jokela; W.K. Moser; Dudley A. Huber

2004-01-01

Developing uneven-aged structure in mature stands of longleaf pine requires scientifically based silvicultural systems that are reliable, productive and sustainable. Understanding seedling responses to varying levels of site resource availability within forest gaps is essential for effectively converting even-aged stands to uneven-aged stands. A project was initiated...

Body Structure and Physical Self-Concept in Early Adolescence

ERIC Educational Resources Information Center

Zsakai, Annamaria; Karkus, Zsolt; Utczas, Katinka; Bodzsar, Eva B.

2017-01-01

In adolescence, the complexity of human ontogenesis embraces biological growth and maturation as well as mental, affective, and cognitive progress, and adaptation to the requirements of society. To accept our morphological constellation as part of our gender may prove a problem even to a child of average rate of maturation. The main purposes of…

Organizational Resilience and Culture a Model for Information Technology Service Management (ITSM)

ERIC Educational Resources Information Center

Granito, Francis A.

2011-01-01

Organizational change and organizational culture have been studied and written about by many authors, most notably by Edgar Schein (1990, 1992), and are named as critical components of organizational maturity through such industry standards as The Capability Maturity Model Integration (CMMI), Control Objectives for Information and Related…

Re-refinement of the spliceosomal U4 snRNP core-domain structure

PubMed Central

Li, Jade; Leung, Adelaine K.; Kondo, Yasushi; Oubridge, Chris; Nagai, Kiyoshi

2016-01-01

The core domain of small nuclear ribonucleoprotein (snRNP), comprised of a ring of seven paralogous proteins bound around a single-stranded RNA sequence, functions as the assembly nucleus in the maturation of U1, U2, U4 and U5 spliceosomal snRNPs. The structure of the human U4 snRNP core domain was initially solved at 3.6 Å resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed by density modification using untwinned data recently led to a structure of the minimal U1 snRNP at 3.3 Å resolution. With the latter structure providing a search model for molecular replacement, the U4 core-domain structure has now been re-refined. The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF–SmE–SmG–SmD3–SmB–SmD1–SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces G. The progression from the initial to the re-refined structure exemplifies a tortuous route to accuracy: where well diffracting crystals of complex assemblies are initially unavailable, the early model errors are rectified by exploiting preliminary interpretations in further experiments involving homologous structures. New insights are obtained from the more accurate model. PMID:26894541

Small-Maturity Asymptotics for the At-The-Money Implied Volatility Slope in Lévy Models

PubMed Central

Gerhold, Stefan; Gülüm, I. Cetin; Pinter, Arpad

2016-01-01

ABSTRACT We consider the at-the-money (ATM) strike derivative of implied volatility as the maturity tends to zero. Our main results quantify the behaviour of the slope for infinite activity exponential Lévy models including a Brownian component. As auxiliary results, we obtain asymptotic expansions of short maturity ATM digital call options, using Mellin transform asymptotics. Finally, we discuss when the ATM slope is consistent with the steepness of the smile wings, as given by Lee’s moment formula. PMID:27660537

Statistical properties of derivatives: A journey in term structures

NASA Astrophysics Data System (ADS)

Lautier, Delphine; Raynaud, Franck

2011-06-01

This article presents an empirical study of 13 derivative markets for commodities and financial assets. The study goes beyond statistical analysis by including the maturity as a variable for the daily returns of futures contracts from 1998 to 2010, and for delivery dates up to 120 months. We observe that the mean and variance of the commodities follow a scaling behavior in the maturity dimension with an exponent characteristic of the Samuelson effect. The comparison between the tails of the probability distribution according to the expiration dates shows that there is a segmentation in the fat tails exponent term structure above the Lévy stable region. Finally, we compute the average tail exponent for each maturity, and we observe two regimes of extreme events for derivative markets, reminiscent of a phase diagram with a sharp transition at the 18th delivery month.

Modeling forest disturbance and recovery in secondary subtropical dry forests of Puerto Rico

NASA Astrophysics Data System (ADS)

Holm, J. A.; Shugart, H. H., Jr.; Van Bloem, S. J.

2015-12-01

Because of human pressures, the need to understand and predict the long-term dynamics of subtropical dry forests is urgent. Through modifications to the ZELIG vegetation demographic model, including the development of species- and site-specific parameters and internal modifications, the capability to predict forest change within the Guanica State Forest in Puerto Rico can now be accomplished. One objective was to test the capability of this new model (i.e. ZELIG-TROP) to predict successional patterns of secondary forests across a gradient of abandoned fields currently being reclaimed as forests. Model simulations found that abandoned fields that are on degraded lands have a delayed response to fully recover and reach a mature forest status during the simulated time period; 200 years. The forest recovery trends matched predictions published in other studies, such that attributes involving early resource acquisition (i.e. canopy height, canopy coverage, density) were the fastest to recover, but attributes used for structural development (i.e. biomass, basal area) were relatively slow in recovery. Biomass and basal area, two attributes that tend to increase during later successional stages, are significantly lower during the first 80-100 years of recovery compared to a mature forest, suggesting that the time scale of resilience in subtropical dry forests needs to be partially redefined. A second objective was to investigate the long and short-term effects of increasing hurricane disturbances on vegetation structure and dynamics, due to hurricanes playing an important role in maintaining dry forest structure in Puerto Rico. Hurricane disturbance simulations within ZELIG-TROP predicted that increasing hurricane intensity (i.e. up to 100% increase) did not lead to a large shift in long-term AGB or NPP. However, increased hurricane frequency did lead to a 5-40% decrease in AGB, and 32-50% increase in NPP, depending on the treatment. In addition, the modeling approach used here was able to track changes in litterfall, coarse woody debris, and other forest carbon components under various hurricane regimes, a critical step for understanding the future state of subtropical dry forests.

Control of complex networks requires both structure and dynamics

NASA Astrophysics Data System (ADS)

Gates, Alexander J.; Rocha, Luis M.

2016-04-01

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.

Burial history, thermal history and hydrocarbon generation modelling of the Jurassic source rocks in the basement of the Polish Carpathian Foredeep and Outer Carpathians (SE Poland)

NASA Astrophysics Data System (ADS)

Kosakowski, Paweł; Wróbel, Magdalena

2012-08-01

Burial history, thermal maturity, and timing of hydrocarbon generation were modelled for the Jurassic source rocks in the basement of the Carpathian Foredeep and marginal part of the Outer Carpathians. The area of investigation was bounded to the west by Kraków, to the east by Rzeszów. The modelling was carried out in profiles of wells: Będzienica 2, Dębica 10K, Góra Ropczycka 1K, Goleszów 5, Nawsie 1, Pławowice E1 and Pilzno 40. The organic matter, containing gas-prone Type III kerogen with an admixture of Type II kerogen, is immature or at most, early mature to 0.7 % in the vitrinite reflectance scale. The highest thermal maturity is recorded in the south-eastern part of the study area, where the Jurassic strata are buried deeper. The thermal modelling showed that the obtained organic matter maturity in the initial phase of the "oil window" is connected with the stage of the Carpathian overthrusting. The numerical modelling indicated that the onset of hydrocarbon generation from the Middle Jurassic source rocks was also connected with the Carpathian thrust belt. The peak of hydrocarbon generation took place in the orogenic stage of the overthrusting. The amount of generated hydrocarbons is generally small, which is a consequence of the low maturity and low transformation degree of kerogen. The generated hydrocarbons were not expelled from their source rock. An analysis of maturity distribution and transformation degree of the Jurassic organic matter shows that the best conditions for hydrocarbon generation occurred most probably in areas deeply buried under the Outer Carpathians. It is most probable that the "generation kitchen" should be searched for there.

Comparative burial and thermal history of lower Upper Cretaceous strata, Powder River basin, Wyoming

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

Nuccio, V.F.

1989-03-01

Burial histories were reconstructed for three localities in the Powder River basin (PRB), Wyoming. Thermal maturity of lower Upper Cretaceous source rocks was determined by vitrinite reflectance (R/sub m/) and time-temperature index (TTI) modeling, producing independent estimates for timing of the oil window (0.55-1.35% R/sub m/). In the northwestern PRB, lower Upper Cretaceous rocks were buried to about 12,500 ft and achieved a thermal maturity of 0.50% to 0.56% at maximum burial, 10 Ma, based on measured R/sub m/. TTI modeling suggests a slightly higher thermal maturity, with an R/sub m/ equivalent of approximately 0.75%, placing the source rocks atmore » the beginning of the oil window 30 Ma. In the southwestern PRB, lower Upper Cretaceous rocks have been buried to about 15,000 ft and achieved thermal maturities between 0.66% and 0.75% about 10 Ma based on measured R/sub m/; therefore, petroleum generation may have begun slightly earlier. TTI modeling estimates an R/sub m/ equivalent of 1.10%, placing the beginning of the oil window at 45 Ma. In the northeastern PRB, lower Upper Cretaceous rocks have been buried only to approximately 5500 ft. Measured R/sub m/ and TTI modeling indicate a thermal maturity for lower Upper Cretaceous rocks between 0.45% and 0.50% R/sub m/, too low for petroleum generation. The higher R/sub m/ values determined by the TTI models may be due to overestimation of maximum burial depth and/or paleogeothermal gradients. The two independent maturity indicators do, however, constrain fairly narrowly the onset of petroleum generation.« less

Enzymatic and Structural Characterization of the Major Endopeptidase in the Venus Flytrap Digestion Fluid*

PubMed Central

Risør, Michael W.; Thomsen, Line R.; Sanggaard, Kristian W.; Nielsen, Tania A.; Thøgersen, Ida B.; Lukassen, Marie V.; Rossen, Litten; Garcia-Ferrer, Irene; Guevara, Tibisay; Scavenius, Carsten; Meinjohanns, Ernst; Gomis-Rüth, F. Xavier; Enghild, Jan J.

2016-01-01

Carnivorous plants primarily use aspartic proteases during digestion of captured prey. In contrast, the major endopeptidases in the digestive fluid of the Venus flytrap (Dionaea muscipula) are cysteine proteases (dionain-1 to -4). Here, we present the crystal structure of mature dionain-1 in covalent complex with inhibitor E-64 at 1.5 Å resolution. The enzyme exhibits an overall protein fold reminiscent of other plant cysteine proteases. The inactive glycosylated pro-form undergoes autoprocessing and self-activation, optimally at the physiologically relevant pH value of 3.6, at which the protective effect of the pro-domain is lost. The mature enzyme was able to efficiently degrade a Drosophila fly protein extract at pH 4 showing high activity against the abundant Lys- and Arg-rich protein, myosin. The substrate specificity of dionain-1 was largely similar to that of papain with a preference for hydrophobic and aliphatic residues in subsite S2 and for positively charged residues in S1. A tentative structure of the pro-domain was obtained by homology modeling and suggested that a pro-peptide Lys residue intrudes into the S2 pocket, which is more spacious than in papain. This study provides the first analysis of a cysteine protease from the digestive fluid of a carnivorous plant and confirms the close relationship between carnivorous action and plant defense mechanisms. PMID:26627834

Linear and curvilinear correlations of brain gray matter volume and density with age using voxel-based morphometry with the Akaike information criterion in 291 healthy children.

PubMed

Taki, Yasuyuki; Hashizume, Hiroshi; Thyreau, Benjamin; Sassa, Yuko; Takeuchi, Hikaru; Wu, Kai; Kotozaki, Yuka; Nouchi, Rui; Asano, Michiko; Asano, Kohei; Fukuda, Hiroshi; Kawashima, Ryuta

2013-08-01

We examined linear and curvilinear correlations of gray matter volume and density in cortical and subcortical gray matter with age using magnetic resonance images (MRI) in a large number of healthy children. We applied voxel-based morphometry (VBM) and region-of-interest (ROI) analyses with the Akaike information criterion (AIC), which was used to determine the best-fit model by selecting which predictor terms should be included. We collected data on brain structural MRI in 291 healthy children aged 5-18 years. Structural MRI data were segmented and normalized using a custom template by applying the diffeomorphic anatomical registration using exponentiated lie algebra (DARTEL) procedure. Next, we analyzed the correlations of gray matter volume and density with age in VBM with AIC by estimating linear, quadratic, and cubic polynomial functions. Several regions such as the prefrontal cortex, the precentral gyrus, and cerebellum showed significant linear or curvilinear correlations between gray matter volume and age on an increasing trajectory, and between gray matter density and age on a decreasing trajectory in VBM and ROI analyses with AIC. Because the trajectory of gray matter volume and density with age suggests the progress of brain maturation, our results may contribute to clarifying brain maturation in healthy children from the viewpoint of brain structure. Copyright © 2012 Wiley Periodicals, Inc.

Optimization of Cost of Building with Concrete Slabs Based on the Maturity Method

NASA Astrophysics Data System (ADS)

Skibicki, Szymon

2017-10-01

The maturity method is a well-known technique for determination of mechanical properties of the concrete (e.g. compressive strength) based on the development of temperature during hardening. The compressive strength of concrete can be used to determine necessary striking time of the formwork. Use of this method for this purpose is economically effective and provides necessary safety measures. This method is used in many construction sites. Time of formwork striking depends on many factors e. g. class of concrete, grade of cement, type of cement, temperature, size of the element and air humidity. The existing technical Standards and scientific research on the striking of formwork present different estimated for the striking time. Striking time for the main structural elements ranges from 14 to 21 days. For structura elements such as slabs or beams with a span of more than 6 m need to reach the minimum of 70-85% of their designed strength to remove the formwork depend on the Standards. During the construction of the buildings in summer concrete acquires the required strength for striking of the formwork faster due to the higher ambient temperature. Knowing the maturity method, we are able to estimate the compressive strength of concrete. If concrete have the required strength, the striking time can be shortened. This allows to reduce the overall costs of construction. The more concrete works are done during the construction phase the bigger the generated savings. In this article formwork striking time for concrete slabs in building based on maturity method was determined. The structure was subjected to 10 different simulated weather conditions typical for the Central and Western Europe that varied by localization of the construction. Based on simulated weather conditions the temperature in structural elements was established. The results allowed to determine the formwork striking time using the maturity method. Presented analysis shows that use of the maturity method on construction site can result in lower overall costs due to shorter time of constructing.

The evolving market structures of gambling: case studies modelling the socioeconomic assignment of gaming machines in Melbourne and Sydney, Australia.

PubMed

Marshall, David C; Baker, Robert G V

2002-01-01

The expansion of gambling industries worldwide is intertwined with the growing government dependence on gambling revenue for fiscal assignments. In Australia, electronic gaming machines (EGMs) have dominated recent gambling industry growth. As EGMs have proliferated, growing recognition has emerged that EGM distribution closely reflects levels of socioeconomic disadvantage. More machines are located in less advantaged regions. This paper analyses time-series socioeconomic distributions of EGMs in Melbourne, Australia, an immature EGM market, and then compares the findings with the mature market in Sydney. Similar findings in both cities suggest that market assignment of EGMs transcends differences in historical and legislative environments. This indicates that similar underlying structures are evident in both markets. Modelling the spatial structures of gambling markets provides an opportunity to identify regions most at risk of gambling related problems. Subsequently, policies can be formulated which ensure fiscal revenue from gambling can be better targeted towards regions likely to be most afflicted by excessive gambling-related problems.

Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

PubMed

Calderon-Gierszal, Esther L; Prins, Gail S

2015-01-01

Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC) into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates long-term structural and functional outcomes in a mouse model.

PubMed

Tremblay, Sophie; Pai, Alex; Richter, Lindsay; Vafaei, Rod; Potluri, Praneetha; Ellegood, Jacob; Lerch, Jason P; Goldowitz, Daniel

2017-11-01

Despite the increased recognition of cerebellar injury in survivors of preterm birth, the neurodevelopmental consequences of isolated cerebellar injury have been largely unexplored and our current understanding of the functional deficits requires further attention in order to translate knowledge to best practices. Preterm infants are exposed to multiple stressors during their postnatal development including perinatal cerebellar haemorrhage (CBH) and postnatal infection, two major risk factors for neurodevelopmental impairments. We developed a translational mouse model of CBH and/or inflammation to measure the short- and long-term outcomes in cerebellar structure and function. Mice exposed to early combined insults of CBH and early inflammatory state (EIS) have a delay in grasping acquisition, neonatal motor deficits and deficient long-term memory. CBH combined with late inflammatory state (LIS) does not induce neonatal motor problems but leads to poor fine motor function and long-term memory deficits at adulthood. Early combined insults result in poor cerebellar growth from postnatal day 15 until adulthood shown by MRI, which are reflected in diminished volumes of cerebellar structures. There are also decreases in volumes of gray matter and hippocampus. Cerebellar microgliosis appears 24h after the combined insults and persists until postnatal day 15 in the cerebellar molecular layer and cerebellar nuclei in association with a disrupted patterning of myelin deposition, a delay of oligodendrocyte maturation and reduced white matter cerebellar volume. Together, these findings reveal poor outcomes in developing brains exposed to combined cerebellar perinatal insults in association with cerebellar hypoplasia, persistence of microgliosis and alterations of cerebellar white matter maturation and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural insights into SAM domain-mediated tankyrase oligomerization.

PubMed

DaRosa, Paul A; Ovchinnikov, Sergey; Xu, Wenqing; Klevit, Rachel E

2016-09-01

Tankyrase 1 (TNKS1; a.k.a. ARTD5) and tankyrase 2 (TNKS2; a.k.a ARTD6) are highly homologous poly(ADP-ribose) polymerases (PARPs) that function in a wide variety of cellular processes including Wnt signaling, Src signaling, Akt signaling, Glut4 vesicle translocation, telomere length regulation, and centriole and spindle pole maturation. Tankyrase proteins include a sterile alpha motif (SAM) domain that undergoes oligomerization in vitro and in vivo. However, the SAM domains of TNKS1 and TNKS2 have not been structurally characterized and the mode of oligomerization is not yet defined. Here we model the SAM domain-mediated oligomerization of tankyrase. The structural model, supported by mutagenesis and NMR analysis, demonstrates a helical, homotypic head-to-tail polymer that facilitates TNKS self-association. Furthermore, we show that TNKS1 and TNKS2 can form (TNKS1 SAM-TNKS2 SAM) hetero-oligomeric structures mediated by their SAM domains. Though wild-type tankyrase proteins have very low solubility, model-based mutations of the SAM oligomerization interface residues allowed us to obtain soluble TNKS proteins. These structural insights will be invaluable for the functional and biophysical characterization of TNKS1/2, including the role of TNKS oligomerization in protein poly(ADP-ribosyl)ation (PARylation) and PARylation-dependent ubiquitylation. © 2016 The Protein Society.

Climbing the ladder: capability maturity model integration level 3

NASA Astrophysics Data System (ADS)

Day, Bryce; Lutteroth, Christof

2011-02-01

This article details the attempt to form a complete workflow model for an information and communication technologies (ICT) company in order to achieve a capability maturity model integration (CMMI) maturity rating of 3. During this project, business processes across the company's core and auxiliary sectors were documented and extended using modern enterprise modelling tools and a The Open Group Architectural Framework (TOGAF) methodology. Different challenges were encountered with regard to process customisation and tool support for enterprise modelling. In particular, there were problems with the reuse of process models, the integration of different project management methodologies and the integration of the Rational Unified Process development process framework that had to be solved. We report on these challenges and the perceived effects of the project on the company. Finally, we point out research directions that could help to improve the situation in the future.

Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae

PubMed Central

Schmidt, Christian; Berninghausen, Otto; Becker, Thomas

2017-01-01

Mechanistic understanding of eukaryotic ribosome formation requires a detailed structural knowledge of the numerous assembly intermediates, generated along a complex pathway. Here, we present the structure of a late pre-40S particle at 3.6 Å resolution, revealing in molecular detail how assembly factors regulate the timely folding of pre-18S rRNA. The structure shows that, rather than sterically blocking 40S translational active sites, the associated assembly factors Tsr1, Enp1, Rio2 and Pno1 collectively preclude their final maturation, thereby preventing untimely tRNA and mRNA binding and error prone translation. Moreover, the structure explains how Pno1 coordinates the 3’end cleavage of the 18S rRNA by Nob1 and how the late factor’s removal in the cytoplasm ensures the structural integrity of the maturing 40S subunit. PMID:29155690

Microporoelastic Modeling of Organic-Rich Shales

NASA Astrophysics Data System (ADS)

Khosh Sokhan Monfared, S.; Abedi, S.; Ulm, F. J.

2014-12-01

Organic-rich shale is an extremely complex, naturally occurring geo-composite. The heterogeneous nature of organic-rich shale and its anisotropic behavior pose grand challenges for characterization, modeling and engineering design The intricacy of organic-rich shale, in the context of its mechanical and poromechanical properties, originates in the presence of organic/inorganic constituents and their interfaces as well as the occurrence of porosity and elastic anisotropy, at multiple length scales. To capture the contributing mechanisms, of 1st order, responsible for organic-rich shale complex behavior, we introduce an original approach for micromechanical modeling of organic-rich shales which accounts for the effect of maturity of organics on the overall elasticity through morphology considerations. This morphology contribution is captured by means of an effective media theory that bridges the gap between immature and mature systems through the choice of system's microtexture; namely a matrix-inclusion morphology (Mori-Tanaka) for immature systems and a polycrystal/granular morphology for mature systems. Also, we show that interfaces play a role on the effective elasticity of mature, organic-rich shales. The models are calibrated by means of ultrasonic pulse velocity measurements of elastic properties and validated by means of nanoindentation results. Sensitivity analyses using Spearman's Partial Rank Correlation Coefficient shows the importance of porosity and Total Organic Carbon (TOC) as key input parameters for accurate model predictions. These modeling developments pave the way to reach a "unique" set of clay properties and highlight the importance of depositional environment, burial and diagenetic processes on overall mechanical and poromechanical behavior of organic-rich shale. These developments also emphasize the importance of understanding and modeling clay elasticity and organic maturity on the overall rock behavior which is of critical importance for a practical rock physics model that accounts for time dependent phenomena which can be employed for seismic inversion.

A framework to optimize the restoration and retention of large mature forest tracts in managed boreal landscapes.

PubMed

Bouchard, Mathieu; Garet, Jérôme

The decreasing abundance of mature forests and their fragmentation have been identified as major threats for the preservation of biodiversity in managed landscapes. In this study, we developed a multi-level framework to coordinate forest harvestings so as to optimize the retention or restoration of large mature forest tracts in managed forests. We used mixed-integer programming for this optimization, and integrated realistic management assumptions regarding stand yield and operational harvest constraints. The model was parameterized for eastern Canadian boreal forests, where clear-cutting is the main silvicultural system, and is used to examine two hypotheses. First, we tested if mature forest tract targets had more negative impacts on wood supplies when implemented in landscapes that are very different from targeted conditions. Second, we tested the hypothesis that using more partial cuts can be useful to attenuate the negative impacts of mature forest targets on wood supplies. The results indicate that without the integration of an explicit mature forest tract target, the optimization leads to relatively high fragmentation levels. Forcing the retention or restoration of large mature forest tracts on 40% of the landscapes had negative impacts on wood supplies in all types of landscapes, but these impacts were less important in landscapes that were initially fragmented. This counter-intuitive result is explained by the presence in the models of an operational constraint that forbids diffuse patterns of harvestings, which are more costly. Once this constraint is applied, the residual impact of the mature forest tract target is low. The results also indicate that partial cuts are of very limited use to attenuate the impacts of mature forest tract targets on wood supplies in highly fragmented landscapes. Partial cuts are somewhat more useful in landscapes that are less fragmented, but they have to be well coordinated with clearcut schedules in order to contribute efficiently to conservation objectives. This modeling framework could easily be adapted and parameterized to test hypotheses or to optimize restoration schedules in landscapes where issues such as forest fragmentation and the abundance of mature or old-growth forests are a concern.

Risk Quantification of Systems Engineering Documents Improves Probability of DOD Project Success

DTIC Science & Technology

2009-09-01

comprehensive risk model for DoD milestone review documentation as well as recommended changes to the Capability Maturity Model Integration ( CMMI ) Project...Milestone Documentation, Project Planning, Rational Frame, Political Frame, CMMI Project Planning Process Area, CMMI Risk Management Process Area...well as recommended changes to the Capability Maturity Model Integration ( CMMI ) Project Planning and Risk Management process areas. The intent is to

Random regression models on Legendre polynomials to estimate genetic parameters for weights from birth to adult age in Canchim cattle.

PubMed

Baldi, F; Albuquerque, L G; Alencar, M M

2010-08-01

The objective of this work was to estimate covariance functions for direct and maternal genetic effects, animal and maternal permanent environmental effects, and subsequently, to derive relevant genetic parameters for growth traits in Canchim cattle. Data comprised 49,011 weight records on 2435 females from birth to adult age. The model of analysis included fixed effects of contemporary groups (year and month of birth and at weighing) and age of dam as quadratic covariable. Mean trends were taken into account by a cubic regression on orthogonal polynomials of animal age. Residual variances were allowed to vary and were modelled by a step function with 1, 4 or 11 classes based on animal's age. The model fitting four classes of residual variances was the best. A total of 12 random regression models from second to seventh order were used to model direct and maternal genetic effects, animal and maternal permanent environmental effects. The model with direct and maternal genetic effects, animal and maternal permanent environmental effects fitted by quadric, cubic, quintic and linear Legendre polynomials, respectively, was the most adequate to describe the covariance structure of the data. Estimates of direct and maternal heritability obtained by multi-trait (seven traits) and random regression models were very similar. Selection for higher weight at any age, especially after weaning, will produce an increase in mature cow weight. The possibility to modify the growth curve in Canchim cattle to obtain animals with rapid growth at early ages and moderate to low mature cow weight is limited.

Cervical Vertebral Body's Volume as a New Parameter for Predicting the Skeletal Maturation Stages.

PubMed

Choi, Youn-Kyung; Kim, Jinmi; Yamaguchi, Tetsutaro; Maki, Koutaro; Ko, Ching-Chang; Kim, Yong-Il

2016-01-01

This study aimed to determine the correlation between the volumetric parameters derived from the images of the second, third, and fourth cervical vertebrae by using cone beam computed tomography with skeletal maturation stages and to propose a new formula for predicting skeletal maturation by using regression analysis. We obtained the estimation of skeletal maturation levels from hand-wrist radiographs and volume parameters derived from the second, third, and fourth cervical vertebrae bodies from 102 Japanese patients (54 women and 48 men, 5-18 years of age). We performed Pearson's correlation coefficient analysis and simple regression analysis. All volume parameters derived from the second, third, and fourth cervical vertebrae exhibited statistically significant correlations (P < 0.05). The simple regression model with the greatest R-square indicated the fourth-cervical-vertebra volume as an independent variable with a variance inflation factor less than ten. The explanation power was 81.76%. Volumetric parameters of cervical vertebrae using cone beam computed tomography are useful in regression models. The derived regression model has the potential for clinical application as it enables a simple and quantitative analysis to evaluate skeletal maturation level.

Cervical Vertebral Body's Volume as a New Parameter for Predicting the Skeletal Maturation Stages

PubMed Central

Choi, Youn-Kyung; Kim, Jinmi; Maki, Koutaro; Ko, Ching-Chang

2016-01-01

This study aimed to determine the correlation between the volumetric parameters derived from the images of the second, third, and fourth cervical vertebrae by using cone beam computed tomography with skeletal maturation stages and to propose a new formula for predicting skeletal maturation by using regression analysis. We obtained the estimation of skeletal maturation levels from hand-wrist radiographs and volume parameters derived from the second, third, and fourth cervical vertebrae bodies from 102 Japanese patients (54 women and 48 men, 5–18 years of age). We performed Pearson's correlation coefficient analysis and simple regression analysis. All volume parameters derived from the second, third, and fourth cervical vertebrae exhibited statistically significant correlations (P < 0.05). The simple regression model with the greatest R-square indicated the fourth-cervical-vertebra volume as an independent variable with a variance inflation factor less than ten. The explanation power was 81.76%. Volumetric parameters of cervical vertebrae using cone beam computed tomography are useful in regression models. The derived regression model has the potential for clinical application as it enables a simple and quantitative analysis to evaluate skeletal maturation level. PMID:27340668

Does the timing of attainment of maturity influence sexual size dimorphism and adult sex ratio in turtles?

USGS Publications Warehouse

Lovich, Jeffrey E.; Gibbons, J. Whitfield; Agha, Mickey

2014-01-01

The attainment of sexual maturity has been shown to affect measures of sexual size dimorphism (SSD) and adult sex ratios in several groups of vertebrates. Using data for turtles, we tested the model that sex ratios are expected to be male-biased when females are larger than males and female-biased when males are larger than females because of the relationship of each with the attainment of maturity. Our model is based on the premise that the earlier-maturing sex remains smaller, on average throughout life, and predominates numerically unless the sexes are strongly affected by differential mortality, differential emigration, and immigration, or biased primary sex ratios. Based on data for 24 species in seven families, SSD and sex ratios were significantly negatively correlated for most analyses, even after the effect of phylogenetic bias was removed. The analyses provide support for the model that SSD and adult sex ratios are correlated in turtles as a result of simultaneous correlation of each with sexual differences in attainment of maturity (bimaturism). Environmental sex determination provides a possible mechanism for the phenomenon in turtles and some other organisms.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Human fetal lung morphometry at autopsy with new modeling to quantitate structural maturity.

PubMed

Lipsett, Jill

2017-06-01

To demonstrate a simplified morphometric procedure, including a new model for acinar structural maturity, applicable to autopsy fetal lung and present reference values for these parameters. Cases with autopsy consent for research were studied. To simplify analysis only critical morphometric parameters were measured to allow calculation of gas-exchange surface area. A total of 58 fetuses, 16-40 weeks were included. Subjects were rejected with any condition predisposing to pulmonary hypo/hyperplasia, significant maceration, or if lung weight/bodyweight or microscopy identified pulmonary hypoplasia or lung growth disorders. Lungs were inflation fixed, weights and volumes determined, sampled, then returned to the body. Volume densities (V V ) of parenchyma/non-parenchyma and air-space/gas-exchange tissue, gas-exchange surface density (S V ), and total surface area (SA) were determined. The number, mean radius, and septal thickness of modeled airspace-spheres were calculated. Equations were generated for each parameter function of gestation and bodyweight. From 16 to 40-week weights and volumes increased as power functions from ∼4 g/mL to ∼90 g/mL. Parenchyma/non-parenchyma changed little-75:25 (16 weeks) to 71:29 (term). Parenchyma was 10% airspace:90% tissue early and 50:50 by term. Gas-exchange S V increased from 175 to 450 cm 2 /cm 3 and total SA increased from 0.059 to 4.793 m 2 . There were 3.31 × 10 6 airspace-spheres, 12 µ radius, septal thickness 30 µ at 16 weeks, increasing to 56.92 × 10 6 , 26 µ radius, septal thickness 13 µ by term. Morphometry can feasibly be performed at autopsy, providing more informative quantitative data on lung structural development than current methods utilized. This reference data set compares well with published data. © 2017 Wiley Periodicals, Inc.

Compound-specific carbon isotope analysis of instantaneous gas generated from shaly coal during hydrous pyrolysis

NASA Astrophysics Data System (ADS)

Tsai, Wen-Yu; Sun, Chih-Hsien; Huang, Wuu-Liang

2010-05-01

Isotopes of natural gases have provided important information for indicating their maturation, origins and influencing factors during the generation processes. In order to distinguish compositions of gas generated at different intervals of maturities, the present study investigates the variation of compound-specific carbon isotope (CSI) ratios of hydrocarbon gases from a shaly coal by instantaneous hydrous pyrolysis, during which the earlier generated gas was evacuated before the start of next maturation stage. The experiments were conducted at ten different maturity stages (0.65 to 2.02 % Ro) from a terrestrial shaly coal with 0.48 % Ro. The gas products were analyzed by GC-IR-MS. The results show that, in general, the δ13C values of methane (C1), ethane (C2), propane (C3) slightly increase, then decrease and finally increase with increasing maturities. This reverse phenomenon indicates the heterogeneous and complex compositions of the kerogen. The isotope compositions of gases exhibit three distinct clusters in natural gas plot of δ13C values versus 1/n (where n is carbon number of the gaseous molecule), corresponding to three different groups of maturity stages. By linking the same maturity stage of δ13C values, all lines show nearly parallel in each group with consistently reverse trend of δ13C3 < δ13C2 > δ13C1. These three distinct clusters were also observed in the cross plotting of iC4/nC4 versus iC5/nC5 isomer ratios. This may imply that the kerogen is composed of three discrete structural domains which were progressively cracked at three major groups of maturity stages. The reverse trend was inconsistent with data for gas collected cumulatively in most prior pyrolysis experiments and the linear relationship predicted from kinetic isotope effect (KIE) model. Although the non-linear relationship or reverse trend, δ13C3 < δ13C2, was also reported for some natural gases, it was interpreted as a result of mixing from different source rocks or other processes. Our results, however, suggest that this non-linear relationship or reverse phenomenon can also be attributed to the mixing of gases generated from different maturity stages solely from a single source formation. Therefore, our results provide a new interpretation for the variation of isotope data of the cumulative and instantaneous gases in hydrous pyrolysis experiments and isotope variation in natural gas.

Changes in physiological attributes of ponderosa pine from seedling to mature tree

Treesearch

Nancy E. Grulke; William A. Retzlaff

2001-01-01

Plant physiological models are generally parameterized from many different sources of data, including chamber experiments and plantations, from seedlings to mature trees. We obtained a comprehensive data set for a natural stand of ponderosa pine (Pinus ponderosa Laws.) and used these data to parameterize the physiologically based model, TREGRO....

The Effect of Prisonization and Self-Esteem on Inmates' Career Maturity.

ERIC Educational Resources Information Center

Homant, Robert J.; Dean, Douglas G.

1988-01-01

Tested model of offender career maturity by dividing 211 inmates into groups based on self-esteem and prisonization (taking on of prison culture). Compared groups on job planning, job attitudes, and stigmatization. Contrary to model, high self-esteem and low prisonization were both correlated significantly with higher scores on job planning and…

An Integrative Social-Cognitive Developmental Model of Supervision for Substance Abuse Counselors-in-Training

ERIC Educational Resources Information Center

Sias, Shari M.; Lambie, Glenn W.

2008-01-01

Substance abuse counselors (SACs) at higher levels of social-cognitive maturity manage complex situations and perform counselor-related tasks more effectively than individuals at lower levels of development. This article presents an integrative clinical supervision model designed to promote the social-cognitive maturity (ego development;…

Cultivating Knowledge Sharing through the Relationship Management Maturity Model

ERIC Educational Resources Information Center

Martin, Valerie A.; Hatzakis, Tally; Lycett, Mark; Macredie, Robert

2005-01-01

Purpose: The purpose of this paper is to present the development of the relationship management maturity model (RMMM), the output of an initiative aimed at bridging the gap between business units and the IT organisation. It does this through improving and assessing knowledge sharing between business and IT staff in Finco, a large financial…

Action Learning for Strategic Innovation in Mature Organizations: Key Cognitive, Design and Contextual Considerations

ERIC Educational Resources Information Center

Kuhn, Jeffrey S.; Marsick, Victoria J.

2005-01-01

This article lays out a model of action learning for catalyzing strategic innovation in mature organizations that are faced with a new competitive playing field. Central to this model is the development of a set of sophisticated cognitive capabilities--sensemaking, strategic thinking, critical thinking, divergent thinking, conceptual capacity and…

A novel modulation of structural and functional changes of mouse bone marrow derived dendritic cells (BMDCs) by interleukin-2(IL-2).

PubMed

Hu, Xiaofang; Cao, Yan; Meng, Yiming; Hou, Mingxiao

2015-01-01

IL-2 is a pleiotropic cytokine produced by T cell after antigen activation of T cell and it is so called T cell growth factor. A large number of documents suggest that Il-2 plays pivotal roles in the immune response and now Il-2 is an approved drug being used for various kinds of diseases such as cancer and dermatitis. (1) The aim of present exploration was to look at effect of IL-2 on structural, phenotypic and functional maturation of murine BMDCs. The structural and phenotypic maturation of BMDCs under influence of IL-2 were evaluated by light microscope and flow cytometry (FCM). The functional maturation of BMDCs was confirmed by cytochemistry assay, FITC-dextran, acid phosphatase (ACP) activity, bio-assay and enzyme linked immunosorbent assay (ELISA).We elucidated that IL-2 up-regulated the expression of key surface markers such as: CD80, CD83, CD86, CD40 and MHC II molecules on BMDCs, down-regulated phagocytosis activity, induced more production of IL-12 and TNF-α secreted by BMDCs. Therefore it can be concluded that IL-2 effectively enhance the maturation of BMDCs. Our results provide direct evidence to support IL-2 would be used as a potent adjuvant in preparation of DC-based vaccines, as well as an immune remedy for cancer situation.

Theory of the development of curved barbs and their effects on feather morphology.

PubMed

Feo, Teresa J; Simon, Emma; Prum, Richard O

2016-08-01

Feathers exhibit an extraordinary diversity of shapes, which are used by birds to accomplish a diverse set of functions. Pennaceous feathers have a double branched morphology that develops from a tube of epidermis, and variation in branch geometry determines feather shape. Feather development is both complex (i.e., a simple developmental modification can have multiple effects on mature feather shape), and redundant (i.e., different developmental modifications can create the same shape). Due to this, it is not readily apparent how different feather shapes develop. In many feathers, barbs are not straight, but instead curve in toward, or away, from the feather tip. Barb curvature can affect the shape of mature feathers but the development of curved barbs is unknown. Previous research has hypothesized that barb curvature could develop either during the helical growth of barb ridges in the tubular feather germ, or during barb angle expansion as the feather unfurls from the sheath. To better understand the development of curved barbs and their effects on mature feathers we present a theoretical model of curved barb development and test the model with empirical investigations of feathers. We find that curved barbs affect many aspects of feather morphology including vane width, barb length, and barb spacing. In real feathers, curved barbs can develop both during helical barb ridge growth and during barb angle expansion, with most of the observed curvature due to barb angle expansion. Our results demonstrate that barb angle expansion as a feather unfurls from the sheath is a complex and dynamic process that plays an important role in determining the shape and structure of mature feathers. Curved barbs create heterogeneity in barb geometry within the feather vane, which could have important implications for aerodynamic function and the development of within feather pigmentation patterns. J. Morphol. 277:995-1013, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Mapping Subcortical Brain Maturation during Adolescence: Evidence of Hemisphere-and Sex-Specific Longitudinal Changes

ERIC Educational Resources Information Center

Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.

2013-01-01

Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells.

PubMed

Chen, Chen; Soto-Gutierrez, Alejandro; Baptista, Pedro M; Spee, Bart

2018-04-01

The incidence of liver disease is increasing globally. The only curative therapy for severe end-stage liver disease, liver transplantation, is limited by the shortage of organ donors. In vitro models of liver physiology have been developed and new technologies and approaches are progressing rapidly. Stem cells might be used as a source of liver tissue for development of models, therapies, and tissue-engineering applications. However, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. We review factors that promote hepatocyte differentiation and maturation, including growth factors, transcription factors, microRNAs, small molecules, and the microenvironment. We discuss how the hepatic circulation, microbiome, and nutrition affect liver function, and the criteria for considering cells derived from stem cells to be fully mature hepatocytes. We explain the challenges to cell transplantation and consider future technologies for use in hepatic stem cell maturation, including 3-dimensional biofabrication and genome modification. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Probabilistic Methods for Structural Reliability and Risk

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

2007-01-01

A formal method is described to quantify structural reliability and risk in the presence of a multitude of uncertainties. The method is based on the materials behavior level where primitive variables with their respective scatters are used to describe that behavior. Computational simulation is then used to propagate those uncertainties to the structural scale where reliability and risk are usually specified. A sample case is described to illustrate the effectiveness, versatility, and maturity of the method. Typical results from this method demonstrate that the method is mature and that it can be used for future strategic projections and planning to assure better, cheaper, faster products for competitive advantages in world markets. The results also indicate that the methods are suitable for predicting remaining life in aging or deteriorating structures.

Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs.

PubMed

Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp

2018-06-06

Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after preterm birth. Acute gastrointestinal NEC lesions were associated with systemic inflammation, increased BCSFB permeability and region-specific neuronal damage. The results demonstrate the importance of early interventions against NEC to prevent brain injury in preterm infants. © 2018 S. Karger AG, Basel.

Preliminary thermal-maturity map of the Cameo and Fairfield or equivalent coal zone in the Piceance Creek Basin, Colorado

USGS Publications Warehouse

Nuccio, Vito F.; Johnson, Ronald C.

1983-01-01

This map was prepared in cooperation with the U.S. Department of Energy's Western Gas Sands Project and was constructed to show the thermal maturity of the Upper Cretaceous Mesaverde Formation (or Group) in the Piceance Creek Basin. The ability of a source rock to generate oil and gas is directly related to its kerogen content and thermal maturity; hence, thermal maturity is commonly used as an exploration tool. This publication consists of two parts: a coal rank map for the basinwide Cameo and Fairfield or equivalent coal zone and three cross sections showing the variation in a coal rank for the entire Mesaverde. Structure contours on the map show the top of the Rollins Sandstone Member of the Mesaverde Formation and its equivalent the Trout Creek Sandstone Member of the Iles Formation of the Mesaverde Group, which immediately underlie the Cameo and Fairfield zone. The structure contours show the fairly strong correlation between structure and coal rank in the basin, suggesting that maximum overburden was the key factor in determining the coal ranks. Even in the southern part of the basin where extensive plutonism occurred during the Oligocene, coal ranks still generally follow structure; indicating that the plutons had little affect on the coals. On the cross sections both the top of the Rollins and Trout Creek, and the top of the Mesaverde Formation/Group are shown. A complete analysis of the entire Mesaverde in the basin would require more information than is presently available.

Systemic regulation of leaf anatomical structure, photosynthetic performance, and high-light tolerance in sorghum.

PubMed

Jiang, Chuang-Dao; Wang, Xin; Gao, Hui-Yuan; Shi, Lei; Chow, Wah Soon

2011-03-01

Leaf anatomy of C3 plants is mainly regulated by a systemic irradiance signal. Since the anatomical features of C4 plants are different from that of C3 plants, we investigated whether the systemic irradiance signal regulates leaf anatomical structure and photosynthetic performance in sorghum (Sorghum bicolor), a C4 plant. Compared with growth under ambient conditions (A), no significant changes in anatomical structure were observed in newly developed leaves by shading young leaves alone (YS). Shading mature leaves (MS) or whole plants (S), on the other hand, caused shade-leaf anatomy in newly developed leaves. By contrast, chloroplast ultrastructure in developing leaves depended only on their local light conditions. Functionally, shading young leaves alone had little effect on their net photosynthetic capacity and stomatal conductance, but shading mature leaves or whole plants significantly decreased these two parameters in newly developed leaves. Specifically, the net photosynthetic rate in newly developed leaves exhibited a positive linear correlation with that of mature leaves, as did stomatal conductance. In MS and S treatments, newly developed leaves exhibited severe photoinhibition under high light. By contrast, newly developed leaves in A and YS treatments were more resistant to high light relative to those in MS- and S-treated seedlings. We suggest that (1) leaf anatomical structure, photosynthetic capacity, and high-light tolerance in newly developed sorghum leaves were regulated by a systemic irradiance signal from mature leaves; and (2) chloroplast ultrastructure only weakly influenced the development of photosynthetic capacity and high-light tolerance. The potential significance of the regulation by a systemic irradiance signal is discussed.

The Role of Capsid Maturation on Adenovirus Priming for Sequential Uncoating*

PubMed Central

Pérez-Berná, Ana J.; Ortega-Esteban, Alvaro; Menéndez-Conejero, Rosa; Winkler, Dennis C.; Menéndez, Margarita; Steven, Alasdair C.; Flint, S. Jane; de Pablo, Pedro J.; San Martín, Carmen

2012-01-01

Adenovirus assembly concludes with proteolytic processing of several capsid and core proteins. Immature virions containing precursor proteins lack infectivity because they cannot properly uncoat, becoming trapped in early endosomes. Structural studies have shown that precursors increase the network of interactions maintaining virion integrity. Using different biophysical techniques to analyze capsid disruption in vitro, we show that immature virions are more stable than the mature ones under a variety of stress conditions and that maturation primes adenovirus for highly cooperative DNA release. Cryoelectron tomography reveals that under mildly acidic conditions mimicking the early endosome, mature virions release pentons and peripheral core contents. At higher stress levels, both mature and immature capsids crack open. The virus core is completely released from cracked capsids in mature virions, but it remains connected to shell fragments in the immature particle. The extra stability of immature adenovirus does not equate with greater rigidity, because in nanoindentation assays immature virions exhibit greater elasticity than the mature particles. Our results have implications for the role of proteolytic maturation in adenovirus assembly and uncoating. Precursor proteins favor assembly by establishing stable interactions with the appropriate curvature and preventing premature ejection of contents by tightly sealing the capsid vertices. Upon maturation, core organization is looser, particularly at the periphery, and interactions preserving capsid curvature are weakened. The capsid becomes brittle, and pentons are more easily released. Based on these results, we hypothesize that changes in core compaction during maturation may increase capsid internal pressure to trigger proper uncoating of adenovirus. PMID:22791715

Participants' evaluation of a group-based organisational assessment tool in Danish general practice: the Maturity Matrix.

PubMed

Buch, Martin Sandberg; Edwards, Adrian; Eriksson, Tina

2009-01-01

The Maturity Matrix is a group-based formative self-evaluation tool aimed at assessing the degree of organisational development in general practice and providing a starting point for local quality improvement. Earlier studies of the Maturity Matrix have shown that participants find the method a useful way of assessing their practice's organisational development. However, little is known about participants' views on the resulting efforts to implement intended changes. To explore users' perspectives on the Maturity Matrix method, the facilitation process, and drivers and barriers for implementation of intended changes. Observation of two facilitated practice meetings, 17 semi-structured interviews with participating general practitioners (GPs) or their staff, and mapping of reasons for continuing or quitting the project. General practices in Denmark Main outcomes: Successful change was associated with: a clearly identified anchor person within the practice, a shared and regular meeting structure, and an external facilitator who provides support and counselling during the implementation process. Failure to implement change was associated with: a high patient-related workload, staff or GP turnover (that seemed to affect small practices more), no clearly identified anchor person or anchor persons who did not do anything, no continuous support from an external facilitator, and no formal commitment to working with agreed changes. Future attempts to improve the impact of the Maturity Matrix, and similar tools for quality improvement, could include: (a) attention to matters of variation caused by practice size, (b) systematic counselling on barriers to implementation and support to structure the change processes, (c) a commitment from participants that goes beyond participation in two-yearly assessments, and (d) an anchor person for each identified goal who takes on the responsibility for improvement in practice.

Maturation-Associated Destabilization of Hepatitis B Virus Nucleocapsid

PubMed Central

Cui, Xiuji; Ludgate, Laurie; Ning, Xiaojun

2013-01-01

The mature nucleocapsid (NC) of hepatitis B virus containing the relaxed circular (RC) DNA genome can be secreted extracellularly as virions after envelopment with the viral surface proteins or, alternatively, can be disassembled to release RC DNA (i.e., uncoating) into the host cell nucleus to form the covalently closed circular (CCC) DNA, which sustains viral replication and persistence. In contrast, immature NCs containing the viral single-stranded DNA or the pregenomic RNA are incompetent for either envelopment or uncoating. Little is currently known about how mature NCs, and not the immature ones, are specifically selected for these processes. Here, we have carried out a biochemical analysis of the different NC populations upon their separation through sucrose gradient centrifugation. We have found that the maturation of NCs is associated with their destabilization, manifested as increased protease and nuclease sensitivity, altered sedimentation during sucrose gradient centrifugation, and retarded mobility during native agarose gel electrophoresis. Also, three distinct populations of intracellular mature NCs could be differentiated based on these characteristics. Furthermore, mature NCs generated in vitro under cell-free conditions acquired similar properties. These results have thus revealed significant structural changes associated with NC maturation that likely play a role in the selective uncoating of the mature NC for CCC DNA formation and/or its preferential envelopment for virion secretion. PMID:23966388

Insulin during in vitro oocyte maturation has an impact on development, mitochondria, and cytoskeleton in bovine day 8 blastocysts.

PubMed

Laskowski, Denise; Båge, Renée; Humblot, Patrice; Andersson, Göran; Sirard, Marc-André; Sjunnesson, Ylva

2017-10-01

Insulin is a key metabolic hormone that controls energy homeostasis in the body, including playing a specific role in regulating reproductive functions. Conditions associated with hyperinsulinemia can lower developmental rates in bovine in vitro embryo production and are linked to decreased fertility in humans, as in cases of obesity or type 2 diabetes. Embryo quality is important for fertility outcome and it can be assessed by choosing scoring standards for various characteristics, such as developmental stage, quality grade, cell number, mitochondrial pattern or actin cytoskeleton structure. Changes in the embryo's gene expression can reflect environmental impacts during maturation and may explain morphological differences. Together with morphological evaluation, this could enable better assessment and possibly prediction of the developmental potential of the embryo. The aim of this study was to use a bovine model to identify potential gene signatures of insulin-induced changes in the embryo by combining gene expression data and confocal microscopy evaluation. Bovine embryos were derived from oocytes matured in two different insulin concentrations (10 µg mL - 1 and 0.1 µg mL - 1 ), then stained to distinguish f-Actin, DNA and active mitochondria. The total cell number of the embryo, quality of the actin cytoskeleton and mitochondrial distribution were assessed and compared to an insulin-free control group. A microarray-based transcriptome analysis was used to investigate key genes involved in cell structure, mitochondrial function and cell division. Our results indicate that insulin supplementation during oocyte maturation leads to lower blastocyst rates and a different phenotype, characterised by an increased cell number and different actin and mitochondrial distribution patterns. These changes were reflected by an up-regulation of genes involved in cell division (MAP2K2; DHCR7), cell structure (LMNA; VIM; TUBB2B; TUBB3; TUBB4B) and mitochondrial activation (ATP5D; CYP11A1; NDUFB7; NDUFB10; NDUFS8). Taken together, we hypothesise that the increased proliferation in the insulin-treated groups might impair the developmental potential of the embryos by inducing metabolic stress on the molecular level, which could be detrimental for the survival of the embryo. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiation of human skeletal muscle cells in culture: maturation as indicated by titin and desmin striation.

PubMed

van der Ven, P F; Schaart, G; Jap, P H; Sengers, R C; Stadhouders, A M; Ramaekers, F C

1992-10-01

This report describes a phenotyping study of differentiating human skeletal muscle cells in tissue culture. Satellite cells (adult myoblasts), isolated from biopsy material, showed a proliferative behaviour in high-nutrition medium, but fused to form myotubes when grown in low-nutrition medium. The expression and structural organization of the intermediate filament proteins desmin and vimentin as well as the sarcomeric constituents alpha-actin, alpha-actinin, nebulin, myosin and especially titin during myofibrillogenesis in vitro, were studied by means of indirect immunofluorescence assays. The proliferating myoblasts contained both desmin and vimentin, alpha-actinin and the filamentous form of actin. Shortly after the change of medium, expression of titin, sarcomeric myosin and skeletal muscle alpha-actin was found in mononuclear cells in a diffuse, filamentous (titin, myosin, alpha-actin) or punctate (titin, myosin) pattern. Four to 10 days after the medium change, mature myotubes showed desmin, titin, alpha-actinin, nebulin, sarcomeric myosin and actin cross-striations, while vimentin was no longer detected. We conclude that human skeletal muscle cell cultures are an appropriate model system to study the molecular basis of myofibrillogenesis. Especially the presence of desmin in a striated fashion points to a high degree of maturation of the muscle cell cultures.

Venture from the Interior-Herpesvirus pUL31 Escorts Capsids from Nucleoplasmic Replication Compartments to Sites of Primary Envelopment at the Inner Nuclear Membrane.

PubMed

Bailer, Susanne M.

2017-11-25

Herpesviral capsid assembly is initiated in the nucleoplasm of the infected cell. Size constraints require that newly formed viral nucleocapsids leave the nucleus by an evolutionarily conserved vescular transport mechanism called nuclear egress. Mature capsids released from the nucleoplasm are engaged in a membrane-mediated budding process, composed of primary envelopment at the inner nuclear membrane and de-envelopment at the outer nuclear membrane. Once in the cytoplasm, the capsids receive their secondary envelope for maturation into infectious virions. Two viral proteins conserved throughout the herpesvirus family, the integral membrane protein pUL34 and the phosphoprotein pUL31, form the nuclear egress complex required for capsid transport from the infected nucleus to the cytoplasm. Formation of the nuclear egress complex results in budding of membrane vesicles revealing its function as minimal virus-encoded membrane budding and scission machinery. The recent structural analysis unraveled details of the heterodimeric nuclear egress complex and the hexagonal coat it forms at the inside of budding vesicles to drive primary envelopment. With this review, I would like to present the capsid-escort-model where pUL31 associates with capsids in nucleoplasmic replication compartments for escort to sites of primary envelopment thereby coupling capsid maturation and nuclear egress.

High-throughput metabolic profiling of diverse green Coffea arabica beans identified tryptophan as a universal discrimination factor for immature beans.

PubMed

Setoyama, Daiki; Iwasa, Keiko; Seta, Harumichi; Shimizu, Hiroaki; Fujimura, Yoshinori; Miura, Daisuke; Wariishi, Hiroyuki; Nagai, Chifumi; Nakahara, Koichi

2013-01-01

The maturity of green coffee beans is the most influential determinant of the quality and flavor of the resultant coffee beverage. However, the chemical compounds that can be used to discriminate the maturity of the beans remain uncharacterized. We herein analyzed four distinct stages of maturity (immature, semi-mature, mature and overripe) of nine different varieties of green Coffea arabica beans hand-harvested from a single experimental field in Hawaii. After developing a high-throughput experimental system for sample preparation and liquid chromatography-mass spectrometry (LC-MS) measurement, we applied metabolic profiling, integrated with chemometric techniques, to explore the relationship between the metabolome and maturity of the sample in a non-biased way. For the multivariate statistical analyses, a partial least square (PLS) regression model was successfully created, which allowed us to accurately predict the maturity of the beans based on the metabolomic information. As a result, tryptophan was identified to be the best contributor to the regression model; the relative MS intensity of tryptophan was higher in immature beans than in those after the semi-mature stages in all arabica varieties investigated, demonstrating a universal discrimination factor for diverse arabica beans. Therefore, typtophan, either alone or together with other metabolites, may be utilized for traders as an assessment standard when purchasing qualified trading green arabica bean products. Furthermore, our results suggest that the tryptophan metabolism may be tightly linked to the development of coffee cherries and/or beans.

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

NASA Astrophysics Data System (ADS)

Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

2016-08-01

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

Tailored tools to improve pharmacotherapy in infants.

PubMed

Allegaert, Karel

2014-08-01

Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacotherapy in infants. Modeling approaches that hold the promise to improve pharmacotherapy in infants are between-compound extrapolation for compounds that undergo the same route of elimination and integration of time-varying physiology to adapt for the fast maturational changes. Besides these maturational covariates (size, age), newly emerging covariates relate to novel treatment modalities (extracorporeal circulation, hypothermia), environmental issues (microbiome, critical illness) or pharmacogenetics. All these covariates interact with the maturational variation. Finally, pharmacovigilance also needs to be tailored to the characteristics of this population. This relates to preventive strategies, signal detection and assessment of causality. Knowledge on pharmacotherapy in infants is lagging. Tailoring available tools to the specific characteristics (maturation) and clinical needs (newly emerging covariates) of infants is feasible but needs creativity and a multidisciplinary collaboration between modelers, academia, clinical researchers and, obviously, the public, including parents.

Inhibition of Bufo arenarum oocyte maturation induced by cholesterol depletion by methyl-beta-cyclodextrin. Role of low-density caveolae-like membranes.

PubMed

Buschiazzo, Jorgelina; Bonini, Ida C; Alonso, Telma S

2008-06-01

The invaginated structure of caveolae seems to provide an optimal environment for hormone binding leading to oocyte meiotic maturation. We conducted a quantitative analysis of lipids and proteins of detergent-free low-density membranes isolated from Bufo arenarum oocytes and we modulated cellular cholesterol to further understand how these domains perform their regulatory functions in the amphibian system. Light membranes derive from the plasma membrane as suggested by the enrichment in the activity of 5'nucleotidase. Lipid analysis by chromatography techniques revealed that this fraction is enriched in phosphatidylserine and cholesterol and that it evidences an important level of sphingomyelin. The finding of a single 21 kDa caveolin in light membranes indicates the presence of caveolae-like structures in B. arenarum oocytes. In support of this finding, c-Src is significantly associated to this fraction. Cholesterol content of oocytes treated with methyl-beta-cyclodextrin (MbetaCD) decreased when compared to control oocytes. Drug treatment inhibited meiotic maturation in a dose-dependent manner and affected the localization of caveolin and c-Src among membrane fractions. Repletion of cholesterol showed a recovery of the ability of MbetaCD-treated oocytes to mature, particularly at the 25 mM concentration in which reversibility was close to the control level. Results highlight the importance of caveolae-like microdomains for maturation signaling in Bufo oocytes.

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill].

PubMed

López Moratalla, Natalia; Errasti Alcalá, Tania; Santiago, Esteban

2011-01-01

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

Morphology and ultrastructure of retrovirus particles

PubMed Central

Zhang, Wei; Cao, Sheng; Martin, Jessica L.; Mueller, Joachim D.; Mansky, Louis M.

2015-01-01

Retrovirus morphogenesis entails assembly of Gag proteins and the viral genome on the host plasma membrane, acquisition of the viral membrane and envelope proteins through budding, and formation of the core through the maturation process. Although in both immature and mature retroviruses, Gag and capsid proteins are organized as paracrystalline structures, the curvatures of these protein arrays are evidently not uniform within one or among all virus particles. The heterogeneity of retroviruses poses significant challenges to studying the protein contacts within the Gag and capsid lattices. This review focuses on current understanding of the molecular organization of retroviruses derived from the sub-nanometer structures of immature virus particles, helical capsid protein assemblies and soluble envelope protein complexes. These studies provide insight into the molecular elements that maintain the stability, flexibility and infectivity of virus particles. Also reviewed are morphological studies of retrovirus budding, maturation, infection and cell-cell transmission, which inform the structural transformation of the viruses and the cells during infection and viral transmission, and lead to better understanding of the interplay between the functioning viral proteins and the host cell. PMID:26448965

Morphological records of oocyte maturation in the parthenogenetic tick Amblyomma rotundatum Koch, 1844 (Acari: Ixodidae).

PubMed

Sanches, Gustavo S; Araujo, Andrea M; Martins, Thiago F; Bechara, Gervásio H; Labruna, Marcelo B; Camargo-Mathias, Maria I

2012-02-01

Oocyte maturation in the thelytokous parthenogenetic tick Amblyomma rotundatum was examined for the first time using light and scanning electron microscopy. The panoistic ovary lacks nurse and follicular cells and is a single continuous tubular structure forming a lumen delimited by the ovarian wall. Oocytes of tick species are usually classified according to cytoplasm appearance, the presence of germinal vesicle, the presence of yolk granules, and the chorion. However, for this species, we also use oocyte size as an auxiliary tool since most oocytes were in stages I-III and were histologically very similar. Oocytes were classified into five development stages, and specific characteristics were observed: mature oocytes with thin chorion, pedicel cells arranged forming an epithelium with two or more oocytes attached by the same structure, and a large number of oocytes in the process of reabsorption. Copyright © 2011 Elsevier GmbH. All rights reserved.

Estimation of Forest Biomass Based on Muliti-Source Remote Sensing Data Set - a Case Study of Shangri-La County

NASA Astrophysics Data System (ADS)

Feng, Wanwan; Wang, Leiguang; Xie, Junfeng; Yue, Cairong; Zheng, Yalan; Yu, Longhua

2018-04-01

Forest biomass is an important indicator for the structure and function of forest ecosystems, and an accurate assessment of forest biomass is crucial for understanding ecosystem changes. Remote sensing has been widely used for inversion of biomass. However, in mature or over-mature forest areas, spectral saturation is prone to occur. Based on existing research, this paper synthesizes domestic high resolution satellites, ZY3-01 satellites, and GLAS14-level data from space-borne Lidar system, and other data set. Extracting texture and elevation features respectively, for the inversion of forest biomass. This experiment takes Shangri-La as the research area. Firstly, the biomass in the laser spot was calculated based on GLAS data and other auxiliary data, DEM, the second type inventory of forest resources data and the Shangri-La vector boundary data. Then, the regression model was established, that is, the relationship between the texture factors of ZY3-01 and biomass in the laser spot. Finally, by using this model and the forest distribution map in Shangri-La, the biomass of the whole area is obtained, which is 1.3972 × 108t.

Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography

PubMed Central

Yousefi, Siavash; Qin, Jia; Dziennis, Suzan; Wang, Ruikang K.

2014-01-01

Abstract. Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies. PMID:25036212

Seismo-thermo-mechanical modeling of mature and immature transform faults

NASA Astrophysics Data System (ADS)

Preuss, Simon; Gerya, Taras; van Dinther, Ylona

2016-04-01

Transform faults (TF) are subdivided into continental and oceanic ones due to their markedly different tectonic position, structure, surface expression, dynamics and seismicity. Both continental and oceanic TFs are zones of rheological weakness, which is a pre-requisite for their existence and long-term stability. Compared to subduction zones, TFs are typically characterized by smaller earthquake magnitudes as both their potential seismogenic width and length are reduced. However, a few very large magnitude (Mw>8) strike-slip events were documented, which are presumably related to the generation of new transform boundaries and/or sudden reactivation of pre-existing fossil structures. In particular, the 11 April 2012 Sumatra Mw 8.6 earthquake is challenging the general concept that such high magnitude events only occur at megathrusts. Hence, the processes of TF nucleation, propagation and their direct relation to the seismic cycle and long-term deformation at both oceanic and continental transforms needs to be investigated jointly to overcome the restricted direct observations in time and space. To gain fundamental understanding of involved physical processes the numerical seismo-thermo-mechanical (STM) modeling approach, validated in a subduction zone setting (Van Dinther et al. 2013), will be adapted for TFs. A simple 2D plane view model geometry using visco-elasto-plastic material behavior will be adopted. We will study and compare seismicity patterns and evolution in two end member TF setups, each with strain-dependent and rate-dependent brittle-plastic weakening processes: (1) A single weak and mature transform fault separating two strong plates (e.g., in between oceanic ridges) and (2) A nucleating or evolving (continental) TF system with disconnected predefined faults within a plate subjected to simple shear deformation (e.g., San Andreas Fault system). The modeling of TFs provides a first tool to establish the STM model approach for transform faults in a more general case.

Experimental and theoretical study of light scattering by individual mature red blood cells by use of scanning flow cytometry and a discrete dipole approximation.

PubMed

Yurkin, Maxim A; Semyanov, Konstantin A; Tarasov, Peter A; Chernyshev, Andrei V; Hoekstra, Alfons G; Maltsev, Valeri P

2005-09-01

Elastic light scattering by mature red blood cells (RBCs) was theoretically and experimentally analyzed by use of the discrete dipole approximation (DDA) and scanning flow cytometry (SFC), respectively. SFC permits measurement of the angular dependence of the light-scattering intensity (indicatrix) of single particles. A mature RBC is modeled as a biconcave disk in DDA simulations of light scattering. We have studied the effect of RBC orientation related to the direction of the light incident upon the indicatrix. Numerical calculations of indicatrices for several axis ratios and volumes of RBC have been carried out. Comparison of the simulated indicatrices and indicatrices measured by SFC showed good agreement, validating the biconcave disk model for a mature RBC. We simulated the light-scattering output signals from the SFC with the DDA for RBCs modeled as a disk-sphere and as an oblate spheroid. The biconcave disk, the disk-sphere, and the oblate spheroid models have been compared for two orientations, i.e., face-on and rim-on incidence, relative to the direction of the incident beam. Only the oblate spheroid model for rim-on incidence gives results similar to those of the rigorous biconcave disk model.

Consequences of stage-structured predators: cannibalism, behavioral effects, and trophic cascades.

PubMed

Rudolf, Volker H W

2007-12-01

Cannibalistic and asymmetrical behavioral interactions between stages are common within stage-structured predator populations. Such direct interactions between predator stages can result in density- and trait-mediated indirect interactions between a predator and its prey. A set of structured predator-prey models is used to explore how such indirect interactions affect the dynamics and structure of communities. Analyses of the separate and combined effects of stage-structured cannibalism and behavior-mediated avoidance of cannibals under different ecological scenarios show that both cannibalism and behavioral avoidance of cannibalism can result in short- and long-term positive indirect connections between predator stages and the prey, including "apparent mutualism." These positive interactions alter the strength of trophic cascades such that the system's dynamics are determined by the interaction between bottom-up and top-down effects. Contrary to the expectation of simpler models, enrichment increases both predator and prey abundance in systems with cannibalism or behavioral avoidance of cannibalism. The effect of behavioral avoidance of cannibalism, however, depends on how strongly it affects the maturation rate of the predator. Behavioral interactions between predator stages reduce the short-term positive effect of cannibalism on the prey density, but can enhance its positive long-term effects. Both interaction types reduce the destabilizing effect of enrichment. These results suggest that inconsistencies between data and simple models can be resolved by accounting for stage-structured interactions within and among species.

A recursive vesicle-based model protocell with a primitive model cell cycle

NASA Astrophysics Data System (ADS)

Kurihara, Kensuke; Okura, Yusaku; Matsuo, Muneyuki; Toyota, Taro; Suzuki, Kentaro; Sugawara, Tadashi

2015-09-01

Self-organized lipid structures (protocells) have been proposed as an intermediate between nonliving material and cellular life. Synthetic production of model protocells can demonstrate the potential processes by which living cells first arose. While we have previously described a giant vesicle (GV)-based model protocell in which amplification of DNA was linked to self-reproduction, the ability of a protocell to recursively self-proliferate for multiple generations has not been demonstrated. Here we show that newborn daughter GVs can be restored to the status of their parental GVs by pH-induced vesicular fusion of daughter GVs with conveyer GVs filled with depleted substrates. We describe a primitive model cell cycle comprising four discrete phases (ingestion, replication, maturity and division), each of which is selectively activated by a specific external stimulus. The production of recursive self-proliferating model protocells represents a step towards eventual production of model protocells that are able to mimic evolution.

Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model.

PubMed

Wu, Liviawati; Mould, Diane R; Perez Ruixo, Juan Jose; Doshi, Sameer

2015-10-01

A population pharmacokinetic pharmacodynamic (PK/PD) model describing the effect of epoetin alfa on hemoglobin (Hb) response in hemodialysis patients was developed. Epoetin alfa pharmacokinetics was described using a linear 2-compartment model. PK parameter estimates were similar to previously reported values. A maturation-structured cytokinetic model consisting of 5 compartments linked in a catenary fashion by first-order cell transfer rates following a zero-order input process described the Hb time course. The PD model described 2 subpopulations, one whose Hb response reflected epoetin alfa dosing and a second whose response was unrelated to epoetin alfa dosing. Parameter estimates from the PK/PD model were physiologically reasonable and consistent with published reports. Numerical and visual predictive checks using data from 2 studies were performed. The PK and PD of epoetin alfa were well described by the model. © 2015, The American College of Clinical Pharmacology.

Comparison of methods used to estimate conventional undiscovered petroleum resources: World examples

USGS Publications Warehouse

Ahlbrandt, T.S.; Klett, T.R.

2005-01-01

Various methods for assessing undiscovered oil, natural gas, and natural gas liquid resources were compared in support of the USGS World Petroleum Assessment 2000. Discovery process, linear fractal, parabolic fractal, engineering estimates, PETRIMES, Delphi, and the USGS 2000 methods were compared. Three comparisons of these methods were made in: (1) the Neuquen Basin province, Argentina (different assessors, same input data); (2) provinces in North Africa, Oman, and Yemen (same assessors, different methods); and (3) the Arabian Peninsula, Arabian (Persian) Gulf, and North Sea (different assessors, different methods). A fourth comparison (same assessors, same assessment methods but different geologic models), between results from structural and stratigraphic assessment units in the North Sea used only the USGS 2000 method, and hence compared the type of assessment unit rather than the method. In comparing methods, differences arise from inherent differences in assumptions regarding: (1) the underlying distribution of the parent field population (all fields, discovered and undiscovered), (2) the population of fields being estimated; that is, the entire parent distribution or the undiscovered resource distribution, (3) inclusion or exclusion of large outlier fields; (4) inclusion or exclusion of field (reserve) growth, (5) deterministic or probabilistic models, (6) data requirements, and (7) scale and time frame of the assessment. Discovery process, Delphi subjective consensus, and the USGS 2000 method yield comparable results because similar procedures are employed. In mature areas such as the Neuquen Basin province in Argentina, the linear and parabolic fractal and engineering methods were conservative compared to the other five methods and relative to new reserve additions there since 1995. The PETRIMES method gave the most optimistic estimates in the Neuquen Basin. In less mature areas, the linear fractal method yielded larger estimates relative to other methods. A geologically based model, such as one using the total petroleum system approach, is preferred in that it combines the elements of petroleum source, reservoir, trap and seal with the tectono-stratigraphic history of basin evolution with petroleum resource potential. Care must be taken to demonstrate that homogeneous populations in terms of geology, geologic risk, exploration, and discovery processes are used in the assessment process. The USGS 2000 method (7th Approximation Model, EMC computational program) is robust; that is, it can be used in both mature and immature areas, and provides comparable results when using different geologic models (e.g. stratigraphic or structural) with differing amounts of subdivisions, assessment units, within the total petroleum system. ?? 2005 International Association for Mathematical Geology.

The effect of glucocorticoids on ERK-1/2 phosphorylation during maturation of lamb oocytes and their subsequent fertilization and cleavage ability in vitro.

PubMed

González, Raquel; Ruiz-León, Yolanda; Gomendio, Montserrat; Roldan, Eduardo R S

2010-04-01

High levels of glucocorticoids may alter reproduction, but little is known about their direct actions on oocyte maturation, fertilization and subsequent development. Earlier work suggested negative effects of cortisol or dexamethasone on oocyte maturation but differences were noted between animal models. Both glucocorticoids reduce the p34(cdc2)-cyclin B1 complex but it is unknown if other signaling pathways important for meiosis progression are affected. In this study, using sheep oocytes as a model system, we assessed in vitro the effects of increasing concentration of glucocorticoids (0-250 microM) on oocyte maturation and underlying changes in the MAP kinase pathway, and the ability of oocytes to undergo fertilization and embryo development. Cortisol decreased oocyte maturation but only at the highest concentration, whereas dexamethasone had no effect. Fertilization and cleavage were not affected. On the other hand, both cortisol and dexamethasone inhibited ERK-1/2 activation in a concentration-dependent manner. It thus seems that oocytes can overcome deleterious effects of glucocorticoids during maturation despite the decrease in ERK-1/2 activity, but repercussions in vivo should be further explored. Copyright 2009 Elsevier Inc. All rights reserved.

Patterns of Innovation in Alzheimer's Disease Drug Development: A Strategic Assessment Based on Technological Maturity.

PubMed

Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Ledley, Fred D

2015-08-01

This article examines the current status of translational science for Alzheimer's disease (AD) drug discovery by using an analytical model of technology maturation. Previous studies using this model have demonstrated that nascent scientific insights and inventions generate few successful leads or new products until achieving a requisite level of maturity. This article assessed whether recent failures and successes in AD research follow patterns of innovation observed in other sectors. The bibliometric-based Technology Innovation Maturation Evaluation model was used to quantify the characteristic S-curve of growth for AD-related technologies, including acetylcholinesterase, N-methyl-d-aspartate (NMDA) receptors, B-amyloid, amyloid precursor protein, presenilin, amyloid precursor protein secretases, apolipoprotein E4, and transactive response DNA binding protein 43 kDa (TDP-43). This model quantifies the accumulation of knowledge as a metric for technological maturity, and it identifies the point of initiation of an exponential growth stage and the point at which growth slows as the technology is established. In contrast to the long-established acetylcholinesterase and NMDA receptor technologies, we found that amyloid-related technologies reached the established point only after 2000, and that the more recent technologies (eg, TDP-43) have not yet approached this point. The first approvals for new molecular entities targeting acetylcholinesterase and the NMDA receptor occurred an average of 22 years after the respective technologies were established, with only memantine (which was phenotypically discovered) entering clinical trials before this point. In contrast, the 6 lead compounds targeting the formation of amyloid plaques that failed in Phase III trials between 2009 and 2014 all entered clinical trials before the respective target technologies were established. This analysis suggests that AD drug discovery has followed a predictable pattern of innovation in which technological maturity is an important determinant of success in development. Quantitative analysis indicates that the lag in emergence of new products, and the much-heralded clinical failures of recent years, should be viewed in the context of the ongoing maturation of AD-related technologies. Although these technologies were not sufficiently mature to generate successful products a decade ago, they may be now. Analytical models of translational science can inform basic and clinical research results as well as strategic development of new therapeutic products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

PubMed

Hurd, Elizabeth A; Adams, Meredith E; Layman, Wanda S; Swiderski, Donald L; Beyer, Lisa A; Halsey, Karin E; Benson, Jennifer M; Gong, Tzy-Wen; Dolan, David F; Raphael, Yehoash; Martin, Donna M

2011-12-01

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. Copyright © 2011 Elsevier B.V. All rights reserved.

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

PubMed Central

Hurd, Elizabeth A.; Adams, Meredith E.; Layman, Wanda S.; Swiderski, Donald L.; Beyer, Lisa A.; Halsey, Karin E.; Benson, Jennifer M.; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Martin, Donna M.

2011-01-01

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by Prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7Gt/+ mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7Gt/+ mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7Gt/+ mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7Gt/+ mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. PMID:21875659

Sinks without borders: Snowshoe hare dynamics in a complex landscape

USGS Publications Warehouse

Griffin, Paul C.; Mills, L. Scott

2009-01-01

A full understanding of population dynamics of wide-ranging animals should account for the effects that movement and habitat use have on individual contributions to population growth or decline. Quantifying the per-capita, habitat-specific contribution to population growth can clarify the value of different patch types, and help to differentiate population sources from population sinks. Snowshoe hares, Lepus americanus, routinely use various habitat types in the landscapes they inhabit in the contiguous US, where managing forests for high snowshoe hare density is a priority for conservation of Canada lynx, Lynx canadensis. We estimated density and demographic rates via mark–recapture live trapping and radio-telemetry within four forest stand structure (FSS) types at three study areas within heterogeneous managed forests in western Montana. We found support for known fate survival models with time-varying individual covariates representing the proportion of locations in each of the FSS types, with survival rates decreasing as use of open young and open mature FSS types increased. The per-capita contribution to overall population growth increased with use of the dense mature or dense young FSS types and decreased with use of the open young or open mature FSS types, and relatively high levels of immigration appear to be necessary to sustain hares in the open FSS types. Our results support a conceptual model for snowshoe hares in the southern range in which sink habitats (open areas) prevent the buildup of high hare densities. More broadly, we use this system to develop a novel approach to quantify demographic sources and sinks for animals making routine movements through complex fragmented landscapes.

Optimizing IV and V for Mature Organizations

NASA Technical Reports Server (NTRS)

Fuhman, Christopher

2003-01-01

NASA is intending for its future software development agencies to have at least a Level 3 rating in the Carnegie Mellon University Capability Maturity Model (CMM). The CMM has built-in Verification and Validation (V&V) processes that support higher software quality. Independent Verification and Validation (IV&V) of software developed by mature agencies can be therefore more effective than for software developed by less mature organizations. How is Independent V&V different with respect to the maturity of an organization? Knowing a priori the maturity of an organization's processes, how can IV&V planners better identify areas of need choose IV&V activities, etc? The objective of this research is to provide a complementary set of guidelines and criteria to assist the planning of IV&V activities on a project using a priori knowledge of the measurable levels of maturity of the organization developing the software.

Autophagy proteins are not universally required for phagosome maturation.

PubMed

Cemma, Marija; Grinstein, Sergio; Brumell, John H

2016-09-01

Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome maturation in a process called LC3-associated phagocytosis (LAP). In this process, autophagy machinery is thought to conjugate LC3 directly onto the phagosomal membrane to promote lysosome fusion. However, a recent study has suggested that ATG proteins may in fact impair phagosome maturation to promote antigen presentation. Here, we examined the impact of ATG proteins on phagosome maturation in murine cells using FCGR2A/FcγR-dependent phagocytosis as a model. We show that phagosome maturation is not affected in Atg5-deficient mouse embryonic fibroblasts, or in Atg5- or Atg7-deficient bone marrow-derived macrophages using standard assays of phagosome maturation. We propose that ATG proteins may be required for phagosome maturation under some conditions, but are not universally required for this process.

Using a Capability Maturity Model to Build on the Generational Approach to Student Engagement Practices

ERIC Educational Resources Information Center

Nelson, K.; Clarke, J.; Stoodley, I.; Creagh, T.

2015-01-01

The generational approach to conceptualising first-year student learning behaviour has made a useful contribution to understanding student engagement. It has an explicit focus on student behaviour and we suggest that a Capability Maturity Model interpretation may provide a complementary extension of that understanding as it builds on the…

Creating a Learning Organization in Law Enforcement: Maturity Levels for Police Oversight Agencies

ERIC Educational Resources Information Center

Filstad, Cathrine; Gottschalk, Petter

2010-01-01

Purpose: The purpose of this paper is to conceptualize a stage model for maturity levels for police oversight agencies. Design/methodology/approach: The paper is based on a literature review covering police oversight organizations and stages of growth models. Findings: As a conceptual paper, the main findings are related to the appropriateness of…

Probabilistic Methods for Structural Design and Reliability

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Whitlow, Woodrow, Jr. (Technical Monitor)

2002-01-01

This report describes a formal method to quantify structural damage tolerance and reliability in the presence of a multitude of uncertainties in turbine engine components. The method is based at the material behavior level where primitive variables with their respective scatter ranges are used to describe behavior. Computational simulation is then used to propagate the uncertainties to the structural scale where damage tolerance and reliability are usually specified. Several sample cases are described to illustrate the effectiveness, versatility, and maturity of the method. Typical results from this method demonstrate, that it is mature and that it can be used to probabilistically evaluate turbine engine structural components. It may be inferred from the results that the method is suitable for probabilistically predicting the remaining life in aging or in deteriorating structures, for making strategic projections and plans, and for achieving better, cheaper, faster products that give competitive advantages in world markets.

Maturity-associated variation in physical activity and health-related quality of life in British adolescent girls: moderating effects of peer acceptance.

PubMed

Pindus, Dominika M; Cumming, Sean P; Sherar, Lauren B; Gammon, Catherine; Coelho e Silva, Manuel; Malina, Robert M

2014-01-01

Using a Biocultural Model of Maturity-Associated Variance in physical activity (PA) as a conceptual framework, the main and interactive effects of biological maturity status and perceived peer acceptance on PA and health-related quality of life (HRQoL) in adolescent girls were examined. Three hundred forty-two female British students in years 7 to 9 (13.2±0.83 years) participated in the study. All participants completed the PA Questionnaire for Adolescents and KIDSCREEN-10, a measure of HRQoL. Self-reported perceptions of peer acceptance were measured by items from the National Longitudinal Study of Adolescent Health.Maturity status was estimated as the percentage of predicted adult (mature) height attained at the time of observation. Analysis of covariance suggested an influence of peer acceptance on maturity-associated differences in PA, but not on HRQoL. Girls early and "on time" in maturation with higher perceptions of peer acceptance reported greater involvement in PA than girls early and "on time" in maturation with lower perceptions of peer acceptance. A reverse association was observed for late-maturing girls. Peer acceptance is an important moderator of maturity-associated variation in PA.

Skeletal responses to spaceflight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1991-01-01

The effect of gravity on the skeletal development and on the bone composition and its regulation in vertebrates is discussed. Results are presented from spaceflight and ground studies in both man and rat on the effect of microgravity on the bone-mineral metabolism (in both species) and on bone maturation and growth (in rats). Special attention is given to a ground-based flight-simulation rat model developed at NASA's Ames Research Center for studies of bone structure at the molecular, organ, and whole-body levels and to comparisons of estimated results with spaceflight data.

Mary and femininity: A psychological critique.

PubMed

Harrington, P A

1984-09-01

This essay uses Freud to interpret the symbolism and theology of Mary in modern Catholicism. In her role as the mother of believers, Mary functions to place the Christian in the position of a child who receives illusory gratification from the mother. In her role as model for Christians to emulate, Mary functions to place the Christian in the position of receptivity and dependence which Freud associated with femininity. Reinterpreting Freud from a feminist perspective, I suggest that the kind of femininity Mary represents serves to perpetuate patriachal social structures and to inhibit full psychological maturity.

Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors.

PubMed

Tang, Jun; Jones, Stacey A; Jeffery, Jerry L; Miranda, Sonia R; Galardi, Cristin M; Irlbeck, David M; Brown, Kevin W; McDanal, Charlene B; Han, Nianhe; Gao, Daxin; Wu, Yongyong; Shen, Bin; Liu, Chunyu; Xi, Caiming; Yang, Heping; Li, Rui; Yu, Yajun; Sun, Yufei; Jin, Zhimin; Wang, Erjuan; Johns, Brian A

2014-01-01

A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganized ring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge to access this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes to macrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potency compared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series of HIV-1 maturation inhibitors will be discussed.

Compaction of basin sediments as a function of time-temperature history

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

Schmoker, J.W.; Gautier, D.L.

1989-03-01

Processes that affect burial diagenesis are dependent on time-temperature history (thermal maturity). Therefore, the porosity loss of sedimentary rocks during burial may often be better treated as a function of time-temperature history than of depth. Loss of porosity in the subsurface for sandstones, carbonates, and shales can be represented by a power function /phi/ = A(M)/sup B/, where /phi/ is porosity, A and B are constants for a given sedimentary rock population of homogeneous properties, and M is a measure of thermal maturity such as vitrinite reflectance (R/sub 0/) or Lopatin's time-temperature index (TTI). Regression lines of carbonate porosity andmore » of sandstone porosity upon thermal maturity form an envelope whose axis is approximated by /phi/ = 7.5(R/sub 0/)/sup /minus/1.18/ or, equivalently, by /phi/ = 30(TTI)/sup /minus/0.33/. These equations are preliminary generic relations of use for the regional modeling of both carbonate and sandstone compaction in sedimentary basins. The dependence of porosity upon time-temperature history incorporates the hypothesis that porosity-reducing processes operate continuously in sedimentary basins and, consequently, that compaction of basin sediments continues as long as porosity exists. Calculations indicate that subsidence due to loss of porosity through time (with depth held constant) can produce a second-stage passively formed basin in which many hundreds of meters of sediments can accumulate and which conforms with the structure of the original underlying basin. Such sediment accumulation results from the thermal maturation of thick sequences of sedimentary rocks rather than from global sea level change or tectonic subsidence.« less