The cytomegalovirus promoter-driven short hairpin RNA constructs mediate effective RNA interference in zebrafish in vivo.

PubMed

Su, Jianguo; Zhu, Zuoyan; Wang, Yaping; Xiong, Feng; Zou, Jun

2008-01-01

The ability to utilize the RNA interference (RNAi) machinery for silencing target-gene expression has created a lot of excitement in the research community. In the present study, we used a cytomegalovirus (CMV) promoter-driven DNA template approach to induce short hairpin RNA (shRNA) triggered RNAi to block exogenous Enhanced Green Fluorescent Protein (EGFP) and endogenous No Tail (NTL) gene expressions. We constructed three plasmids, pCMV-EGFP-CMV-shGFP-SV40, pCMV-EGFP-CMV-shNTL-SV40, and pCMV-EGFP-CMV-shScrambled-SV40, each containing a CMV promoter driving an EGFP reporter cDNA and DNA coding for one shRNA under the control of another CMV promoter. The three shRNA-generating plasmids and pCMV-EGFP control plasmid were introduced into zebrafish embryos by microinjection. Samples were collected at 48 h after injection. Results were evaluated by phenotype observation and real-time fluorescent quantitative reverse-transcription polymerase chain reaction (Q-PCR). The shGFP-generating plasmid significantly inhibited the EGFP expression viewed under fluorescent microscope and reduced by 70.05 +/- 1.26% of exogenous EGFP gene mRNA levels compared with controls by Q-PCR. The shRNA targeting endogenous NTL gene resulted in obvious NTL phenotype of 30 +/- 4% and decreased the level of their corresponding mRNAs up to 54.52 +/- 2.05% compared with nontargeting control shRNA. These data proved the feasibility of the CMV promoter-driven shRNA expression technique to be used to inhibit exogenous and endogenous gene expressions in zebrafish in vivo.

Nonlinear data-driven identification of polymer electrolyte membrane fuel cells for diagnostic purposes: A Volterra series approach

NASA Astrophysics Data System (ADS)

Ritzberger, D.; Jakubek, S.

2017-09-01

In this work, a data-driven identification method, based on polynomial nonlinear autoregressive models with exogenous inputs (NARX) and the Volterra series, is proposed to describe the dynamic and nonlinear voltage and current characteristics of polymer electrolyte membrane fuel cells (PEMFCs). The structure selection and parameter estimation of the NARX model is performed on broad-band voltage/current data. By transforming the time-domain NARX model into a Volterra series representation using the harmonic probing algorithm, a frequency-domain description of the linear and nonlinear dynamics is obtained. With the Volterra kernels corresponding to different operating conditions, information from existing diagnostic tools in the frequency domain such as electrochemical impedance spectroscopy (EIS) and total harmonic distortion analysis (THDA) are effectively combined. Additionally, the time-domain NARX model can be utilized for fault detection by evaluating the difference between measured and simulated output. To increase the fault detectability, an optimization problem is introduced which maximizes this output residual to obtain proper excitation frequencies. As a possible extension it is shown, that by optimizing the periodic signal shape itself that the fault detectability is further increased.

Modelling the molecular mechanisms of aging

PubMed Central

Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

2017-01-01

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

The dynamics of information-driven coordination phenomena: A transfer entropy analysis

PubMed Central

Borge-Holthoefer, Javier; Perra, Nicola; Gonçalves, Bruno; González-Bailón, Sandra; Arenas, Alex; Moreno, Yamir; Vespignani, Alessandro

2016-01-01

Data from social media provide unprecedented opportunities to investigate the processes that govern the dynamics of collective social phenomena. We consider an information theoretical approach to define and measure the temporal and structural signatures typical of collective social events as they arise and gain prominence. We use the symbolic transfer entropy analysis of microblogging time series to extract directed networks of influence among geolocalized subunits in social systems. This methodology captures the emergence of system-level dynamics close to the onset of socially relevant collective phenomena. The framework is validated against a detailed empirical analysis of five case studies. In particular, we identify a change in the characteristic time scale of the information transfer that flags the onset of information-driven collective phenomena. Furthermore, our approach identifies an order-disorder transition in the directed network of influence between social subunits. In the absence of clear exogenous driving, social collective phenomena can be represented as endogenously driven structural transitions of the information transfer network. This study provides results that can help define models and predictive algorithms for the analysis of societal events based on open source data. PMID:27051875

The dynamics of information-driven coordination phenomena: A transfer entropy analysis.

PubMed

Borge-Holthoefer, Javier; Perra, Nicola; Gonçalves, Bruno; González-Bailón, Sandra; Arenas, Alex; Moreno, Yamir; Vespignani, Alessandro

2016-04-01

Data from social media provide unprecedented opportunities to investigate the processes that govern the dynamics of collective social phenomena. We consider an information theoretical approach to define and measure the temporal and structural signatures typical of collective social events as they arise and gain prominence. We use the symbolic transfer entropy analysis of microblogging time series to extract directed networks of influence among geolocalized subunits in social systems. This methodology captures the emergence of system-level dynamics close to the onset of socially relevant collective phenomena. The framework is validated against a detailed empirical analysis of five case studies. In particular, we identify a change in the characteristic time scale of the information transfer that flags the onset of information-driven collective phenomena. Furthermore, our approach identifies an order-disorder transition in the directed network of influence between social subunits. In the absence of clear exogenous driving, social collective phenomena can be represented as endogenously driven structural transitions of the information transfer network. This study provides results that can help define models and predictive algorithms for the analysis of societal events based on open source data.

Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

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

Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.

In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE{sub 2} on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure ofmore » ECs to PGE{sub 2} increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF{sub 1{alpha}} release and EC proliferation. In contrast, PGE{sub 2} attenuated VEGF{sub 165}-induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE{sub 2} restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH{sub 2} (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling.« less

Data collection and analysis strategies for phMRI.

PubMed

Mandeville, Joseph B; Liu, Christina H; Vanduffel, Wim; Marota, John J A; Jenkins, Bruce G

2014-09-01

Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed "phMRI". The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking.

PubMed

Zhou, Ping; Guo, Dongwei; Wang, Hong; Chai, Tianyou

2017-09-29

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVR (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. This indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking

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

Zhou, Ping; Guo, Dongwei; Wang, Hong

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVRmore » (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. In conclusion, this indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.« less

Data-Driven Robust M-LS-SVR-Based NARX Modeling for Estimation and Control of Molten Iron Quality Indices in Blast Furnace Ironmaking

DOE PAGES

Zhou, Ping; Guo, Dongwei; Wang, Hong; ...

2017-09-29

Optimal operation of an industrial blast furnace (BF) ironmaking process largely depends on a reliable measurement of molten iron quality (MIQ) indices, which are not feasible using the conventional sensors. This paper proposes a novel data-driven robust modeling method for the online estimation and control of MIQ indices. First, a nonlinear autoregressive exogenous (NARX) model is constructed for the MIQ indices to completely capture the nonlinear dynamics of the BF process. Then, considering that the standard least-squares support vector regression (LS-SVR) cannot directly cope with the multioutput problem, a multitask transfer learning is proposed to design a novel multioutput LS-SVRmore » (M-LS-SVR) for the learning of the NARX model. Furthermore, a novel M-estimator is proposed to reduce the interference of outliers and improve the robustness of the M-LS-SVR model. Since the weights of different outlier data are properly given by the weight function, their corresponding contributions on modeling can properly be distinguished, thus a robust modeling result can be achieved. Finally, a novel multiobjective evaluation index on the modeling performance is developed by comprehensively considering the root-mean-square error of modeling and the correlation coefficient on trend fitting, based on which the nondominated sorting genetic algorithm II is used to globally optimize the model parameters. Both experiments using industrial data and industrial applications illustrate that the proposed method can eliminate the adverse effect caused by the fluctuation of data in BF process efficiently. In conclusion, this indicates its stronger robustness and higher accuracy. Moreover, control testing shows that the developed model can be well applied to realize data-driven control of the BF process.« less

The importance of different frequency bands in predicting subcutaneous glucose concentration in type 1 diabetic patients.

PubMed

Lu, Yinghui; Gribok, Andrei V; Ward, W Kenneth; Reifman, Jaques

2010-08-01

We investigated the relative importance and predictive power of different frequency bands of subcutaneous glucose signals for the short-term (0-50 min) forecasting of glucose concentrations in type 1 diabetic patients with data-driven autoregressive (AR) models. The study data consisted of minute-by-minute glucose signals collected from nine deidentified patients over a five-day period using continuous glucose monitoring devices. AR models were developed using single and pairwise combinations of frequency bands of the glucose signal and compared with a reference model including all bands. The results suggest that: for open-loop applications, there is no need to explicitly represent exogenous inputs, such as meals and insulin intake, in AR models; models based on a single-frequency band, with periods between 60-120 min and 150-500 min, yield good predictive power (error <3 mg/dL) for prediction horizons of up to 25 min; models based on pairs of bands produce predictions that are indistinguishable from those of the reference model as long as the 60-120 min period band is included; and AR models can be developed on signals of short length (approximately 300 min), i.e., ignoring long circadian rhythms, without any detriment in prediction accuracy. Together, these findings provide insights into efficient development of more effective and parsimonious data-driven models for short-term prediction of glucose concentrations in diabetic patients.

Role of genetics in infection-associated arthritis.

PubMed

Benham, Helen; Robinson, Philip C; Baillet, Athan C; Rehaume, Linda M; Thomas, Ranjeny

2015-04-01

Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune-mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Response to a periodic stimulus in a perfect integrate-and-fire neuron model driven by colored noise.

PubMed

Mankin, Romi; Rekker, Astrid

2016-12-01

The output interspike interval statistics of a stochastic perfect integrate-and-fire neuron model driven by an additive exogenous periodic stimulus is considered. The effect of temporally correlated random activity of synaptic inputs is modeled by an additive symmetric dichotomous noise. Using a first-passage-time formulation, exact expressions for the output interspike interval density and for the serial correlation coefficient are derived in the nonsteady regime, and their dependence on input parameters (e.g., the noise correlation time and amplitude as well as the frequency of an input current) is analyzed. It is shown that an interplay of a periodic forcing and colored noise can cause a variety of nonequilibrium cooperation effects, such as sign reversals of the interspike interval correlations versus noise-switching rate as well as versus the frequency of periodic forcing, a power-law-like decay of oscillations of the serial correlation coefficients in the long-lag limit, amplification of the output signal modulation in the instantaneous firing rate of the neural response, etc. The features of spike statistics in the limits of slow and fast noises are also discussed.

Response to a periodic stimulus in a perfect integrate-and-fire neuron model driven by colored noise

NASA Astrophysics Data System (ADS)

Mankin, Romi; Rekker, Astrid

2016-12-01

The output interspike interval statistics of a stochastic perfect integrate-and-fire neuron model driven by an additive exogenous periodic stimulus is considered. The effect of temporally correlated random activity of synaptic inputs is modeled by an additive symmetric dichotomous noise. Using a first-passage-time formulation, exact expressions for the output interspike interval density and for the serial correlation coefficient are derived in the nonsteady regime, and their dependence on input parameters (e.g., the noise correlation time and amplitude as well as the frequency of an input current) is analyzed. It is shown that an interplay of a periodic forcing and colored noise can cause a variety of nonequilibrium cooperation effects, such as sign reversals of the interspike interval correlations versus noise-switching rate as well as versus the frequency of periodic forcing, a power-law-like decay of oscillations of the serial correlation coefficients in the long-lag limit, amplification of the output signal modulation in the instantaneous firing rate of the neural response, etc. The features of spike statistics in the limits of slow and fast noises are also discussed.

Distinguishing mechanisms of gamma frequency oscillations in human current source signals using a computational model of a laminar neocortical network

PubMed Central

Lee, Shane; Jones, Stephanie R.

2013-01-01

Gamma frequency rhythms have been implicated in numerous studies for their role in healthy and abnormal brain function. The frequency band has been described to encompass as broad a range as 30–150 Hz. Crucial to understanding the role of gamma in brain function is an identification of the underlying neural mechanisms, which is particularly difficult in the absence of invasive recordings in macroscopic human signals such as those from magnetoencephalography (MEG) and electroencephalography (EEG). Here, we studied features of current dipole (CD) signals from two distinct mechanisms of gamma generation, using a computational model of a laminar cortical circuit designed specifically to simulate CDs in a biophysically principled manner (Jones et al., 2007, 2009). We simulated spiking pyramidal interneuronal gamma (PING) whose period is regulated by the decay time constant of GABAA-mediated synaptic inhibition and also subthreshold gamma driven by gamma-periodic exogenous excitatory synaptic drive. Our model predicts distinguishable CD features created by spiking PING compared to subthreshold driven gamma that can help to disambiguate mechanisms of gamma oscillations in human signals. We found that gamma rhythms in neocortical layer 5 can obscure a simultaneous, independent gamma in layer 2/3. Further, we arrived at a novel interpretation of the origin of high gamma frequency rhythms (100–150 Hz), showing that they emerged from a specific temporal feature of CDs associated with single cycles of PING activity and did not reflect a separate rhythmic process. Last we show that the emergence of observable subthreshold gamma required highly coherent exogenous drive. Our results are the first to demonstrate features of gamma oscillations in human current source signals that distinguish cellular and circuit level mechanisms of these rhythms and may help to guide understanding of their functional role. PMID:24385958

Matching cue size and task properties in exogenous attention.

PubMed

Burnett, Katherine E; d'Avossa, Giovanni; Sapir, Ayelet

2013-01-01

Exogenous attention is an involuntary, reflexive orienting response that results in enhanced processing at the attended location. The standard view is that this enhancement generalizes across visual properties of a stimulus. We test whether the size of an exogenous cue sets the attentional field and whether this leads to different effects on stimuli with different visual properties. In a dual task with a random-dot kinematogram (RDK) in each quadrant of the screen, participants discriminated the direction of moving dots in one RDK and localized one red dot. Precues were uninformative and consisted of either a large or a small luminance-change frame. The motion discrimination task showed attentional effects following both large and small exogenous cues. The red dot probe localization task showed attentional effects following a small cue, but not a large cue. Two additional experiments showed that the different effects on localization were not due to reduced spatial uncertainty or suppression of RDK dots in the surround. These results indicate that the effects of exogenous attention depend on the size of the cue and the properties of the task, suggesting the involvement of receptive fields with different sizes in different tasks. These attentional effects are likely to be driven by bottom-up mechanisms in early visual areas.

How Does Awareness Modulate Goal-Directed and Stimulus-Driven Shifts of Attention Triggered by Value Learning?

PubMed Central

Bourgeois, Alexia; Neveu, Rémi; Vuilleumier, Patrik

2016-01-01

In order to behave adaptively, attention can be directed in space either voluntarily (i.e., endogenously) according to strategic goals, or involuntarily (i.e., exogenously) through reflexive capture by salient or novel events. The emotional or motivational value of stimuli can also strongly influence attentional orienting. However, little is known about how reward-related effects compete or interact with endogenous and exogenous attention mechanisms, particularly outside of awareness. Here we developed a visual search paradigm to study subliminal value-based attentional orienting. We systematically manipulated goal-directed or stimulus-driven attentional orienting and examined whether an irrelevant, but previously rewarded stimulus could compete with both types of spatial attention during search. Critically, reward was learned without conscious awareness in a preceding phase where one among several visual symbols was consistently paired with a subliminal monetary reinforcement cue. Our results demonstrated that symbols previously associated with a monetary reward received higher attentional priority in the subsequent visual search task, even though these stimuli and reward were no longer task-relevant, and despite reward being unconsciously acquired. Thus, motivational processes operating independent of conscious awareness may provide powerful influences on mechanisms of attentional selection, which could mitigate both stimulus-driven and goal-directed shifts of attention. PMID:27483371

Modeling the integration of bacterial rRNA fragments into the human cancer genome.

PubMed

Sieber, Karsten B; Gajer, Pawel; Dunning Hotopp, Julie C

2016-03-21

Cancer is a disease driven by the accumulation of genomic alterations, including the integration of exogenous DNA into the human somatic genome. We previously identified in silico evidence of DNA fragments from a Pseudomonas-like bacteria integrating into the 5'-UTR of four proto-oncogenes in stomach cancer sequencing data. The functional and biological consequences of these bacterial DNA integrations remain unknown. Modeling of these integrations suggests that the previously identified sequences cover most of the sequence flanking the junction between the bacterial and human DNA. Further examination of these reads reveals that these integrations are rich in guanine nucleotides and the integrated bacterial DNA may have complex transcript secondary structures. The models presented here lay the foundation for future experiments to test if bacterial DNA integrations alter the transcription of the human genes.

Endogenous circadian regulation of carbon dioxide exchange in terrestrial ecosystems

Treesearch

Victor Resco de Dios; Michael L. Goulden; Kiona Ogle; Andrew D. Richardson; David Y. Hollinger; Eric A. Davidson; Josu G. Alday; Greg A. Barron-Gafford; Arnaud Carrara; Andrew S. Kowalski; Walt C. Oechel; Borja R. Reverter; Russell L. Scott; Ruth K. Varner; Ruben Diaz-Sierra; Jose M. Moreno

2012-01-01

It is often assumed that daytime patterns of ecosystem carbon assimilation are mostly driven by direct physiological responses to exogenous environmental cues. Under limited environmental variability, little variation in carbon assimilation should thus be expected unless endogenous plant controls on carbon assimilation, which regulate photosynthesis in time, are active...

Placental growth factor neutralising antibodies give limited anti-angiogenic effects in an in vitro organotypic angiogenesis model.

PubMed

Brave, Sandra R; Eberlein, Cath; Shibuya, Masabumi; Wedge, Stephen R; Barry, Simon T

2010-12-01

Vascular Endothelial Growth Factor Receptor (VEGFR) mediated signalling drives angiogenesis. This is predominantly attributed to the activity of VEGFR-2 following binding of VEGF-A. Whether other members of the VEGFR and ligand families such as VEGFR-1 and its ligand Placental Growth Factor (PlGF) can also contribute to developmental and pathological angiogenesis is less clear. We explored the function of PlGF in VEGF-A dependent angiogenesis using an in vitro co-culture assay in which endothelial cells are cultured on a fibroblast feeder layer. In the presence of 2% FS MCDB media (containing limited growth factors) in vitro endothelial tube formation is driven by endogenous angiogenic stimuli which are produced by the fibroblast and endothelial cells. Under these conditions independent sequestration of either free VEGF-A or PlGF with polyclonal and monoclonal antibodies inhibited tube formation suggesting that both ligands are required to drive an angiogenic response. Endothelial tube formation could only be driven within this assay by the addition of exogenous VEGF-A, VEGF-E or VEGF-A/PlGF heterodimer, but not by PlGF alone, implying that activation of either VEGFR-2/VEGFR-1 heterodimers or VEGFR-2 homodimers were responsible for eliciting an angiogenic response directly, but not VEGFR-1 homodimers. In contrast to results obtained with an endogenous angiogenic drive, sequestration of PlGF did not affect endothelial tube formation when the assay was driven by 1 ng/ml exogenous VEGF-A. These data suggest that although neutralising PlGF can be shown to reduce endothelial tube formation in vitro, this effect is only observed under restricted culture conditions and is influenced by VEGF-A. Such data questions whether neutralising PlGF would have a therapeutic benefit in vivo in the presence of pathological concentrations of VEGF-A.

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

PubMed

Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

2015-07-01

Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

A Data-driven Approach for Forecasting Next-day River Discharge

NASA Astrophysics Data System (ADS)

Sharif, H. O.; Billah, K. S.

2017-12-01

This study focuses on evaluating the performance of the Soil and Water Assessment Tool (SWAT) eco-hydrological model, a simple Auto-Regressive with eXogenous input (ARX) model, and a Gene expression programming (GEP)-based model in one-day-ahead forecasting of discharge of a subtropical basin (the upper Kentucky River Basin). The three models were calibrated with daily flow at the US Geological Survey (USGS) stream gauging station not affected by flow regulation for the period of 2002-2005. The calibrated models were then validated at the same gauging station as well as another USGS gauge 88 km downstream for the period of 2008-2010. The results suggest that simple models outperform a sophisticated hydrological model with GEP having the advantage of being able to generate functional relationships that allow scientific investigation of the complex nonlinear interrelationships among input variables. Unlike SWAT, GEP, and to some extent, ARX are less sensitive to the length of the calibration time series and do not require a spin-up period.

Exogenous attention to fear: Differential behavioral and neural responses to snakes and spiders.

PubMed

Soares, Sandra C; Kessel, Dominique; Hernández-Lorca, María; García-Rubio, María J; Rodrigues, Paulo; Gomes, Nuno; Carretié, Luis

2017-05-01

Research has consistently shown that threat stimuli automatically attract attention in order to activate the defensive response systems. Recent findings have provided evidence that snakes tuned the visual system of evolving primates for their astute detection, particularly under challenging perceptual conditions. The goal of the present study was to measure behavioral and electrophysiological indices of exogenous attention to snakes, compared with spiders - matched for rated fear levels but for which sources of natural selection are less well grounded, and to innocuous animals (birds), which were presented as distracters, while participants were engaged in a letter discrimination task. Duration of stimuli, consisting in a letter string and a concurrent distracter, was either presented for 180 or 360ms to explore if the stimulus duration was a modulating effect of snakes in capturing attention. Results showed a specific early (P1) exogenous attention-related brain potential with maximal amplitude to snakes in both durations, which was followed by an enhanced late attention-related potential (LPP) showing enhanced amplitudes to spiders, particularly under the longer exposure durations. These results suggest that exogenous attention to different classes of threat stimuli follows a gradual process, with the most evolutionary-driven stimulus, i.e., snakes, being more efficient at attracting early exogenous attention, thus more dependent on bottom-up processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unique sudden onsets capture attention even when observers are in feature-search mode.

PubMed

Spalek, Thomas M; Yanko, Matthew R; Poiese, Paola; Lagroix, Hayley E P

2012-01-01

Two sources of attentional capture have been proposed: stimulus-driven (exogenous) and goal-oriented (endogenous). A resolution between these modes of capture has not been straightforward. Even such a clearly exogenous event as the sudden onset of a stimulus can be said to capture attention endogenously if observers operate in singleton-detection mode rather than feature-search mode. In four experiments we show that a unique sudden onset captures attention even when observers are in feature-search mode. The displays were rapid serial visual presentation (RSVP) streams of differently coloured letters with the target letter defined by a specific colour. Distractors were four #s, one of the target colour, surrounding one of the non-target letters. Capture was substantially reduced when the onset of the distractor array was not unique because it was preceded by other sets of four grey # arrays in the RSVP stream. This provides unambiguous evidence that attention can be captured both exogenously and endogenously within a single task.

Increased oxidative phosphorylation in response to acute and chronic DNA damage

PubMed Central

Brace, Lear E; Vose, Sarah C; Stanya, Kristopher; Gathungu, Rose M; Marur, Vasant R; Longchamp, Alban; Treviño-Villarreal, Humberto; Mejia, Pedro; Vargas, Dorathy; Inouye, Karen; Bronson, Roderick T; Lee, Chih-Hao; Neilan, Edward; Kristal, Bruce S; Mitchell, James R

2016-01-01

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa−/−|Xpa−/− mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes. PMID:28721274

Optimization of autoregressive, exogenous inputs-based typhoon inundation forecasting models using a multi-objective genetic algorithm

NASA Astrophysics Data System (ADS)

Ouyang, Huei-Tau

2017-07-01

Three types of model for forecasting inundation levels during typhoons were optimized: the linear autoregressive model with exogenous inputs (LARX), the nonlinear autoregressive model with exogenous inputs with wavelet function (NLARX-W) and the nonlinear autoregressive model with exogenous inputs with sigmoid function (NLARX-S). The forecast performance was evaluated by three indices: coefficient of efficiency, error in peak water level and relative time shift. Historical typhoon data were used to establish water-level forecasting models that satisfy all three objectives. A multi-objective genetic algorithm was employed to search for the Pareto-optimal model set that satisfies all three objectives and select the ideal models for the three indices. Findings showed that the optimized nonlinear models (NLARX-W and NLARX-S) outperformed the linear model (LARX). Among the nonlinear models, the optimized NLARX-W model achieved a more balanced performance on the three indices than the NLARX-S models and is recommended for inundation forecasting during typhoons.

Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor.

PubMed

Piccotti, J R; Li, K; Chan, S Y; Eichwald, E J; Bishop, D K

1999-06-15

Interleukin-12 (IL-12) mediates its biologic activities via binding high-affinity receptors on T and natural killer cells. Although emphasis has been placed on the requirement for IL-12Rbeta2 in IL-12 bioactivity, the role of IL-12Rbeta1 is less well defined. The current study evaluated the effects of exogenous IL-12 on alloantigen-specific immune responses and determined the requirement for IL-12Rbeta1 in IL-12-mediated alloimmunity. The mouse heterotopic cardiac transplant model was employed to evaluate the effects of IL-12 on alloantigen-specific immune responses in vivo. In addition, IFN-gamma production in mixed lymphocyte cultures (MLC) supplemented with IL-12 was measured to assess the effects of IL-12 on Th1 function in vitro. Mice deficient in IL-12Rbeta1 (IL-12Rbeta1-/-) were used to determine the requirement for this receptor component in IL-12-driven alloimmune responses. Addition of IL-12 to MLC consisting of wild-type splenocytes enhanced alloantigen-specific proliferative responses and Th1 development. In contrast, IL-12 did not alter these in vitro immune parameters in IL-12Rbeta1-/- MLC. Treatment of wild-type cardiac allograft recipients with IL-12 resulted in high concentrations of serum interferon-gamma (IFN-gamma) and a 10-fold increase in IFN-gamma production by recipient splenocytes after restimulation in vitro. However, this fulminate Th1 response did not accelerate allograft rejection. Importantly, IL-12 had no effect on serum IFN-gamma or in vivo priming of Thl in IL-12Rbeta1-/- recipients. Finally, administration of IL-12 to WT allograft recipients resulted in a bimodal alloantibody response: antibody production was suppressed at high doses of IL-12, and enhanced at lower doses. IL-12 markedly enhances alloantigen-specific immune function; however, these exaggerated Th1-driven responses do not culminate in accelerated allograft rejection. Further, these data indicate that IL-12Rbeta1 is essential for the enhancement of both in vitro and in vivo alloimmune responses by exogenous IL-12.

The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

PubMed

Puntorieri, Valeria; Hiansen, Josh Qua; McCaig, Lynda A; Yao, Li-Juan; Veldhuizen, Ruud A W; Lewis, James F

2013-11-20

Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation. Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours). For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate. The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

New Evidence of the Causal Effect of Family Size on Child Quality in a Developing Country

ERIC Educational Resources Information Center

Ponczek, Vladimir; Souza, Andre Portela

2012-01-01

This paper presents new evidence of the causal effect of family size on child quality in a developing-country context. We estimate the impact of family size on child labor and educational outcomes among Brazilian children and young adults by exploring the exogenous variation of family size driven by the presence of twins in the family. Using the…

Exogenous spatial attention decreases audiovisual integration.

PubMed

Van der Stoep, N; Van der Stigchel, S; Nijboer, T C W

2015-02-01

Multisensory integration (MSI) and spatial attention are both mechanisms through which the processing of sensory information can be facilitated. Studies on the interaction between spatial attention and MSI have mainly focused on the interaction between endogenous spatial attention and MSI. Most of these studies have shown that endogenously attending a multisensory target enhances MSI. It is currently unclear, however, whether and how exogenous spatial attention and MSI interact. In the current study, we investigated the interaction between these two important bottom-up processes in two experiments. In Experiment 1 the target location was task-relevant, and in Experiment 2 the target location was task-irrelevant. Valid or invalid exogenous auditory cues were presented before the onset of unimodal auditory, unimodal visual, and audiovisual targets. We observed reliable cueing effects and multisensory response enhancement in both experiments. To examine whether audiovisual integration was influenced by exogenous spatial attention, the amount of race model violation was compared between exogenously attended and unattended targets. In both Experiment 1 and Experiment 2, a decrease in MSI was observed when audiovisual targets were exogenously attended, compared to when they were not. The interaction between exogenous attention and MSI was less pronounced in Experiment 2. Therefore, our results indicate that exogenous attention diminishes MSI when spatial orienting is relevant. The results are discussed in terms of models of multisensory integration and attention.

Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin

PubMed Central

Saha, Suvrajit; Lee, Il-Hyung; Polley, Anirban; Groves, Jay T.; Rao, Madan; Mayor, Satyajit

2015-01-01

Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24–37°C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature-dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI-anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an “active actin-membrane composite” cell surface. PMID:26378258

Dynamics of tuberculosis transmission with exogenous reinfections and endogenous reactivation

NASA Astrophysics Data System (ADS)

Khajanchi, Subhas; Das, Dhiraj Kumar; Kar, Tapan Kumar

2018-05-01

We propose and analyze a mathematical model for tuberculosis (TB) transmission to study the role of exogenous reinfection and endogenous reactivation. The model exhibits two equilibria: a disease free and an endemic equilibria. We observe that the TB model exhibits transcritical bifurcation when basic reproduction number R0 = 1. Our results demonstrate that the disease transmission rate β and exogenous reinfection rate α plays an important role to change the qualitative dynamics of TB. The disease transmission rate β give rises to the possibility of backward bifurcation for R0 < 1, and hence the existence of multiple endemic equilibria one of which is stable and another one is unstable. Our analysis suggests that R0 < 1 may not be sufficient to completely eliminate the disease. We also investigate that our TB transmission model undergoes Hopf-bifurcation with respect to the contact rate β and the exogenous reinfection rate α. We conducted some numerical simulations to support our analytical findings.

Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid

PubMed Central

Menon, Deepak; Salloum, Darin; Bernfeld, Elyssa; Gorodetsky, Elizabeth; Akselrod, Alla; Frias, Maria A.; Sudderth, Jessica; Chen, Pei-Hsuan; DeBerardinis, Ralph; Foster, David A.

2017-01-01

mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA) interacts with the FK506-binding protein–12-rapamycin-binding (FRB) domain of mTOR, which stabilizes both mTOR complexes: mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis. We examined the impact of exogenously supplied fatty acids on mTOR in KRas-driven cancer cells, which are programmed to utilize exogenous lipids. The induction of mTOR by oleic acid was dependent upon the enzymes responsible for de novo synthesis of PA. Suppression of the de novo synthesis of PA resulted in G1 cell cycle arrest. Although it has long been appreciated that mTOR is a sensor of amino acids and glucose, this study reveals that mTOR also senses the presence of lipids via production of PA. PMID:28223357

Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid.

PubMed

Menon, Deepak; Salloum, Darin; Bernfeld, Elyssa; Gorodetsky, Elizabeth; Akselrod, Alla; Frias, Maria A; Sudderth, Jessica; Chen, Pei-Hsuan; DeBerardinis, Ralph; Foster, David A

2017-04-14

mTOR, the mammalian target of rapamycin, integrates growth factor and nutrient signals to promote a transformation from catabolic to anabolic metabolism, cell growth, and cell cycle progression. Phosphatidic acid (PA) interacts with the FK506-binding protein-12-rapamycin-binding (FRB) domain of mTOR, which stabilizes both mTOR complexes: mTORC1 and mTORC2. We report here that mTORC1 and mTORC2 are activated in response to exogenously supplied fatty acids via the de novo synthesis of PA, a central metabolite for membrane phospholipid biosynthesis. We examined the impact of exogenously supplied fatty acids on mTOR in KRas-driven cancer cells, which are programmed to utilize exogenous lipids. The induction of mTOR by oleic acid was dependent upon the enzymes responsible for de novo synthesis of PA. Suppression of the de novo synthesis of PA resulted in G 1 cell cycle arrest. Although it has long been appreciated that mTOR is a sensor of amino acids and glucose, this study reveals that mTOR also senses the presence of lipids via production of PA. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Time-Perception Network and Default Mode Network Are Associated with Temporal Prediction in a Periodic Motion Task

PubMed Central

Carvalho, Fabiana M.; Chaim, Khallil T.; Sanchez, Tiago A.; de Araujo, Draulio B.

2016-01-01

The updating of prospective internal models is necessary to accurately predict future observations. Uncertainty-driven internal model updating has been studied using a variety of perceptual paradigms, and have revealed engagement of frontal and parietal areas. In a distinct literature, studies on temporal expectations have also characterized a time-perception network, which relies on temporal orienting of attention. However, the updating of prospective internal models is highly dependent on temporal attention, since temporal attention must be reoriented according to the current environmental demands. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate to what extend the continuous manipulation of temporal prediction would recruit update-related areas and the time-perception network areas. We developed an exogenous temporal task that combines rhythm cueing and time-to-contact principles to generate implicit temporal expectation. Two patterns of motion were created: periodic (simple harmonic oscillation) and non-periodic (harmonic oscillation with variable acceleration). We found that non-periodic motion engaged the exogenous temporal orienting network, which includes the ventral premotor and inferior parietal cortices, and the cerebellum, as well as the presupplementary motor area, which has previously been implicated in internal model updating, and the motion-sensitive area MT+. Interestingly, we found a right-hemisphere preponderance suggesting the engagement of explicit timing mechanisms. We also show that the periodic motion condition, when compared to the non-periodic motion, activated a particular subset of the default-mode network (DMN) midline areas, including the left dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and bilateral posterior cingulate cortex/precuneus (PCC/PC). It suggests that the DMN plays a role in processing contextually expected information and supports recent evidence that the DMN may reflect the validation of prospective internal models and predictive control. Taken together, our findings suggest that continuous manipulation of temporal predictions engages representations of temporal prediction as well as task-independent updating of internal models. PMID:27313526

Testing competing forms of the Milankovitch hypothesis: A multivariate approach

NASA Astrophysics Data System (ADS)

Kaufmann, Robert K.; Juselius, Katarina

2016-02-01

We test competing forms of the Milankovitch hypothesis by estimating the coefficients and diagnostic statistics for a cointegrated vector autoregressive model that includes 10 climate variables and four exogenous variables for solar insolation. The estimates are consistent with the physical mechanisms postulated to drive glacial cycles. They show that the climate variables are driven partly by solar insolation, determining the timing and magnitude of glaciations and terminations, and partly by internal feedback dynamics, pushing the climate variables away from equilibrium. We argue that the latter is consistent with a weak form of the Milankovitch hypothesis and that it should be restated as follows: internal climate dynamics impose perturbations on glacial cycles that are driven by solar insolation. Our results show that these perturbations are likely caused by slow adjustment between land ice volume and solar insolation. The estimated adjustment dynamics show that solar insolation affects an array of climate variables other than ice volume, each at a unique rate. This implies that previous efforts to test the strong form of the Milankovitch hypothesis by examining the relationship between solar insolation and a single climate variable are likely to suffer from omitted variable bias.

Exogenous and Endogenous Learning Resources in the Actiotope Model of Giftedness and Its Significance for Gifted Education

ERIC Educational Resources Information Center

Ziegler, Albert; Chandler, Kimberley L.; Vialle, Wilma; Stoeger, Heidrun

2017-01-01

Based on the Actiotope Model of Giftedness, this article introduces a learning-resource-oriented approach for gifted education. It provides a comprehensive categorization of learning resources, including five exogenous learning resources termed "educational capital" and five endogenous learning resources termed "learning…

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

Rewards modulate saccade latency but not exogenous spatial attention.

PubMed

Dunne, Stephen; Ellison, Amanda; Smith, Daniel T

2015-01-01

The eye movement system is sensitive to reward. However, whilst the eye movement system is extremely flexible, the extent to which changes to oculomotor behavior induced by reward paradigms persist beyond the training period or transfer to other oculomotor tasks is unclear. To address these issues we examined the effects of presenting feedback that represented small monetary rewards to spatial locations on the latency of saccadic eye movements, the time-course of learning and extinction of the effects of rewarding saccades on exogenous spatial attention and oculomotor inhibition of return. Reward feedback produced a relative facilitation of saccadic latency in a stimulus driven saccade task which persisted for three blocks of extinction trials. However, this hemifield-specific effect failed to transfer to peripheral cueing tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor or attention systems.

When can the cause of a population decline be determined?

PubMed

Hefley, Trevor J; Hooten, Mevin B; Drake, John M; Russell, Robin E; Walsh, Daniel P

2016-11-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time. © 2016 John Wiley & Sons Ltd/CNRS.

When can the cause of a population decline be determined?

USGS Publications Warehouse

Hefley, Trevor J.; Hooten, Mevin B.; Drake, John M.; Russell, Robin E.; Walsh, Daniel P.

2016-01-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.

Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis.

PubMed

Zhou, S; Wang, Z; Tang, J; Li, W; Huang, J; Xu, W; Luo, F; Xu, M; Wang, J; Wen, X; Chen, L; Chen, H; Su, N; Shen, Y; Du, X; Xie, Y; Chen, L

2016-12-01

The aim of the present study is to investigate the effects of exogenous fibroblast growth factor (FGF)9 on the progression of post-traumatic osteoarthritis (OA). The expression of FGF9 in articular cartilage with OA is detected by immunohistochemistry (IHC). The effects of intra-articular exogenous FGF9 injection on post-traumatic OA induced by the destabilization of the medial meniscus (DMM) surgery are evaluated. Cartilage changes and osteophyte formation in knee joints are investigated by histological analysis. Changes in subchondral bone are evaluated by microcomputed tomography (micro-CT). The effect of exogenous FGF9 on an interleukin-1β (IL-1β)-induced ex vivo OA model of human articular cartilage tissues is also evaluated. FGF9 expression was down-regulated in articular chondrocytes of OA but ectopically induced at sites of osteophyte formation. Intra-articular injection of exogenous FGF9 attenuated articular cartilage degradation in mice after DMM surgery. Exogenous FGF9 suppressed collagen X and MMP13 expressions in OA cartilage, while promoted collagen II expression. Similar results were observed in IL-1β-induced ex vivo OA model. Intra-articular injection of FGF9 had no significant effect on the subchondral bone of knee joints after DMM surgery, but aggravated osteophyte formation. The expressions of SOX9 and collagen II, and cell proliferation were up-regulated at sites of initial osteophyte formation in mice with exogenous FGF9 treatment. Intra-articular injection of exogenous FGF9 delays articular cartilage degradation in post-traumatic OA, while aggravates osteophyte formation. Copyright © 2016. Published by Elsevier Ltd.

[Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer].

PubMed

Wang, Qing-fei; Ding, Hui; Liu, Bao-rui; Zhang, Kui

2014-07-01

To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties. The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed. Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models. Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.

Restoring the encoding properties of a stochastic neuron model by an exogenous noise

PubMed Central

Paffi, Alessandra; Camera, Francesca; Apollonio, Francesca; d'Inzeo, Guglielmo; Liberti, Micaela

2015-01-01

Here we evaluate the possibility of improving the encoding properties of an impaired neuronal system by superimposing an exogenous noise to an external electric stimulation signal. The approach is based on the use of mathematical neuron models consisting of stochastic HH-like circuit, where the impairment of the endogenous presynaptic inputs is described as a subthreshold injected current and the exogenous stimulation signal is a sinusoidal voltage perturbation across the membrane. Our results indicate that a correlated Gaussian noise, added to the sinusoidal signal can significantly increase the encoding properties of the impaired system, through the Stochastic Resonance (SR) phenomenon. These results suggest that an exogenous noise, suitably tailored, could improve the efficacy of those stimulation techniques used in neuronal systems, where the presynaptic sensory neurons are impaired and have to be artificially bypassed. PMID:25999845

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

PubMed

Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Micro-level dynamics of the online information propagation: A user behavior model based on noisy spiking neurons.

PubMed

Lymperopoulos, Ilias N; Ioannou, George D

2016-10-01

We develop and validate a model of the micro-level dynamics underlying the formation of macro-level information propagation patterns in online social networks. In particular, we address the dynamics at the level of the mechanism regulating a user's participation in an online information propagation process. We demonstrate that this mechanism can be realistically described by the dynamics of noisy spiking neurons driven by endogenous and exogenous, deterministic and stochastic stimuli representing the influence modulating one's intention to be an information spreader. Depending on the dynamically changing influence characteristics, time-varying propagation patterns emerge reflecting the temporal structure, strength, and signal-to-noise ratio characteristics of the stimulation driving the online users' information sharing activity. The proposed model constitutes an overarching, novel, and flexible approach to the modeling of the micro-level mechanisms whereby information propagates in online social networks. As such, it can be used for a comprehensive understanding of the online transmission of information, a process integral to the sociocultural evolution of modern societies. The proposed model is highly adaptable and suitable for the study of the propagation patterns of behavior, opinions, and innovations among others. Copyright © 2016 Elsevier Ltd. All rights reserved.

The stochastic resonance for the incidence function model of metapopulation

NASA Astrophysics Data System (ADS)

Li, Jiang-Cheng; Dong, Zhi-Wei; Zhou, Ruo-Wei; Li, Yun-Xian; Qian, Zhen-Wei

2017-06-01

A stochastic model with endogenous and exogenous periodicities is proposed in this paper on the basis of metapopulation dynamics to model the crop yield losses due to pests and diseases. The rationale is that crop yield losses occur because the physiology of the growing crop is negatively affected by pests and diseases in a dynamic way over time as crop both grows and develops. Metapopulation dynamics can thus be used to model the resultant crop yield losses. The stochastic metapopulation process is described by using the Simplified Incidence Function model (IFM). Compared to the original IFMs, endogenous and exogenous periodicities are considered in the proposed model to handle the cyclical patterns observed in pest infestations, diseases epidemics, and exogenous affecting factors such as temperature and rainfalls. Agricultural loss data in China are used to fit the proposed model. Experimental results demonstrate that: (1) Model with endogenous and exogenous periodicities is a better fit; (2) When the internal system fluctuations and external environmental fluctuations are negatively correlated, EIL or the cost of loss is monotonically increasing; when the internal system fluctuations and external environmental fluctuations are positively correlated, an outbreak of pests and diseases might occur; (3) If the internal system fluctuations and external environmental fluctuations are positively correlated, an optimal patch size can be identified which will greatly weaken the effects of external environmental influence and hence inhibit pest infestations and disease epidemics.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

PubMed

Zhao, Rong; Chen, Ni-Nan; Zhou, Xiao-Wei; Miao, Ping; Hu, Chao-Ying; Qian, Liu; Yu, Qi-Wen; Zhang, Ji-Ying; Nie, Hong; Chen, Xue-hua; Li, Pu; Xu, Rong; Xiao, Lian-Bo; Zhang, Xin; Liu, Jian-Ren; Zhang, Dong-Qing

2014-12-10

Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon β (IFN-β) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-β on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-β was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-β expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-β on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-β. The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-β intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-β in the joint bones was decreased. After IFN-β administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-β directly inhibited RANKL-induced osteoclastogenesis. Exogenous IFN-β administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-β intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-β expression.

US Food Security and Climate Change: Mid-Century Projections of Commodity Crop Production by the IMPACT Model

NASA Astrophysics Data System (ADS)

Takle, E. S.; Gustafson, D. I.; Beachy, R.; Nelson, G. C.; Mason-D'Croz, D.; Palazzo, A.

2013-12-01

Agreement is developing among agricultural scientists on the emerging inability of agriculture to meet growing global food demands. The lack of additional arable land and availability of freshwater have long been constraints on agriculture. Changes in trends of weather conditions that challenge physiological limits of crops, as projected by global climate models, are expected to exacerbate the global food challenge toward the middle of the 21st century. These climate- and constraint-driven crop production challenges are interconnected within a complex global economy, where diverse factors add to price volatility and food scarcity. We use the DSSAT crop modeling suite, together with mid-century projections of four AR4 global models, as input to the International Food Policy Research Institute IMPACT model to project the impact of climate change on food security through the year 2050 for internationally traded crops. IMPACT is an iterative model that responds to endogenous and exogenous drivers to dynamically solve for the world prices that ensure global supply equals global demand. The modeling methodology reconciles the limited spatial resolution of macro-level economic models that operate through equilibrium-driven relationships at a national level with detailed models of biophysical processes at high spatial resolution. The analysis presented here suggests that climate change in the first half of the 21st century does not represent a near-term threat to food security in the US due to the availability of adaptation strategies (e.g., loss of current growing regions is balanced by gain of new growing regions). However, as climate continues to trend away from 20th century norms current adaptation measures will not be sufficient to enable agriculture to meet growing food demand. Climate scenarios from higher-level carbon emissions exacerbate the food shortfall, although uncertainty in climate model projections (particularly precipitation) is a limitation to impact studies.

Understanding the Effects of Users' Behaviors on Effectiveness of Different Exogenous Regulatory Common Pool Resource Management Institutions

NASA Astrophysics Data System (ADS)

Madani, K.; Dinar, A.

2013-12-01

Tragedy of the commons is generally recognized as one of the possible destinies for common pool resources (CPRs). To avoid the tragedy of the commons and prolonging the life of CPRs, users may show different behavioral characteristics and use different rationales for CPR planning and management. Furthermore, regulators may adopt different strategies for sustainable management of CPRs. The effectiveness of different regulatory exogenous management institutions cannot be evaluated through conventional CPR models since they assume that either users base their behavior on individual rationality and adopt a selfish behavior (Nash behavior), or that the users seek the system's optimal solution without giving priority to their own interests. Therefore, conventional models fail to reliably predict the outcome of CPR problems in which parties may have a range of behavioral characteristics, putting them somewhere in between the two types of behaviors traditionally considered. This work examines the effectiveness of different regulatory exogenous CPR management institutions through a user-based model (as opposed to a system-based model). The new modeling framework allows for consideration of sensitivity of the results to different behavioral characteristics of interacting CPR users. The suggested modeling approach is applied to a benchmark groundwater management problem. Results indicate that some well-known exogenous management institutions (e.g. taxing) are ineffective in sustainable management of CPRs in most cases. Bankruptcy-based management can be helpful, but determination of the fair level of cutbacks remains challenging under this type of institution. Furthermore, some bankruptcy rules such as the Constrained Equal Award (CEA) method are more beneficial to wealthier users, failing to establish social justice. Quota-based and CPR status-based management perform as the most promising and robust regulatory exogenous institutions in prolonging the CPR's life and increasing the long-term benefits to its users.

Long-chain bases and their phosphorylated derivatives differentially regulate cryptogein-induced production of reactive oxygen species in tobacco (Nicotiana tabacum) BY-2 cells.

PubMed

Coursol, Sylvie; Fromentin, Jérôme; Noirot, Elodie; Brière, Christian; Robert, Franck; Morel, Johanne; Liang, Yun-Kuan; Lherminier, Jeannine; Simon-Plas, Françoise

2015-02-01

The proteinaceous elicitor cryptogein triggers defence reactions in Nicotiana tabacum (tobacco) through a signalling cascade, including the early production of reactive oxygen species (ROS) by the plasma membrane (PM)-located tobacco respiratory burst oxidase homologue D (NtRbohD). Sphingolipid long-chain bases (LCBs) are emerging as potent positive regulators of plant defence-related mechanisms. This led us to question whether both LCBs and their phosphorylated derivatives (LCB-Ps) are involved in the early signalling process triggered by cryptogein in tobacco BY-2 cells. Here, we showed that cryptogein-induced ROS production was inhibited by LCB kinase (LCBK) inhibitors. Additionally, Arabidopsis thaliana sphingosine kinase 1 and exogenously supplied LCB-Ps increased cryptogein-induced ROS production, whereas exogenously supplied LCBs had a strong opposite effect, which was not driven by a reduction in cellular viability. Immunogold-electron microscopy assay also revealed that LCB-Ps are present in the PM, which fits well with the presence of a high LCBK activity associated with this fraction. Our data demonstrate that LCBs and LCB-Ps differentially regulate cryptogein-induced ROS production in tobacco BY-2 cells, and support a model in which a cooperative synergism between LCBK/LCB-Ps and NtRbohD/ROS in the cryptogein signalling pathway is likely at the PM in tobacco BY-2 cells. © 2014 INRA New Phytologist © 2014 New Phytologist Trust.

A Mathematical Model of the Circadian Phase-Shifting Effects of Exogenous Melatonin

PubMed Central

Breslow, Emily R.; Phillips, Andrew J.K.; Huang, Jean M.; St. Hilaire, Melissa A.; Klerman, Elizabeth B.

2013-01-01

Melatonin is endogenously produced and released in humans during nighttime darkness and is suppressed by ocular light exposure. Exogenous melatonin is used to induce circadian phase shifts and sleep. The circadian phase-shifting ability of a stimulus (e.g., melatonin or light) relative to its timing may be displayed as a phase response curve (PRC). Published PRCs to exogenous melatonin show a transition from phase advances to delays approximately 1 h after dim light melatonin onset. A previously developed mathematical model simulates endogenous production and clearance of melatonin as a function of circadian phase, light-induced suppression, and resetting of circadian phase by light. We extend this model to include the pharmacokinetics of oral exogenous melatonin and phase-shifting effects via melatonin receptors in the suprachiasmatic nucleus of the mammalian hypothalamus. Model parameters are fit using 2 data sets: (1) blood melatonin concentration following a 0.3- or 5.0-mg dose, and (2) a PRC to a 3.0-mg dose of melatonin. After fitting to the 3.0-mg PRC, the model correctly predicts that, by comparison, the 0.5-mg PRC is slightly decreased in amplitude and shifted to a later circadian phase. This model also reproduces blood concentration profiles of various melatonin preparations that differ only in absorption rate and percentage degradation by first-pass hepatic metabolism. This model can simulate experimental protocols using oral melatonin, with potential application to guide dose size and timing to optimally shift and entrain circadian rhythms. PMID:23382594

EFFECTS OF EXOGENOUS ESTROGEN ON MATE SELECTION OF HOUSE FINCHES

EPA Science Inventory

Concern about the potential for endocrine disrupting chemicals to interfere with normal breeding behaviors of wildlife has prompted this study of effects of exogenous estrogen on mate selection in songbirds. The house finch (Carpodacus mexicanus) was selected as a model as it is ...

Exogenic and endogenic albedo and color patterns on Europa

NASA Technical Reports Server (NTRS)

Mcewen, A. S.

1986-01-01

New global and high-resolution multispectral mosaics of Europa have been produced from the Voyager imaging data. Photometric normalizations are based on multiple-image techniques that explicitly account for intrinsic albedo variations through pixel-by-pixel solutions. The exogenic color and albedo pattern on Europa is described by a second-order function of the cosine of the angular distance from the apex of orbital motion. On the basis of this second-order function and of color trends that are different on the leading and trailing hemispheres, the exogenic pattern is interpreted as being due to equilibrium between two dominant processes: (1) impact gardening and (2) magnetospheric interactions, including sulfur-ion implantation and sputtering redistribution. Removal of the model exogenic pattern in the mosaics reveals the endogenic variations, consisting of only two major units: darker (redder) and bright materials. Therefore Europa's visual spectral reflectivity is simple, having one continuous exogenic pattern and two discrete endogenic units.

Buyer and seller data from pay what you want and name your own price laboratory markets.

PubMed

Krämer, Florentin; Schmidt, Klaus M; Spann, Martin; Stich, Lucas

2017-06-01

Pay What You Want (PWYW) and Name Your Own Price (NYOP) are customer-driven pricing mechanisms that give customers (some) pricing power and that have been used in service industries with high fixed costs to price discriminate without setting a reference price. This paper describes buyer and seller data in a series of induced-value laboratory experiments that compare PWYW and NYOP in monopoly and competitive situations. Sellers are in a one-shot interaction with buyers. Sellers using customer-driven pricing mechanisms may exogenously or endogenously receive additional promotional benefits, for instance through word-of-mouth effects. The major findings based on the data presented here are reported in the paper "Delegating Pricing Power to Customers: Pay What You Want or Name Your Own Price?" (Krämer et al., 2017) [3].

Macro-level vulnerable road users crash analysis: A Bayesian joint modeling approach of frequency and proportion.

PubMed

Cai, Qing; Abdel-Aty, Mohamed; Lee, Jaeyoung

2017-10-01

This study aims at contributing to the literature on pedestrian and bicyclist safety by building on the conventional count regression models to explore exogenous factors affecting pedestrian and bicyclist crashes at the macroscopic level. In the traditional count models, effects of exogenous factors on non-motorist crashes were investigated directly. However, the vulnerable road users' crashes are collisions between vehicles and non-motorists. Thus, the exogenous factors can affect the non-motorist crashes through the non-motorists and vehicle drivers. To accommodate for the potentially different impact of exogenous factors we convert the non-motorist crash counts as the product of total crash counts and proportion of non-motorist crashes and formulate a joint model of the negative binomial (NB) model and the logit model to deal with the two parts, respectively. The formulated joint model is estimated using non-motorist crash data based on the Traffic Analysis Districts (TADs) in Florida. Meanwhile, the traditional NB model is also estimated and compared with the joint model. The result indicates that the joint model provides better data fit and can identify more significant variables. Subsequently, a novel joint screening method is suggested based on the proposed model to identify hot zones for non-motorist crashes. The hot zones of non-motorist crashes are identified and divided into three types: hot zones with more dangerous driving environment only, hot zones with more hazardous walking and cycling conditions only, and hot zones with both. It is expected that the joint model and screening method can help decision makers, transportation officials, and community planners to make more efficient treatments to proactively improve pedestrian and bicyclist safety. Published by Elsevier Ltd.

Dihydroxyacetone induces G2/M arrest and apoptotic cell death in A375P melanoma cells.

PubMed

Smith, Kelly R; Granberry, Molley; Tan, Marcus C B; Daniel, Casey L; Gassman, Natalie R

2018-03-01

The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by-product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress. Therefore, exogenous and endogenous exposures to DHA may be harmful to cells, and it has already been demonstrated that exogenous exposure to DHA is cytotoxic in immortalized keratinocytes. Still, little is known about the exogenous DHA exposure effects on other skin components. In this study, we explore the effects of exogenous DHA exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to DHA and displayed a transient burst of reactive oxygen species within an hour of exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and apoptosis, monitored by the cleavage of PARP-1 and Caspase-3, was detected within 72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to DHA has cytotoxic effects in our selected cell model and indicates the need to further investigate the exogenous exposure effects of DHA in other relevant exposure models. © 2017 Wiley Periodicals, Inc.

A MISO-ARX-Based Method for Single-Trial Evoked Potential Extraction.

PubMed

Yu, Nannan; Wu, Lingling; Zou, Dexuan; Chen, Ying; Lu, Hanbing

2017-01-01

In this paper, we propose a novel method for solving the single-trial evoked potential (EP) estimation problem. In this method, the single-trial EP is considered as a complex containing many components, which may originate from different functional brain sites; these components can be distinguished according to their respective latencies and amplitudes and are extracted simultaneously by multiple-input single-output autoregressive modeling with exogenous input (MISO-ARX). The extraction process is performed in three stages: first, we use a reference EP as a template and decompose it into a set of components, which serve as subtemplates for the remaining steps. Then, a dictionary is constructed with these subtemplates, and EPs are preliminarily extracted by sparse coding in order to roughly estimate the latency of each component. Finally, the single-trial measurement is parametrically modeled by MISO-ARX while characterizing spontaneous electroencephalographic activity as an autoregression model driven by white noise and with each component of the EP modeled by autoregressive-moving-average filtering of the subtemplates. Once optimized, all components of the EP can be extracted. Compared with ARX, our method has greater tracking capabilities of specific components of the EP complex as each component is modeled individually in MISO-ARX. We provide exhaustive experimental results to show the effectiveness and feasibility of our method.

Defining forces that are associated with shoulder dystocia: the use of a mathematic dynamic computer model.

PubMed

Gonik, Bernard; Zhang, Ning; Grimm, Michele J

2003-04-01

A computer model was modified to study the impact of maternal endogenous and clinician-applied exogenous delivery loads on the contact force between the anterior fetal shoulder and the maternal symphysis pubis. Varying endogenous and exogenous loads were applied, and the contact force was determined. Experiments also examined the effect of pelvic orientation and the direction of load application on contact force behind the symphysis pubis. Exogenous loading forces (50-100 N) resulted in anterior shoulder contact forces of 107 to 127 N, with delivery accomplished at 100 N of applied load. Higher contact forces (147-272 N) were noted for endogenously applied loads (100-400 N), with delivery occurring at 400 N of maternal force. Pelvic rotation from lithotomy to McRoberts' positioning resulted in reduced contact forces. Downward lateral flexion of the fetal head led to little difference in contact force but required 30% more exogenous load to achieve delivery. Compared with clinician-applied exogenous force, larger maternally derived endogenous forces are needed to clear the impacted anterior fetal shoulder. This is associated with >2 times more contact force by the obstructing symphysis pubis. McRoberts' positioning reduces shoulder-symphysis pubis contact force. Lateral flexion of the fetal head results in the larger forces that are needed for delivery but has little effect on contact force. Model refinements are needed to examine delivery forces and brachial plexus stretching more specifically.

Local cascades induced global contagion: How heterogeneous thresholds, exogenous effects, and unconcerned behaviour govern online adoption spreading

NASA Astrophysics Data System (ADS)

Karsai, Márton; Iñiguez, Gerardo; Kikas, Riivo; Kaski, Kimmo; Kertész, János

2016-06-01

Adoption of innovations, products or online services is commonly interpreted as a spreading process driven to large extent by social influence and conditioned by the needs and capacities of individuals. To model this process one usually introduces behavioural threshold mechanisms, which can give rise to the evolution of global cascades if the system satisfies a set of conditions. However, these models do not address temporal aspects of the emerging cascades, which in real systems may evolve through various pathways ranging from slow to rapid patterns. Here we fill this gap through the analysis and modelling of product adoption in the world’s largest voice over internet service, the social network of Skype. We provide empirical evidence about the heterogeneous distribution of fractional behavioural thresholds, which appears to be independent of the degree of adopting egos. We show that the structure of real-world adoption clusters is radically different from previous theoretical expectations, since vulnerable adoptions—induced by a single adopting neighbour—appear to be important only locally, while spontaneous adopters arriving at a constant rate and the involvement of unconcerned individuals govern the global emergence of social spreading.

Local cascades induced global contagion: How heterogeneous thresholds, exogenous effects, and unconcerned behaviour govern online adoption spreading

PubMed Central

Karsai, Márton; Iñiguez, Gerardo; Kikas, Riivo; Kaski, Kimmo; Kertész, János

2016-01-01

Adoption of innovations, products or online services is commonly interpreted as a spreading process driven to large extent by social influence and conditioned by the needs and capacities of individuals. To model this process one usually introduces behavioural threshold mechanisms, which can give rise to the evolution of global cascades if the system satisfies a set of conditions. However, these models do not address temporal aspects of the emerging cascades, which in real systems may evolve through various pathways ranging from slow to rapid patterns. Here we fill this gap through the analysis and modelling of product adoption in the world’s largest voice over internet service, the social network of Skype. We provide empirical evidence about the heterogeneous distribution of fractional behavioural thresholds, which appears to be independent of the degree of adopting egos. We show that the structure of real-world adoption clusters is radically different from previous theoretical expectations, since vulnerable adoptions—induced by a single adopting neighbour—appear to be important only locally, while spontaneous adopters arriving at a constant rate and the involvement of unconcerned individuals govern the global emergence of social spreading. PMID:27272744

Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

PubMed Central

Oliveira, Gisele P.; de Abreu, Marcelo Gama; Pelosi, Paolo; Rocco, Patricia R. M.

2016-01-01

Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting. PMID:26861387

Evidence of strategic periodicities in collective conflict dynamics.

PubMed

Dedeo, Simon; Krakauer, David; Flack, Jessica

2011-09-07

We analyse the timescales of conflict decision-making in a primate society. We present evidence for multiple, periodic timescales associated with social decision-making and behavioural patterns. We demonstrate the existence of periodicities that are not directly coupled to environmental cycles or known ultraridian mechanisms. Among specific biological and socially defined demographic classes, periodicities span timescales between hours and days. Our results indicate that these periodicities are not driven by exogenous or internal regularities but are instead driven by strategic responses to social interaction patterns. Analyses also reveal that a class of individuals, playing a critical functional role, policing, have a signature timescale of the order of 1 h. We propose a classification of behavioural timescales analogous to those of the nervous system, with high frequency, or α-scale, behaviour occurring on hour-long scales, through to multi-hour, or β-scale, behaviour, and, finally γ periodicities observed on a timescale of days.

Symmetry in cold-to-hot and hot-to-cold valuation gaps.

PubMed

Fisher, Geoffrey; Rangel, Antonio

2014-01-01

Individuals commonly mispredict their future preferences when they make decisions in a visceral state different from their anticipated state at consumption. In the research reported here, we asked subjects to bid on different foods while exogenously varying their hunger levels at the time of decision and at the time of consumption. This procedure allowed us to test whether cold-to-hot and hot-to-cold gaps are symmetric in size and driven by similar mechanisms. We found that the effect size was symmetric: Hungry subjects overbid 20¢ for a snack they would eat later when they were satiated, and satiated subjects underbid 19¢ for a snack they would eat later when they were hungry. Furthermore, we found evidence that these gaps were driven by symmetric mechanisms that operate on the evaluation of visceral features of food, such as taste, as opposed to more cognitive features, such as healthiness.

Learning-Based Adaptive Optimal Tracking Control of Strict-Feedback Nonlinear Systems.

PubMed

Gao, Weinan; Jiang, Zhong-Ping; Weinan Gao; Zhong-Ping Jiang; Gao, Weinan; Jiang, Zhong-Ping

2018-06-01

This paper proposes a novel data-driven control approach to address the problem of adaptive optimal tracking for a class of nonlinear systems taking the strict-feedback form. Adaptive dynamic programming (ADP) and nonlinear output regulation theories are integrated for the first time to compute an adaptive near-optimal tracker without any a priori knowledge of the system dynamics. Fundamentally different from adaptive optimal stabilization problems, the solution to a Hamilton-Jacobi-Bellman (HJB) equation, not necessarily a positive definite function, cannot be approximated through the existing iterative methods. This paper proposes a novel policy iteration technique for solving positive semidefinite HJB equations with rigorous convergence analysis. A two-phase data-driven learning method is developed and implemented online by ADP. The efficacy of the proposed adaptive optimal tracking control methodology is demonstrated via a Van der Pol oscillator with time-varying exogenous signals.

Comparison of Classifiers for Decoding Sensory and Cognitive Information from Prefrontal Neuronal Populations

PubMed Central

Astrand, Elaine; Enel, Pierre; Ibos, Guilhem; Dominey, Peter Ford; Baraduc, Pierre; Ben Hamed, Suliann

2014-01-01

Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF): the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders. PMID:24466019

Assessment of the water balance over France using regionalized Turc-Pike formula

NASA Astrophysics Data System (ADS)

Le Lay, Matthieu; Garçon, Rémy; Gailhard, Joël; Garavaglia, Federico

2016-04-01

With extensive use of hydrological models over a wide range of hydro-climatic contexts, bias in hydro-climatic data may lead to unreliable models and thus hydrological forecasts and projections. This issue is particularly pregnant when considering mountainous areas with great uncertainties on precipitations, or when considering complex unconservative catchments (e.g. karstic systems). The Turc-Pike water balance formula, analogous to the classical Budyko formula, is a simple and efficient mathematical formulation relating long-term average streamflow to long-term average precipitation and potential evaporation. In this study, we propose to apply this framework to assess and eventually adjust the water-balance before calibrating an operational hydrologic model (MORDOR model). Considering a large set of 350 french catchments, the Turc-Pike formula is regionalized based on ecohydrologic criterions to handle various hydro-climatic contexts. This interannual regional model is then applied to assess the water-balance over numerous catchments and various conditions, such as karstic, snow-driven or glaciarized and even anthropized catchments. Results show that it is possible to obtain pretty realistic corrections of meteorological inputs (precipitations, temperature or potential evaporation) or hydrologic surface (or runoff). These corrections can often be confirmed a posteriori by exogenous information. Positive impacts on hydrologic model's calibration are also demonstrated. This methodology is now operational for hydrologic applications at EDF (Electricité de France, French electric utility company), and therefore applied on hundreds of catchments.

Experimental Model to Study the Role of Retinoblastoma Gene Product (pRb) for Determination of Adipocyte Differentiation.

PubMed

Popov, B V; Shilo, P S; Zhidkova, O V; Zaichik, A M; Petrov, N S

2015-06-01

Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines hyperexpressing functionally active or inactive mutant pRb. The cells producing active exogenous pRb demonstrated high sensitivity to adipocyte differentiation inductors, whereas production of inactive form of the exogenous protein suppressed adipocyte differentiation. The obtained lines can serve as the experimental model for studying the role of pRb in determination of adipocyte differentiation.

Expression analysis of dihydroflavonol 4-reductase genes in Petunia hybrida.

PubMed

Chu, Y X; Chen, H R; Wu, A Z; Cai, R; Pan, J S

2015-05-12

Dihydroflavonol 4-reductase (DFR) genes from Rosa chinensis (Asn type) and Calibrachoa hybrida (Asp type), driven by a CaMV 35S promoter, were integrated into the petunia (Petunia hybrida) cultivar 9702. Exogenous DFR gene expression characteristics were similar to flower-color changes, and effects on anthocyanin concentration were observed in both types of DFR gene transformants. Expression analysis showed that exogenous DFR genes were expressed in all of the tissues, but the expression levels were significantly different. However, both of them exhibited a high expression level in petals that were starting to open. The introgression of DFR genes may significantly change DFR enzyme activity. Anthocyanin ultra-performance liquid chromatography results showed that anthocyanin concentrations changed according to DFR enzyme activity. Therefore, the change in flower color was probably the result of a DFR enzyme change. Pelargonidin 3-O-glucoside was found in two different transgenic petunias, indicating that both CaDFR and RoDFR could catalyze dihydrokaempferol. Our results also suggest that transgenic petunias with DFR gene of Asp type could biosynthesize pelargonidin 3-O-glucoside.

Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin, PIK3CA and MET.

PubMed

Liu, Jacey J; Li, Yanjie; Chen, Wendy S; Liang, Yan; Wang, Gaowei; Zong, Min; Kaneko, Kota; Xu, Ruiyun; Karin, Michael; Feng, Gen-Sheng

2018-07-01

Shp2 is an SH2-tyrosine phosphatase acting downstream of receptor tyrosine kinases (RTKs). Most recent data demonstrated a liver tumor-suppressing role for Shp2, as ablating Shp2 in hepatocytes aggravated hepatocellular carcinoma (HCC) induced by chemical carcinogens or Pten loss. We further investigated the effect of Shp2 deficiency on liver tumorigenesis driven by classical oncoproteins c-Met (receptor for HGF), β-catenin and PIK3CA. We performed hydrodynamic tail vein injection of two pairs of plasmids expressing c-Met and ΔN90-β-catenin (MET/CAT), or c-Met and PIK3CA H1047R (MET/PIK), into WT and Shp2 hep-/- mice. We compared liver tumor loads and investigated the pathogenesis and molecular mechanisms involved using multidisciplinary approaches. Despite the induction of oxidative and metabolic stresses, Shp2 deletion in hepatocytes suppressed hepatocarcinogenesis driven by overexpression of oncoproteins MET/CAT or MET/PIK. Shp2 loss inhibited proliferative signaling from c-Met, Wnt/β-catenin, Ras/Erk and PI3K/Akt pathways, but triggered cell senescence following exogenous expression of the oncogenes. Shp2, acting downstream of RTKs, is positively required for hepatocyte-intrinsic tumorigenic signaling from these oncoproteins, even if Shp2 deficiency induces a tumor-promoting hepatic microenvironment. These data suggest a new and more effective therapeutic strategy for HCCs driven by oncogenic RTKs and other upstream molecules, by inhibiting Shp2 and also suppressing any tumor-enhancing stromal factors produced because of Shp2 inhibition. Primary liver cancer is a malignant disease with poor prognosis, largely because there are limited systemic therapies available. We show here that a cytoplasmic tyrosine phosphatase Shp2 is required for liver tumorigenesis. This tumorigenesis is driven by two oncoproteins that are implicated in human liver cancer. This, together with our previous studies, uncovers the complexity of liver tumorigenesis, by elucidating the pro- and anti-tumor effects of Shp2 in mouse models. This data can be used to guide new therapies. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A Novel Modeling Method for Aircraft Engine Using Nonlinear Autoregressive Exogenous (NARX) Models Based on Wavelet Neural Networks

NASA Astrophysics Data System (ADS)

Yu, Bing; Shu, Wenjun; Cao, Can

2018-05-01

A novel modeling method for aircraft engine using nonlinear autoregressive exogenous (NARX) models based on wavelet neural networks is proposed. The identification principle and process based on wavelet neural networks are studied, and the modeling scheme based on NARX is proposed. Then, the time series data sets from three types of aircraft engines are utilized to build the corresponding NARX models, and these NARX models are validated by the simulation. The results show that all the best NARX models can capture the original aircraft engine's dynamic characteristic well with the high accuracy. For every type of engine, the relative identification errors of its best NARX model and the component level model are no more than 3.5 % and most of them are within 1 %.

Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin.

PubMed

Saha, Suvrajit; Lee, Il-Hyung; Polley, Anirban; Groves, Jay T; Rao, Madan; Mayor, Satyajit

2015-11-05

Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24-37 °C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature-dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI-anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an "active actin-membrane composite" cell surface. © 2015 Saha et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Two models for identification and predicting behaviour of an induction motor system

NASA Astrophysics Data System (ADS)

Kuo, Chien-Hsun

2018-01-01

System identification or modelling is the process of building mathematical models of dynamical systems based on the available input and output data from the systems. This paper introduces system identification by using ARX (Auto Regressive with eXogeneous input) and ARMAX (Auto Regressive Moving Average with eXogeneous input) models. Through the identified system model, the predicted output could be compared with the measured one to help prevent the motor faults from developing into a catastrophic machine failure and avoid unnecessary costs and delays caused by the need to carry out unscheduled repairs. The induction motor system is illustrated as an example. Numerical and experimental results are shown for the identified induction motor system.

Endogenous versus Exogenous Origins of Crises

NASA Astrophysics Data System (ADS)

Sornette, Didier

Are large biological extinctions such as the Cretaceous/Tertiary KT boundary due to a meteorite, extreme volcanic activity or self-organized critical extinction cascades? Are commercial successes due to a progressive reputation cascade or the result of a well orchestrated advertisement? Determining the chain of causality for Xevents in complex systems requires disentangling interwoven exogenous and endogenous contributions with either no clear signature or too many signatures. Here, I review several efforts carried out with collaborators which suggest a general strategy for understanding the organizations of several complex systems under the dual effect of endogenous and exogenous fluctuations. The studied examples are: internet download shocks, book sale shocks, social shocks, financial volatility shocks, and financial crashes. Simple models are offered to quantitatively relate the endogenous organization to the exogenous response of the system. Suggestions for applications of these ideas to many other systems are offered.

Iapetus and Phoebe as Measured by the Cassini UVIS

NASA Technical Reports Server (NTRS)

Hendrix, A. R.; Hansen, C. J.

2005-01-01

The bizarre appearance of Iapetus has long intrigued researchers of this Saturnian moon. The leading hemisphere is very dark and reddish in color at visible-near-IR wavelengths. In contrast, the trailing hemisphere is relatively bright and its near-IR spectrum is dominated by water ice. The severe hemispherical brightness dichotomy has been explained by both endogenic and exogenic models. The primary endogenic model involves eruption of dark material onto the leading hemisphere from the interior of Iapetus. Exogenic models include exposure of dark underlying material by micrometeorite bombardment, contamination of Iapetus leading hemisphere by Titan tholin material, and the coating of the leading hemisphere by Phoebe dust. It has been shown that the dark material on Iapetus leading hemisphere is redder in color at visible wavelengths than Phoebe, which is spectrally gray at visible wavelengths. An additional exogenic model involves the coating of both Iapetus leading hemisphere and Hyperion with material from small retrograde satellites, which are reddish in color at visible wavelengths. We present the first FUV spectra of Iapetus and Phoebe to investigate whether the UV wavelength range can contribute to solving the puzzle of Iapetus.

Indigenous Carbonaceous Phases Embedded Within Surface Deposits on Apollo 17 Volcanic Glass Beads

NASA Technical Reports Server (NTRS)

Thomas-Keprta, K. L.; Clemett, S. J.; Ross, D. K.; Le, L.; McKay, D. S.; Gibson, E. K.; Gonzalez, C.

2012-01-01

The assessment of indigenous organic matter in returned lunar samples was one of the primary scientific goals of the Apollo program. Prior studies of Apollo samples have shown the total amount of organic matter to be in the range of approx 50 to 250 ppm. Low concentrations of lunar organics may be a consequence not only of its paucity but also its heterogeneous distribution. Several processes should have contributed to the lunar organic inventory including exogenous carbonaceous accretion from meteoroids and interplanetary dust particles, and endogenous synthesis driven by early planetary volcanism and cosmic and solar radiation.

Combination of exogenous cell transplantation and 5-HT{sub 4} receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

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

Yu, Hui; Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi; Zheng, Bai-Jun

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT{sub 4} receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT{sub 4} receptor agonist/antagonist. The labeled ENCCs were then transplantedmore » into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75{sup NTR} and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT{sub 4} receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.« less

Endogenous versus exogenous generic reference pricing for pharmaceuticals.

PubMed

Antoñanzas, F; Juárez-Castelló, C A; Rodríguez-Ibeas, R

2017-12-01

In this paper we carry out a vertical differentiation duopoly model applied to pharmaceutical markets to analyze how endogenous and exogenous generic reference pricing influence competition between generic and branded drugs producers. Unlike the literature, we characterize for the exogenous case the equilibrium prices for all feasible relevant reference prices. Competition is enhanced after the introduction of a reference pricing system. We also compare both reference pricing systems on welfare grounds, assuming two different objective functions for health authorities: (i) standard social welfare and (ii) gross consumer surplus net of total pharmaceutical expenditures. We show that regardless of the objective function, health authorities will never choose endogenous reference pricing. When health authorities are paternalistic, the exogenous reference price that maximizes standard social welfare is such that the price of the generic drug is the reference price while the price of the branded drug is higher than the reference price. When health authorities are not paternalistic, the optimal exogenous reference price is such that the price of the branded drug is the reference price while the price of the generic drug is lower than the reference price.

Effects of Exogenous and Endogenous Distracters on Immediate and Long-Term Recall in Toddlers

ERIC Educational Resources Information Center

Dixon, Wallace E., Jr.; Lawman, Hannah G.; Johnson, Elizabeth B. H.; May, Sarah; Patton, Leslie A.; Lowe, Allison K.; Snyder, Courtney M.

2012-01-01

We explored the role that exogenous and endogenous competitors for attention play in infants' abilities to encode and retain information over a 6-month period. Sixty-six children visited the laboratory at 15 months, and 32 returned for a second visit at 21 months. Children observed models of conventional- relation and enabling-relation action…

Modeling the effect of exogenous melatonin on the sleep-wake switch.

PubMed

Johnson, Nicholas; Jain, Gauray; Sandberg, Lianne; Sheets, Kevin

2012-01-01

According to the Centers for Disease Control and Prevention and the Institute of Medicine of the National Academies, insufficient sleep has become a public health epidemic. Approximately 50-70 million adults (20 years or older) suffer from some disorder of sleep and wakefulness, hindering daily functioning and adversely affecting health and longevity. Melatonin, a naturally produced hormone which plays a role in sleep-wake regulation, is currently offered as an over-the-counter sleep aid. However, the effects of melatonin on the sleep-wake cycle are incompletely understood. The goal of this modeling study was to incorporate the effects of exogenous melatonin administration into a mathematical model of the human sleep-wake switch. The model developed herein adds a simple kinetic model of the MT1 melatonin receptor to an existing model which simulates the interactions of different neuronal groups thought to be involved in sleep-wake regulation. Preliminary results were obtained by simulating the effects of an exogenous melatonin dose typical of over-the-counter sleep aids. The model predicted an increase in homeostatic sleep drive and a resulting alteration in circadian rhythm consistent with experimental results. The time of melatonin administration was also observed to have a strong influence on the sleep-wake effects elicited, which is also consistent with prior experimental findings.

Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor.

PubMed

Xian, Hua; Xian, Yun; Liu, Lili; Wang, Yongjun; He, Jianghong; Huang, Jianfei

2015-04-01

With the exception of standard inguinal orchidopexy, treatment of cryptorchidism with human chorionic gonadotropin has been performed for several years; however, its side effects have limited its application. The β‑nerve growth factor (NGF) and homeobox A10 (HoxA10) genes are closely associated with the development of the testes. To the best of our knowledge, whether exogenous NGF alters the endogenous levels of NGF and HoxA10 in cryptorchidism in rats remains to be elucidated. The aim of the present study was to evaluate the gene and protein expression of NGF and HoxA10 in experimental cryptorchidism following treatment with exogenous NGF. A unilateral mechanical cryptorchidism model in Sprague-Dawley rats was established and different concentrations of exogenous NGF were administered to observe the effects of NGF on cryptorchidism. Changes in the gene and protein expression levels of NGF and HoxA10 in the cryptorchid tissues of each group were identified using one step reverse transcription-quantitative polymerase chain reaction, in situ hybridization with digoxigenin‑labeled‑β‑NGF RNA probes, immunofluorescence and immunohistochemistry, respectively. The expression levels of NGF and HoxA10 were markedly higher in the group treated with a high dose of exogenous NGF compared with the group treated with a low dose of exogenous NGF and the group treated with human chorionic gonadotropin. These results confirmed the potential therapeutic effect of exogenous NGF in human cryptorchidism.

Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function.

PubMed

Molineaux, Anna C; Maier, Jennifer A; Schecker, Teresa; Sears, Karen E

2015-03-01

Retinoic acid (RA) is a vitamin A derivative. Exposure to exogenous RA generates congenital limb malformations (CLMs) in species from frogs to humans. These CLMs include but are not limited to oligodactyly and long-bone hypoplasia. The processes by which exogenous RA induces CLMs in mammals have been best studied in mouse, but as of yet remain unresolved. We investigated the impact of exogenous RA on the cellular and molecular development of the limbs of a nonrodent model mammal, the opossum Monodelphis domestica. Opossums exposed to exogenous retinoic acid display CLMs including oligodactly, and results are consistent with opossum development being more susceptible to RA-induced disruptions than mouse development. Exposure of developing opossums to exogenous RA leads to an increase in cell death in the limb mesenchyme that is most pronounced in the zone of polarizing activity, and a reduction in cell proliferation throughout the limb mesenchyme. Exogenous RA also disrupts the expression of Shh in the zone of polarizing activity, and Fgf8 in the apical ectodermal ridge, and other genes with roles in the regulation of limb development and cell death. Results are consistent with RA inducing CLMs in opossum limbs by disrupting the functions of the apical ectodermal ridge and zone of polarizing activity, and driving an increase in cell death and reduction of cell proliferation in the mesenchyme of the developing limb. © 2015 Wiley Periodicals, Inc.

Notch3 drives development and progression of cholangiocarcinoma

PubMed Central

Guest, Rachel V.; Dwyer, Benjamin J.; Kendall, Timothy J.; Man, Tak-Yung; Minnis-Lyons, Sarah E.; Lu, Wei-Yu; Robson, Andrew J.; Gonzalez, Sofia Ferreira; Raven, Alexander; Wojtacha, Davina; Morton, Jennifer P.; Komuta, Mina; Roskams, Tania; Wigmore, Stephen J.; Sansom, Owen J.; Forbes, Stuart J.

2016-01-01

The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide. We find that across species, the atypical receptor NOTCH3 is differentially overexpressed; it is progressively up-regulated with disease development and promotes tumor cell survival via activation of PI3k-Akt. We use genetic KO studies to show that tumor growth significantly attenuates after Notch3 deletion and demonstrate signaling occurs via a noncanonical pathway independent of the mediator of classical Notch, Recombinant Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). These data present an opportunity in this aggressive cancer to selectively target Notch, bypassing toxicities known to be RBPJ dependent. PMID:27791012

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

PubMed Central

Yu, Rui; Lai, Yongquan; Hartwell, Hadley J.; Moeller, Benjamin C.; Doyle-Eisele, Melanie; Kracko, Dean; Bodnar, Wanda M.; Starr, Thomas B.; Swenberg, James A.

2015-01-01

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N2-hydroxymethyl-dG (N2-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N2-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [13CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N2-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency’s Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair. PMID:25904104

IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

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

Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki

2014-10-15

We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3more » mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.« less

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review.

PubMed

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.

Adaptive self-organization of Bali's ancient rice terraces.

PubMed

Lansing, J Stephen; Thurner, Stefan; Chung, Ning Ning; Coudurier-Curveur, Aurélie; Karakaş, Çağil; Fesenmyer, Kurt A; Chew, Lock Yue

2017-06-20

Spatial patterning often occurs in ecosystems as a result of a self-organizing process caused by feedback between organisms and the physical environment. Here, we show that the spatial patterns observable in centuries-old Balinese rice terraces are also created by feedback between farmers' decisions and the ecology of the paddies, which triggers a transition from local to global-scale control of water shortages and rice pests. We propose an evolutionary game, based on local farmers' decisions that predicts specific power laws in spatial patterning that are also seen in a multispectral image analysis of Balinese rice terraces. The model shows how feedbacks between human decisions and ecosystem processes can evolve toward an optimal state in which total harvests are maximized and the system approaches Pareto optimality. It helps explain how multiscale cooperation from the community to the watershed scale could persist for centuries, and why the disruption of this self-organizing system by the Green Revolution caused chaos in irrigation and devastating losses from pests. The model shows that adaptation in a coupled human-natural system can trigger self-organized criticality (SOC). In previous exogenously driven SOC models, adaptation plays no role, and no optimization occurs. In contrast, adaptive SOC is a self-organizing process where local adaptations drive the system toward local and global optima.

Use of TSHβ:EGFP transgenic zebrafish as a rapid in vivo model for assessing thyroid-disrupting chemicals

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

Ji, Cheng; Graduate University of Chinese Academy of Sciences, Beijing; Jin, Xia

Accumulating evidence indicates that a wide range of chemicals have the ability to interfere with the hypothalamic–pituitary–thyroid (HPT) axis. Novel endpoints should be evaluated in addition to existing methods in order to effectively assess the effects of these chemicals on the HPT axis. Thyroid-stimulating hormone subunit β (TSHβ) plays central regulatory roles in the HPT system. We identified the regulatory region that determines the expression level of zebrafish TSHβ in the anterior pituitary. In the transgenic zebrafish with EGFP driven by the TSHβ promoter, the similar responsive patterns between the expression levels of TSHβ:EGFP and endogenous TSHβ mRNA in themore » pituitary are observed following treatments with goitrogen chemicals and exogenous thyroid hormones (THs). These results suggest that the TSHβ:EGFP transgenic reporter zebrafish may be a useful alternative in vivo model for the assessment of chemicals interfering with the HPT system. Highlights: ► The promoter of zebrafish TSHβ gene has been identified. ► The stable TSHβ:EGFP transgenic zebrafish reporter germline has been generated. ► The EGFP in the transgenic fish recapitulated the pattern of pituitary TSHβ mRNA. ► The transgenic zebrafish may be an in vivo model for EDC assessment.« less

A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH.

PubMed

Lindeman, Leila R; Randtke, Edward A; High, Rachel A; Jones, Kyle M; Howison, Christine M; Pagel, Mark D

2018-05-01

Extracellular pH (pHe) is an important biomarker for cancer cell metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the contrast agent iopamidol to create spatial maps of pHe. Measurements of amide proton transfer exchange rates (k ex ) from endogenous CEST MRI were compared to pHe measurements by exogenous acido-CEST MRI to determine whether endogenous k ex could be used as a proxy for pHe measurements. Spatial maps of pHe and k ex were obtained using exogenous acidoCEST MRI and an endogenous CEST MRI analyzed with the omega plot method, respectively, to evaluate mouse kidney, a flank tumor model, and a spontaneous lung tumor model. The pHe and k ex results were evaluated using pixelwise comparisons. The k ex values obtained from endogenous CEST measurements did not correlate with the pHe results from exogenous CEST measurements. The k ex measurements were limited to fewer pixels and had a limited dynamic range relative to pHe measurements. Measurements of k ex with endogenous CEST MRI cannot substitute for pHe measurements with acidoCEST MRI. Whereas endogenous CEST MRI may still have good utility for evaluating some specific pathologies, exogenous acido-CEST MRI is more appropriate when evaluating pathologies based on pHe values. Magn Reson Med 79:2766-2772, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Revealing the long-term landscape evolution of the South Atlantic passive continental margin, Brazil and Namibia, by thermokinematic numerical modeling using the software code Pecube.

NASA Astrophysics Data System (ADS)

Stippich, Christian; Glasmacher, Ulrich Anton; Hackspacher, Peter

2015-04-01

The aim of the research is to quantify the long-term landscape evolution of the South Atlantic passive continental margin (SAPCM) in SE-Brazil and NW-Namibia. Excellent onshore outcrop conditions and complete rift to post-rift archives between Sao Paulo and Porto Alegre and in the transition from Namibia to Angola (onshore Walvis ridge) allow a high precision quantification of exhumation, and uplift rates, influencing physical parameters, long-term acting forces, and process-response systems. Research will integrate the published and partly published thermochronological data from Brazil and Namibia, and test lately published new concepts on causes of long-term landscape evolution at rifted margins. The climate-continental margin-mantle coupled process-response system is caused by the interaction between endogenous and exogenous forces, which are related to the mantle-process driven rift - drift - passive continental margin evolution of the South Atlantic, and the climate change since the Early/Late Cretaceous climate maximum. Special emphasis will be given to the influence of long-living transform faults such as the Florianopolis Fracture Zone (FFZ) on the long-term topography evolution of the SAPCM's. A long-term landscape evolution model with process rates will be achieved by thermo-kinematic 3-D modeling (software code PECUBE1,2 and FastScape3). Testing model solutions obtained for a multidimensional parameter space against the real thermochronological and geomorphological data set, the most likely combinations of parameter rates, and values can be constrained. The data and models will allow separating the exogenous and endogenous forces and their process rates. References 1. Braun, J., 2003. Pecube: A new finite element code to solve the 3D heat transport equation including the effects of a time-varying, finite amplitude surface topography. Computers and Geosciences, v.29, pp.787-794. 2. Braun, J., van der Beek, P., Valla, P., Robert, X., Herman, F., Goltzbacj, C., Pedersen, V., Perry, C., Simon-Labric, T., Prigent, C. 2012. Quantifying rates of landscape evolution and tectonic processes by thermochronology and numerical modeling of crustal heat transport using PECUBE. Tectonophysics, v.524-525, pp.1-28. 3. Braun, J. and Willett, S.D., 2013. A very efficient, O(n), implicit and parallel method to solve the basic stream power law equation governing fluvial incision and landscape evolution. Geomorphology, v.180-181, 170-179.

Employment, Production and Consumption model: Patterns of phase transitions

NASA Astrophysics Data System (ADS)

Lavička, H.; Lin, L.; Novotný, J.

2010-04-01

We have simulated the model of Employment, Production and Consumption (EPC) using Monte Carlo. The EPC model is an agent based model that mimics very basic rules of industrial economy. From the perspective of physics, the nature of the interactions in the EPC model represents multi-agent interactions where the relations among agents follow the key laws for circulation of capital and money. Monte Carlo simulations of the stochastic model reveal phase transition in the model economy. The two phases are the phase with full unemployment and the phase with nearly full employment. The economy switches between these two states suddenly as a reaction to a slight variation in the exogenous parameter, thus the system exhibits strong non-linear behavior as a response to the change of the exogenous parameters.

Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion.

PubMed

Brentnall, Teresa A; Lai, Lisa A; Coleman, Joshua; Bronner, Mary P; Pan, Sheng; Chen, Ru

2012-01-01

Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (α-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduction of exogenous 90 kD palladin into normal human dermal fibroblasts (HDFs) induces activation of stromal fibroblasts into myofibroblasts as marked by induction of α-SMA and vimentin, and through the physical change of cell morphology. Moreover, palladin expression in the fibroblasts enhances cellular migration, invasion through the extracellular matrix, and creation of tunnels through which cancer cells can follow. The fibroblast invasion and creation of tunnels results from the development of invadopodia-like cellular protrusions which express invadopodia proteins and proteolytic enzymes. Palladin expression in fibroblasts is triggered by the co-culture of normal fibroblasts with k-ras-expressing epithelial cells. Overall, palladin expression can impart myofibroblast properties, in turn promoting the invasive potential of these peri-tumoral cells with invadopodia-driven degradation of extracellular matrix. Palladin expression in fibroblasts can be triggered by k-ras expression in adjacent epithelial cells. This data supports a model whereby palladin-activated fibroblasts facilitate stromal-dependent metastasis and outgrowth of tumorigenic epithelium.

Protease activity, localization and inhibition in the human hair follicle.

PubMed

Bhogal, R K; Mouser, P E; Higgins, C A; Turner, G A

2014-02-01

In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

The attention habit: how reward learning shapes attentional selection.

PubMed

Anderson, Brian A

2016-04-01

There is growing consensus that reward plays an important role in the control of attention. Until recently, reward was thought to influence attention indirectly by modulating task-specific motivation and its effects on voluntary control over selection. Such an account was consistent with the goal-directed (endogenous) versus stimulus-driven (exogenous) framework that had long dominated the field of attention research. Now, a different perspective is emerging. Demonstrations that previously reward-associated stimuli can automatically capture attention even when physically inconspicuous and task-irrelevant challenge previously held assumptions about attentional control. The idea that attentional selection can be value driven, reflecting a distinct and previously unrecognized control mechanism, has gained traction. Since these early demonstrations, the influence of reward learning on attention has rapidly become an area of intense investigation, sparking many new insights. The result is an emerging picture of how the reward system of the brain automatically biases information processing. Here, I review the progress that has been made in this area, synthesizing a wealth of recent evidence to provide an integrated, up-to-date account of value-driven attention and some of its broader implications. © 2015 New York Academy of Sciences.

Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT

PubMed Central

Mitra, Shreya; Federico, Lorenzo; Zhao, Wei; Dennison, Jennifer; Sarkar, Tapasree Roy; Zhang, Fan; Takiar, Vinita; Cheng, Kwai W.; Mani, Sendurai; Lee, Ju Seog; Mills, Gordon B.

2016-01-01

The Rab GTPases regulate vesicular trafficking machinery that transports and delivers a diverse pool of cargo, including growth factor receptors, integrins, nutrient receptors and junction proteins to specific intracellular sites. The trafficking machinery is indeed a major posttranslational modifier and is critical for cellular homeostasis. Deregulation of this stringently controlled system leads to a wide spectrum of disorders including cancer. Herein we demonstrate that Rab25, a key GTPase, mostly decorating the apical recycling endosome, is a dichotomous variable in breast cancer cell lines with higher mRNA and protein expression in Estrogen Receptor positive (ER+ve) lines. Rab25 and its effector, Rab Coupling Protein (RCP) are frequently coamplified and coordinately elevated in ER+ve breast cancers. In contrast, Rab25 levels are decreased in basal-like and almost completely lost in claudin-low tumors. This dichotomy exists despite the presence of the 1q amplicon that hosts Rab25 across breast cancer subtypes and is likely due to differential methylation of the Rab25 promoter. Functionally, elevated levels of Rab25 drive major hallmarks of cancer including indefinite growth and metastasis but in case of luminal B breast cancer only. Importantly, in such ER+ve tumors, coexpression of Rab25 and its effector, RCP is significantly associated with a markedly worsened clinical outcome. Importantly, in claudin-low cell lines, exogenous Rab25 markedly inhibits cell migration. Similarly, during Snail-induced epithelial to mesenchymal transition (EMT) exogenous Rab25 potently reverses Snail-driven invasion. Overall, this study substantiates a striking context dependent role of Rab25 in breast cancer where Rab25 is amplified and enhances aggressiveness in luminal B cancers while in claudin-low tumors, Rab25 is lost indicating possible anti-tumor functions. PMID:27259233

Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT.

PubMed

Mitra, Shreya; Federico, Lorenzo; Zhao, Wei; Dennison, Jennifer; Sarkar, Tapasree Roy; Zhang, Fan; Takiar, Vinita; Cheng, Kwai W; Mani, Sendurai; Lee, Ju Seog; Mills, Gordon B

2016-06-28

The Rab GTPases regulate vesicular trafficking machinery that transports and delivers a diverse pool of cargo, including growth factor receptors, integrins, nutrient receptors and junction proteins to specific intracellular sites. The trafficking machinery is indeed a major posttranslational modifier and is critical for cellular homeostasis. Deregulation of this stringently controlled system leads to a wide spectrum of disorders including cancer. Herein we demonstrate that Rab25, a key GTPase, mostly decorating the apical recycling endosome, is a dichotomous variable in breast cancer cell lines with higher mRNA and protein expression in Estrogen Receptor positive (ER+ve) lines. Rab25 and its effector, Rab Coupling Protein (RCP) are frequently coamplified and coordinately elevated in ER+ve breast cancers. In contrast, Rab25 levels are decreased in basal-like and almost completely lost in claudin-low tumors. This dichotomy exists despite the presence of the 1q amplicon that hosts Rab25 across breast cancer subtypes and is likely due to differential methylation of the Rab25 promoter. Functionally, elevated levels of Rab25 drive major hallmarks of cancer including indefinite growth and metastasis but in case of luminal B breast cancer only. Importantly, in such ER+ve tumors, coexpression of Rab25 and its effector, RCP is significantly associated with a markedly worsened clinical outcome. Importantly, in claudin-low cell lines, exogenous Rab25 markedly inhibits cell migration. Similarly, during Snail-induced epithelial to mesenchymal transition (EMT) exogenous Rab25 potently reverses Snail-driven invasion. Overall, this study substantiates a striking context dependent role of Rab25 in breast cancer where Rab25 is amplified and enhances aggressiveness in luminal B cancers while in claudin-low tumors, Rab25 is lost indicating possible anti-tumor functions.

A Competition Model of Exogenous Orienting in 3.5-Month-Old Infants.

ERIC Educational Resources Information Center

Dannemiller, James L.

1998-01-01

Four experiments examined exogenous orienting in 3.5-month-olds. Found that sensitivity to a small moving bar was lower when most of the red bars were in the visual field contra-lateral to this probe. The distribution of color within the visual field biased attention, making it either more or less likely that the infant detected a moving stimulus.…

Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution

PubMed Central

Han, Xue; Boyden, Edward S.

2007-01-01

The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells. PMID:17375185

Grouper tshβ Promoter-Driven Transgenic Zebrafish Marks Proximal Kidney Tubule Development

PubMed Central

Wang, Yang; Sun, Zhi-Hui; Zhou, Li; Li, Zhi; Gui, Jian-Fang

2014-01-01

Kidney tubule plays a critical role in recovering or secreting solutes, but the detailed morphogenesis remains unclear. Our previous studies have found that grouper tshβ (gtshβ) is also expressed in kidney, however, the distribution significance is still unknown. To understand the gtshβ role and kidney tubule morphogenesis, here, we have generated a transgenic zebrafish line Tg(gtshβ:GFP) with green fluorescent protein driven by the gtshβ promoter. Similar to the endogenous tshβ in zebrafish or in grouper, the gtshβ promoter-driven GFP is expressed in pituitary and kidney, and the developing details of proximal kidney tubule are marked in the transgenic zebrafish line. The gfp initially transcribes at 16 hours post fertilization (hpf) above the dorsal mesentery, and partially co-localizes with pronephric tubular markers slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal pronephric segments during embryogenesis and resides at kidney duct epithelium in adult fish. To test whether the gtshβ promoter-driven GFP may serve as a readout signal of the tubular development, we have treated the embryos with retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a distal extension of the proximal segments, while RA inhibition induces a weakness and shortness of the proximal segments. Therefore, this transgenic line provides a useful tool for genetic or chemical analysis of kidney tubule. PMID:24905828

Structural Equation Models in a Redundancy Analysis Framework With Covariates.

PubMed

Lovaglio, Pietro Giorgio; Vittadini, Giorgio

2014-01-01

A recent method to specify and fit structural equation modeling in the Redundancy Analysis framework based on so-called Extended Redundancy Analysis (ERA) has been proposed in the literature. In this approach, the relationships between the observed exogenous variables and the observed endogenous variables are moderated by the presence of unobservable composites, estimated as linear combinations of exogenous variables. However, in the presence of direct effects linking exogenous and endogenous variables, or concomitant indicators, the composite scores are estimated by ignoring the presence of the specified direct effects. To fit structural equation models, we propose a new specification and estimation method, called Generalized Redundancy Analysis (GRA), allowing us to specify and fit a variety of relationships among composites, endogenous variables, and external covariates. The proposed methodology extends the ERA method, using a more suitable specification and estimation algorithm, by allowing for covariates that affect endogenous indicators indirectly through the composites and/or directly. To illustrate the advantages of GRA over ERA we propose a simulation study of small samples. Moreover, we propose an application aimed at estimating the impact of formal human capital on the initial earnings of graduates of an Italian university, utilizing a structural model consistent with well-established economic theory.

Limit Theory for Panel Data Models with Cross Sectional Dependence and Sequential Exogeneity.

PubMed

Kuersteiner, Guido M; Prucha, Ingmar R

2013-06-01

The paper derives a general Central Limit Theorem (CLT) and asymptotic distributions for sample moments related to panel data models with large n . The results allow for the data to be cross sectionally dependent, while at the same time allowing the regressors to be only sequentially rather than strictly exogenous. The setup is sufficiently general to accommodate situations where cross sectional dependence stems from spatial interactions and/or from the presence of common factors. The latter leads to the need for random norming. The limit theorem for sample moments is derived by showing that the moment conditions can be recast such that a martingale difference array central limit theorem can be applied. We prove such a central limit theorem by first extending results for stable convergence in Hall and Hedye (1980) to non-nested martingale arrays relevant for our applications. We illustrate our result by establishing a generalized estimation theory for GMM estimators of a fixed effect panel model without imposing i.i.d. or strict exogeneity conditions. We also discuss a class of Maximum Likelihood (ML) estimators that can be analyzed using our CLT.

Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate

PubMed Central

Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

2016-01-01

Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers. PMID:27374086

VEGF-A is increased in exogenous endophthalmitis.

PubMed

Seamone, Mark E; Lewis, Darrell R; Haidl, Ian D; Gupta, R Rishi; O' Brien, Daniel M; Dickinson, John; Samad, Arif; Marshall, Jean S; Cruess, Alan F

2017-06-01

Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8). Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole (p < 0.001). VEGF-A was significantly upregulated in individuals with exogenous endophthalmitis after cataract surgery (p = 0.001), vitrectomy (p = 0.024), and intravitreal injection (p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations (p > 0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 (p = 0.028). We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate.

PubMed

Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

2016-07-26

Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers.

A little anthropomorphism goes a long way: Effects of oxytocin on trust, compliance and team performance with automated agents

PubMed Central

de Visser, Ewart J.; Monfort, Samuel S.; Goodyear, Kimberly; Lu, Li; O’Hara, Martin; Lee, Mary R.; Parasuraman, Raja; Krueger, Frank

2017-01-01

Objective We investigated the effects of exogenous oxytocin on trust, compliance, and team decision making with agents varying in anthropomorphism (computer, avatar, human) and reliability (100%, 50%). Background Recent work has explored psychological similarities in how we trust human-like automation compared to how we trust other humans. Exogenous administration of oxytocin, a neuropeptide associated with trust among humans, offers a unique opportunity to probe the anthropomorphism continuum of automation to infer when agents are trusted like another human or merely a machine. Method Eighty-four healthy male participants collaborated with automated agents varying in anthropomorphism that provided recommendations in a pattern recognition task. Results Under placebo, participants exhibited less trust and compliance with automated aids as the anthropomorphism of those aids increased. Under oxytocin, participants interacted with aids on the extremes of the anthropomorphism continuum similarly to placebos, but increased their trust, compliance, and performance with the avatar, an agent on the midpoint of the anthropomorphism continuum. Conclusion This study provided the first evidence that administration of exogenous oxytocin affected trust, compliance, and team decision making with automated agents. These effects provide support for the premise that oxytocin increases affinity for social stimuli in automated aids. Application Designing automation to mimic basic human characteristics is sufficient to elicit behavioral trust outcomes that are driven by neurological processes typically observed in human-human interactions. Designers of automated systems should consider the task, the individual, and the level of anthropomorphism to achieve the desired outcome. PMID:28146673

Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

PubMed

Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

2017-08-01

Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Artificial Neural Network Models for Long Lead Streamflow Forecasts using Climate Information

NASA Astrophysics Data System (ADS)

Kumar, J.; Devineni, N.

2007-12-01

Information on season ahead stream flow forecasts is very beneficial for the operation and management of water supply systems. Daily streamflow conditions at any particular reservoir primarily depend on atmospheric and land surface conditions including the soil moisture and snow pack. On the other hand recent studies suggest that developing long lead streamflow forecasts (3 months ahead) typically depends on exogenous climatic conditions particularly Sea Surface Temperature conditions (SST) in the tropical oceans. Examples of some oceanic variables are El Nino Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO). Identification of such conditions that influence the moisture transport into a given basin poses many challenges given the nonlinear dependency between the predictors (SST) and predictand (stream flows). In this study, we apply both linear and nonlinear dependency measures to identify the predictors that influence the winter flows into the Neuse basin. The predictor identification approach here adopted uses simple correlation coefficients to spearman rank correlation measures for detecting nonlinear dependency. All these dependency measures are employed with a lag 3 time series of the high flow season (January - February - March) using 75 years (1928-2002) of stream flows recorded in to the Falls Lake, Neuse River Basin. Developing streamflow forecasts contingent on these exogenous predictors will play an important role towards improved water supply planning and management. Recently, the soft computing techniques, such as artificial neural networks (ANNs) have provided an alternative method to solve complex problems efficiently. ANNs are data driven models which trains on the examples given to it. The ANNs functions as universal approximators and are non linear in nature. This paper presents a study aiming towards using climatic predictors for 3 month lead time streamflow forecast. ANN models representing the physical process of the system are developed between the identified predictors and the predictand. Predictors used are the scores of Principal Components Analysis (PCA). The models were tested and validated. The feed- forward multi-layer perceptron (MLP) type neural networks trained using the back-propagation algorithms are employed in the current study. The performance of the ANN-model forecasts are evaluated using various performance evaluation measures such as correlation coefficient, root mean square error (RMSE). The preliminary results shows that ANNs are efficient to forecast long lead time streamflows using climatic predictors.

Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells.

PubMed

Yang, Chih-Sheng; Stampouloglou, Eleni; Kingston, Nathan M; Zhang, Liye; Monti, Stefano; Varelas, Xaralabos

2018-06-01

The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro-tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine-derived metabolites suggest an essential role for glutamate and α-ketoglutarate (AKG) in TAZ/YAP-driven cell growth in the absence of glutamine. Analysis of enzymes that mediate the conversion of glutamate to AKG shows that TAZ/YAP induce glutamic-oxaloacetic transaminase (GOT1) and phosphoserine aminotransferase (PSAT1) expression and that TAZ/YAP activity positively correlates with transaminase expression in breast cancer patients. Notably, we find that the transaminase inhibitor aminooxyacetate (AOA) represses cell growth in a TAZ/YAP-dependent manner, identifying transamination as a potential vulnerable metabolic requirement for TAZ/YAP-driven breast cancer. © 2018 The Authors.

Modelling and Closed-Loop System Identification of a Quadrotor-Based Aerial Manipulator

NASA Astrophysics Data System (ADS)

Dube, Chioniso; Pedro, Jimoh O.

2018-05-01

This paper presents the modelling and system identification of a quadrotor-based aerial manipulator. The aerial manipulator model is first derived analytically using the Newton-Euler formulation for the quadrotor and Recursive Newton-Euler formulation for the manipulator. The aerial manipulator is then simulated with the quadrotor under Proportional Derivative (PD) control, with the manipulator in motion. The simulation data is then used for system identification of the aerial manipulator. Auto Regressive with eXogenous inputs (ARX) models are obtained from the system identification for linear accelerations \\ddot{X} and \\ddot{Y} and yaw angular acceleration \\ddot{\\psi }. For linear acceleration \\ddot{Z}, and pitch and roll angular accelerations \\ddot{θ } and \\ddot{φ }, Auto Regressive Moving Average with eXogenous inputs (ARMAX) models are identified.

Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake: An Extended Kalman Filter Approach.

PubMed

Wang, Qian; Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

2014-03-01

An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model. We evaluate our empirical modeling using (1) the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical data of 5 type 1 diabetic patients under natural living conditions. Compared to a forgetting-factor-based recursive ARX model of the same order, the EKF model predictions have higher fit, and significantly better temporal gain and J index and thus are superior in early detection of upward and downward trends in glucose. The EKF based state-space model developed in this article is particularly suitable for model-based state-feedback control designs since the Kalman filter estimates the state variable of the glucose dynamics based on the measured glucose time series. In addition, since the model parameters are estimated in real time, this model is also suitable for adaptive control. © 2014 Diabetes Technology Society.

Emotion and anxiety potentiate the way attention alters visual appearance.

PubMed

Barbot, Antoine; Carrasco, Marisa

2018-04-12

The ability to swiftly detect and prioritize the processing of relevant information around us is critical for the way we interact with our environment. Selective attention is a key mechanism that serves this purpose, improving performance in numerous visual tasks. Reflexively attending to sudden information helps detect impeding threat or danger, a possible reason why emotion modulates the way selective attention affects perception. For instance, the sudden appearance of a fearful face potentiates the effects of exogenous (involuntary, stimulus-driven) attention on performance. Internal states such as trait anxiety can also modulate the impact of attention on early visual processing. However, attention does not only improve performance; it also alters the way visual information appears to us, e.g. by enhancing perceived contrast. Here we show that emotion potentiates the effects of exogenous attention on both performance and perceived contrast. Moreover, we found that trait anxiety mediates these effects, with stronger influences of attention and emotion in anxious observers. Finally, changes in performance and appearance correlated with each other, likely reflecting common attentional modulations. Altogether, our findings show that emotion and anxiety interact with selective attention to truly alter how we see.

Reservoir optimisation using El Niño information. Case study of Daule Peripa (Ecuador)

NASA Astrophysics Data System (ADS)

Gelati, Emiliano; Madsen, Henrik; Rosbjerg, Dan

2010-05-01

The optimisation of water resources systems requires the ability to produce runoff scenarios that are consistent with available climatic information. We approach stochastic runoff modelling with a Markov-modulated autoregressive model with exogenous input, which belongs to the class of Markov-switching models. The model assumes runoff parameterisation to be conditioned on a hidden climatic state following a Markov chain, whose state transition probabilities depend on climatic information. This approach allows stochastic modeling of non-stationary runoff, as runoff anomalies are described by a mixture of autoregressive models with exogenous input, each one corresponding to a climate state. We calibrate the model on the inflows of the Daule Peripa reservoir located in western Ecuador, where the occurrence of El Niño leads to anomalously heavy rainfall caused by positive sea surface temperature anomalies along the coast. El Niño - Southern Oscillation (ENSO) information is used to condition the runoff parameterisation. Inflow predictions are realistic, especially at the occurrence of El Niño events. The Daule Peripa reservoir serves a hydropower plant and a downstream water supply facility. Using historical ENSO records, synthetic monthly inflow scenarios are generated for the period 1950-2007. These scenarios are used as input to perform stochastic optimisation of the reservoir rule curves with a multi-objective Genetic Algorithm (MOGA). The optimised rule curves are assumed to be the reservoir base policy. ENSO standard indices are currently forecasted at monthly time scale with nine-month lead time. These forecasts are used to perform stochastic optimisation of reservoir releases at each monthly time step according to the following procedure: (i) nine-month inflow forecast scenarios are generated using ENSO forecasts; (ii) a MOGA is set up to optimise the upcoming nine monthly releases; (iii) the optimisation is carried out by simulating the releases on the inflow forecasts, and by applying the base policy on a subsequent synthetic inflow scenario in order to account for long-term costs; (iv) the optimised release for the first month is implemented; (v) the state of the system is updated and (i), (ii), (iii), and (iv) are iterated for the following time step. The results highlight the advantages of using a climate-driven stochastic model to produce inflow scenarios and forecasts for reservoir optimisation, showing potential improvements with respect to the current management. Dynamic programming was used to find the best possible release time series given the inflow observations, in order to benchmark any possible operational improvement.

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

PubMed Central

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field. PMID:23805224

Modeling the spread of tuberculosis in semiclosed communities.

PubMed

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play.

Modeling the Spread of Tuberculosis in Semiclosed Communities

PubMed Central

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play. PMID:23762194

A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer.

PubMed

Borniger, Jeremy C; Walker Ii, William H; Surbhi; Emmer, Kathryn M; Zhang, Ning; Zalenski, Abigail A; Muscarella, Stevie L; Fitzgerald, Julie A; Smith, Alexandra N; Braam, Cornelius J; TinKai, Tial; Magalang, Ulysses J; Lustberg, Maryam B; Nelson, Randy J; DeVries, A Courtney

2018-05-14

We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. We used a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

Extracorporeal Perfusion without Exogenous Anticoagulation: Its Protective Role in Endotoxin Shock.

DTIC Science & Technology

1982-02-19

lethal effects of endotoxin . Group E: Heparinized dogs given endotoxin ; no perfusion. This group served to evaluate the effects of heparin on...recovery from endotoxin shock. Group F: Heparinized dogs perfused 90 minutes; then given endotoxin . This group served to assay the effects of exogenous...stable model and is preperfusion neces- sary to provide protection against the lethal effects of endotoxin ? The first series of experiments (Group B) were

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

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

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. Here, we argue that in order to understand the dynamics of either system, Earth System Models must be coupled withmore » Human System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections.This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. Lastly, the importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

NASA Technical Reports Server (NTRS)

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia; Asrar, Ghassem R.; Busalacchi, Antonio J.; Cahalan, Robert F.; Cane, Mark A.; Colwell, Rita R.; Feng, Kuishuang; Franklin, Rachel S.;

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

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

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. We argue that in order to understand the dynamics of either system, Earth System Models must be coupled with Humanmore » System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections. This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. The importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

Modeling Sustainability: Population, Inequality, Consumption, and Bidirectional Coupling of the Earth and Human Systems

DOE PAGES

Motesharrei, Safa; Rivas, Jorge; Kalnay, Eugenia; ...

2016-12-11

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. Here, we argue that in order to understand the dynamics of either system, Earth System Models must be coupled withmore » Human System Models through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections.This makes current models likely to miss important feedbacks in the real Earth–Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models. Lastly, the importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth–Human system models for devising effective science-based policies and measures to benefit current and future generations.« less

Olive Fruit Fly (Bactrocera oleae) Population Dynamics in the Eastern Mediterranean: Influence of Exogenous Uncertainty on a Monophagous Frugivorous Insect

PubMed Central

Ordano, Mariano; Engelhard, Izhar; Rempoulakis, Polychronis; Nemny-Lavy, Esther; Blum, Moshe; Yasin, Sami; Lensky, Itamar M.; Papadopoulos, Nikos T.; Nestel, David

2015-01-01

Despite of the economic importance of the olive fly (Bactrocera oleae) and the large amount of biological and ecological studies on the insect, the factors driving its population dynamics (i.e., population persistence and regulation) had not been analytically investigated until the present study. Specifically, our study investigated the autoregressive process of the olive fly populations, and the joint role of intrinsic and extrinsic factors molding the population dynamics of the insect. Accounting for endogenous dynamics and the influences of exogenous factors such as olive grove temperature, the North Atlantic Oscillation and the presence of potential host fruit, we modeled olive fly populations in five locations in the Eastern Mediterranean region. Our models indicate that the rate of population change is mainly shaped by first and higher order non-monotonic, endogenous dynamics (i.e., density-dependent population feedback). The olive grove temperature was the main exogenous driver, while the North Atlantic Oscillation and fruit availability acted as significant exogenous factors in one of the five populations. Seasonal influences were also relevant for three of the populations. In spite of exogenous effects, the rate of population change was fairly stable along time. We propose that a special reproductive mechanism, such as reproductive quiescence, allows populations of monophagous fruit flies such as the olive fly to remain stable. Further, we discuss how weather factors could impinge constraints on the population dynamics at the local level. Particularly, local temperature dynamics could provide forecasting cues for management guidelines. Jointly, our results advocate for establishing monitoring programs and for a major focus of research on the relationship between life history traits and populations dynamics. PMID:26010332

Nonlinear Autoregressive Exogenous modeling of a large anaerobic digester producing biogas from cattle waste.

PubMed

Dhussa, Anil K; Sambi, Surinder S; Kumar, Shashi; Kumar, Sandeep; Kumar, Surendra

2014-10-01

In waste-to-energy plants, there is every likelihood of variations in the quantity and characteristics of the feed. Although intermediate storage tanks are used, but many times these are of inadequate capacity to dampen the variations. In such situations an anaerobic digester treating waste slurry operates under dynamic conditions. In this work a special type of dynamic Artificial Neural Network model, called Nonlinear Autoregressive Exogenous model, is used to model the dynamics of anaerobic digesters by using about one year data collected on the operating digesters. The developed model consists of two hidden layers each having 10 neurons, and uses 18days delay. There are five neurons in input layer and one neuron in output layer for a day. Model predictions of biogas production rate are close to plant performance within ±8% deviation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exogenous indirect photoinactivation of bacterial pathogens and indicators in water with natural and synthetic photosensitizers in simulated sunlight with reduced UVB.

PubMed

Maraccini, P A; Wenk, J; Boehm, A B

2016-08-01

To investigate the UVB-independent and exogenous indirect photoinactivation of eight human health-relevant bacterial species in the presence of photosensitizers. Eight bacterial species were exposed to simulated sunlight with greatly reduced UVB light intensity in the presence of three synthetic photosensitizers and two natural photosensitizers. Inactivation curves were fit with shoulder log-linear or first-order kinetic models, from which the presence of a shoulder and magnitude of inactivation rate constants were compared. Eighty-four percent reduction in the UVB light intensity roughly matched a 72-95% reduction in the overall bacterial photoinactivation rate constants in sensitizer-free water. With the UVB light mostly reduced, the exogenous indirect mechanism contribution was evident for most bacteria and photosensitizers tested, although most prominently with the Gram-positive bacteria. Results confirm the importance of UVB light in bacterial photoinactivation and, with the reduction of the UVB light intensity, that the Gram-positive bacteria are more vulnerable to the exogenous indirect mechanism than Gram-negative bacteria. UVB is the most important range of the sunlight spectrum for bacterial photoinactivation. In aquatic environments where photosensitizers are present and there is high UVB light attenuation, UVA and visible wavelengths can contribute to exogenous indirect photoinactivation. © 2016 The Society for Applied Microbiology.

Detection of exogenous gene doping of IGF-I by a real-time quantitative PCR assay.

PubMed

Zhang, Jin-Ju; Xu, Jing-Feng; Shen, Yong-Wei; Ma, Shi-Jiao; Zhang, Ting-Ting; Meng, Qing-Lin; Lan, Wen-Jun; Zhang, Chun; Liu, Xiao-Mei

2017-07-01

Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Effect of Antioxidants Supplementation on Aging and Longevity

PubMed Central

Bartosz, Grzegorz

2014-01-01

If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, resveratrol, curcumin, other polyphenols, and synthetic antioxidants including antioxidant nanoparticles) on the lifespan of model organisms. Mechanisms of effects of antioxidants, often due to indirect antioxidant action or to action not related to the antioxidant properties of the compounds administered, are discussed. The legitimacy of antioxidant supplementation in human is considered. PMID:24783202

Limit Theory for Panel Data Models with Cross Sectional Dependence and Sequential Exogeneity

PubMed Central

Kuersteiner, Guido M.; Prucha, Ingmar R.

2013-01-01

The paper derives a general Central Limit Theorem (CLT) and asymptotic distributions for sample moments related to panel data models with large n. The results allow for the data to be cross sectionally dependent, while at the same time allowing the regressors to be only sequentially rather than strictly exogenous. The setup is sufficiently general to accommodate situations where cross sectional dependence stems from spatial interactions and/or from the presence of common factors. The latter leads to the need for random norming. The limit theorem for sample moments is derived by showing that the moment conditions can be recast such that a martingale difference array central limit theorem can be applied. We prove such a central limit theorem by first extending results for stable convergence in Hall and Hedye (1980) to non-nested martingale arrays relevant for our applications. We illustrate our result by establishing a generalized estimation theory for GMM estimators of a fixed effect panel model without imposing i.i.d. or strict exogeneity conditions. We also discuss a class of Maximum Likelihood (ML) estimators that can be analyzed using our CLT. PMID:23794781

The impact of 2-dose routine measles, mumps, rubella, and varicella vaccination in France on the epidemiology of varicella and zoster using a dynamic model with an empirical contact matrix.

PubMed

Ouwens, Mario J N M; Littlewood, Kavi J; Sauboin, Christophe; Téhard, Bertrand; Denis, François; Boëlle, Pierre-Yves; Alain, Sophie

2015-04-01

Varicella has a high incidence affecting the vast majority of the population in France and can lead to severe complications. Almost every individual infected by varicella becomes susceptible to herpes zoster later in life due to reactivation of the latent virus. Zoster is characterized by pain that can be long-lasting in some cases and has no satisfactory treatment. Routine varicella vaccination can prevent varicella. The vaccination strategy of replacing both doses of measles, mumps, and rubella (MMR) with a combined MMR and varicella (MMRV) vaccine is a means of reaching high vaccination coverage for varicella immunization. The objective of this analysis was to assess the impact of routine varicella vaccination, with MMRV in place of MMR, on the incidence of varicella and zoster diseases in France and to assess the impact of exogenous boosting of zoster incidence, age shift in varicella cases, and other possible indirect effects. A dynamic transmission population-based model was developed using epidemiological data for France to determine the force of infection, as well as an empirically derived contact matrix to reduce assumptions underlying these key drivers of dynamic models. Scenario analyses tested assumptions regarding exogenous boosting, vaccine waning, vaccination coverage, risk of complications, and contact matrices. The model provides a good estimate of the incidence before varicella vaccination implementation in France. When routine varicella vaccination is introduced with French current coverage levels, varicella incidence is predicted to decrease by 57%, and related complications are expected to decrease by 76% over time. After vaccination, it is observed that exogenous boosting is the main driver of change in zoster incidence. When exogenous boosting is assumed, there is a temporary increase in zoster incidence before it gradually decreases, whereas without exogenous boosting, varicella vaccination leads to a gradual decrease in zoster incidence. Changing vaccine efficacy waning levels and coverage assumptions are still predicted to result in overall benefits with varicella vaccination. In conclusion, the model predicted that MMRV vaccination can significantly reduce varicella incidence. With suboptimal coverage, a limited age shift of varicella cases is predicted to occur post-vaccination with MMRV. However, it does not result in an increase in the number of complications. GSK study identifier: HO-12-6924. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of exogenous galanin on neuropathic pain state and change of galanin and its receptors in DRG and SDH after sciatic nerve-pinch injury in rat.

PubMed

Xu, Xiaofeng; Yang, Xiangdong; Zhang, Ping; Chen, Xiuying; Liu, Huaxiang; Li, Zhenzhong

2012-01-01

A large number of neuroanatomical, neurophysiologic, and neurochemical mechanisms are thought to contribute to the development and maintenance of neuropathic pain. However, mechanisms responsible for neuropathic pain have not been completely delineated. It has been demonstrated that neuropeptide galanin (Gal) is upregulated after injury in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) where it plays a predominantly antinociceptive role. In the present study, sciatic nerve-pinch injury rat model was used to determine the effects of exogenous Gal on the expression of the Gal and its receptors (GalR1, GalR2) in DRG and SDH, the alterations of pain behavior, nerve conduction velocity (NCV) and morphology of sciatic nerve. The results showed that exogenous Gal had antinociceptive effects in this nerve-pinch injury induced neuropathic pain animal model. It is very interesting that Gal, GalR1 and GalR2 change their expression greatly in DRG and SDH after nerve injury and intrathecal injection of exougenous Gal. Morphological investigation displays a serious damage after nerve-pinch injury and an amendatory regeneration after exogenous Gal treatment. These findings imply that Gal, via activation of GalR1 and/or GalR2, may have neuroprotective effects in reducing neuropathic pain behaviors and improving nerve regeneration after nerve injury.

Real-time point-of-care measurement of impaired renal function in a rat acute injury model employing exogenous fluorescent tracer agents

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Fitch, Richard M.; Galen, Karen P.; Wojdyla, Jolette K.; Poreddy, Amruta R.; Freskos, John N.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Demirjian, Sevag G.

2013-02-01

Renal function assessment is needed for the detection of acute kidney injury and chronic kidney disease. Glomerular filtration rate (GFR) is now widely accepted as the best indicator of renal function, and current clinical guidelines advocate its use in the staging of kidney disease. The optimum measure of GFR is by the use of exogenous tracer agents. However current clinically employed agents lack sensitivity or are cumbersome to use. An exogenous GFR fluorescent tracer agent, whose elimination rate could be monitored noninvasively through skin would provide a substantial improvement over currently available methods. We developed a series of novel aminopyrazine analogs for use as exogenous fluorescent GFR tracer agents that emit light in the visible region for monitoring GFR noninvasively over skin. In rats, these compounds are eliminated by the kidney with urine recovery greater than 90% of injected dose, are not broken down or metabolized in vivo, are not secreted by the renal tubules, and have clearance values similar to a GFR reference compound, iothalamate. In addition, biological half-life of these compounds measured in rats by noninvasive optical methods correlated with plasma derived methods. In this study, we show that this noninvasive methodology with our novel fluorescent tracer agents can detect impaired renal function. A 5/6th nephrectomy rat model is employed.

Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease.

PubMed

Vinchi, Francesca; Costa da Silva, Milene; Ingoglia, Giada; Petrillo, Sara; Brinkman, Nathan; Zuercher, Adrian; Cerwenka, Adelheid; Tolosano, Emanuela; Muckenthaler, Martina U

2016-01-28

Hemolytic diseases, such as sickle cell anemia and thalassemia, are characterized by enhanced release of hemoglobin and heme into the circulation, heme-iron loading of reticulo-endothelial system macrophages, and chronic inflammation. Here we show that in addition to activating the vascular endothelium, hemoglobin and heme excess alters the macrophage phenotype in sickle cell disease. We demonstrate that exposure of cultured macrophages to hemolytic aged red blood cells, heme, or iron causes their functional phenotypic change toward a proinflammatory state. In addition, hemolysis and macrophage heme/iron accumulation in a mouse model of sickle disease trigger similar proinflammatory phenotypic alterations in hepatic macrophages. On the mechanistic level, this critically depends on reactive oxygen species production and activation of the Toll-like receptor 4 signaling pathway. We further demonstrate that the heme scavenger hemopexin protects reticulo-endothelial macrophages from heme overload in heme-loaded Hx-null mice and reduces production of cytokines and reactive oxygen species. Importantly, in sickle mice, the administration of human exogenous hemopexin attenuates the inflammatory phenotype of macrophages. Taken together, our data suggest that therapeutic administration of hemopexin is beneficial to counteract heme-driven macrophage-mediated inflammation and its pathophysiologic consequences in sickle cell disease. © 2016 by The American Society of Hematology.

Dengue Virus Infection Differentially Regulates Endothelial Barrier Function over Time through Type I Interferon Effects

PubMed Central

Liu, Ping; Woda, Marcia; Ennis, Francis A.; Libraty, Daniel H.

2013-01-01

Background The morbidity and mortality resulting from dengue hemorrhagic fever (DHF) are largely caused by endothelial barrier dysfunction and a unique vascular leakage syndrome. The mechanisms that lead to the location and timing of vascular leakage in DHF are poorly understood. We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome. Methods We used an in vitro model of human endothelium to study the combined effects of dengue virus (DENV) type 2 (DENV2) infection and inflammatory mediators on paracellular macromolecule permeability over time. Results Over the initial 72 h after infection, DENV2 suppressed tumor necrosis factor (TNF)–α–mediated hyperpermeability in human umbilical vein endothelial cell (HUVEC) monolayers. This suppressive effect was mediated by type I interferon (IFN). By 1 week, TNF-α stimulation of DENV2-infected HUVECs synergistically increased cell cycling, angiogenic changes, and macromolecule permeability. This late effect could be prevented by the addition of exogenous type I IFN. Conclusions DENV infection of primary human endothelial cells differentially modulates TNF-α–driven angiogenesis and hyperpermeability over time. Type I IFN plays a central role in this process. Our findings suggest a rational model for the DHF vascular leakage syndrome. PMID:19530939

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

PubMed

Sandler, Roman A; Fetterhoff, Dustin; Hampson, Robert E; Deadwyler, Sam A; Marmarelis, Vasilis Z

2017-07-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3

PubMed Central

Fetterhoff, Dustin; Hampson, Robert E.; Deadwyler, Sam A.; Marmarelis, Vasilis Z.

2017-01-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs. PMID:28686594

Synthetic polymeric substrates as potent pro-oxidant versus anti-oxidant regulators of cytoskeletal remodeling and cell apoptosis.

PubMed

Sung, Hak-Joon; Chandra, Prafulla; Treiser, Matthew D; Liu, Er; Iovine, Carmine P; Moghe, Prabhas V; Kohn, Joachim

2009-03-01

The role of reactive oxygen species (ROS)-mediated cell signal transduction pathways emanating from engineered cell substrates remains unclear. To elucidate the role, polymers derived from the amino acid L-tyrosine were used as synthetic matrix substrates. Variations in their chemical properties were created by co-polymerizing hydrophobic L-tyrosine derivatives with uncharged hydrophilic poly(ethylene glycol) (PEG, Mw = 1,000 Da), and negatively charged desaminotyrosyl-tyrosine (DT). These substrates were characterized for their intrinsic ability to generate ROS, as well as their ability to elicit Saos-2 cell responses in terms of intracellular ROS production, actin remodeling, and apoptosis. PEG-containing substrates induced both exogenous and intracellular ROS production, whereas the charged substrates reduced production of both types, indicating a coupling of exogenous ROS generation and intracellular ROS production. Furthermore, PEG-mediated ROS induction caused nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase and an increase in caspase-3 activity, confirming a link with apoptosis. PEG-rich pro-oxidant substrates caused cytoskeletal actin remodeling through beta-actin cleavage by caspase-3 into fractins. The fractins co-localized to the mitochondria and reduced the mitochondrial membrane potential. The remnant cytosolic beta-actin was polymerized and condensed, events consistent with apoptotic cell shrinkage. The cytoskeletal remodeling was integral to the further augmentation of intracellular ROS production. Conversely, the anti-oxidant DT-containing charged substrates suppressed the entire cascade of apoptotic progression. We demonstrate that ROS activity serves an important role in "outside-in" signaling for cells grown on substrates: the ROS activity couples exogenous stress, driven by substrate composition, to changes in intracellular signaling. This signaling causes cell apoptosis, which is mediated by actin remodeling.

Dental implant customization using numerical optimization design and 3-dimensional printing fabrication of zirconia ceramic.

PubMed

Cheng, Yung-Chang; Lin, Deng-Huei; Jiang, Cho-Pei; Lin, Yuan-Min

2017-05-01

This study proposes a new methodology for dental implant customization consisting of numerical geometric optimization and 3-dimensional printing fabrication of zirconia ceramic. In the numerical modeling, exogenous factors for implant shape include the thread pitch, thread depth, maximal diameter of implant neck, and body size. Endogenous factors are bone density, cortical bone thickness, and non-osseointegration. An integration procedure, including uniform design method, Kriging interpolation and genetic algorithm, is applied to optimize the geometry of dental implants. The threshold of minimal micromotion for optimization evaluation was 100 μm. The optimized model is imported to the 3-dimensional slurry printer to fabricate the zirconia green body (powder is bonded by polymer weakly) of the implant. The sintered implant is obtained using a 2-stage sintering process. Twelve models are constructed according to uniform design method and simulated the micromotion behavior using finite element modeling. The result of uniform design models yields a set of exogenous factors that can provide the minimal micromotion (30.61 μm), as a suitable model. Kriging interpolation and genetic algorithm modified the exogenous factor of the suitable model, resulting in 27.11 μm as an optimization model. Experimental results show that the 3-dimensional slurry printer successfully fabricated the green body of the optimization model, but the accuracy of sintered part still needs to be improved. In addition, the scanning electron microscopy morphology is a stabilized t-phase microstructure, and the average compressive strength of the sintered part is 632.1 MPa. Copyright © 2016 John Wiley & Sons, Ltd.

Economic and other determinants of infant and child mortality in small developing countries: the case of Central America and the Caribbean.

PubMed

Hojman, D E

1996-03-01

This analysis involves empirically testing a theoretical model among 22 Central American and Caribbean countries during the 1990s that explains differences in infant and child mortality. Explanatory measures capture demographic, economic, health care, and educational characteristics. The model is expected to allow for an assessment of the potential impact of structural adjustment and external debt. It is pointed out that birth rates and child mortality rates followed similar patterns over time and between countries. In this study's regression analyses all variables in the three models that explain infant mortality are exogenous: low birth weight, immunization, gross domestic product per capita, years of schooling for women, population/nurse, and debt as a proportion of gross national product. As nations became richer, infant mortality declined. Infant mortality was lower in countries with high external debt. In models for explaining the birth rate and the child mortality rate, the best fit included variables for debt, real public expenditure on health care, water supply, and malnutrition. Analysis in a simultaneous model for 10 countries revealed that the birth rate and the child mortality rate were more responsive to shocks in exogenous variables in Barbados than in the Dominican Republic, and more responsive in the Dominican Republic than in Guatemala. The impact of each exogenous variable varied by country. In Barbados education was four times more effective in explaining the birth rate than water. In Guatemala, the most effective exogenous variable was malnutrition. Child mortality rates were affected more by multiplier effects. In richer countries, the most important impact on child survival was improved access to safe water, and the most important impact on the birth rate was increased real public expenditure on education per capita. For the poorest countries, findings suggest first improvement in malnutrition and then improvement in safe water supplies. Structural adjustment variables were found to have small impacts on the birth rate or limited impacts on child survival in poorer countries.

Extreme-volatility dynamics in crude oil markets

NASA Astrophysics Data System (ADS)

Jiang, Xiong-Fei; Zheng, Bo; Qiu, Tian; Ren, Fei

2017-02-01

Based on concepts and methods from statistical physics, we investigate extreme-volatility dynamics in the crude oil markets, using the high-frequency data from 2006 to 2010 and the daily data from 1986 to 2016. The dynamic relaxation of extreme volatilities is described by a power law, whose exponents usually depend on the magnitude of extreme volatilities. In particular, the relaxation before and after extreme volatilities is time-reversal symmetric at the high-frequency time scale, but time-reversal asymmetric at the daily time scale. This time-reversal asymmetry is mainly induced by exogenous events. However, the dynamic relaxation after exogenous events exhibits the same characteristics as that after endogenous events. An interacting herding model both with and without exogenous driving forces could qualitatively describe the extreme-volatility dynamics.

Measurement Model Specification Error in LISREL Structural Equation Models.

ERIC Educational Resources Information Center

Baldwin, Beatrice; Lomax, Richard

This LISREL study examines the robustness of the maximum likelihood estimates under varying degrees of measurement model misspecification. A true model containing five latent variables (two endogenous and three exogenous) and two indicator variables per latent variable was used. Measurement model misspecification considered included errors of…

Endo- vs. exogenous shocks and relaxation rates in book and music “sales”

NASA Astrophysics Data System (ADS)

Lambiotte, R.; Ausloos, M.

2006-04-01

In this paper, we analyse the response of music and book sales to an external field and a buyer herding. We distinguish endogenous and exogenous shocks. We focus on some case studies, whose data have been collected from ranking on amazon.com. We show that an ensemble of equivalent systems quantitatively respond in a same way to a similar “external shock”, indicating roads to universality features. In contrast to Sornette et al. [Phys. Rev. Lett. 93 (2004) 228701] who seemed to find power-law behaviours, in particular at long times, a law interpreted in terms of an epidemic activity, we observe that the relaxation process can be as well seen as an exponential one that saturates toward an asymptotic state, itself different from the pre-shock state. By studying an ensemble of 111 shocks, on books or records, we show that exogenous and endogenous shocks are discriminated by their short-time behaviour: the relaxation time seems to be twice shorter in endogenous shocks than in exogenous ones. We interpret the finding through a simple thermodynamic model with a dissipative force.

Lake System Development on the northern Tibetan Plateau during the last 12 ka

NASA Astrophysics Data System (ADS)

Ramisch, A. C.; Lockot, G.; Kasper, T.; Schulte, P.; Zhang, Y.; Daut, G.; Haberzettl, T.; Stauch, G.; Hartmann, K.; Zhu, L.; Lehmkuhl, F.; Maeusbacher, R.; Wuennemann, B.; Diekmann, B.

2013-12-01

Lake systems and their drainage basins provide valuable information of late Quaternary palaeo-environmental conditions on the Tibetan Plateau (TP). This information is often difficult to interpret because of a complex forcing-response mechanism of lake systems and their environment. Here we present an analysis of the endogenic mineral precipitation of Lake Heihai (northern TP) and its environmental constrains expressed by the exogenic mineral input. The mineralogical analysis of carbonate phases by means of X-ray diffraction revealed three distinct stages of carbonate precipitation: Aragonite (late Glacial), Monohydrocalcite (early to mid-Holocene) and Mg bearing Calcite (late Holocene). Each phase precipitates under steady state conditions of exogenic mineral input, as determined by a phase space analysis. This suggests a self-organized precipitation process driven by interactions of different ions. Hence, under steady environmental conditions carbonate precipitation is strongly dependent on the ionic compositions of the lake water and thus controlled by sources of the exogenic mineral input. To analyze the provenance of the exogenic mineral input, a Fuzzy C-Means (FCM) Clustering algorithm was performed on the minerogenic detrital fraction of the total mineral content of 57 surface reference samples. Three major sources can be distinguished: (a) glacially mediated, far distant transport originating from SE catchment (b) precipitation generated, close distant runoff originating from the SW catchment and (c) close distant transport of granite weathering products in the northern parts of the drainage basin. A change from the compositional dominance of (b) over (a) to (a) over (b) in lake sediments suggests a transition from rainfall to glacier dominated runoff production and hence drier climate conditions in the study area during the late Holocene. The environmentally controlled changes in the exogenic mineral input are compared to two different lake systems: Lake Donggi Cona (northern Tibetan Plateau) and Lake Nam Co (southern Tibetan Plateau). Major differences occur during two broad Holocene episodes: Until ~6 ka cal BP the differences reach their maximum with a peak around 9.5 cal ka BP. An intensification of the Indian Summer Monsoon (ISM) led to wetter conditions and an increased minerogenic input into Lake Nam Co. Subsequently, the aridification on the TP led to decreased minerogenic input in all three lakes especially since ~2 ka cal BP. Short term divergences from this trend are caused by dry spells on the northern TP. Their timing is quasi synchronous to Holocene Bond events, suggesting a teleconnection of northern TP climate to the circulation of the North Atlantic Ocean.

The analgesic effects of exogenous melatonin in humans.

PubMed

Andersen, Lars Peter Holst

2016-10-01

The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.

Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

PubMed

Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

2015-02-01

Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Update on the effect of exogenous hormone use on glioma risk in women: a meta-analysis of case-control and cohort studies.

PubMed

Lan, Yu-Long; Wang, Xun; Lou, Jia-Cheng; Ma, Bin-Bin; Xing, Jin-Shan; Zou, Shuang; Zhang, Bo

2018-04-01

Various studies have confirmed the important roles of endogenous hormones in the development of gliomas, while the roles of exogenous hormones remain controversial. Based on case-control studies and cohort studies, a meta-analysis was exerted to explore the effect of two exogenous hormones use (HRT: hormone replacement therapy; OC: oral contraceptives) on glioma risk. 16 eligible studies, including 11 case-control studies and 5 cohort studies, containing 8055027 women, were included in our study. All included studies have reported the relative risks (RRs) or odds ratios (ORs), and 95% confidence intervals (CIs). We use the fixed-effects model to calculate the estimated overall risk. In case-control studies, the risk of glioma was lower in women who had ever been treated with an exogenous hormone than in the control group (HRT: OR 0.91, 95% CI 0.84-0.99; OC: OR 0.99, 95% CI 0.91-1.07). In research of cohort studies, similar results have been obtained (HRT: RR 0.95, 95% CI 0.83-1.08; OC: RR 0.75, 95% CI 0.66-0.84). Our study further confirmed that the use of exogenous hormones has an important impact on the risk of glioma in women. However, more prospective studies are needed to further confirm this conclusion.

Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes*

PubMed Central

Karaivanov, Alexander; Townsend, Robert M.

2014-01-01

We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured. PMID:25246710

The Relationship Between Grammatical Development and Disfluencies in Preschool Children Who Stutter and Those Who Recover

PubMed Central

Van Horne, Amanda Owen; Zebrowski, Patricia

2017-01-01

Purpose The dual diathesis stressor model indicates that a mismatch between a child's endogenous linguistic abilities and exogenous linguistic contexts is one factor that contributes to stuttering behavior. In the present study, we used a developmental framework to investigate if reducing the gap between endogenous and exogenous linguistics factors would result in less disfluency for typical children, children who recover from stuttering (CWS-R), and children who persist. Method Children between 28 and 43 months of age participated in this study: 8 typical children, 5 CWS-R, and 8 children who persist. The children were followed for 18 months with language samples collected every 6 months. The Index of Productive Syntax (Scarborough, 1990) served as a measure of endogenous grammatical ability. Length and complexity of active declarative sentences served as a measure of exogenous linguistic demand. A hierarchical linear model analysis was conducted using a mixed-model approach. Results The results partially corroborate the dual diathesis stressor model. Disfluencies significantly decreased in CWS-R as grammatical abilities (not age) increased. Language development may serve as a protective factor or catalyst for recovery for CWS-R. As grammatical ability grew and the gap between linguistic ability and demand decreased; however, none of the three groups was more likely to produce disfluencies in longer and more complex utterances. PMID:27936278

HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region.

PubMed

Han, Songyan; Lu, Jun; Zhang, Yu; Cheng, Cao; Li, Lin; Han, Liping; Huang, Baiqu

2007-02-15

The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histones H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5.

Investigation of potential targets of Porphyromonas CRISPRs among the genomes of Porphyromonas species

PubMed Central

Shibasaki, Masaki; Maruyama, Fumito; Sekizaki, Tsutomu; Nakagawa, Ichiro

2017-01-01

The oral bacterial species Porphyromonas gingivalis, a periodontal pathogen, has plastic genomes that may be driven by homologous recombination with exogenous deoxyribonucleic acid (DNA) that is incorporated by natural transformation and conjugation. However, bacteriophages and plasmids, both of which are main resources of exogenous DNA, do not exist in the known P. gingivalis genomes. This could be associated with an adaptive immunity system conferred by clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated (cas) genes in P. gingivalis as well as innate immune systems such as a restriction-modification system. In a previous study, few immune targets were predicted for P. gingivalis CRISPR/Cas. In this paper, we analyzed 51 P. gingivalis genomes, which were newly sequenced, and publicly available genomes of 13 P. gingivalis and 46 other Porphyromonas species. We detected 6 CRISPR/Cas types (classified by sequence similarity of repeat) in P. gingivalis and 12 other types in the remaining species. The Porphyromonas CRISPR spacers with potential targets in the genus Porphyromonas were approximately 23 times more abundant than those with potential targets in other genus taxa (1,720/6,896 spacers vs. 74/6,896 spacers). Porphyromonas CRISPR/Cas may be involved in genome plasticity by exhibiting selective interference against intra- and interspecies nucleic acids. PMID:28837670

Endogenous Versus Exogenous Shocks in Complex Networks: An Empirical Test Using Book Sale Rankings

NASA Astrophysics Data System (ADS)

Sornette, D.; Deschâtres, F.; Gilbert, T.; Ageon, Y.

2004-11-01

We study the precursory and recovery signatures accompanying shocks in complex networks, that we test on a unique database of the Amazon.com ranking of book sales. We find clear distinguishing signatures classifying two types of sales peaks. Exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. These results are rationalized quantitatively by a simple model of epidemic propagation of interactions with long memory within a network of acquaintances. The observed relaxation of sales implies that the sales dynamics is dominated by cascades rather than by the direct effects of news or advertisements, indicating that the social network is close to critical.

Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish.

PubMed

Kawahara, Atsuo; Hisano, Yu; Ota, Satoshi; Taimatsu, Kiyohito

2016-05-13

The zebrafish (Danio rerio) is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs) at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

Endogenous versus exogenous shocks in complex networks: an empirical test using book sale rankings.

PubMed

Sornette, D; Deschâtres, F; Gilbert, T; Ageon, Y

2004-11-26

We study the precursory and recovery signatures accompanying shocks in complex networks, that we test on a unique database of the Amazon.com ranking of book sales. We find clear distinguishing signatures classifying two types of sales peaks. Exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. These results are rationalized quantitatively by a simple model of epidemic propagation of interactions with long memory within a network of acquaintances. The observed relaxation of sales implies that the sales dynamics is dominated by cascades rather than by the direct effects of news or advertisements, indicating that the social network is close to critical.

Olivine on Vesta as exogenous contaminants brought by impacts: Constraints from modeling Vesta's collisional history and from impact simulations

NASA Astrophysics Data System (ADS)

Turrini, D.; Svetsov, V.; Consolmagno, G.; Sirono, S.; Pirani, S.

2016-12-01

The survival of asteroid Vesta during the violent early history of the Solar System is a pivotal constraint on theories of planetary formation. Particularly important from this perspective is the amount of olivine excavated from the vestan mantle by impacts, as this constrains both the interior structure of Vesta and the number of major impacts the asteroid suffered during its life. The NASA Dawn mission revealed that olivine is present on Vesta's surface in limited quantities, concentrated in small patches at a handful of sites not associated with the two large impact basins Rheasilvia and Veneneia. The first detections were interpreted as the result of the excavation of endogenous olivine, even if the depth at which the detected olivine originated was a matter of debate. Later works raised instead the possibility that the olivine had an exogenous origin, based on the geologic and spectral features of the deposits. In this work, we quantitatively explore the proposed scenario of a exogenous origin for the detected vestan olivine to investigate whether its presence on Vesta can be explained as a natural outcome of the collisional history of the asteroid over the last one or more billion years. To perform this study we took advantage of the impact contamination model previously developed to study the origin and amount of dark and hydrated materials observed by Dawn on Vesta, a model we updated by performing dedicated hydrocode impact simulations. We show that the exogenous delivery of olivine by the same impacts that shaped the vestan surface can offer a viable explanation for the currently identified olivine-rich sites without violating the constraint posed by the lack of global olivine signatures on Vesta. Our results indicate that no mantle excavation is in principle required to explain the observations of the Dawn mission and support the idea that the vestan crust could be thicker than indicated by simple geochemical models based on the Howardite-Eucrite-Diogenite family of meteorites.

Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells

NASA Astrophysics Data System (ADS)

Dorier, M.; Brun, E.; Veronesi, G.; Barreau, F.; Pernet-Gallay, K.; Desvergne, C.; Rabilloud, T.; Carapito, C.; Herlin-Boime, N.; Carrière, M.

2015-04-01

TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients.TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients. Electronic supplementary information (ESI) available: Nanoparticle physico-chemical characterization: size distribution in exposure medium, as measured by DLS (Fig. S1), and X-ray diffraction patterns of A12 and R20 (Fig. S2); characterization of the protein corona on A12 and R20 (Table S1-S4 and experimental). See DOI: 10.1039/c5nr00505a

Application of uniform design to improve dental implant system.

PubMed

Cheng, Yung-Chang; Lin, Deng-Huei; Jiang, Cho-Pei

2015-01-01

This paper introduces the application of uniform experimental design to improve dental implant systems subjected to dynamic loads. The dynamic micromotion of the Zimmer dental implant system is calculated and illustrated by explicit dynamic finite element analysis. Endogenous and exogenous factors influence the success rate of dental implant systems. Endogenous factors include: bone density, cortical bone thickness and osseointegration. Exogenous factors include: thread pitch, thread depth, diameter of implant neck and body size. A dental implant system with a crest module was selected to simulate micromotion distribution and stress behavior under dynamic loads using conventional and proposed methods. Finally, the design which caused minimum micromotion was chosen as the optimal design model. The micromotion of the improved model is 36.42 μm, with an improvement is 15.34% as compared to the original model.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

NASA Astrophysics Data System (ADS)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-03-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer.

On definition and use of the term bioavailability.

PubMed

Rescigno, A; Thakur, A K; Marzo, A

1994-10-01

In common usage, the rate of absorption of an active ingredient or its therapeutic moiety is generally not mentioned in the context of bioavailability. In this communication it is shown that exclusion of the rate of absorption may have serious consequence on the interpretation of bioavailability depending on the underlying model for the system under study. In the case of endogenous substances, the term "bioavailability" is ambiguous unless one specifies whether it refers to availability of the exogenous substance only or the sum total of the exogenous and endogenous substances.

The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster

PubMed Central

Marangi, Luigi; Mirinaviciute, Grazina; Flem, Elmira; Scalia Tomba, Gianpaolo; Guzzetta, Giorgio; Freiesleben de Blasio, Birgitte; Manfredi, Piero

2017-01-01

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3–5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation. PMID:28545047

Neurophysiology and Neuroanatomy of Reflexive and Volitional Saccades: Evidence from Studies of Humans

PubMed Central

McDowell, Jennifer E.; Dyckman, Kara A.; Austin, Benjamin; Clementz, Brett A.

2008-01-01

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually-guided saccades (redirections of gaze to a visual stimulus or prosaccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human primates (e.g. single unit recordings) and humans (e.g. lesions and neuroimaging). Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in prosaccade generation (by definition exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical structures (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields). Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g. antisaccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution. PMID:18835656

Shaping Social Activity by Incentivizing Users

PubMed Central

Farajtabar, Mehrdad; Du, Nan; Rodriguez, Manuel Gomez; Valera, Isabel; Zha, Hongyuan; Song, Le

2015-01-01

Events in an online social network can be categorized roughly into endogenous events, where users just respond to the actions of their neighbors within the network, or exogenous events, where users take actions due to drives external to the network. How much external drive should be provided to each user, such that the network activity can be steered towards a target state? In this paper, we model social events using multivariate Hawkes processes, which can capture both endogenous and exogenous event intensities, and derive a time dependent linear relation between the intensity of exogenous events and the overall network activity. Exploiting this connection, we develop a convex optimization framework for determining the required level of external drive in order for the network to reach a desired activity level. We experimented with event data gathered from Twitter, and show that our method can steer the activity of the network more accurately than alternatives. PMID:26005312

A multivariate auto-regressive combined-harmonics analysis and its application to ozone time series data

NASA Astrophysics Data System (ADS)

Yang, Eun-Su

2001-07-01

A new statistical approach is used to analyze Dobson Umkehr layer-ozone measurements at Arosa for 1979-1996 and Total Ozone Mapping Spectrometer (TOMS) Version 7 zonal mean ozone for 1979-1993, accounting for stratospheric aerosol optical depth (SAOD), quasi-biennial oscillation (QBO), and solar flux effects. A stepwise regression scheme selects statistically significant periodicities caused by season, SAOD, QBO, and solar variations and filters them out. Auto-regressive (AR) terms are included in ozone residuals and time lags are assumed for the residuals of exogenous variables. Then, the magnitudes of responses of ozone to the SAOD, QBO, and solar index (SI) series are derived from the stationary time series of the residuals. These Multivariate Auto-Regressive Combined Harmonics (MARCH) processes possess the following significant advantages: (1)the ozone trends are estimated more precisely than the previous methods; (2)the influences of the exogenous SAOD, QBO, and solar variations are clearly separated at various time lags; (3)the collinearity of the exogenous variables in the regression is significantly reduced; and (4)the probability of obtaining misleading correlations between ozone and exogenous times series is reduced. The MARCH results indicate that the Umkehr ozone response to SAOD (not a real ozone response but rather an optical interference effect), QBO, and solar effects is driven by combined dynamical radiative-chemical processes. These results are independently confirmed using the revised Standard models that include aerosol and solar forcing mechanisms with all possible time lags but not by the Standard model when restricted to a zero time lag in aerosol and solar ozone forcings. As for Dobson Umkehr ozone measurements at Arosa, the aerosol effects are most significant in layers 8, 7, and 6 with no time lag, as is to be expected due to the optical contamination of Umkehr measurements by SAOD. The QBO and solar UV effects appear in all layers 4-8, and in total ozone. In order to account for annual modulation of the equatorial winds that affects ozone at midlatitudes, a new QBO proxy is selected and applied to the Dobson Umkehr measurements at Arosa. The QBO proxy turns out to be more effective to filter the modulated ozone signals at midlatitudes than the mostly used QBO proxy, the Singapore winds at 30 mb. A statistically significant negative phase relationship is found between solar UV variation and ozone response, especially in layer 4, implying dynamical effects of solar variations on ozone at midlatitudes. Linear negative trends in ozone of -7.8 +/- 1.1 and -5.2 +/- 1.4 [%/decade +/- 2σ] are calculated in layers 7 (~35 km) and 8 (~40 km), respectively, for the period of 1979-1996, with smaller trends of -2.2 +/- 1.0, 1.8 +/- 0.9, and -1.4 +/- 1.1 in layers 6 (~30 km), 5 (~25 km), and 4 (~20 km), respectively. A trend in total ozone (layers 1 through 10) of -2.9 +/- 1.2 [%/decade +/- 2σ] is found over this same period. The aerosol effects obtained from the TOMS zonal means become significant at midlatitudes. QBO ozone contributes to the TOMS zonal means by +/-2 to 4% of their means. The negative solar ozone responses are also found at midlatitudes from the TOMS measurements. The most negative trends from TOMS zonal means are about -6.3 +/- 0.6%/decade at 40-50°N.

The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract.

PubMed

Bilski, Jan; Mazur-Bialy, Agnieszka; Wojcik, Dagmara; Zahradnik-Bilska, Janina; Brzozowski, Bartosz; Magierowski, Marcin; Mach, Tomasz; Magierowska, Katarzyna; Brzozowski, Tomasz

2017-01-01

Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.

The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract

PubMed Central

Wojcik, Dagmara; Zahradnik-Bilska, Janina; Mach, Tomasz

2017-01-01

Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients. PMID:28316376

Converting cancer genes into killer genes.

PubMed Central

Da Costa, L T; Jen, J; He, T C; Chan, T A; Kinzler, K W; Vogelstein, B

1996-01-01

Over the past decade, it has become clear that tumorigenesis is driven by alterations in genes that control cell growth or cell death. Theoretically, the proteins encoded by these genes provide excellent targets for new therapeutic agents. Here, we describe a gene therapy approach to specifically kill tumor cells expressing such oncoproteins. In outline, the target oncoprotein binds to exogenously introduced gene products, resulting in transcriptional activation of a toxic gene. As an example, we show that this approach can be used to specifically kill cells overexpressing a mutant p53 gene in cell culture. The strategy may be generally applicable to neoplastic diseases in which the underlying patterns of genetic alterations or abnormal gene expression are known. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 PMID:8633039

Genotype-driven isolation of enterocin with novel bioactivities from mangrove-derived Streptomyces qinglanensis 172205.

PubMed

Xu, Dong-Bo; Ma, Min; Deng, Zi-Xin; Hong, Kui

2015-07-01

The type II polyketide synthase (PKS) natural product enterocin (1) was isolated from a mangrove-derived novel species Streptomyces qinglanensis 172205 guided by genome sequence, and its putative biosynthetic gene cluster was revealed. Its natural analogues 5-deoxyenterocin (2) and wailupemycin A-C (3-5) were also identified by tandem mass spectrometry. By feeding experiments with aryl acids, strain 172205 was proved to incorporate partial exogenous starter units into enterocin- and wailupemycin-based analogues, thus being a new and suitable microorganism for engineering unnatural enc-derived polyketide metabolites. In addition, biological assays indicated that enterocin showed obvious inhibitory activity against β-amyloid protein (Aβ1-42) fibrillation and moderate cytotoxicity against HeLa and HepG2 for the first time.

Stochastic dynamics for reinfection by transmitted diseases

NASA Astrophysics Data System (ADS)

Barros, Alessandro S.; Pinho, Suani T. R.

2017-06-01

The use of stochastic models to study the dynamics of infectious diseases is an important tool to understand the epidemiological process. For several directly transmitted diseases, reinfection is a relevant process, which can be expressed by endogenous reactivation of the pathogen or by exogenous reinfection due to direct contact with an infected individual (with smaller reinfection rate σ β than infection rate β ). In this paper, we examine the stochastic susceptible, infected, recovered, infected (SIRI) model simulating the endogenous reactivation by a spontaneous reaction, while exogenous reinfection by a catalytic reaction. Analyzing the mean-field approximations of a site and pairs of sites, and Monte Carlo (MC) simulations for the particular case of exogenous reinfection, we obtained continuous phase transitions involving endemic, epidemic, and no transmission phases for the simple approach; the approach of pairs is better to describe the phase transition from endemic phase (susceptible, infected, susceptible (SIS)-like model) to epidemic phase (susceptible, infected, and removed or recovered (SIR)-like model) considering the comparison with MC results; the reinfection increases the peaks of outbreaks until the system reaches endemic phase. For the particular case of endogenous reactivation, the approach of pairs leads to a continuous phase transition from endemic phase (SIS-like model) to no transmission phase. Finally, there is no phase transition when both effects are taken into account. We hope the results of this study can be generalized for the susceptible, exposed, infected, and removed or recovered (SEIRIE) model, for which the state exposed (infected but not infectious), describing more realistically transmitted diseases such as tuberculosis. In future work, we also intend to investigate the effect of network topology on phase transitions when the SIRI model describes both transmitted diseases (σ <1 ) and social contagions (σ >1 ).

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

PubMed

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

2016-05-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

PubMed Central

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.

2016-01-01

Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. PMID:26987353

Reference Pricing with Endogenous or Exogenous Payment Limits: Impacts on Insurer and Consumer Spending.

PubMed

Brown, Timothy T; Robinson, James C

2016-06-01

Reference pricing (RP) theories predict different outcomes when reference prices are fixed (exogenous) versus being a function of market prices (MPs) (endogenous). Exogenous RP results in MPs at both high-price and low-price firms converging towards the reference price from above and below, respectively. Endogenous RP results in MPs at both high-price and low-price firms decreasing, with low-price firms acting strategically to decrease the reference price in order to gain market share. We extend these models to a hospital context focusing on insurer and consumer payments. Under exogenous RP, insurer and consumer payments to low-price hospitals increase, and insurer payments to high-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. Under endogenous RP, insurer payments to high-price and low-price hospitals decrease, and consumer payments to low-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. We test these predictions with difference-in-differences specifications using 2008-2013 data on patients undergoing joint replacement. For 2 years following RP implementation, insurer payments to high-price and low-price hospitals moved downward, consistent with endogenous RP. However, when the reference price was not reset to account for changes in MPs, insurer payments to low-price hospitals reverted to pre-implementation levels, consistent with exogenous RP. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Detecting Mixtures from Structural Model Differences Using Latent Variable Mixture Modeling: A Comparison of Relative Model Fit Statistics

ERIC Educational Resources Information Center

Henson, James M.; Reise, Steven P.; Kim, Kevin H.

2007-01-01

The accuracy of structural model parameter estimates in latent variable mixture modeling was explored with a 3 (sample size) [times] 3 (exogenous latent mean difference) [times] 3 (endogenous latent mean difference) [times] 3 (correlation between factors) [times] 3 (mixture proportions) factorial design. In addition, the efficacy of several…

A Model of International Communication Media Appraisal: Phase IV, Generalizing the Model to Film.

ERIC Educational Resources Information Center

Johnson, J. David

A study tested a causal model of international communication media appraisal using audience evaluations of tests of two films conducted in the Philippines. It was the fourth in a series of tests of the model in both developed and developing countries. In general the model posited determinative relationships between three exogenous variables…

The Effects of Model Misspecification and Sample Size on LISREL Maximum Likelihood Estimates.

ERIC Educational Resources Information Center

Baldwin, Beatrice

The robustness of LISREL computer program maximum likelihood estimates under specific conditions of model misspecification and sample size was examined. The population model used in this study contains one exogenous variable; three endogenous variables; and eight indicator variables, two for each latent variable. Conditions of model…

Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome.

PubMed

Spencer, Thomas E; Palmarini, Massimo

2012-01-01

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

The control of fruiting body formation in the ascomycete Sordaria macrospora Auersw. by regulation of hyphal development : An analysis based on scanning electron and light microscopic observations.

PubMed

Hock, B; Bahn, M; Walk, R A; Nitschke, U

1978-01-01

The morphological effects of biotin and L-arginine on fruiting body formation of the ascomycete Sordaria macrospora are investigated by scanning electron and light microscopy. Biotin is recognized as an elongation factor and arginine as a branching factor in vegetative and reproductive hyphae. In the absence of exogenous biotin, development is blocked after the ascogonium-core hypha stage of protoperithecial morphogenesis, whereas linear growth of the myceliar front is maintained. The addition of exogenous arginine to a biotin deficient culture induces the formation of numerous side branches even in the older mycelium. Fruiting body formation, however, remains blocked at the protoperithecial stage as before, because of the inability of the side branches to elongate. When biotin and arginine are administered simultaneously, a most vigorous branching and growth are induced in the older mycelium, accompanied by a rapid and maximal formation of fruiting bodies. The results are summarized in a model of the exogenous control of hyphal morphogenesis. The model is designed to explain the relationship between fruiting and hyphal density as well as the edge effect on fruiting body formation.

Exogenous skeletal muscle satellite cells promote the repair of levator palpebrae superioris mechanical damage in rat.

PubMed

Ye, Lin; Yao, Yuanyuan; Guo, Hui; Peng, Yun

2018-05-17

Blepharoptosis is a drooping of the upper eyelid, usually due to dysfunction of the levator palpebrae superioris (LPS). Recently, skeletal muscle satellite cells (SSCs) have been reported to promote the repair of damaged skeletal muscle. This study aims to investigate the potential contribution of exogenous SSCs to the regeneration of mechanically damaged LPS. Thirty-two rats were randomly divided into four groups, including control group, SSCs-treated group, SSCs-treated injury group and non-treated injury group. After rats in injury groups were artificially lacerated on both the left and right LPS, HBBS (Hank's Balanced Salt Solution) containing SSCs was injected into upper eyelid tissue. After 7 days, the LPS muscle tissues were excised. In addition, skeletal muscle cells (SMCs) and SSCs were cocultured for use as an in vitro model, and the protective effects of SSCs on cultured SMCs were also investigated. Histological staining revealed that exogenous SSCs repaired the damaged muscle fibers and attenuated the fibrosis of LPS, possibly due to the increased level of IGF-1. In contrast, the level of IL-1β, IL-6, TGF-β1 and Smad2/3 (phospho-T8) were significantly reduced in the SSCs-treated group. The in vitro model using coculture of skeletal muscle cells (SMCs) and SSCs also revealed an increased level of IGF-1 and reduced level of inflammatory factors, resulting in a better cell survival rate. This study found that exogenous SSCs can promote the repair of LPS mechanical damage and provides new insight into the development of novel therapeutic approaches for blepharoptosis.

Treatment with Uric Acid Reduces Infarct and Improves Neurologic Function in Female Mice After Transient Cerebral Ischemia.

PubMed

Dhanesha, Nirav; Vázquez-Rosa, Edwin; Cintrón-Pérez, Coral J; Thedens, Daniel; Kort, Alexa J; Chuong, Vicky; Rivera-Dompenciel, Adriana M; Chauhan, Anil K; Leira, Enrique C; Pieper, Andrew A

2018-05-01

Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. Before clinical trials can be initiated in the United States, however, confirmation of efficacy in alternative preclinical models is required in accordance with stroke therapy academic industry roundtable-RIGOR criteria. To date, preclinical efficacy has only been established in the acute setting in male rodents. To address this need, we subjected 7- to 9-week old ovariectomized female mice to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry. A separate lab randomly assigned animals to vehicle versus uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Poststroke analysis of infarction size and neurologic function were conducted by investigators blind to treatment group, with a 7-day primary endpoint and a 3-day intermediary analysis at 1and. Infarct size and neurologic function at 7 days poststroke were significantly improved in uric acid-treated animals, relative to vehicle. Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a later time point than has been investigated previously. These results support stroke therapy academic industry roundtable-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke. Published by Elsevier Inc.

Dynamics of book sales: endogenous versus exogenous shocks in complex networks.

PubMed

Deschâtres, F; Sornette, D

2005-07-01

We present an extensive study of the foreshock and aftershock signatures accompanying peaks of book sales. The time series of book sales are derived from the ranking system of Amazon.com. We present two independent ways of classifying peaks, one based on the acceleration pattern of sales and the other based on the exponent of the relaxation. They are found to be consistent and reveal the coexistence of two types of sales peaks: exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous sale peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. We develop a simple epidemic model of buyers connected within a network of acquaintances which propagates rumors and opinions on books. The comparison between the predictions of the model and the empirical data confirms the validity of the model and suggests in addition that social networks have evolved to converge very close to criticality (here in the sense of critical branching processes of opinion spreading). We test in detail the evidence for a power law distribution of book sales and confirm a previous indirect study suggesting that the fraction of books (density distribution) P (S) of sales S is a power law P(S) approximately 1/ S(1+mu) with mu approximately equal to 2 .

Climate effects and feedback structure determining weed population dynamics in a long-term experiment.

PubMed

Lima, Mauricio; Navarrete, Luis; González-Andujar, José Luis

2012-01-01

Pest control is one of the areas in which population dynamic theory has been successfully applied to solve practical problems. However, the links between population dynamic theory and model construction have been less emphasized in the management and control of weed populations. Most management models of weed population dynamics have emphasized the role of the endogenous process, but the role of exogenous variables such as climate have been ignored in the study of weed populations and their management. Here, we use long-term data (22 years) on two annual weed species from a locality in Central Spain to determine the importance of endogenous and exogenous processes (local and large-scale climate factors). Our modeling study determined two different feedback structures and climate effects in the two weed species analyzed. While Descurainia sophia exhibited a second-order feedback and low climate influence, Veronica hederifolia was characterized by a first-order feedback structure and important effects from temperature and rainfall. Our results strongly suggest the importance of theoretical population dynamics in understanding plant population systems. Moreover, the use of this approach, discerning between the effect of exogenous and endogenous factors, can be fundamental to applying weed management practices in agricultural systems and to controlling invasive weedy species. This is a radical change from most approaches currently used to guide weed and invasive weedy species managements.

Causal relationship model between variables using linear regression to improve professional commitment of lecturer

NASA Astrophysics Data System (ADS)

Setyaningsih, S.

2017-01-01

The main element to build a leading university requires lecturer commitment in a professional manner. Commitment is measured through willpower, loyalty, pride, loyalty, and integrity as a professional lecturer. A total of 135 from 337 university lecturers were sampled to collect data. Data were analyzed using validity and reliability test and multiple linear regression. Many studies have found a link on the commitment of lecturers, but the basic cause of the causal relationship is generally neglected. These results indicate that the professional commitment of lecturers affected by variables empowerment, academic culture, and trust. The relationship model between variables is composed of three substructures. The first substructure consists of endogenous variables professional commitment and exogenous three variables, namely the academic culture, empowerment and trust, as well as residue variable ɛ y . The second substructure consists of one endogenous variable that is trust and two exogenous variables, namely empowerment and academic culture and the residue variable ɛ 3. The third substructure consists of one endogenous variable, namely the academic culture and exogenous variables, namely empowerment as well as residue variable ɛ 2. Multiple linear regression was used in the path model for each substructure. The results showed that the hypothesis has been proved and these findings provide empirical evidence that increasing the variables will have an impact on increasing the professional commitment of the lecturers.

Dynamics of book sales: Endogenous versus exogenous shocks in complex networks

NASA Astrophysics Data System (ADS)

Deschâtres, F.; Sornette, D.

2005-07-01

We present an extensive study of the foreshock and aftershock signatures accompanying peaks of book sales. The time series of book sales are derived from the ranking system of Amazon.com. We present two independent ways of classifying peaks, one based on the acceleration pattern of sales and the other based on the exponent of the relaxation. They are found to be consistent and reveal the coexistence of two types of sales peaks: exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous sale peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. We develop a simple epidemic model of buyers connected within a network of acquaintances which propagates rumors and opinions on books. The comparison between the predictions of the model and the empirical data confirms the validity of the model and suggests in addition that social networks have evolved to converge very close to criticality (here in the sense of critical branching processes of opinion spreading). We test in detail the evidence for a power law distribution of book sales and confirm a previous indirect study suggesting that the fraction of books (density distribution) P(S) of sales S is a power law P(S)˜1/S1+μ with μ≈2 .

Climate Effects and Feedback Structure Determining Weed Population Dynamics in a Long-Term Experiment

PubMed Central

Lima, Mauricio; Navarrete, Luis; González-Andujar, José Luis

2012-01-01

Pest control is one of the areas in which population dynamic theory has been successfully applied to solve practical problems. However, the links between population dynamic theory and model construction have been less emphasized in the management and control of weed populations. Most management models of weed population dynamics have emphasized the role of the endogenous process, but the role of exogenous variables such as climate have been ignored in the study of weed populations and their management. Here, we use long-term data (22 years) on two annual weed species from a locality in Central Spain to determine the importance of endogenous and exogenous processes (local and large-scale climate factors). Our modeling study determined two different feedback structures and climate effects in the two weed species analyzed. While Descurainia sophia exhibited a second-order feedback and low climate influence, Veronica hederifolia was characterized by a first-order feedback structure and important effects from temperature and rainfall. Our results strongly suggest the importance of theoretical population dynamics in understanding plant population systems. Moreover, the use of this approach, discerning between the effect of exogenous and endogenous factors, can be fundamental to applying weed management practices in agricultural systems and to controlling invasive weedy species. This is a radical change from most approaches currently used to guide weed and invasive weedy species managements. PMID:22272362

μ-PIV/Shadowgraphy measurements to elucidate dynamic physicochemical interactions in a multiphase model of pulmonary airway reopening

NASA Astrophysics Data System (ADS)

Yamaguchi, Eiichiro

2010-10-01

We employ micro-particle image velocimetry (μ-PIV) and shadowgraphy to measure the ensemble-averaged fluid-phase velocity field and interfacial geometry during pulsatile bubble propagation that includes a reverse-flow phase under influence of exogenous lung surfactant (Infasurf). Disease states such as respiratory distress syndrome (RDS) are characterized by insufficient pulmonary surfactant concentrations that enhance airway occlusion and collapse. Subsequent airway reopening, driven by mechanical ventilation, may generate damaging stresses that cause ventilator-induced lung injury (VILI). It is hypothesized that reverse flow may enhance surfactant uptake and protect the lung from VILI. The microscale observations conducted in this study will provide us with a significant understanding of dynamic physicochemical interactions that can be manipulated to reduce the magnitude of this damaging mechanical stimulus during airway reopening. Bubble propagation through a liquid-occluded fused glass capillary tube is controlled by linear-motor-driven syringe pumps that provide mean and sinusoidal velocity components. A translating microscope stage mechanically subtracts the mean velocity of the bubble tip in order to hold the progressing bubble tip in the microscope field of view. To optimize the signal-to-noise ratio near the bubble tip, μ-PIV and shadow images are recorded in separate trials then combined during post-processing with help of a custom-designed micro scale marker. Non-specific binding of Infasurf proteins to the channel wall is controlled by oxidation and chemical treatment of the glass surface. The colloidal stability and dynamic/static surface properties of the Infasurf-PIV particle solution are carefully adjusted based on Langmuir trough measurements. The Finite Time Lyapunov Exponent (FTLE) is computed to provide a Lagrangian perspective for comparison with our boundary element predictions.

Predictors of Latina/o Community College Student Vocational Choice of STEM Fields: Testing of the STEM-Vocational Choice Model

ERIC Educational Resources Information Center

Johnson, Joel D.

2013-01-01

This study confirmed appropriate measurement model fit for a theoretical model, the STEM vocational choice (STEM-VC) model. This model identifies exogenous factors that successfully predicted, at a statistically significant level, a student's vocational choice decision to pursue a STEM degree at transfer. The student population examined for this…

Boko Haram: A Systemic and Strategic Analysis

DTIC Science & Technology

2016-06-01

21 5 Example Structural System Model …..……………………………….…………21 6 Interconnections ...…………………………………………………….…………23 vii 7...result from exogenous, endogenous, or structural factors. Endogenous factors exist within the geographical bounds of the system state, but exogenous...of the system, the structural factors are a result of the anarchic nature of the international system. Changes in system states reveal long-term

Model documentation, Coal Market Module of the National Energy Modeling System

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

NONE

This report documents the objectives and the conceptual and methodological approach used in the development of the National Energy Modeling System`s (NEMS) Coal Market Module (CMM) used to develop the Annual Energy Outlook 1998 (AEO98). This report catalogues and describes the assumptions, methodology, estimation techniques, and source code of CMM`s two submodules. These are the Coal Production Submodule (CPS) and the Coal Distribution Submodule (CDS). CMM provides annual forecasts of prices, production, and consumption of coal for NEMS. In general, the CDS integrates the supply inputs from the CPS to satisfy demands for coal from exogenous demand models. The internationalmore » area of the CDS forecasts annual world coal trade flows from major supply to major demand regions and provides annual forecasts of US coal exports for input to NEMS. Specifically, the CDS receives minemouth prices produced by the CPS, demand and other exogenous inputs from other NEMS components, and provides delivered coal prices and quantities to the NEMS economic sectors and regions.« less

Defective B cell response to T-dependent immunization in lupus-prone mice

PubMed Central

Niu, Haitao; Sobel, Eric S.; Morel, Laurence

2009-01-01

Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

Mechanism and analyses for extracting photosynthetic electrons using exogenous quinones - what makes a good extraction pathway?

PubMed

Longatte, G; Rappaport, F; Wollman, F-A; Guille-Collignon, M; Lemaître, F

2016-08-04

Plants or algae take many benefits from oxygenic photosynthesis by converting solar energy into chemical energy through the synthesis of carbohydrates from carbon dioxide and water. However, the overall yield of this process is rather low (about 4% of the total energy available from sunlight is converted into chemical energy). This is the principal reason why recently many studies have been devoted to extraction of photosynthetic electrons in order to produce a sustainable electric current. Practically, the electron transfer occurs between the photosynthetic organism and an electrode and can be assisted by an exogenous mediator, mainly a quinone. In this regard, we recently reported on a method involving fluorescence measurements to estimate the ability of different quinones to extract photosynthetic electrons from a mutant of Chlamydomonas reinhardtii. In the present work, we used the same kind of methodology to establish a zone diagram for predicting the most suitable experimental conditions to extract photoelectrons from intact algae (quinone concentration and light intensity) as a function of the purpose of the study. This will provide further insights into the extraction mechanism of photosynthetic electrons using exogenous quinones. Indeed fluorescence measurements allowed us to model the capacity of photosynthetic algae to donate electrons to an exogenous quinone by considering a numerical parameter called "open center ratio" which is related to the Photosystem II acceptor redox state. Then, using it as a proxy for investigating the extraction of photosynthetic electrons by means of an exogenous quinone, 2,6-DCBQ, we suggested an extraction mechanism that was globally found consistent with the experimentally extracted parameters.

Reproductive factors, exogenous estrogen use and risk of Parkinson’s disease

PubMed Central

Simon, Kelly Claire; Chen, Honglei; Gao, Xiang; Schwarzschild, Michael A.; Ascherio, Alberto

2009-01-01

To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson’s disease (PD), we conducted a prospective study with 22 years of follow-up among post-menopausal participants in the Nurses’ Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of post-menopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of post-menopausal hormones (p for interaction = 0.05). Similar results were obtained for caffeine (p for interaction = 0.09). In exploratory analyses, women using progestin-only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n=4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of post-menopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations. PMID:19424986

Exogenous attention can be counter-selective: onset cues disrupt sensitivity to color changes.

PubMed

Müller-Plath, Gisela; Klöckner, Nils

2014-03-01

In peripheral spatial cueing paradigms, exogenous attentional capture is commonly observed after salient onset cues or with cues contingent on target characteristics. We proposed that exogenously captured attention disrupts the selectivity to target features. We tested this by experimentally emulating the everyday observation that in a viewing situation in which the observer is monitoring a stationary display fort change to occur, the onset of a salient stimulus (onset cue) or a change in a stationary stimulus similar to the expected one (contingent cue) has a distracting effect. As predicted, we found that both types of cues reduced the target detection sensitivity but enhanced the bias to respond in a go-nogo-paradigm. With the onset cue, the sensitivity loss was more pronounced at the side of the cue, whereas the contingent cue affected both sides likewise. Moreover, the effects of the onset cue interacted with the task difficulty: the more selectivity a task required the more immune it was against disruption, but the more likely was a response. We concluded that onset capture disrupts selective attention by adding noise to the processing of the target location. The effects of contingent capture could be explained with cue-target confounding. Finally, we suggest a new model of attentional capture in which exogenous and endogenous components interact in a dynamic way.

Social Interactions under Incomplete Information: Games, Equilibria, and Expectations

NASA Astrophysics Data System (ADS)

Yang, Chao

My dissertation research investigates interactions of agents' behaviors through social networks when some information is not shared publicly, focusing on solutions to a series of challenging problems in empirical research, including heterogeneous expectations and multiple equilibria. The first chapter, "Social Interactions under Incomplete Information with Heterogeneous Expectations", extends the current literature in social interactions by devising econometric models and estimation tools with private information in not only the idiosyncratic shocks but also some exogenous covariates. For example, when analyzing peer effects in class performances, it was previously assumed that all control variables, including individual IQ and SAT scores, are known to the whole class, which is unrealistic. This chapter allows such exogenous variables to be private information and models agents' behaviors as outcomes of a Bayesian Nash Equilibrium in an incomplete information game. The distribution of equilibrium outcomes can be described by the equilibrium conditional expectations, which is unique when the parameters are within a reasonable range according to the contraction mapping theorem in function spaces. The equilibrium conditional expectations are heterogeneous in both exogenous characteristics and the private information, which makes estimation in this model more demanding than in previous ones. This problem is solved in a computationally efficient way by combining the quadrature method and the nested fixed point maximum likelihood estimation. In Monte Carlo experiments, if some exogenous characteristics are private information and the model is estimated under the mis-specified hypothesis that they are known to the public, estimates will be biased. Applying this model to municipal public spending in North Carolina, significant negative correlations between contiguous municipalities are found, showing free-riding effects. The Second chapter "A Tobit Model with Social Interactions under Incomplete Information", is an application of the first chapter to censored outcomes, corresponding to the situation when agents" behaviors are subjected to some binding restrictions. In an interesting empirical analysis for property tax rates set by North Carolina municipal governments, it is found that there is a significant positive correlation among near-by municipalities. Additionally, some private information about its own residents is used by a municipal government to predict others' tax rates, which enriches current empirical work about tax competition. The third chapter, "Social Interactions under Incomplete Information with Multiple Equilibria", extends the first chapter by investigating effective estimation methods when the condition for a unique equilibrium may not be satisfied. With multiple equilibria, the previous model is incomplete due to the unobservable equilibrium selection. Neither conventional likelihoods nor moment conditions can be used to estimate parameters without further specifications. Although there are some solutions to this issue in the current literature, they are based on strong assumptions such as agents with the same observable characteristics play the same strategy. This paper relaxes those assumptions and extends the all-solution method used to estimate discrete choice games to a setting with both discrete and continuous choices, bounded and unbounded outcomes, and a general form of incomplete information, where the existence of a pure strategy equilibrium has been an open question for a long time. By the use of differential topology and functional analysis, it is found that when all exogenous characteristics are public information, there are a finite number of equilibria. With privately known exogenous characteristics, the equilbria can be represented by a compact set in a Banach space and be approximated by a finite set. As a result, a finite-state probability mass function can be used to specify a probability measure for equilibrium selection, which completes the model. From Monte Carlo experiments about two types of binary choice models, it is found that assuming equilibrium uniqueness can bring in estimation biases when the true value of interaction intensity is large and there are multiple equilibria in the data generating process.

The Importance of Isomorphism for Conclusions about Homology: A Bayesian Multilevel Structural Equation Modeling Approach with Ordinal Indicators.

PubMed

Guenole, Nigel

2016-01-01

We describe a Monte Carlo study examining the impact of assuming item isomorphism (i.e., equivalent construct meaning across levels of analysis) on conclusions about homology (i.e., equivalent structural relations across levels of analysis) under varying degrees of non-isomorphism in the context of ordinal indicator multilevel structural equation models (MSEMs). We focus on the condition where one or more loadings are higher on the between level than on the within level to show that while much past research on homology has ignored the issue of psychometric isomorphism, psychometric isomorphism is in fact critical to valid conclusions about homology. More specifically, when a measurement model with non-isomorphic items occupies an exogenous position in a multilevel structural model and the non-isomorphism of these items is not modeled, the within level exogenous latent variance is under-estimated leading to over-estimation of the within level structural coefficient, while the between level exogenous latent variance is overestimated leading to underestimation of the between structural coefficient. When a measurement model with non-isomorphic items occupies an endogenous position in a multilevel structural model and the non-isomorphism of these items is not modeled, the endogenous within level latent variance is under-estimated leading to under-estimation of the within level structural coefficient while the endogenous between level latent variance is over-estimated leading to over-estimation of the between level structural coefficient. The innovative aspect of this article is demonstrating that even minor violations of psychometric isomorphism render claims of homology untenable. We also show that posterior predictive p-values for ordinal indicator Bayesian MSEMs are insensitive to violations of isomorphism even when they lead to severely biased within and between level structural parameters. We highlight conditions where poor estimation of even correctly specified models rules out empirical examination of isomorphism and homology without taking precautions, for instance, larger Level-2 sample sizes, or using informative priors.

The Importance of Isomorphism for Conclusions about Homology: A Bayesian Multilevel Structural Equation Modeling Approach with Ordinal Indicators

PubMed Central

Guenole, Nigel

2016-01-01

We describe a Monte Carlo study examining the impact of assuming item isomorphism (i.e., equivalent construct meaning across levels of analysis) on conclusions about homology (i.e., equivalent structural relations across levels of analysis) under varying degrees of non-isomorphism in the context of ordinal indicator multilevel structural equation models (MSEMs). We focus on the condition where one or more loadings are higher on the between level than on the within level to show that while much past research on homology has ignored the issue of psychometric isomorphism, psychometric isomorphism is in fact critical to valid conclusions about homology. More specifically, when a measurement model with non-isomorphic items occupies an exogenous position in a multilevel structural model and the non-isomorphism of these items is not modeled, the within level exogenous latent variance is under-estimated leading to over-estimation of the within level structural coefficient, while the between level exogenous latent variance is overestimated leading to underestimation of the between structural coefficient. When a measurement model with non-isomorphic items occupies an endogenous position in a multilevel structural model and the non-isomorphism of these items is not modeled, the endogenous within level latent variance is under-estimated leading to under-estimation of the within level structural coefficient while the endogenous between level latent variance is over-estimated leading to over-estimation of the between level structural coefficient. The innovative aspect of this article is demonstrating that even minor violations of psychometric isomorphism render claims of homology untenable. We also show that posterior predictive p-values for ordinal indicator Bayesian MSEMs are insensitive to violations of isomorphism even when they lead to severely biased within and between level structural parameters. We highlight conditions where poor estimation of even correctly specified models rules out empirical examination of isomorphism and homology without taking precautions, for instance, larger Level-2 sample sizes, or using informative priors. PMID:26973580

Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

PubMed

Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

2017-09-07

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

Nonlinear and Synchronous Dissolved Organic Matter Dynamics in Streams Across an Agriculture Land Use and Climate Setting

NASA Astrophysics Data System (ADS)

Xenopoulos, M. A.; Vogt, R. J.

2014-12-01

There is now increasing evidence that non-linearity is a common response in ecological systems to pressures caused by human activities. There is also increasing evidence that exogenous environmental drivers, such as climate, induce spatial and temporal synchrony in a wide range of ecological variables. Using Moran's I and Pearson's correlation, we quantified the synchrony of dissolved organic carbon concentration (DOC) and quality (DOM; e.g., specific UV absorbance, Fluorescence Index, PARAFAC), nutrients, discharge and temperature in 40 streams that span an agriculture gradient (0 to >70% cropland), over 10 years. We then used breakpoint regression, 2D-Kolmogorov-Smirnov test and significant zero crossings (SiZer) analyses to quantify the prevalence of nonlinearity and ecological thresholds (breakpoints) where applicable. There was a high degree of synchrony in DOM quality (r > 0.7) but not DOC (r < 0.4). The degree of synchrony was driven in part by the catchment's land use. With respect to the nonlinear analyses we found non-linearity in ~50% of bivariate datasets analyzed. Non-linearity was also driven in part by the catchment's land use. Breakpoints defined different DOM properties. Nonlinearity and synchronous behaviour in DOM are intimately linked to land use.

Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells.

PubMed

Dorier, M; Brun, E; Veronesi, G; Barreau, F; Pernet-Gallay, K; Desvergne, C; Rabilloud, T; Carapito, C; Herlin-Boime, N; Carrière, M

2015-04-28

TiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients.

77 FR 46523 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Prohibited...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

... by Index and Model-Driven Funds ACTION: Notice. SUMMARY: The Department of Labor (DOL) is submitting...) titled, ``Prohibited Transaction Class Exemption for Cross-Trades of Securities by Index and Model-Driven... and Model-Driven Funds permits cross-trades of securities between index and model-driven funds managed...

Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

PubMed Central

Ruiz, Daniel; Poveda, Germán; Vélez, Iván D; Quiñones, Martha L; Rúa, Guillermo L; Velásquez, Luz E; Zuluaga, Juan S

2006-01-01

Background Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. Methods The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Results Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. Conclusion The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System. PMID:16882349

Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System.

PubMed

Ruiz, Daniel; Poveda, Germán; Vélez, Iván D; Quiñones, Martha L; Rúa, Guillermo L; Velásquez, Luz E; Zuluaga, Juan S

2006-08-01

Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897-0.668 (P > 0.95) and 0.0002-0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System.

A Paradigm for Virus–Host Coevolution: Sequential Counter-Adaptations between Endogenous and Exogenous Retroviruses

PubMed Central

Arnaud, Frederick; Caporale, Marco; Varela, Mariana; Biek, Roman; Chessa, Bernardo; Alberti, Alberto; Golder, Matthew; Mura, Manuela; Zhang, Ya-ping; Yu, Li; Pereira, Filipe; DeMartini, James C; Leymaster, Kreg; Spencer, Thomas E; Palmarini, Massimo

2007-01-01

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5–7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (∼ 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections. PMID:17997604

Mechanical tension as a driver of connective tissue growth in vitro.

PubMed

Wilson, Cameron J; Pearcy, Mark J; Epari, Devakara R

2014-07-01

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells' innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a "scaffold" of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards a Model for Research on the Effects of School Organizational Health Factors on Primary School Performance in Trinidad & Tobago

ERIC Educational Resources Information Center

Ramdass, Mala; Lewis, Theodore

2012-01-01

This article presents a model for research on the effects of school organizational heath factors on primary school academic achievement in Trinidad and Tobago. The model can be applicable for evaluating schools in other developing countries. As proposed, the model hypothesizes relationships between external factors (exogenous variables),…

NETWORK STRUCTURE, MULTIPLEXITY, AND EVOLUTION AS INFLUENCES ON COMMUNITY-BASED PARTICIPATORY INTERVENTIONS.

PubMed

Wang, Rong; Tanjasiri, Sora Park; Palmer, Paula; Valente, Thomas W

2016-08-01

This study applies an ecological perspective to the context of community-based participatory research (CBPR). Specifically, it examines how endogenous and exogenous factors influence the dynamics of CBPR partnerships, including the tendency toward reciprocity and transitivity, the organizational type, the level of resource sufficiency, the level of organizational influence, and the perceived CBPR effect on organizations. The results demonstrate that network structure is related to the selection and retention of interorganizational networks over time, and organizations of the same type are more likely to form partnerships with each other. It shows that the dynamics of the CBPR initiative presented in this article were driven by the structure of the interorganizational networks rather than their individual organizational attributes. Implications for sustaining CBPR partnerships are drawn from the findings.

NETWORK STRUCTURE, MULTIPLEXITY, AND EVOLUTION AS INFLUENCES ON COMMUNITY-BASED PARTICIPATORY INTERVENTIONS

PubMed Central

Wang, Rong; Tanjasiri, Sora Park; Palmer, Paula; Valente, Thomas W.

2017-01-01

This study applies an ecological perspective to the context of community-based participatory research (CBPR). Specifically, it examines how endogenous and exogenous factors influence the dynamics of CBPR partnerships, including the tendency toward reciprocity and transitivity, the organizational type, the level of resource sufficiency, the level of organizational influence, and the perceived CBPR effect on organizations. The results demonstrate that network structure is related to the selection and retention of interorganizational networks over time, and organizations of the same type are more likely to form partnerships with each other. It shows that the dynamics of the CBPR initiative presented in this article were driven by the structure of the interorganizational networks rather than their individual organizational attributes. Implications for sustaining CBPR partnerships are drawn from the findings. PMID:29430067

Distinct modes of adventitious rooting in Arabidopsis thaliana.

PubMed

Correa, L da Rocha; Troleis, J; Mastroberti, A A; Mariath, J E A; Fett-Neto, A G

2012-01-01

The literature describes different rooting protocols for Arabidopsis thaliana as models to study adventitious rooting, and results are generally perceived as comparable. However, there is a lack of investigations focusing on the distinct features, advantages and limitations of each method in the study of adventitious rooting with both wild-type (WT) ecotypes and their respective mutants. This investigation was undertaken to evaluate the adventitious rooting process in three different experimental systems, all using A. thaliana, analysing the same rooting parameters after transient exposure to auxin (indole-3-acetic acid) and control conditions: excised leaves, de-rooted plants and etiolated seedlings. The founding tissues and sites of origin of roots differed depending on the system used, whereas all rooting patterns were of the direct type (i.e., without callus formation). None of the systems had an absolute requirement for exogenous auxin, although rooting was enhanced by this phytohormone, with the exception of de-rooted plants, which had adventitious rooting strongly inhibited by exogenous auxin. Root elongation was much favoured in isolated leaves. Auxin-overproducing mutants could not be used in the detached leaf system due to precocious senescence; in the de-rooted plant system, these mutants had a WT-like rooting response, whereas the expression of the 'rooty' phenotype was only evident in the etiolated seedling system. Adventitious rooting of etiolated WT seedlings in the presence of exogenous auxin was inhibited by exogenous flavonoids, which act as auxin transport inhibitors; surprisingly, the flavonoid-deficient mutant chs had a lower rooting response compared to WT. Although Arabidopsis is an excellent model system to study adventitious rooting, physiological and developmental responses differed significantly, underlining the importance of avoiding data generalisation on rooting responses derived from different experimental systems with this species. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Exogenous carbonaceous matter in ancient martian sediments

NASA Astrophysics Data System (ADS)

Mojzsis, S. J.; Abramov, O.; Kereszturi, A.

2015-12-01

We re-evaluate the early evolution of an organic-matter rich (~10 wt. %) interplanetary dust particle flux to early Mars. Our work builds upon physical models that rely on plausible sources of exogenous debris and their dynamical rates of decay, the martian cratering record, and preservation of Noachian-Hesperian sedimentary units that have the potential to host organics. Post primary-accretionary scenarios that would have delivered abundant exogenous carbon to Mars can be imagined in two ways: a simple exponential decay with an approximately 100 Myr half-life, or as a "Sawtooth" timeline characterized by both faster-than-exponential decay from primary accretion and reduced total delivered mass. Indications are that a late bombardment spike was superposed on an otherwise broadly monotonic decline from primary accretion, of which two types are explored: a classical "Late Heavy Bombardment" (LHB) peak of impactors centered at ca. 3950 Ma and lasting 100 Myr, and a protracted bombardment typified by a sudden increase in impactor flux at ca. 4240-4100 Ma with a correspondingly longer decay time (400 Myr). Numerical models for each of the four bombardment scenarios explored in this work shows that exogenous organic matter could be a significant component of Noachian (ca. 4200-3700 Ma) and pre-Noachian (4500-4200 Ma) sediments. The discovery of organic-matter in martian sediments will be obfuscated by material of extra-areological origin. We predict that an earmark for the origin of this carbon would be correlated siderophile element abundances (e.g. Ni, Cr, and the platinoids). A time-dependent compositional relationship of C:HSEs would allow us to derive a chemochronology for pre-Hesperian (pre-3700 Ma) sedimentary units.

Ghrelin enhancer, rikkunshito, improves postprandial gastric motor dysfunction in an experimental stress model.

PubMed

Harada, Y; Ro, S; Ochiai, M; Hayashi, K; Hosomi, E; Fujitsuka, N; Hattori, T; Yakabi, K

2015-08-01

Functional dyspepsia (FD) is one of the most common disorders of gastrointestinal (GI) diseases. However, no curable treatment is available for FD because the detailed mechanism of GI dysfunction in stressed conditions remains unclear. We aimed to clarify the association between endogenous acylated ghrelin signaling and gastric motor dysfunction and explore the possibility of a drug with ghrelin signal-enhancing action for FD treatment. Solid gastric emptying (GE) and plasma acylated ghrelin levels were evaluated in an urocortin1 (UCN1) -induced stress model. To clarify the role of acylated ghrelin on GI dysfunction in the model, exogenous acylated ghrelin, an endogenous ghrelin enhancer, rikkunshito, or an α2 -adrenergic receptor (AR) antagonist was administered. Postprandial motor function was investigated using a strain gauge force transducer in a free-moving condition. Exogenous acylated ghrelin supplementation restored UCN1-induced delayed GE. Alpha2 -AR antagonist and rikkunshito inhibited the reduction in plasma acylated ghrelin and GE in the stress model. The action of rikkunshito on delayed GE was blocked by co-administration of the ghrelin receptor antagonist. UCN1 decreased the amplitude of contraction in the antrum while increasing it in the duodenum. The motility index of the antrum but not the duodenum was significantly reduced by UCN1 treatment, which was improved by acylated ghrelin or rikkunshito. The UCN1-induced gastric motility dysfunction was mediated by abnormal acylated ghrelin dynamics. Supplementation of exogenous acylated ghrelin or enhancement of endogenous acylated ghrelin secretion by rikkunshito may be effective in treating functional GI disorders. © 2015 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Computational modeling of lava domes using particle dynamics to investigate the effect of conduit flow mechanics on flow patterns

NASA Astrophysics Data System (ADS)

Husain, Taha Murtuza

Large (1--4 x 106 m3) to major (> 4 x 106 m3) dome collapses for andesitic lava domes such as Soufriere Hills Volcano, Montserrat are observed for elevated magma discharge rates (6--13 m3/s). The gas rich magma pulses lead to pressure build up in the lava dome that result in structural failure of the over steepened canyon-like walls which may lead to rockfall or pyroclastic flow. This indicates that dome collapse intimately related to magma extrusion rate. Variation in magma extrusion rate for open-system magma chambers is observed to follow alternating periods of high and low activity. Periodic behavior of magma exhibits a rich diversity in the nature of its eruptive history due to variation in magma chamber size, total crystal content, linear crystal growth rate and magma replenishment rate. Distinguished patterns of growth were observed at different magma flow rates ranging from endogenous to exogenous dome growth for magma with varying strengths. Determining the key parameters that control the transition in flow pattern of the magma during its lava dome building eruption is the main focus. This dissertation examines the mechanical effects on the morphology of the evolving lava dome on the extrusion of magma from a central vent using a 2D particle dynamics model. The particle dynamics model is coupled with a conduit flow model that incorporates the kinetics of crystallization and rheological stiffening to investigate important mechanisms during lava dome building eruptions. Chapter I of this dissertation explores lava dome growth and failure mechanics using a two-dimensional particle-dynamics model. The model follows the evolution of fractured lava, with solidification driven by degassing induced crystallization of magma. The particle-dynamics model emulates the natural development of dome growth and rearrangement of the lava dome which is difficult in mesh-based analyses due to mesh entanglement effects. The deformable talus evolves naturally as a frictional carapace that caps a ductile magma core. Extrusion rate and magma rheology together with crystallization temperature and volatile content govern the distribution of strength in the composite structure. This new model is calibrated against existing observational models of lava dome growth. Chapter II of this dissertation explores the effects of a spectrum of different rheological regimes, on eruptive style and morphologic evolution of lava domes, using a two-dimensional (2D) particle-dynamics model for a spreading viscoplastic (Bingham) fluid. We assume that the ductile magma core of a 2-D synthetic lava dome develops finite yield strength, and that deformable frictional talus evolves from a carapace that caps the magma core. Our new model is calibrated against an existing analytical model for a spreading viscoplastic lava dome and is further compared against observational data of lava dome growth. Chapter III of this dissertation explores different lava-dome styles by developing a two-dimensional particle-dynamics model. These growth patterns range from endogenous lava dome growth comprising expansion of a ductile dome core to the exogenous extrusion of a degassed lava plug resulting in generation of a lava spine. We couple conduit flow dynamics with surface growth of the evolving lava dome, fueled by an open-system magma chamber undergoing continuous replenishment. The conduit flow model accounts for the variation in rheology of ascending magma that results from degassing-induced crystallization. Chapter IV of this dissertation explores the Variation in the extruding lava flow patterns range from endogenous dome growth with a ductile core to the exogenous extrusion of a degassed lava plug that results in the generation of a spine. The variations are a manifestation of the changes in the magma rheology which is governed by magma composition and rate of decompression of the ascending magma. We simulate using a two-dimensional particle-dynamics model, the cyclic behavior of lava dome growth with endogenous growth at high discharge rates followed by exogenous extrusion of rheologically stiffened lava due to degassing induced crystallization at low discharge rates. We couple conduit flow dynamics with surface growth of the evolving lava dome which is fueled by an overpressured reservoir undergoing constant replenishment. The periodic behavior between magma chamber pressure and discharge rate is reproduced as a result of the temporal and spatial change in magma viscosity controlled by crystallization kinetics. Dimensionless numbers are used to map the flow behaviors with the changing extrusion regime. A dimensionless plot identifying the flow transition region during the growth cycle of an evolving lava dome in its lava dome eruptive period is presented. The plot provides a the threshold value of a dimensionless strength parameter (pi 2 < 3.31 x 10-4) below which the transition in flow pattern occurs from endogenously evolving lava dome with a ductile core to the development of a shear lobe for short or long lived periodic episode of the extrusion of magma. (Abstract shortened by UMI.).

Partial Granger causality--eliminating exogenous inputs and latent variables.

PubMed

Guo, Shuixia; Seth, Anil K; Kendrick, Keith M; Zhou, Cong; Feng, Jianfeng

2008-07-15

Attempts to identify causal interactions in multivariable biological time series (e.g., gene data, protein data, physiological data) can be undermined by the confounding influence of environmental (exogenous) inputs. Compounding this problem, we are commonly only able to record a subset of all related variables in a system. These recorded variables are likely to be influenced by unrecorded (latent) variables. To address this problem, we introduce a novel variant of a widely used statistical measure of causality--Granger causality--that is inspired by the definition of partial correlation. Our 'partial Granger causality' measure is extensively tested with toy models, both linear and nonlinear, and is applied to experimental data: in vivo multielectrode array (MEA) local field potentials (LFPs) recorded from the inferotemporal cortex of sheep. Our results demonstrate that partial Granger causality can reveal the underlying interactions among elements in a network in the presence of exogenous inputs and latent variables in many cases where the existing conditional Granger causality fails.

Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria.

PubMed

Peng, Bo; Su, Yu-Bin; Li, Hui; Han, Yi; Guo, Chang; Tian, Yao-Mei; Peng, Xuan-Xian

2015-02-03

Multidrug-resistant bacteria are an increasingly serious threat to human and animal health. However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. Here we show that glucose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda by GC-MS-based metabolomics. Exogenous alanine or glucose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin, demonstrating an approach to killing multidrug-resistant bacteria. The mechanism underlying this approach is that exogenous glucose or alanine promotes the TCA cycle by substrate activation, which in turn increases production of NADH and proton motive force and stimulates uptake of antibiotic. Similar results are obtained with other Gram-negative bacteria (Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacterium (Staphylococcus aureus), and the results are also reproduced in a mouse model for urinary tract infection. This study establishes a functional metabolomics-based strategy to manage infection by antibiotic-resistant bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantifying reflexivity in financial markets: Toward a prediction of flash crashes

NASA Astrophysics Data System (ADS)

Filimonov, Vladimir; Sornette, Didier

2012-05-01

We introduce a measure of activity of financial markets that provides a direct access to their level of endogeneity. This measure quantifies how much of price changes is due to endogenous feedback processes, as opposed to exogenous news. For this, we calibrate the self-excited conditional Poisson Hawkes model, which combines in a natural and parsimonious way exogenous influences with self-excited dynamics, to the E-mini S&P 500 futures contracts traded in the Chicago Mercantile Exchange from 1998 to 2010. We find that the level of endogeneity has increased significantly from 1998 to 2010, with only 70% in 1998 to less than 30% since 2007 of the price changes resulting from some revealed exogenous information. Analogous to nuclear plant safety measures concerned with avoiding “criticality,” our measure provides a direct quantification of the distance of the financial market from a critical state defined precisely as the limit of diverging trading activity in the absence of any external driving.

"Ménage à Trois": the evolutionary interplay between JSRV, enJSRVs and domestic sheep.

PubMed

Armezzani, Alessia; Varela, Mariana; Spencer, Thomas E; Palmarini, Massimo; Arnaud, Frédérick

2014-12-09

Sheep betaretroviruses represent a fascinating model to study the complex evolutionary interplay between host and pathogen in natural settings. In infected sheep, the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) coexists with a variety of highly related endogenous JSRVs, referred to as enJSRVs. During evolution, some of them were co-opted by the host as they fulfilled important biological functions, including placental development and protection against related exogenous retroviruses. In particular, two enJSRV loci, enJS56A1 and enJSRV-20, were positively selected during sheep domestication due to their ability to interfere with the replication of related competent retroviruses. Interestingly, viruses escaping these transdominant enJSRVs have recently emerged, probably less than 200 years ago. Overall, these findings suggest that in sheep the process of endogenization is still ongoing and, therefore, the evolutionary interplay between endogenous and exogenous sheep betaretroviruses and their host has not yet reached an equilibrium.

“Ménage à Trois”: The Evolutionary Interplay between JSRV, enJSRVs and Domestic Sheep

PubMed Central

Armezzani, Alessia; Varela, Mariana; Spencer, Thomas E.; Palmarini, Massimo; Arnaud, Frédérick

2014-01-01

Sheep betaretroviruses represent a fascinating model to study the complex evolutionary interplay between host and pathogen in natural settings. In infected sheep, the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) coexists with a variety of highly related endogenous JSRVs, referred to as enJSRVs. During evolution, some of them were co-opted by the host as they fulfilled important biological functions, including placental development and protection against related exogenous retroviruses. In particular, two enJSRV loci, enJS56A1 and enJSRV-20, were positively selected during sheep domestication due to their ability to interfere with the replication of related competent retroviruses. Interestingly, viruses escaping these transdominant enJSRVs have recently emerged, probably less than 200 years ago. Overall, these findings suggest that in sheep the process of endogenization is still ongoing and, therefore, the evolutionary interplay between endogenous and exogenous sheep betaretroviruses and their host has not yet reached an equilibrium. PMID:25502326

Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract.

PubMed

Carias, Ann M; Allen, Shannon A; Fought, Angela J; Kotnik Halavaty, Katarina; Anderson, Meegan R; Jimenez, Maria L; McRaven, Michael D; Gioia, Casey J; Henning, Tara R; Kersh, Ellen N; Smith, James M; Pereira, Lara E; Butler, Katherine; McNicholl, S Janet M; Hendry, R Michael; Kiser, Patrick F; Veazey, Ronald S; Hope, Thomas J

2016-09-01

Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.

Analysis of Multispectral Galileo SSI Images of the Conamara Chaos Region, Europa

NASA Technical Reports Server (NTRS)

Spaun, N. A.; Phillips, C. B.

2003-01-01

Multispectral imaging of Europa s surface by Galileo s Solid State Imaging (SSI) camera has revealed two major surface color units, which appear as white and red-brown regions in enhanced color images of the surface (see figure). The Galileo Near- Infrared Mapping Spectrometer (NIMS) experiment suggests that the whitish material is icy, almost pure water ice, while the spectral signatures of the reddish regions are dominated by a non-ice material. Two endmember models have been proposed for the composition of the non-ice material: magnesium sulfate hydrates [1] and sulfuric acid and its byproducts [2]. There is also debate concerning whether the origin of this non-ice material is exogenic or endogenic [3].Goals: The key questions this work addresses are: 1) Is the non-ice material exogenic or endogenic in origin? 2) Once emplaced, is this non-ice material primarily modified by exogenic or endogenic processes? 3) Is the non-ice material within ridges, bands, chaos, and lenticulae the same non-ice material across all such geological features? 4) Does the distribution of the non-ice material provide any evidence for or against any of the various models for feature formation? 5) To what extent do the effects of scattered light in SSI images change the spectral signatures of geological features?

Exogenous Nkx2.5- or GATA-4-transfected rabbit bone marrow mesenchymal stem cells and myocardial cell co-culture on the treatment of myocardial infarction in rabbits.

PubMed

Li, Pu; Zhang, Lei

2015-08-01

The present study aimed to investigate the effects of Nkx2.5 or GATA-4 transfection with myocardial extracellular environment co-culture on the transformation of bone marrow mesenchymal stem cells (BMSCs) into differentiated cardiomyocytes. Nkx2.5 or GATA-4 were transfected into myocardial extracellular environment co-cultured BMSCs, and then injected into the periphery of infarcted myocardium of a myocardial infarction rabbit model. The effects of these gene transfections and culture on the infarcted myocardium were observed and the results may provide an experimental basis for the efficient myocardial cell differentiation of BMSCs. The present study also suggested that these cells may provide a source and clinical basis for myocardial injury repair via stem cell transplantation. The present study examined whether Nkx2.5 or GATA-4 exogenous gene transfection with myocardial cell extracellular environment co-culture were able to induce the differentiation of BMSCs into cardiac cells. In addition, the effect of these transfected BMSCs on the repair of the myocardium following myocardial infarction was determined using New Zealand rabbit models. The results demonstrated that myocardial cell differentiation was significantly less effective following exogenous gene transfection of Nkx2.5 or GATA-4 alone compared with that of transfection in combination with extracellular environment co-culture. In addition, the results of the present study showed that exogenous gene transfection of Nkx2.5 or GATA-4 into myocardial cell extracellular environment co-cultured BMSCs was able to significantly enhance the ability to repair, mitigating the death of myocardial cells and activation of the myocardium in rabbits with myocardial infarction compared with those of the rabbits transplanted with untreated BMSCs. In conclusion, the exogenous Nkx2.5 and GATA-4 gene transfection into myocardial extracellular environment co-cultured BMSCs induced increased differentiation into myocardial cells compared with that of gene transfection alone. Furthermore, significantly enhanced reparative effects were observed in the myocardium of rabbits following treatment with Nkx2.5-or GATA-4-transfected myocardial cell extracellular environment co-cultured BMSCs compared with those treated with untreated BMSCs.

[Effect of exogenous sucrose on growth and active ingredient content of licorice seedlings under salt stress conditions].

PubMed

Liu, Fu-zhi; Yang, Jun

2015-11-01

Licorice seedlings were taken as experimental materials, an experiment was conducted to study the effects of exogenous sucrose on growth and active ingredient content of licorice seedlings under NaCl stress conditions. The results of this study showed that under salt stress conditions, after adding a certain concentration of exogenous sucrose, the licorice seedlings day of relative growth rate was increasing, and this stress can be a significant weakening effect, indicating that exogenous sucrose salt stress-relieving effect. The total flavonoids and phenylalanine ammonia lyase (PAL) activity were significantly increased, the exogenous sucrose can mitigated the seedling roots under salt stress, the licorice flavonoid content in the enhanced growth was largely due to the activity of PAL an increased, when the concentration of exogenous sucrose wae 10 mmol x L(-1), PAL activity reaching a maximum, when the concentration of exogenous sucrose was 15 mmol x L(-1), PAL activity turned into a downward trend, the results indicating that this mitigation has concentration effect. After applying different concentrations of exogenous sugar, the contents of liquiritin changes with the change of flavonoids content was similar. After applying different concentrations of exogenous sucrose, the content of licorice acid under salt stress was higher than the levels were not reached during salt stress, the impact of exogenous sucrose concentration gradient of licorice acid accumulation was not obvious.

Determinants of Students' Outcome: A Full-Fledged Structural Equation Modelling Approach

ERIC Educational Resources Information Center

Musah, Mohammed Borhandden; Ali, Hairuddin Bin Mohd; Al-Hudawi, Shafeeq Hussain Vazhathodi; Tahir, Lokman Mohd; Daud, Khadijah Binti; Hamdan, Abdul Rahim

2015-01-01

The vibrant demand for academic excellence in the twenty-first century has brought diverse determinants of students' outcome into play. However, few studies have validated the instruments and examined the mediating effect between exogenous and endogenous variables of the student outcome model. This study, therefore, investigates the psychometric…

Effects of Background and School Factors on the Mathematics Achievement.

ERIC Educational Resources Information Center

Papanastasiou, Constantinos

2002-01-01

Using a structural equation model, this study investigated the mathematics achievement of eighth graders in Cyprus enrolled in the year 1994-1995. The model considered two exogenous constructs related to student background and five endogenous constructs. Although attitudes, teaching, and beliefs had direct effect on mathematics outcomes, these…

An Optimization-Based System Model of Disturbance-Generated Forest Biomass Utilization

ERIC Educational Resources Information Center

Curry, Guy L.; Coulson, Robert N.; Gan, Jianbang; Tchakerian, Maria D.; Smith, C. Tattersall

2008-01-01

Disturbance-generated biomass results from endogenous and exogenous natural and cultural disturbances that affect the health and productivity of forest ecosystems. These disturbances can create large quantities of plant biomass on predictable cycles. A systems analysis model has been developed to quantify aspects of system capacities (harvest,…

Directional output distance functions: endogenous directions based on exogenous normalization constraints

USDA-ARS?s Scientific Manuscript database

In this paper we develop a model for computing directional output distance functions with endogenously determined direction vectors. We show how this model is related to the slacks-based directional distance function introduced by Fare and Grosskopf and show how to use the slacks-based function to e...

Customer-Driven Reliability Models for Multistate Coherent Systems

DTIC Science & Technology

1992-01-01

AENCYUSEONLY(Leae bank)2. RPO- COVERED 1 11992DISSERTATION 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Customer -Driven Reliability Models For Multistate Coherent...UNIVERSITY OF OKLAHOMA GRADUATE COLLEGE CUSTOMER -DRIVEN RELIABILITY MODELS FOR MULTISTATE COHERENT SYSTEMS A DISSERTATION SUBMITTED TO THE GRADUATE FACULTY...BOEDIGHEIMER I Norman, Oklahoma Distribution/ Av~ilability Codes 1992 A vil andior Dist Special CUSTOMER -DRIVEN RELIABILITY MODELS FOR MULTISTATE

Determination of the Parameter Sets for the Best Performance of IPS-driven ENLIL Model

NASA Astrophysics Data System (ADS)

Yun, Jongyeon; Choi, Kyu-Cheol; Yi, Jonghyuk; Kim, Jaehun; Odstrcil, Dusan

2016-12-01

Interplanetary scintillation-driven (IPS-driven) ENLIL model was jointly developed by University of California, San Diego (UCSD) and National Aeronaucics and Space Administration/Goddard Space Flight Center (NASA/GSFC). The model has been in operation by Korean Space Weather Cetner (KSWC) since 2014. IPS-driven ENLIL model has a variety of ambient solar wind parameters and the results of the model depend on the combination of these parameters. We have conducted researches to determine the best combination of parameters to improve the performance of the IPS-driven ENLIL model. The model results with input of 1,440 combinations of parameters are compared with the Advanced Composition Explorer (ACE) observation data. In this way, the top 10 parameter sets showing best performance were determined. Finally, the characteristics of the parameter sets were analyzed and application of the results to IPS-driven ENLIL model was discussed.

A General and Efficient Method for Incorporating Precise Spike Times in Globally Time-Driven Simulations

PubMed Central

Hanuschkin, Alexander; Kunkel, Susanne; Helias, Moritz; Morrison, Abigail; Diesmann, Markus

2010-01-01

Traditionally, event-driven simulations have been limited to the very restricted class of neuronal models for which the timing of future spikes can be expressed in closed form. Recently, the class of models that is amenable to event-driven simulation has been extended by the development of techniques to accurately calculate firing times for some integrate-and-fire neuron models that do not enable the prediction of future spikes in closed form. The motivation of this development is the general perception that time-driven simulations are imprecise. Here, we demonstrate that a globally time-driven scheme can calculate firing times that cannot be discriminated from those calculated by an event-driven implementation of the same model; moreover, the time-driven scheme incurs lower computational costs. The key insight is that time-driven methods are based on identifying a threshold crossing in the recent past, which can be implemented by a much simpler algorithm than the techniques for predicting future threshold crossings that are necessary for event-driven approaches. As run time is dominated by the cost of the operations performed at each incoming spike, which includes spike prediction in the case of event-driven simulation and retrospective detection in the case of time-driven simulation, the simple time-driven algorithm outperforms the event-driven approaches. Additionally, our method is generally applicable to all commonly used integrate-and-fire neuronal models; we show that a non-linear model employing a standard adaptive solver can reproduce a reference spike train with a high degree of precision. PMID:21031031

Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

PubMed Central

Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

2014-01-01

Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p < 0.05). Conclusions: Hemin may be beneficial in protecting against focal cerebral hypoxic-ischemia through inducing the expression of exogenous Ngb. PMID:24966924

Use of Exogenous Testosterone for the Treatment of Male Factor Infertility: A Survey of Nigerian Doctors.

PubMed

Omisanjo, Olufunmilade Akinfolarin; Ikuerowo, Stephen Odunayo; Abdulsalam, Moruf Adekunle; Ajenifuja, Sheriff Olabode; Shittu, Khadijah Adebisi

2017-01-01

Though exogenous testosterone is known for its contraceptive effects in men, it is sometimes prescribed by medical practitioners for the treatment of male factor infertility in the mistaken belief that exogenous testosterone improves sperm count. The aim of this study was to evaluate the scope of testosterone use in the treatment of male factor infertility by medical practitioners in Lagos, Nigeria. A survey using a structured questionnaire was carried out amongst doctors attending a regular Continuing Medical Education (CME) programme in Lagos, Nigeria. There were 225 respondents. Most of the respondents (69.8%, n = 157) indicated that exogenous testosterone increases sperm count. Only 22 respondents (9.8%) indicated (correctly) that exogenous testosterone decreases sperm count. Seventy-seven respondents (34.2%) had prescribed some form of exogenous testosterone in the treatment of male factor infertility. The vast majority of respondents who had prescribed testosterone (81.8%, n = 63) thought exogenous testosterone increases sperm count. There was no statistically significant difference in the pattern of prescription across the respondents' specialty ( p = 0.859) or practice type ( p = 0.747). The misuse of exogenous testosterone for the treatment of male infertility was common amongst the respondents, with most of them wrongly believing that exogenous testosterone increases sperm count.

Do purely capital layers exist among flying birds? Evidence of exogenous contribution to arctic-nesting common eider eggs.

PubMed

Sénéchal, Edith; Bêty, Joël; Gilchrist, H Grant; Hobson, Keith A; Jamieson, Sarah E

2011-03-01

The strategy of relying extensively on stored resources for reproduction has been termed capital breeding and is in contrast to income breeding, where needs of reproduction are satisfied by exogenous (dietary) resources. Most species likely fall somewhere between these two extremes, and the position of an organism along this gradient can influence several key life-history traits. Common eiders (Somateria mollissima) are the only flying birds that are still typically considered pure capital breeders, suggesting that they depend exclusively on endogenous reserves to form their eggs and incubate. We investigated the annual and seasonal variation in contributions of endogenous and exogenous resources to egg formation in eiders breeding at the East Bay colony in the Canadian Arctic. We collected prey items along with females and their eggs during various stages of breeding and used two complementary analytical approaches: body reserve dynamics and stable isotope [δ(13)C, δ(15)N] mixing models. Indices of protein reserves remained stable from pre-laying to post-laying stages, while lipid reserves declined significantly during laying. Similarly, stable isotope analyses indicated that (1) exogenous nutrients derived from marine invertebrates strongly contributed to the formation of lipid-free egg constituents, and (2) yolk lipids were constituted mostly from endogenous lipids. We also found evidence of seasonal variation in the use of body reserves, with early breeders using proportionally more exogenous proteins to form each egg than late breeders. Based on these results, we reject the hypothesis that eiders are pure capital layers. In these flying birds, the fitness costs of a strict capital breeding strategy, such as temporary loss of flight capability and limitation of clutch and egg size, may outweigh benefits such as a reduction in egg predation rate.

Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1.

PubMed

Carofiglio, Fabrizia; Sleddens-Linkels, Esther; Wassenaar, Evelyne; Inagaki, Akiko; van Cappellen, Wiggert A; Grootegoed, J Anton; Toth, Attila; Baarends, Willy M

2018-03-01

Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11 YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11 YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes. Repair of radiation-induced DSBs was incomplete in Spo11 YF/YF compared to Spo11 +/YF meiocytes. Still, repair of exogenous DSBs promoted partial recovery of chromosome pairing and synapsis in Spo11 YF/YF meiocytes. This indicates that at least part of the exogenous DSBs can be processed in an interhomolog recombination repair pathway. Interestingly, in a seperate experiment, using 3 Gy of irradiation, we observed that Spo11/Hormad1 dko spermatocytes contained fewer remaining DSB repair foci at 48 h after irradiation compared to irradiated Spo11 knockout spermatocytes. Together, these results show that recruitment of exogenous DSBs to the synaptonemal complex, in conjunction with repair of exogenous DSBs via the homologous chromosome, contributes to homology recognition. In addition, the data suggest a role for HORMAD1 in DNA repair pathway choice in mouse meiocytes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Anti-ghrelin Spiegelmer inhibits exogenous ghrelin-induced increases in food intake, hoarding, and neural activation, but not food deprivation-induced increases

PubMed Central

Teubner, Brett J. W.

2013-01-01

Circulating concentrations of the stomach-derived “hunger-peptide” ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11–2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1–2 h and 2–4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear. PMID:23804279

Associations among personal care product use patterns and exogenous hormone use in the NIEHS Sister Study.

PubMed

Taylor, Kyla W; Baird, Donna D; Herring, Amy H; Engel, Lawrence S; Nichols, Hazel B; Sandler, Dale P; Troester, Melissa A

2017-09-01

It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N=47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.

Associations among personal care product use patterns and exogenous hormone use in the NIEHS Sister Study

PubMed Central

Taylor, Kyla W.; Baird, Donna D.; Herring, Amy H.; Engel, Lawrence S.; Nichols, Hazel B.; Sandler, Dale P.; Troester, Melissa A.

2017-01-01

It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N = 47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks. PMID:28120835

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

PubMed

Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Overwhelming tPA Release, not PAI-1 Degradation, is Responsible for Hyperfibrinolysis in Severely Injured Trauma Patients

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Moore, Hunter B.; Gonzalez, Eduardo; Gamboni, Fabia; Chandler, James G.; Mitra, Sanchayita; Ghasabyan, Arsen; Chin, Theresa L.; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C.

2015-01-01

Background Trauma induced coagulopathy (TIC) is associated with a four-fold increased risk of mortality. Hyperfibrinolysis is a component of TIC, but its mechanism is poorly understood. PAI-1 degradation by activated protein C has been proposed as mechanism for deregulation of the plasmin system in hemorrhagic shock, but in other settings of ischemia, tPA has been shown to be elevated. We hypothesized that the hyperfibrinolysis in TIC is not the result of PAI-1 degradation, but is driven by an increase in tPA, with resultant loss of PAI-1 activity through complexation with tPA. Methods 86 consecutive trauma activation patients had blood collected at the earliest time after injury, and were screened for hyperfibrinolysis using thrombelastography (TEG). Twenty-five hyperfibrinolytic patients were compared to 14 healthy controls using ELISAs for active tPA, active PAI-1 and PAI-1/tPA complex. Blood was also subjected to TEG with exogenous tPA-challenge as a functional assay for PAI-1 reserve. Results Total levels of PAI-1 (the sum of the active PAI-1 species and its covalent complex with tPA) are not significantly different between hyperfibrinolytic trauma patients and healthy controls: median 104 pM (IQR 48—201 pM) versus 115 pM (IQR 54—202 pM). The ratio of active to complexed PAI-1, however, was two orders of magnitude lower in hyperfibrinolysis than controls. Conversely, total tPA levels (active plus complex) were significantly higher in hyperfibrinolysis than controls: 139 pM (IQR 68—237 pM) versus 32 pM (IQR 16—37 pM). Hyperfibrinolytic trauma patients displayed increased sensitivity to exogenous challenge with tPA: median LY30 of 66.8% compared to 9.6% for controls. Conclusions Depletion of PAI-1 in TIC is driven by an increase in tPA, not PAI-1 degradation. The tPA-challenged TEG, based on this principle, is a functional test for PAI-1 reserves. Exploration of the mechanism of upregulation of tPA is critical to an understanding of hyperfibrinolysis in trauma. PMID:26491796

Exogenous fatty acid metabolism in bacteria.

PubMed

Yao, Jiangwei; Rock, Charles O

2017-10-01

Bacterial type II fatty acid synthesis (FASII) is a target for novel antibiotic development. All bacteria encode for mechanisms to incorporate exogenous fatty acids, and some bacteria can use exogenous fatty acids to bypass FASII inhibition. Bacteria encode three different mechanisms for activating exogenous fatty acids for incorporation into phospholipid synthesis. Exogenous fatty acids are converted into acyl-CoA in Gammaproteobacteria such as E. coli. Acyl-CoA molecules constitute a separate pool from endogenously synthesized acyl-ACP. Acyl-CoA can be used for phospholipid synthesis or broken down by β-oxidation, but cannot be used for lipopolysaccharide synthesis. Exogenous fatty acids are converted into acyl-ACP in some Gram-negative bacteria. The resulting acyl-ACP undergoes the same fates as endogenously synthesized acyl-ACP. Exogenous fatty acids are converted into acyl-phosphates in Gram-positive bacteria, and can be used for phospholipid synthesis or become acyl-ACP. Only the order Lactobacillales can use exogenous fatty acids to bypass FASII inhibition. FASII shuts down completely in presence of exogenous fatty acids in Lactobacillales, allowing Lactobacillales to synthesize phospholipids entirely from exogenous fatty acids. Inhibition of FASII cannot be bypassed in other bacteria because FASII is only partially down-regulated in presence of exogenous fatty acid or FASII is required to synthesize essential metabolites such as β-hydroxyacyl-ACP. Certain selective pressures such as FASII inhibition or growth in biofilms can select for naturally occurring one step mutations that attenuate endogenous fatty acid synthesis. Although attempts have been made to estimate the natural prevalence of these mutants, culture-independent metagenomic methods would provide a better estimate. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Update rules and interevent time distributions: slow ordering versus no ordering in the voter model.

PubMed

Fernández-Gracia, J; Eguíluz, V M; San Miguel, M

2011-07-01

We introduce a general methodology of update rules accounting for arbitrary interevent time (IET) distributions in simulations of interacting agents. We consider in particular update rules that depend on the state of the agent, so that the update becomes part of the dynamical model. As an illustration we consider the voter model in fully connected, random, and scale-free networks with an activation probability inversely proportional to the time since the last action, where an action can be an update attempt (an exogenous update) or a change of state (an endogenous update). We find that in the thermodynamic limit, at variance with standard updates and the exogenous update, the system orders slowly for the endogenous update. The approach to the absorbing state is characterized by a power-law decay of the density of interfaces, observing that the mean time to reach the absorbing state might be not well defined. The IET distributions resulting from both update schemes show power-law tails.

Bayesian Estimation of Panel Data Fractional Response Models with Endogeneity: An Application to Standardized Test Rates

ERIC Educational Resources Information Center

Kessler, Lawrence M.

2013-01-01

In this paper I propose Bayesian estimation of a nonlinear panel data model with a fractional dependent variable (bounded between 0 and 1). Specifically, I estimate a panel data fractional probit model which takes into account the bounded nature of the fractional response variable. I outline estimation under the assumption of strict exogeneity as…

Macroeconomics and oil-supply disruptions

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

Hubbard, R.G.; Fry, R.C. Jr.

1981-04-01

Energy-economy interactions and domestic linkages have been used in a system of models. Domestic economic aggregates are linked with a model of the world oil market by a core macroeconomic model with real and financial sectors. The model can be used to examine the policy ramifications of various short-run scenarios. Demand factors are not taken as exogenous to the world oil market, nor are oil prices taken as exogenous to the US economy. Simulations of the model have generated endogenous cycles in the world oil market; which then affect the US economy primarily through output and inflation channels. Policy simulationmore » was centered around the short-run imposition of a disruption tariff. The disruption tariff exhibited at least some of the desirable features noted by its proponents, though it did not function as a shield against the short-run output loss forced by the disruption. One might also simulate the rebate of tariff revenues as a reduction in the social security payroll tax. Other possible simulations include the use of any of the fiscal and monetary instruments included in the model. The effectiveness of these other policy instruments will be examined in a later paper.« less

Giant lipid vesicles under electric field pulses assessed by non invasive imaging.

PubMed

Mauroy, Chloé; Portet, Thomas; Winterhalder, Martin; Bellard, Elisabeth; Blache, Marie-Claire; Teissié, Justin; Zumbusch, Andreas; Rols, Marie-Pierre

2012-10-01

We present experimental results regarding the effects of electric pulses on giant unilamellar vesicles (GUVs). We have used phase contrast and coherent anti-Stokes Raman scattering (CARS) microscopy as relevant optical approaches to gain insight into membrane changes under electropermeabilization. No addition of exogenous molecules (lipid analogue, fluorescent dye) was needed. Therefore, experiments were performed on pure lipid systems avoiding possible artefacts linked to their use. Structural membrane changes were assessed by loss of contrast inside the GUVs due to sucrose and glucose mixing. Our observations, performed at the single vesicle level, indicate these changes are under the control of the number of pulses and field intensity. Larger number of pulses enhances membrane alterations. A threshold value of the field intensity must be applied to allow exchange of molecules between GUVs and the external medium. This threshold depends on the size of the vesicles, the larger GUVs being affected at lower electric field strengths than the smaller ones. Our experimental data are well described by a simple model in which molecule entry is driven by direct exchange. The CARS microscopic study of the effect of pulse duration confirms that pulses, in the ms time range, induce loss of lipids and membrane deformations facing the electrodes. Copyright © 2012 Elsevier B.V. All rights reserved.

Knock probability estimation through an in-cylinder temperature model with exogenous noise

NASA Astrophysics Data System (ADS)

Bares, P.; Selmanaj, D.; Guardiola, C.; Onder, C.

2018-01-01

This paper presents a new knock model which combines a deterministic knock model based on the in-cylinder temperature and an exogenous noise disturbing this temperature. The autoignition of the end-gas is modelled by an Arrhenius-like function and the knock probability is estimated by propagating a virtual error probability distribution. Results show that the random nature of knock can be explained by uncertainties at the in-cylinder temperature estimation. The model only has one parameter for calibration and thus can be easily adapted online. In order to reduce the measurement uncertainties associated with the air mass flow sensor, the trapped mass is derived from the in-cylinder pressure resonance, which improves the knock probability estimation and reduces the number of sensors needed for the model. A four stroke SI engine was used for model validation. By varying the intake temperature, the engine speed, the injected fuel mass, and the spark advance, specific tests were conducted, which furnished data with various knock intensities and probabilities. The new model is able to predict the knock probability within a sufficient range at various operating conditions. The trapped mass obtained by the acoustical model was compared in steady conditions by using a fuel balance and a lambda sensor and differences below 1 % were found.

Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity.

PubMed

Gentile, Maria Teresa; Nawa, Yukino; Lunardi, Gianluigi; Florio, Tullio; Matsui, Hiroaki; Colucci-D'Amato, Luca

2012-12-01

Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain. Following TPH2 discovery, it was reported that polymorphisms of both gene and non-coding regions are associated with a spectrum of psychiatric disorders. Thus, insights into the mechanisms that specifically regulate TPH2 expression and its modulation by exogenous stimuli may represent a new therapeutic approach to modify serotonergic neurotransmission. To this aim, a CNS-originated cell line expressing TPH2 endogenously represents a valid model system. In this study, we report that TPH2 transcript and protein are modulated by neuronal differentiation in the cell line A1 mes-c-myc (A1). Moreover, we show luciferase activity driven by the human TPH2 promoter region and demonstrate that upon mutation of the NRSF/REST responsive element, the promoter activity strongly increases with cell differentiation. Our data suggest that A1 cells could represent a model system, allowing an insight into the mechanisms of regulation of TPH2 and to identify novel therapeutic targets in the development of drugs for the management of psychiatric disorders. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Fibroblast growth factor 21 has no direct role in regulating fertility in female mice.

PubMed

Singhal, Garima; Douris, Nicholas; Fish, Alan J; Zhang, Xinyao; Adams, Andrew C; Flier, Jeffrey S; Pissios, Pavlos; Maratos-Flier, Eleftheria

2016-08-01

Reproduction is an energetically expensive process. Insufficient calorie reserves, signaled to the brain through peripheral signals such as leptin, suppress fertility. Recently, fibroblast growth factor 21 (FGF21) was implicated as a signal from the liver to the hypothalamus that directly inhibits the hypothalamic-gonadotropin axis during fasting and starvation. However, FGF21 itself increases metabolic rate and can induce weight loss, which suggests that the effects of FGF21 on fertility may not be direct and may reflect changes in energy balance. To address this important question, we evaluated fertility in several mouse models with elevated FGF21 levels including ketogenic diet fed mice, fasted mice, mice treated with exogenous FGF21 and transgenic mice over-expressing FGF21. We find that ketogenic diet fed mice remain fertile despite significant elevation in serum FGF21 levels. Absence of FGF21 does not alter transient infertility induced by fasting. Centrally infused FGF21 does not suppress fertility despite its efficacy in inducing browning of inguinal white adipose tissue. Furthermore, a high fat diet (HFD) can restore fertility of female FGF21-overexpressing mice, a model of growth restriction, even in the presence of supraphysiological serum FGF21 levels. We conclude that FGF21 is not a direct physiological regulator of fertility in mice. The infertility observed in FGF21 overexpressing mice is likely driven by the increased energy expenditure and consequent excess calorie requirements resulting from high FGF21 levels.

Study on the interactions between toxic nitroanilines and lysozyme by spectroscopic approaches and molecular modeling.

PubMed

Gu, Yunlan; Wang, Yanqing; Zhang, Hongmei

2018-05-05

Being exogenous environmental pollutants, nitroanilines (NAs) are highly toxic and have mutagenic and carcinogenic activity. Being lack of studies on interactions between NAs and lysozyme at molecular level, the binding interactions of lysozyme with o-nitroaniline (oNA), m-nitroaniline (mNA) and p-nitroaniline (pNA) were investigated by means of steady-state fluorescence, synchronous fluorescence, UV-vis absorption spectroscopy, as well as molecular modeling. The experimental results revealed that the fluorescence of lysozyme is quenched by oNA and mNA through a static quenching, while the fluorescence quenching triggered by pNA is a combined dynamic and static quenching. The number of binding sites (n) and the binding constant (K b ) corresponding thermodynamic parameters ΔH ⊖ , ΔS ⊖ , ΔG ⊖ at different temperatures were calculated. The reactions between NAs and lysozyme were spontaneous and entropy driven and the binding of NAs to lysozyme induced conformation changes of lysozyme. The difference of the position of -NO 2 group affected the binding and the binding constants K b decreased in the following pattern: K b (pNA) >K b (mNA) >K b (oNA). Molecular docking studies were performed to reveal the most favorable binding sites of NAs on lysozyme. Our recently results could offer mechanistic insights into the nature of the binding interactions between NAs and lysozyme and provide information about the toxicity risk of NAs to human health. Copyright © 2018 Elsevier B.V. All rights reserved.

Bayesian Analysis of Structural Equation Models with Nonlinear Covariates and Latent Variables

ERIC Educational Resources Information Center

Song, Xin-Yuan; Lee, Sik-Yum

2006-01-01

In this article, we formulate a nonlinear structural equation model (SEM) that can accommodate covariates in the measurement equation and nonlinear terms of covariates and exogenous latent variables in the structural equation. The covariates can come from continuous or discrete distributions. A Bayesian approach is developed to analyze the…

Corticosterone and Dispersal in Western Screech-Owls (Otus kennicottii)

Treesearch

James R. Belthoff; Alfred M., Jr. Dufty

1997-01-01

Belthoff and Dufty (in press) posed a model for dispersal in screech-owls and similar nonmigratory birds. The model is based on interactions among hormonal changes, body condition, and locomotor activity patterns. It predicts that corticosterone increases in blood plasma prior to dispersal under endogenous and exogenous influences, and this increase mediates the...

An econometric model of the hardwood lumber market

Treesearch

William G. Luppold

1982-01-01

A recursive econometric model with causal flow originating from the demand relationship is used to analyze the effects of exogenous variables on quantity and price of hardwood lumber. Wage rates, interest rates, stumpage price, lumber exports, and price of lumber demanders' output were the major factors influencing quantities demanded and supplied and hardwood...

Defense Spending and Regional Growth: An Examination of an Export-Base Model and an Econometric Model.

DTIC Science & Technology

1987-06-01

consumer preferences provide influences that can stimulate the rate of growth of the endogenous and/or exogenous income industries. B. EXPORT INDUSTRIES...location quotient was selected to alleviate 12 some of the problems created by consumer preferences and expendi- ture patterns. This value was compared

Identification of multivariable nonlinear systems in the presence of colored noises using iterative hierarchical least squares algorithm.

PubMed

Jafari, Masoumeh; Salimifard, Maryam; Dehghani, Maryam

2014-07-01

This paper presents an efficient method for identification of nonlinear Multi-Input Multi-Output (MIMO) systems in the presence of colored noises. The method studies the multivariable nonlinear Hammerstein and Wiener models, in which, the nonlinear memory-less block is approximated based on arbitrary vector-based basis functions. The linear time-invariant (LTI) block is modeled by an autoregressive moving average with exogenous (ARMAX) model which can effectively describe the moving average noises as well as the autoregressive and the exogenous dynamics. According to the multivariable nature of the system, a pseudo-linear-in-the-parameter model is obtained which includes two different kinds of unknown parameters, a vector and a matrix. Therefore, the standard least squares algorithm cannot be applied directly. To overcome this problem, a Hierarchical Least Squares Iterative (HLSI) algorithm is used to simultaneously estimate the vector and the matrix of unknown parameters as well as the noises. The efficiency of the proposed identification approaches are investigated through three nonlinear MIMO case studies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries.

PubMed

Damm, Oliver; Ultsch, Bernhard; Horn, Johannes; Mikolajczyk, Rafael T; Greiner, Wolfgang; Wichmann, Ole

2015-06-05

A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies. A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries. A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold. While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.

Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

PubMed

Jones, Alexander; Forster, Bettina

2014-07-01

Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

On the stability and dynamics of stochastic spiking neuron models: Nonlinear Hawkes process and point process GLMs

PubMed Central

Truccolo, Wilson

2017-01-01

Point process generalized linear models (PP-GLMs) provide an important statistical framework for modeling spiking activity in single-neurons and neuronal networks. Stochastic stability is essential when sampling from these models, as done in computational neuroscience to analyze statistical properties of neuronal dynamics and in neuro-engineering to implement closed-loop applications. Here we show, however, that despite passing common goodness-of-fit tests, PP-GLMs estimated from data are often unstable, leading to divergent firing rates. The inclusion of absolute refractory periods is not a satisfactory solution since the activity then typically settles into unphysiological rates. To address these issues, we derive a framework for determining the existence and stability of fixed points of the expected conditional intensity function (CIF) for general PP-GLMs. Specifically, in nonlinear Hawkes PP-GLMs, the CIF is expressed as a function of the previous spike history and exogenous inputs. We use a mean-field quasi-renewal (QR) approximation that decomposes spike history effects into the contribution of the last spike and an average of the CIF over all spike histories prior to the last spike. Fixed points for stationary rates are derived as self-consistent solutions of integral equations. Bifurcation analysis and the number of fixed points predict that the original models can show stable, divergent, and metastable (fragile) dynamics. For fragile models, fluctuations of the single-neuron dynamics predict expected divergence times after which rates approach unphysiologically high values. This metric can be used to estimate the probability of rates to remain physiological for given time periods, e.g., for simulation purposes. We demonstrate the use of the stability framework using simulated single-neuron examples and neurophysiological recordings. Finally, we show how to adapt PP-GLM estimation procedures to guarantee model stability. Overall, our results provide a stability framework for data-driven PP-GLMs and shed new light on the stochastic dynamics of state-of-the-art statistical models of neuronal spiking activity. PMID:28234899

On the stability and dynamics of stochastic spiking neuron models: Nonlinear Hawkes process and point process GLMs.

PubMed

Gerhard, Felipe; Deger, Moritz; Truccolo, Wilson

2017-02-01

Point process generalized linear models (PP-GLMs) provide an important statistical framework for modeling spiking activity in single-neurons and neuronal networks. Stochastic stability is essential when sampling from these models, as done in computational neuroscience to analyze statistical properties of neuronal dynamics and in neuro-engineering to implement closed-loop applications. Here we show, however, that despite passing common goodness-of-fit tests, PP-GLMs estimated from data are often unstable, leading to divergent firing rates. The inclusion of absolute refractory periods is not a satisfactory solution since the activity then typically settles into unphysiological rates. To address these issues, we derive a framework for determining the existence and stability of fixed points of the expected conditional intensity function (CIF) for general PP-GLMs. Specifically, in nonlinear Hawkes PP-GLMs, the CIF is expressed as a function of the previous spike history and exogenous inputs. We use a mean-field quasi-renewal (QR) approximation that decomposes spike history effects into the contribution of the last spike and an average of the CIF over all spike histories prior to the last spike. Fixed points for stationary rates are derived as self-consistent solutions of integral equations. Bifurcation analysis and the number of fixed points predict that the original models can show stable, divergent, and metastable (fragile) dynamics. For fragile models, fluctuations of the single-neuron dynamics predict expected divergence times after which rates approach unphysiologically high values. This metric can be used to estimate the probability of rates to remain physiological for given time periods, e.g., for simulation purposes. We demonstrate the use of the stability framework using simulated single-neuron examples and neurophysiological recordings. Finally, we show how to adapt PP-GLM estimation procedures to guarantee model stability. Overall, our results provide a stability framework for data-driven PP-GLMs and shed new light on the stochastic dynamics of state-of-the-art statistical models of neuronal spiking activity.

Effect of exogenous reductant on growth and iron mobilization from ferrihydrite by the Pseudomonas mendocina ymp strain.

PubMed

Dhungana, Suraj; Anthony, Charles R; Hersman, Larry E

2007-05-01

Growth of the Pseudomonas mendocina ymp strain on insoluble ferrihydrite is enhanced by exogenous reductants with concurrent increase in soluble iron concentrations. This shows that exogenous reductants play a substantial role in the overall microbial iron bioavailability. The exogenous reductants may work together with the siderophores, Fe-scavenging agents, to facilitate ferrihydrite dissolution.

Reward can modulate attentional capture, independent of top-down set.

PubMed

Munneke, Jaap; Hoppenbrouwers, Sylco S; Theeuwes, Jan

2015-11-01

The traditional distinction between exogenous and endogenous attentional control has recently been enriched with an additional mode of control, termed "selection history." Recent findings have indicated, for instance, that previously rewarded or punished stimuli capture more attention than their physical attributes would predict. As such, the value that is associated with certain stimuli modulates attentional capture. This particular influence has also been shown for endogenous attention. Although recent leads have emerged, elucidating the influences of reward on exogenous and endogenous attention, it remains unclear to what extent exogenous attention is modulated by reward when endogenous attention is already deployed. We used a Posner cueing task in which exogenous and endogenous cues were presented to guide attention. Crucially, the exogenous cue also indicated the reward value. That is, the color of the exogenous cue indicated how much reward could be obtained on a given trial. The results showed main effects of endogenous and exogenous attention (i.e., speeded reaction times when either cue was valid, as compared to when it was invalid). Crucially, an interaction between exogenous cue validity and reward level was observed, indicating that reward-based associative-learning processes rapidly influence attentional capture, even when endogenous attention has been actively deployed.

Perspectives of breast cancer etiology: synergistic interaction between smoking and exogenous hormone use

PubMed Central

Zhu, Hong-Hong; Hu, Cao-Hui; Strickland, Paul

2011-01-01

To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast Carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing of breast cells; (3) role of exogenous hormones in breast Carcinogenesis; (4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast Carcinogenesis; and (5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer. PMID:21718589

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

PubMed Central

Clendinnen, B. Guy; Reeder, David D.; Brandt, E. N.; Thompson, James C.

1973-01-01

Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2·54 min to 5·15 min at the low rate, and from 2·85 min to 7·88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin. PMID:4719213

A historical analysis of natural gas demand

NASA Astrophysics Data System (ADS)

Dalbec, Nathan Richard

This thesis analyzes demand in the US energy market for natural gas, oil, and coal over the period of 1918-2013 and examines their price relationship over the period of 2007-2013. Diagnostic tests for time series were used; Augmented Dickey-Fuller, Kwiatkowski-Phillips-Schmidt-Shin, Johansen cointegration, Granger Causality and weak exogeneity tests. Directed acyclic graphs were used as a complimentary test for endogeneity. Due to the varied results in determining endogeneity, a seemingly unrelated regression model was used which assumes all right hand side variables in the three demand equations were exogenous. A number of factors were significant in determining demand for natural gas including its own price, lagged demand, a number of structural break dummies, and trend, while oil indicate some substitutability with natural gas. An error correction model was used to examine the price relationships. Natural gas price was found not to have a significant cointegrating vector.

Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

PubMed

Soderstrom, Ken; Gilbert, Marcoita T

2013-03-19

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling an exogenic origin for the equatorial ridge on Iapetus

NASA Astrophysics Data System (ADS)

Stickle, Angela M.; Roberts, James H.

2018-06-01

Iapetus has a ridge along the equator that extends continuously for more than 110° in longitude. Parts of the ridge rise as much as 20 km above the surrounding terrains. Most models for the formation of this enigmatic ridge are endogenic, generally requiring the formation of a fast-spinning Iapetus with an oblate shape due to the rotation speed. Many of these require specific scenarios and have constraining parameters in order to generate a ridge comparable to what is seen today. An exogenic formation mechanism has also been proposed, that the ridge represents the remains of an early ring system around Iapetus that collapsed onto the surface. Thus far, none of the models have conclusively identified the origin of the ridge. In this study, an exogenic origin for the ridge is assumed, which is derived from a collapsing disk of debris around Iapetus, without invoking any specific model for the generation of the debris disk. Here, we evaluate whether it is possible to generate a ridge of the size and shape as observed by simulating the impact of the collapsing debris using the CTH hydrocode. Pi-scaling calculations suggest that extremely oblique impact angles (1°-10°) are needed to add to ridge topography. These extreme impact angles severely reduce the cratering efficiency compared to a vertical impact, adding material rather than eroding it during crater formation. Furthermore, material is likely to be excavated at low angles, enhancing downrange accumulation. Multiple impacts from debris pieces will heighten this effect. Because infalling debris is predicted to impact at extremely low angles, both of these effects might have contributed to ridge formation on Iapetus. The extreme grazing angles of the impacts modeled here decouple much of the projectile energy from the target, and impact heating of the surface is not significant. These models suggest that a collapsing disk of debris should have been able to build topography to create a ridge around Iapetus.

A Hierarchical Approach Embedding Hydrologic and Population Modeling for a West Nile Virus Vector Prediction

NASA Astrophysics Data System (ADS)

Jian, Y.; Silvestri, S.; Marani, M.; Saltarin, A.; Chillemi, G.

2012-12-01

We applied a hierarchical state space model to predict the abundance of Cx.pipiens (a West Nile Virus vector) in the Po River Delta Region, Northeastern Italy. The study area has large mosquito abundance, due to a favorable environment and climate as well as dense human population. Mosquito data were collected on a weekly basis at more than 20 sites from May to September in 2010 and 2011. Cx.pipiens was the dominant species in our samples, accounting for about 90% of the more than 300,000 total captures. The hydrological component of the model accounted for evapotranspiration, infiltration and deep percolation to infer, in a 0D context, the local dynamics of soil moisture as a direct exogenous forcing of mosquito dynamics. The population model had a Gompertz structure, which included exogenous meteorological forcings and delayed internal dynamics. The models were coupled within a hierarchical statistical structure to overcome the relatively short length of the samples by exploiting the large number of concurrent observations available. The results indicated that Cx.pipiens abundance had significant density dependence at 1 week lag, which approximately matched its development time from larvae to adult. Among the exogenous controls, temperature, daylight hours, and soil moisture explained most of the dynamics. Longer daylight hours and lower soil moisture values resulted in higher abundance. The negative correlation of soil moisture and mosquito population can be explained with the abundance of water in the region (e.g. due to irrigation) and the preference for eutrophic habitats by Cx.pipien. Variations among sites were explained by land use factors as represented by distance to the nearest rice field and NDVI values: the carrying capacity decreased with increased distance to the nearest rice filed, while the maximum growth rate was positively related with NDVI. The model shows a satisfactory performance in predicting (potentially one week in advance) mosquito abundance and particularly its peak timing and magnitude.

Viral nanoparticle-encapsidated enzyme and restructured DNA for cell delivery and gene expression

PubMed Central

Liu, Jinny L.; Dixit, Aparna Banerjee; Robertson, Kelly L.; Qiao, Eric; Black, Lindsay W.

2014-01-01

Packaging specific exogenous active proteins and DNAs together within a single viral-nanocontainer is challenging. The bacteriophage T4 capsid (100 × 70 nm) is well suited for this purpose, because it can hold a single long DNA or multiple short pieces of DNA up to 170 kb packed together with more than 1,000 protein molecules. Any linear DNA can be packaged in vitro into purified procapsids. The capsid-targeting sequence (CTS) directs virtually any protein into the procapsid. Procapsids are assembled with specific CTS-directed exogenous proteins that are encapsidated before the DNA. The capsid also can display on its surface high-affinity eukaryotic cell-binding peptides or proteins that are in fusion with small outer capsid and head outer capsid surface-decoration proteins that can be added in vivo or in vitro. In this study, we demonstrate that the site-specific recombinase cyclic recombination (Cre) targeted into the procapsid is enzymatically active within the procapsid and recircularizes linear plasmid DNA containing two terminal loxP recognition sites when packaged in vitro. mCherry expression driven by a cytomegalovirus promoter in the capsid containing Cre-circularized DNA is enhanced over linear DNA, as shown in recipient eukaryotic cells. The efficient and specific packaging into capsids and the unpackaging of both DNA and protein with release of the enzymatically altered protein–DNA complexes from the nanoparticles into cells have potential in numerous downstream drug and gene therapeutic applications. PMID:25161284

Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling.

PubMed

Bendz, Henriette; Ruhland, Sibylle C; Pandya, Maya J; Hainzl, Otmar; Riegelsberger, Stefan; Braüchle, Christoph; Mayer, Matthias P; Buchner, Johannes; Issels, Rolf D; Noessner, Elfriede

2007-10-26

Heat shock proteins (HSPs) have shown promise for the optimization of protein-based vaccines because they can transfer exogenous antigens to dendritic cells and at the same time induce their maturation. Great care must be exercised in interpretating HSP-driven studies, as by-products linked to the recombinant generation of these proteins have been shown to mediate immunological effects. We generated highly purified human recombinant Hsp70 and demonstrated that it strongly enhances the cross-presentation of exogenous antigens resulting in better antigen-specific T cell stimulation. Augmentation of T cell stimulation was a direct function of the degree of complex formation between Hsp70 and peptides and correlated with improved antigen delivery to endosomal compartments. The Hsp70 activity was independent of TAP proteins and was not inhibited by exotoxin A or endosomal acidification. Consequently, Hsp70 enhanced cross-presentation of various antigenic sequences, even when they required different post-uptake processing and trafficking, as exemplified by the tumor antigens tyrosinase and Melan-A/MART-1. Furthermore, Hsp70 enhanced cross-presentation by different antigen-presenting cells (APCs), including dendritic cells and B cells. Importantly, enhanced cross-presentation and antigen-specific T cell activation were observed in the absence of innate signals transmitted by Hsp70. As Hsp70 supports the cross-presentation of different antigens and APCs and is inert to APC function, it may show efficacy in various settings of immune modulation, including induction of antigen-specific immunity or tolerance.

Regulation of Floral Terpenoid Emission and Biosynthesis in Sweet Basil (Ocimum basilicum).

PubMed

Jiang, Yifan; Ye, Jiayan; Li, Shuai; Niinemets, Ülo

2016-12-01

Past studies have focused on the composition of essential oil of Ocimum basilicum leaves, but data on composition and regulation of its aerial emissions, especially floral volatile emissions are scarce. We studied the chemical profile, within-flower spatial distribution (sepals, petals, pistils with stamina and pedicels), diurnal emission kinetics and effects of exogenous methyl jasmonate (MeJA) application on the emission of floral volatiles by dynamic headspace collection and identification using gas chromatography-mass spectrometry (GC-MS) and proton transfer reaction mass spectrometry (PTR-MS). We observed more abundant floral emissions from flowers compared with leaves. Sepals were the main emitters of floral volatiles among the flower parts studied. The emissions of lipoxygenase compounds (LOX) and monoterpenoids, but not sesquiterpene emissions, displayed a diurnal variation driven by light. Response to exogenous MeJA treatment of flowers consisted of a rapid stress response and a longer-term acclimation response. The initial response was associated with enhanced emissions of fatty acid derivatives, monoterpenoids, and sesquiterpenoids without variation of the composition of individual compounds. The longer-term response was associated with enhanced monoterpenoid and sesquiterpenoid emissions with profound changes in the emission spectrum. According to correlated patterns of terpenoid emission changes upon stress, highlighted by a hierarchical cluster analysis, candidate terpenoid synthases responsible for observed diversity and complexity of released terpenoid blends were postulated. We conclude that flower volatile emissions differ quantitatively and qualitatively from leaf emissions, and overall contribute importantly to O. basilicum flavor, especially under stress conditions.

Regulation of Floral Terpenoid Emission and Biosynthesis in Sweet Basil (Ocimum basilicum)

PubMed Central

Jiang, Yifan; Ye, Jiayan; Li, Shuai; Niinemets, Ülo

2018-01-01

Past studies have focused on the composition of essential oil of Ocimum basilicum leaves, but data on composition and regulation of its aerial emissions, especially floral volatile emissions are scarce. We studied the chemical profile, within-flower spatial distribution (sepals, petals, pistils with stamina and pedicels), diurnal emission kinetics and effects of exogenous methyl jasmonate (MeJA) application on the emission of floral volatiles by dynamic headspace collection and identification using gas chromatography-mass spectrometry (GC-MS) and proton transfer reaction mass spectrometry (PTR-MS). We observed more abundant floral emissions from flowers compared with leaves. Sepals were the main emitters of floral volatiles among the flower parts studied. The emissions of lipoxygenase compounds (LOX) and monoterpenoids, but not sesquiterpene emissions, displayed a diurnal variation driven by light. Response to exogenous MeJA treatment of flowers consisted of a rapid stress response and a longer-term acclimation response. The initial response was associated with enhanced emissions of fatty acid derivatives, monoterpenoids, and sesquiterpenoids without variation of the composition of individual compounds. The longer-term response was associated with enhanced monoterpenoid and sesquiterpenoid emissions with profound changes in the emission spectrum. According to correlated patterns of terpenoid emission changes upon stress, highlighted by a hierarchical cluster analysis, candidate terpenoid synthases responsible for observed diversity and complexity of released terpenoid blends were postulated. We conclude that flower volatile emissions differ quantitatively and qualitatively from leaf emissions, and overall contribute importantly to O. basilicum flavor, especially under stress conditions. PMID:29367803

Vitamin panacea: Is advertising fueling demand for products with uncertain scientific benefit?

PubMed

Eisenberg, Matthew D; Avery, Rosemary J; Cantor, Jonathan H

2017-09-01

This study examines the effect of advertising on demand for vitamins-products with spiraling sales despite little evidence of efficacy. We merge seven years (2003-2009) of advertising data from Kantar Media with the Simmons National Consumer Survey to estimate individual-level vitamin print and television ad exposure effects. Identification relies on exploiting exogenous variation in year-to-year advertising exposure by controlling for each individual's unique media consumption. We find that increasing advertising exposure from zero to the mean number of ads increases the probability of consumption by 1.2 and 0.8% points (or 2 and 1.4%) in print and television respectively. Stratifications by the presence of health conditions suggests that in print demand is being driven by both healthy and sick individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Iapetus: Unique Surface Properties and a Global Color Dichotomy from Cassini Imaging

NASA Astrophysics Data System (ADS)

Denk, Tilmann; Neukum, Gerhard; Roatsch, Thomas; Porco, Carolyn C.; Burns, Joseph A.; Galuba, Götz G.; Schmedemann, Nico; Helfenstein, Paul; Thomas, Peter C.; Wagner, Roland J.; West, Robert A.

2010-01-01

Since 2004, Saturn’s moon Iapetus has been observed repeatedly with the Imaging Science Subsystem of the Cassini spacecraft. The images show numerous impact craters down to the resolution limit of ~10 meters per pixel. Small, bright craters within the dark hemisphere indicate a dark blanket thickness on the order of meters or less. Dark, equator-facing and bright, poleward-facing crater walls suggest temperature-driven water-ice sublimation as the process responsible for local albedo patterns. Imaging data also reveal a global color dichotomy, wherein both dark and bright materials on the leading side have a substantially redder color than the respective trailing-side materials. This global pattern indicates an exogenic origin for the redder leading-side parts and suggests that the global color dichotomy initiated the thermal formation of the global albedo dichotomy.

Iapetus: unique surface properties and a global color dichotomy from Cassini imaging.

PubMed

Denk, Tilmann; Neukum, Gerhard; Roatsch, Thomas; Porco, Carolyn C; Burns, Joseph A; Galuba, Götz G; Schmedemann, Nico; Helfenstein, Paul; Thomas, Peter C; Wagner, Roland J; West, Robert A

2010-01-22

Since 2004, Saturn's moon Iapetus has been observed repeatedly with the Imaging Science Subsystem of the Cassini spacecraft. The images show numerous impact craters down to the resolution limit of approximately 10 meters per pixel. Small, bright craters within the dark hemisphere indicate a dark blanket thickness on the order of meters or less. Dark, equator-facing and bright, poleward-facing crater walls suggest temperature-driven water-ice sublimation as the process responsible for local albedo patterns. Imaging data also reveal a global color dichotomy, wherein both dark and bright materials on the leading side have a substantially redder color than the respective trailing-side materials. This global pattern indicates an exogenic origin for the redder leading-side parts and suggests that the global color dichotomy initiated the thermal formation of the global albedo dichotomy.

Photobiological hydrogen production with switchable photosystem-II designer algae

DOEpatents

Lee, James Weifu

2014-02-18

A process for enhanced photobiological H.sub.2 production using transgenic alga. The process includes inducing exogenous genes in a transgenic alga by manipulating selected environmental factors. In one embodiment inducing production of an exogenous gene uncouples H.sub.2 production from existing mechanisms that would downregulate H.sub.2 production in the absence of the exogenous gene. In other embodiments inducing an exogenous gene triggers a cascade of metabolic changes that increase H.sub.2 production. In some embodiments the transgenic alga are rendered non-regenerative by inducing exogenous transgenes for proton channel polypeptides that are targeted to specific algal membranes.

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

PubMed Central

Elkasrawy, Moataz; Immel, David; Wen, Xuejun; Liu, Xiaoyan; Liang, Li-Fang

2012-01-01

The time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a “pool” of intense myostatin staining was observed among injured skeletal muscle fibers 12–24 hr postsurgery and that myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 µg/ml recombinant myostatin decreased fracture callus cartilage area relative to total callus area in a dose-dependent manner by 41% and 80% (p<0.05), respectively, compared to vehicle treatment. Myostatin treatment also decreased fracture callus total bone volume by 30.6% and 38.8% (p<0.05), with the higher dose of recombinant myostatin yielding the greatest decrease in callus bone volume. Finally, exogenous myostatin treatment caused a significant dose-dependent increase in fibrous tissue formation in skeletal muscle. Together, these findings suggest that early pharmacological inhibition of myostatin is likely to improve the regenerative potential of both muscle and bone following deep penetrant musculoskeletal injury. PMID:22205678

Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

PubMed

Mikolka, P; Kopincová, J; Košútová, P; Čierny, D; Čalkovská, A; Mokrá, D

2016-12-22

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

Immunolocalization of myostatin (GDF-8) following musculoskeletal injury and the effects of exogenous myostatin on muscle and bone healing.

PubMed

Elkasrawy, Moataz; Immel, David; Wen, Xuejun; Liu, Xiaoyan; Liang, Li-Fang; Hamrick, Mark W

2012-01-01

The time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a "pool" of intense myostatin staining was observed among injured skeletal muscle fibers 12-24 hr postsurgery and that myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 µg/ml recombinant myostatin decreased fracture callus cartilage area relative to total callus area in a dose-dependent manner by 41% and 80% (p<0.05), respectively, compared to vehicle treatment. Myostatin treatment also decreased fracture callus total bone volume by 30.6% and 38.8% (p<0.05), with the higher dose of recombinant myostatin yielding the greatest decrease in callus bone volume. Finally, exogenous myostatin treatment caused a significant dose-dependent increase in fibrous tissue formation in skeletal muscle. Together, these findings suggest that early pharmacological inhibition of myostatin is likely to improve the regenerative potential of both muscle and bone following deep penetrant musculoskeletal injury. © The Author(s) 2012

Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

NASA Astrophysics Data System (ADS)

Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

2016-06-01

Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

A comparative analysis of errors in long-term econometric forecasts

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

Tepel, R.

1986-04-01

The growing body of literature that documents forecast accuracy falls generally into two parts. The first is prescriptive and is carried out by modelers who use simulation analysis as a tool for model improvement. These studies are ex post, that is, they make use of known values for exogenous variables and generate an error measure wholly attributable to the model. The second type of analysis is descriptive and seeks to measure errors, identify patterns among errors and variables and compare forecasts from different sources. Most descriptive studies use an ex ante approach, that is, they evaluate model outputs based onmore » estimated (or forecasted) exogenous variables. In this case, it is the forecasting process, rather than the model, that is under scrutiny. This paper uses an ex ante approach to measure errors in forecast series prepared by Data Resources Incorporated (DRI), Wharton Econometric Forecasting Associates (Wharton), and Chase Econometrics (Chase) and to determine if systematic patterns of errors can be discerned between services, types of variables (by degree of aggregation), length of forecast and time at which the forecast is made. Errors are measured as the percent difference between actual and forecasted values for the historical period of 1971 to 1983.« less

Direct Mouse Trauma/Burn Model of Heterotopic Ossification

PubMed Central

Peterson, Jonathan R.; Agarwal, Shailesh; Brownley, R. Cameron; Loder, Shawn J.; Ranganathan, Kavitha; Cederna, Paul S.; Mishina, Yuji; Wang, Stewart C.; Levi, Benjamin

2015-01-01

Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation. PMID:26274052

Landscape self organisation: Modelling Sediment trains

NASA Astrophysics Data System (ADS)

Schoorl, J. M.; Temme, A. J. A. M.; Veldkamp, A.

2012-04-01

Rivers tend to develop towards an equilibrium length profile, independently of exogenous factors. In general, although still under debate, this so-called self-organisation is assumed to be caused by simple feedbacks between sedimentation and erosion. Erosion correlates positively with gradient and discharge and sedimentation negatively. With the LAPSUS model, which was run for the catchment of the Sabinal, a small river in the South of Spain, this interplay of erosion and sedimentation results in sediment pulses (sequences of incision and sedimentation through time). These pulses are visualised in a short movie ( see http://www.youtube.com/watch?v=V5LDUMvYZxU). In this case the LAPSUS model run did not take climate, base level nor tectonics into account. Therefore, these pulses can be considered independent of them. Furthermore, different scenarios show that the existence of the pulses is independent of precipitation, erodibility and sedimentation rate, although they control the number and shape of the pulses. A fieldwork check showed the plausibility of the occurrence of these sediment pulses. We conclude that the pulses as modelled with LAPSUS are indeed the consequence of the feedbacks between erosion and sedimentation and are not depending on exogenous factors. Keywords: Landscape self-organisation, Erosion, Deposition, LAPSUS, Modelling

Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation.

PubMed

Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

2016-11-28

Joint defects are complex and difficult to reconstruct. By exploiting the body's own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach.

Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation

PubMed Central

Wei, Jiao; Herrler, Tanja; Han, Dong; Liu, Kai; Huang, Rulin; Guba, Markus; Dai, Chuanchang; Li, Qingfeng

2016-01-01

Joint defects are complex and difficult to reconstruct. By exploiting the body’s own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach. PMID:27892493

Exogenic geomorphic processes dynamics at the Black Sea coast, Russia

NASA Astrophysics Data System (ADS)

Kuznetsova, Yulia; Tsvetkova, Daria

2017-04-01

Nowadays there is an obvious grow of anthropogenic load going on in many areas worldwide. Under such conditions, intensive activation of a number of exogenic geomorphic processes may be observed. Moreover, if natural environment is aggressive itself their dynamics and rates may reach enormous values. Our work is conducted at the Black Sea coast, known for its mountainous topography, wet subtropical climate and intensive anthropogenic development (especially during the last decade due to the recent Olympic games). We chose two key basins near Sochi, Russia to study a number of presented exogenic processes, including rill, gully and channel erosion, weathering, suffusion and piping, soil creep. A set of field study methods is used to monitor the processes dynamics since 2005 (and late 1970s for soil creep). In addition, soil erosion rates and landslide susceptibility were modelled to get information of the watersheds dynamics. This is ongoing work, but the results of the passed period of observations will be resented. Special attention is paid to the processes connectivity and their input into sediment redistribution over the river basins.

Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach.

PubMed

Huang, Zhi-Yong; Xie, Hong; Cao, Ying-Lan; Cai, Chao; Zhang, Zhi

2014-02-15

The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of (206)Pb, the contamination of exogenous Pb(2+) ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60-85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60-66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation. Copyright © 2014 Elsevier B.V. All rights reserved.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PubMed

Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

2017-01-01

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].

PubMed

Yuan, Lei; Fan, Wen-Juan; Yang, Xu-Guang; Rao, Shu-Mei; Song, Jin-Ling; Song, Guo-Hua

2013-10-25

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

MLV integration site selection is driven by strong enhancers and active promoters

PubMed Central

LaFave, Matthew C.; Varshney, Gaurav K.; Gildea, Derek E.; Wolfsberg, Tyra G.; Baxevanis, Andreas D.; Burgess, Shawn M.

2014-01-01

Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors. PMID:24464997

Consumer price sensitivity and health plan choice in a regulated competition setting.

PubMed

Bischof, Tamara; Schmid, Christian P R

2018-05-21

We estimate premium elasticities in a regulated competition market based on a quasi-exogenous premium increase for young adults in Switzerland. We exploit that individuals born before the turn of the year ("treatment group") face a larger increase in premiums than individuals born after the turn of the year ("control group"). We find that the treatment group is 1.5 times more likely to switch their health plan than the control group. Overall, individuals respond to premium increases by choosing more frequently health plans with managed care features, increasing the deductible, and by switching the insurer. Regarding health plan choice, we find an average elasticity of -0.56 with regard to the relative premium difference of any plan to the status quo contract. The elasticity is up to 5 times larger for the treated (-1.03) than for the controls (-0.19). Our results are not driven by health status as measured by health care expenditures and chronic conditions. Rather, our findings suggest that the difference in the premium elasticity is driven by the salience of the premium increase. We argue that this finding is of high relevance for health care policies that aim at fostering health plan competition. Copyright © 2018 John Wiley & Sons, Ltd.

The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy.

PubMed

Garcia, David; Tessone, Claudio J; Mavrodiev, Pavlin; Perony, Nicolas

2014-10-06

What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy

PubMed Central

Garcia, David; Tessone, Claudio J.; Mavrodiev, Pavlin; Perony, Nicolas

2014-01-01

What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage. PMID:25100315

Empirical Modeling of Information Communication Technology Usage Behaviour among Business Education Teachers in Tertiary Colleges of a Developing Country

ERIC Educational Resources Information Center

Isiyaku, Dauda Dansarki; Ayub, Ahmad Fauzi Mohd; Abdulkadir, Suhaida

2015-01-01

This study has empirically tested the fitness of a structural model in explaining the influence of two exogenous variables (perceived enjoyment and attitude towards ICTs) on two endogenous variables (behavioural intention and teachers' Information Communication Technology (ICT) usage behavior), based on the proposition of Technology Acceptance…

Review and Study of Physics Driven Pitting Corrosion Modeling in 2024-T3 Aluminum Alloys (Postprint)

DTIC Science & Technology

2015-05-01

AFRL-RX-WP-JA-2015-0218 REVIEW AND STUDY OF PHYSICS DRIVEN PITTING CORROSION MODELING IN 2024-T3 ALUMINUM ALLOYS (POSTPRINT) Lingyu...2014 – 1 April 2015 4. TITLE AND SUBTITLE REVIEW AND STUDY OF PHYSICS DRIVEN PITTING CORROSION MODELING IN 2024-T3 ALUMINUM ALLOYS (POSTPRINT) 5a...18 Review and Study of Physics Driven Pitting Corrosion Modeling in 2024-T3 Aluminum Alloys Lingyu Yu 1*, Kumar V. Jata2 1Mechanical Engineering

Out with the new, in with the old: Exogenous orienting to locations with physically constant stimulation.

PubMed

Taylor, J Eric T; Hilchey, Matthew D; Pratt, Jay

2018-01-24

Dominant methods of investigating exogenous orienting presume that attention is captured most effectively at locations containing new events. This is evidenced by the ubiquitous use of transient stimuli as cues in the literature on exogenous orienting. In the present study, we showed that attention can be oriented exogenously toward a location containing a completely unchanging stimulus by modifying Posner's landmark exogenous spatial-cueing paradigm. Observers searched a six-element array of placeholder stimuli for an onset target. The target was preceded by a decrement in luminance to five of the six placeholders, such that one location remained physically constant. This "nonset" stimulus (so named to distinguish it from a traditional onsetting transient) acted as an exogenous cue, eliciting patterns of facilitation and inhibition at the nonset location and demonstrating that exogenous orienting is not always evident at the location of a visual transient. This method eliminates the decades-long confounding of orienting to a location with the processing of new events at that location, permitting alternative considerations of the nature of attentional selection.

A novel pathway to detect and cope with exogenous dsDNA.

PubMed

Kobayashi, Shouhei; Haraguchi, Tokuko

2015-01-01

How a living cell responds to exogenous materials is one of the fundamental questions in the life sciences. In particular, understanding the mechanisms by which a cell recognizes exogenous double-stranded DNA (dsDNA) is important for immunology research because it will facilitate the control of pathogen infections that entail the presence of exogenous dsDNA in the cytoplasm of host cells. Several cytosolic dsDNA sensor proteins that trigger innate immune responses have been identified and the downstream signaling pathways have been investigated. However, the events that occur at the site of exogenous dsDNA when it is exposed to the cytosol of the host cell remain unknown. Using dsDNA-coated polystyrene beads incorporated into living cells, we recently found that barrier-to-autointegration factor (BAF) binds to the exogenous dsDNA immediately after its appearance in the cytosol and plays a role in DNA avoidance of autophagy. Our findings reveal a novel pathway in which BAF plays a key role in the detection of and response to exogenous dsDNA.

Statistical Time Series Models of Pilot Control with Applications to Instrument Discrimination

NASA Technical Reports Server (NTRS)

Altschul, R. E.; Nagel, P. M.; Oliver, F.

1984-01-01

A general description of the methodology used in obtaining the transfer function models and verification of model fidelity, frequency domain plots of the modeled transfer functions, numerical results obtained from an analysis of poles and zeroes obtained from z plane to s-plane conversions of the transfer functions, and the results of a study on the sequential introduction of other variables, both exogenous and endogenous into the loop are contained.

Assessment of Health Effects of Exogenous Urea: Summary and Key Findings.

PubMed

Dickerson, Aisha S; Lee, Janice S; Keshava, Channa; Hotchkiss, Andrew; Persad, Amanda S

2018-05-01

Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.

Development and validation of a turbulent-mix model for variable-density and compressible flows.

PubMed

Banerjee, Arindam; Gore, Robert A; Andrews, Malcolm J

2010-10-01

The modeling of buoyancy driven turbulent flows is considered in conjunction with an advanced statistical turbulence model referred to as the BHR (Besnard-Harlow-Rauenzahn) k-S-a model. The BHR k-S-a model is focused on variable-density and compressible flows such as Rayleigh-Taylor (RT), Richtmyer-Meshkov (RM), and Kelvin-Helmholtz (KH) driven mixing. The BHR k-S-a turbulence mix model has been implemented in the RAGE hydro-code, and model constants are evaluated based on analytical self-similar solutions of the model equations. The results are then compared with a large test database available from experiments and direct numerical simulations (DNS) of RT, RM, and KH driven mixing. Furthermore, we describe research to understand how the BHR k-S-a turbulence model operates over a range of moderate to high Reynolds number buoyancy driven flows, with a goal of placing the modeling of buoyancy driven turbulent flows at the same level of development as that of single phase shear flows.

Influence of ensiling, exogenous protease addition, and bacterial inoculation on fermentation profile, nitrogen fractions, and ruminal in vitro starch digestibility in rehydrated and high-moisture corn.

PubMed

Ferraretto, L F; Fredin, S M; Shaver, R D

2015-10-01

Exogenous protease addition may be an option to increase proteolysis of zein proteins and thus starch digestibility in rehydrated and high-moisture corn (HMC) ensiled for short periods. In addition, microbial inoculation may accelerate fermentation and increase acid production and thus increase solubilization of zein proteins. Four experiments were performed to evaluate the effect on fermentation profile, N fractions, and ruminal in vitro starch digestibility (ivSD) of the following: (1) rehydration and ensiling of dry ground corn; (2) exogenous protease addition to rehydrated un-ensiled and ensiled corn; (3) exogenous protease addition or inoculation in rehydrated ensiled corn; and (4) exogenous protease addition or inoculation in HMC. Experiments 1, 2, and 3 were performed with 7 treatments: dry ground corn (DGC); DGC rehydrated to a targeted dry matter content of 70% (REH); REH treated with exogenous protease (REH+); REH ensiled for 30 d (ENS); ENS treated with exogenous protease (ENS+); ENS treated with a microbial inoculant containing Lactobacillus plantarum, Lactobacillus casei, Enterococcus faecium, and Pediococcus sp. (ENSI); and ENS treated with exogenous protease and microbial inoculant (ENSI+). Experiment 1 compared DGC, REH, and ENS with ivSD being greater for ENS (64.9%) than DGC and REH (51.7% on average). Experiment 2 compared REH and ENS without or with exogenous protease addition (REH+ and ENS+, respectively). Ensiling and exogenous protease addition increased ivSD, but exogenous protease addition was more effective in ENS than REH (6.4 vs. 2.6 percentage unit increase). Experiment 3 compared the effects of exogenous protease addition and inoculation in ENS corn (ENS, ENS+, ENSI, and ENSI+). The addition of protease, but not inoculant, increased ivSD. Inoculation reduced pH and acetate, propionate, and ethanol concentrations, and increased lactate and total acid concentrations. In experiment 4, 8 treatments were a combination of HMC noninoculated or inoculated with 1 of 3 microbial inoculants and with or without exogenous protease addition. The inoculant treatments contained (1) Lactobacillus buchneri 40788 and Pediococcus pentosaceus, (2) L. buchneri 40788, and (3) a mixture of P. pentosaceus and Propionibacterium freudenreichii. Protease, but not inoculation, increased ivSD by 7.5 percentage units (44.4 vs. 51.9%). Protease addition increased ivSD in rehydrated corn and HMC. Microbial inoculation improved fermentation profiles but did not affect ivSD. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Model Driven Engineering

NASA Astrophysics Data System (ADS)

Gaševic, Dragan; Djuric, Dragan; Devedžic, Vladan

A relevant initiative from the software engineering community called Model Driven Engineering (MDE) is being developed in parallel with the Semantic Web (Mellor et al. 2003a). The MDE approach to software development suggests that one should first develop a model of the system under study, which is then transformed into the real thing (i.e., an executable software entity). The most important research initiative in this area is the Model Driven Architecture (MDA), which is Model Driven Architecture being developed under the umbrella of the Object Management Group (OMG). This chapter describes the basic concepts of this software engineering effort.

Closed-form solutions in stress-driven two-phase integral elasticity for bending of functionally graded nano-beams

NASA Astrophysics Data System (ADS)

Barretta, Raffaele; Fabbrocino, Francesco; Luciano, Raimondo; Sciarra, Francesco Marotti de

2018-03-01

Strain-driven and stress-driven integral elasticity models are formulated for the analysis of the structural behaviour of fuctionally graded nano-beams. An innovative stress-driven two-phases constitutive mixture defined by a convex combination of local and nonlocal phases is presented. The analysis reveals that the Eringen strain-driven fully nonlocal model cannot be used in Structural Mechanics since it is ill-posed and the local-nonlocal mixtures based on the Eringen integral model partially resolve the ill-posedeness of the model. In fact, a singular behaviour of continuous nano-structures appears if the local fraction tends to vanish so that the ill-posedness of the Eringen integral model is not eliminated. On the contrary, local-nonlocal mixtures based on the stress-driven theory are mathematically and mechanically appropriate for nanosystems. Exact solutions of inflected functionally graded nanobeams of technical interest are established by adopting the new local-nonlocal mixture stress-driven integral relation. Effectiveness of the new nonlocal approach is tested by comparing the contributed results with the ones corresponding to the mixture Eringen theory.

Comparative approaches to studying strategy: towards an evolutionary account of primate decision making.

PubMed

Brosnan, Sarah F; Beran, Michael J; Parrish, Audrey E; Price, Sara A; Wilson, Bart J

2013-07-18

How do primates, humans included, deal with novel problems that arise in interactions with other group members? Despite much research regarding how animals and humans solve social problems, few studies have utilized comparable procedures, outcomes, or measures across different species. Thus, it is difficult to piece together the evolution of decision making, including the roots from which human economic decision making emerged. Recently, a comparative body of decision making research has emerged, relying largely on the methodology of experimental economics in order to address these questions in a cross-species fashion. Experimental economics is an ideal method of inquiry for this approach. It is a well-developed method for distilling complex decision making involving multiple conspecifics whose decisions are contingent upon one another into a series of simple decision choices. This allows these decisions to be compared across species and contexts. In particular, our group has used this approach to investigate coordination in New World monkeys, Old World monkeys, and great apes (including humans), using identical methods. We find that in some cases there are remarkable continuities of outcome, as when some pairs in all species solved a coordination game, the Assurance game. On the other hand, we also find that these similarities in outcomes are likely driven by differences in underlying cognitive mechanisms. New World monkeys required exogenous information about their partners' choices in order to solve the task, indicating that they were using a matching strategy. Old World monkeys, on the other hand, solved the task without exogenous cues, leading to investigations into what mechanisms may be underpinning their responses (e.g., reward maximization, strategy formation, etc.). Great apes showed a strong experience effect, with cognitively enriched apes following what appears to be a strategy. Finally, humans were able to solve the task with or without exogenous cues. However, when given the chance to do so, they incorporated an additional mechanism unavailable to the other primates - language - to coordinate outcomes with their partner. We discuss how these results inform not only comparative psychology, but also evolutionary psychology, as they provide an understanding of the evolution of human economic behavior, and the evolution of decision making more broadly.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

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

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Fouling resistance prediction using artificial neural network nonlinear auto-regressive with exogenous input model based on operating conditions and fluid properties correlations

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

Biyanto, Totok R.

Fouling in a heat exchanger in Crude Preheat Train (CPT) refinery is an unsolved problem that reduces the plant efficiency, increases fuel consumption and CO{sub 2} emission. The fouling resistance behavior is very complex. It is difficult to develop a model using first principle equation to predict the fouling resistance due to different operating conditions and different crude blends. In this paper, Artificial Neural Networks (ANN) MultiLayer Perceptron (MLP) with input structure using Nonlinear Auto-Regressive with eXogenous (NARX) is utilized to build the fouling resistance model in shell and tube heat exchanger (STHX). The input data of the model aremore » flow rates and temperatures of the streams of the heat exchanger, physical properties of product and crude blend data. This model serves as a predicting tool to optimize operating conditions and preventive maintenance of STHX. The results show that the model can capture the complexity of fouling characteristics in heat exchanger due to thermodynamic conditions and variations in crude oil properties (blends). It was found that the Root Mean Square Error (RMSE) are suitable to capture the nonlinearity and complexity of the STHX fouling resistance during phases of training and validation.« less

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

DOE PAGES

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.; ...

2017-08-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Why is the Great Red Spot Red? The Exogenic, Photolytic Origin of the UV/Blue-Absorbing Chromophores of Jupiter’s Great Red Spot as Determined by Spectral Analysis of Cassini/VIMS Observations using New Laboratory Optical Coefficients

NASA Astrophysics Data System (ADS)

Baines, Kevin H.; Carlson, Robert W.; Momary, Thomas W.

2014-11-01

For centuries, a major question for Jupiter has been: Why is the Great Red Spot red? In particular, two major theories have been proposed: (1) that the coloring is due to photolytic processes in the upper cloud layer, or (2) it is due to the upwellimg of red materials processed relatively deep within the troposphere. Utilizing indices of refraction for red choromophores generated by the photolysis of ammonia and acetylene in the laboratory, we present results of a spectral analysis of the core of Jupiter’s Great Red Spot (GRS) as observed by the visual channel of the Cassini/Visual Infrared Mapping Spectrometer (VIMS). Consistent with the physical origin of such laboratory-generated chromophores in Jupiter - i.e., by solar-driven UV photolysis within the upper levels of the GRS structure near ~ 0.3 bar - our spectral modeling yields satisfactory results for such Mie scattering chromophores only when they are confined to the upper ~ 100 mbar of the GRS. Beneath this reddish upper cloud layer, our models indicate that the remainder of the GRS cloud - assumed to extend down to at least the ammonia condensation level near 0.6 bar - must be relatively spectrally bright throughout the UV-red spectrum; that is, they must be predominantly a whitish or grey color at depth. Thus, our 0.35-1.0 micron spectral models of the GRS are inconsistent with an endogenic origin of the reddish coloring originating in the depths of Jupiter, but are consistent with a photolytic origin due to the photolysis of ammonia and acetylene in the upper troposphere.

Temporal Information of Directed Causal Connectivity in Multi-Trial ERP Data using Partial Granger Causality.

PubMed

Youssofzadeh, Vahab; Prasad, Girijesh; Naeem, Muhammad; Wong-Lin, KongFatt

2016-01-01

Partial Granger causality (PGC) has been applied to analyse causal functional neural connectivity after effectively mitigating confounding influences caused by endogenous latent variables and exogenous environmental inputs. However, it is not known how this connectivity obtained from PGC evolves over time. Furthermore, PGC has yet to be tested on realistic nonlinear neural circuit models and multi-trial event-related potentials (ERPs) data. In this work, we first applied a time-domain PGC technique to evaluate simulated neural circuit models, and demonstrated that the PGC measure is more accurate and robust in detecting connectivity patterns as compared to conditional Granger causality and partial directed coherence, especially when the circuit is intrinsically nonlinear. Moreover, the connectivity in PGC settles faster into a stable and correct configuration over time. After method verification, we applied PGC to reveal the causal connections of ERP trials of a mismatch negativity auditory oddball paradigm. The PGC analysis revealed a significant bilateral but asymmetrical localised activity in the temporal lobe close to the auditory cortex, and causal influences in the frontal, parietal and cingulate cortical areas, consistent with previous studies. Interestingly, the time to reach a stable connectivity configuration (~250–300 ms) coincides with the deviation of ensemble ERPs of oddball from standard tones. Finally, using a sliding time window, we showed higher resolution dynamics of causal connectivity within an ERP trial. In summary, time-domain PGC is promising in deciphering directed functional connectivity in nonlinear and ERP trials accurately, and at a sufficiently early stage. This data-driven approach can reduce computational time, and determine the key architecture for neural circuit modeling.

A Pre- and Co-Knockdown of RNAseT Enzyme, Eri-1, Enhances the Efficiency of RNAi Induced Gene Silencing in Caenorhabditis elegans

PubMed Central

Jadiya, Pooja; Nazir, Aamir

2014-01-01

Background The approach of RNAi mediated gene knockdown, employing exogenous dsRNA, is being beneficially exploited in various fields of functional genomics. The immense utility of the approach came to fore from studies with model system C. elegans, but quickly became applicable with varied research models ranging from in vitro to various in vivo systems. Previously, there have been reports on the refractoriness of the neuronal cells to RNAi mediated gene silencing following which several modulators like eri-1 and lin-15 were described in C. elegans which, when present, would negatively impact the gene knockdown. Methodology/Principal Findings Taking a clue from these findings, we went on to screen hypothesis-driven- methodologies towards exploring the efficiency in the process of RNAi under various experimental conditions, wherein these genes would be knocked down preceding to, or concurrently with, the knocking down of a gene of interest. For determining the efficiency of gene knockdown, we chose to study visually stark phenotypes of uncoordinated movement, dumpy body morphology and blistered cuticle obtained by knocking down of genes unc-73, dpy-9 and bli-3 respectively, employing the RNAi-by-feeding protocol in model system C. elegans. Conclusions/Significance Our studies led to a very interesting outcome as the results reveal that amongst various methods tested, pre-incubation with eri-1 dsRNA synthesizing bacteria followed by co-incubation with eri-1 and gene-of-interest dsRNA synthesizing bacteria leads to the most efficient gene silencing as observed by the analysis of marker phenotypes. This provides an approach for effectively employing RNAi induced gene silencing while working with different genetic backgrounds including transgenic and mutant strains. PMID:24475317

Dry-grind processing using amylase corn and superior yeast to reduce the exogenous enzyme requirements in bioethanol production.

PubMed

Kumar, Deepak; Singh, Vijay

2016-01-01

Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Use of amylase corn and superior yeast in the dry-grind processing industry can reduce the total external enzyme usage by more than 80 %, and combining their use with in situ removal of ethanol during fermentation allows efficient high-solid fermentation.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bureaucrats Versus the Ballot Box in Foreign Policy Decision Making: An Experimental Analysis of the Bureaucratic Politics Model and the Poliheuristic Theory

ERIC Educational Resources Information Center

Christensen, Eben J.; Redd, Steven B.

2004-01-01

The bureaucratic politics model and the poliheuristic theory are used to examine how political advice presented in various contexts influences choice. Organizational advisers who offer endogenous political advice are compared with situations in which the decision maker is offered advice by a separate, or exogenous, political adviser. Results show…

[Effects of exogenous AsA and GSH on the growth of Dianthus chinensis seedlings exposed to Cd].

PubMed

Ding, Ji-Jun; Liu, Shi-Liang; Pan, Yuan-Zhi; Li, Li

2014-02-01

A pot experiment was carried out under greenhouse condition to investigate the effects of different concentrations (0, 20, 40, 60, 80 and 100 mg x L(-1)) of exogenous AsA, GSH on Dianthus chinensis seedlings which were stressed by 50 mg x kg(-1) Cd in the soil. The results indicated that 50 mg x kg(-1) of Cd significantly inhibited the growth of D. chinensis seedlings. An appropriate concentration of exogenous AsA significantly improved the biomass, plant height, tiller number, GAT and APX activities, and AsA and GSH contents. However, with the increase of exogenous AsA concentration, the ameliorating effect decreased and prooxidant effect occurred. Exogenous GSH could replenish the non-enzymatic antioxidants of D. chinensis seedlings, but the changes of antioxidant enzyme activities were relatively slight. The main mechanisms of GSH to alleviate Cd toxicity might be promoting root PCs synthesis, thereby reducing the Cd concentration in the seedlings. Both 35-45 mg x L(-1) exogenous AsA and 55-65 mg x L(-1) exogenous GSH could alleviate the Cd toxicity on D. chinensis seedlings, and the former was superior to the latter.

Comparative proteomic analysis reveals the positive effect of exogenous spermidine on photosynthesis and salinity tolerance in cucumber seedlings.

PubMed

Sang, Ting; Shan, Xi; Li, Bin; Shu, Sheng; Sun, Jin; Guo, Shirong

2016-08-01

Our results based on proteomics data and physiological alterations proposed the putative mechanism of exogenous Spd enhanced salinity tolerance in cucumber seedlings. Current studies showed that exogenous spermidine (Spd) could alleviate harmful effects of salinity. It is important to increase our understanding of the beneficial physiological responses of exogenous Spd treatment, and to determine the molecular responses underlying these responses. Here, we combined a physiological analysis with iTRAQ-based comparative proteomics of cucumber (Cucumis sativus L.) leaves, treated with 0.1 mM exogenous Spd, 75 mM NaCl and/or exogenous Spd. A total of 221 differentially expressed proteins were found and involved in 30 metabolic pathways, such as photosynthesis, carbohydrate metabolism, amino acid metabolism, stress response, signal transduction and antioxidant. Based on functional classification of the differentially expressed proteins and the physiological responses, we found cucumber seedlings treated with Spd under salt stress had higher photosynthesis efficiency, upregulated tetrapyrrole synthesis, stronger ROS scavenging ability and more protein biosynthesis activity than NaCl treatment, suggesting that these pathways may promote salt tolerance under high salinity. This study provided insights into how exogenous Spd protects photosynthesis and enhances salt tolerance in cucumber seedlings.

Exogenous temporal cues enhance recognition memory in an object-based manner.

PubMed

Ohyama, Junji; Watanabe, Katsumi

2010-11-01

Exogenous attention enhances the perception of attended items in both a space-based and an object-based manner. Exogenous attention also improves recognition memory for attended items in the space-based mode. However, it has not been examined whether object-based exogenous attention enhances recognition memory. To address this issue, we examined whether a sudden visual change in a task-irrelevant stimulus (an exogenous cue) would affect participants' recognition memory for items that were serially presented around a cued time. The results showed that recognition accuracy for an item was strongly enhanced when the visual cue occurred at the same location and time as the item (Experiments 1 and 2). The memory enhancement effect occurred when the exogenous visual cue and an item belonged to the same object (Experiments 3 and 4) and even when the cue was counterpredictive of the timing of an item to be asked about (Experiment 5). The present study suggests that an exogenous temporal cue automatically enhances the recognition accuracy for an item that is presented at close temporal proximity to the cue and that recognition memory enhancement occurs in an object-based manner.

Constructivism: Principles, Paradigms, and Integration.

ERIC Educational Resources Information Center

Harris, Karen R.; Graham, Steve

1994-01-01

This article presents major principles of constructivism for teaching and learning of students with disabilities and those at risk for school failure. It describes three idealized constructivist models (endogenous, exogenous, and dialectical) and explores major issues related to constructivism, including the possibility of integrative stances.…

Timing Interactions in Social Simulations: The Voter Model

NASA Astrophysics Data System (ADS)

Fernández-Gracia, Juan; Eguíluz, Víctor M.; Miguel, Maxi San

The recent availability of huge high resolution datasets on human activities has revealed the heavy-tailed nature of the interevent time distributions. In social simulations of interacting agents the standard approach has been to use Poisson processes to update the state of the agents, which gives rise to very homogeneous activity patterns with a well defined characteristic interevent time. As a paradigmatic opinion model we investigate the voter model and review the standard update rules and propose two new update rules which are able to account for heterogeneous activity patterns. For the new update rules each node gets updated with a probability that depends on the time since the last event of the node, where an event can be an update attempt (exogenous update) or a change of state (endogenous update). We find that both update rules can give rise to power law interevent time distributions, although the endogenous one more robustly. Apart from that for the exogenous update rule and the standard update rules the voter model does not reach consensus in the infinite size limit, while for the endogenous update there exist a coarsening process that drives the system toward consensus configurations.

Bending of Euler-Bernoulli nanobeams based on the strain-driven and stress-driven nonlocal integral models: a numerical approach

NASA Astrophysics Data System (ADS)

Oskouie, M. Faraji; Ansari, R.; Rouhi, H.

2018-04-01

Eringen's nonlocal elasticity theory is extensively employed for the analysis of nanostructures because it is able to capture nanoscale effects. Previous studies have revealed that using the differential form of the strain-driven version of this theory leads to paradoxical results in some cases, such as bending analysis of cantilevers, and recourse must be made to the integral version. In this article, a novel numerical approach is developed for the bending analysis of Euler-Bernoulli nanobeams in the context of strain- and stress-driven integral nonlocal models. This numerical approach is proposed for the direct solution to bypass the difficulties related to converting the integral governing equation into a differential equation. First, the governing equation is derived based on both strain-driven and stress-driven nonlocal models by means of the minimum total potential energy. Also, in each case, the governing equation is obtained in both strong and weak forms. To solve numerically the derived equations, matrix differential and integral operators are constructed based upon the finite difference technique and trapezoidal integration rule. It is shown that the proposed numerical approach can be efficiently applied to the strain-driven nonlocal model with the aim of resolving the mentioned paradoxes. Also, it is able to solve the problem based on the strain-driven model without inconsistencies of the application of this model that are reported in the literature.

Exogenous and endogenous hormones and breast cancer

PubMed Central

ChenMD, Wendy Y.

2008-01-01

Exposure to higher levels of both exogenous and endogenous hormone is associated with breast cancer risk. Because of the association between breast cancer and HRT, only the minimal duration of HRT use is recommended for symptom control, and it is not recommended for chronic disease management. Current research issues include the role of progestins, other types of HRT, duration of unopposed estrogen use, and characteristics of cancers that develop on HRT. Circulating sex steroid levels are associated with breast cancer risk, but multiple issues need to be addressed before they are used routinely in clinical practice. Current research issues include measurement of levels for routine clinical practice, integration with standard breast cancer risk models and genetic polymorphism data, and applicability to estrogen-receptor-negative cancers. PMID:18971119

Life cycle responses to health insurance status.

PubMed

Pelgrin, Florian; St-Amour, Pascal

2016-09-01

This paper studies the lifetime effects of exogenous changes in health insurance coverage (e.g. Medicare, PPACA, termination of employer-provided plans) on the dynamic optimal allocation (consumption, leisure, health expenditures), status (health and wealth), and welfare. We solve, simulate, and structurally estimate a parsimonious life cycle model with endogenous exposure to morbidity and mortality risks, and exogenous health insurance. By varying coverage, we identify the marginal effects of insurance when young and/or when old on allocations, statuses, and welfare. Our results highlight positive effects of insurance on health, wealth and welfare, as well as mid-life substitution away from healthy leisure in favor of more health expenses, caused by peaking wages, and accelerating health issues. Copyright © 2016 Elsevier B.V. All rights reserved.

Exogenous Estrogen as Mediator of Racial Differences in Bioactive Insulin-Like Growth Factor-I Levels Among Postmenopausal Women

PubMed Central

Vitolins, Mara Z.; Paskett, Electra D.; Chang, Shine

2015-01-01

Background. The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race–IGF-I relationship in postmenopausal women. Methods. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women’s Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race–IGF-I relationship, we used the Baron–Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Results. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race–IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Conclusions. Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. PMID:25238773

Instrumenting Beliefs in Threshold Public Goods

PubMed Central

2016-01-01

Understanding the causal impact of beliefs on contributions in Threshold Public Goods (TPGs) is particularly important since the social optimum can be supported as a Nash Equilibrium and best-response contributions are a function of beliefs. Unfortunately, investigations of the impact of beliefs on behavior are plagued with endogeneity concerns. We create a set of instruments by cleanly and exogenously manipulating beliefs without deception. Tests indicate that the instruments are valid and relevant. Perhaps surprisingly, we fail to find evidence that beliefs are endogenous in either the one-shot or repeated-decision settings. TPG allocations are determined by a base contribution and beliefs in a one shot-setting. In the repeated-decision environment, once we instrument for first-round allocations, we find that second-round allocations are driven equally by beliefs and history. Moreover, we find that failing to instrument prior decisions overstates their importance. PMID:26859492

Exogenous attentional capture by subliminal abrupt-onset cues: evidence from contrast-polarity independent cueing effects.

PubMed

Fuchs, Isabella; Theeuwes, Jan; Ansorge, Ulrich

2013-08-01

In the present study, we tested whether subliminal abrupt-onset cues capture attention in a bottom-up or top-down controlled manner. For our tests, we varied the searched-for target-contrast polarity (i.e., dark or light targets against a gray background) over four experiments. In line with the bottom-up hypothesis, our results indicate that subliminal-onset cues capture attention independently of the searched-for target-contrast polarity (Experiment 1), and this effect is not stronger for targets that matched the searched-for target-contrast polarity (Experiment 2). In fact, even to-be-ignored cues associated with a no-go response captured attention in a salience-driven way (Experiment 3). For supraliminal cues, we found attentional capture only by cues with a matching contrast polarity, reflecting contingent capture (Experiment 4). The results point toward a specific role of subliminal abrupt onsets for attentional capture. 2013 APA, all rights reserved

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

NASA Astrophysics Data System (ADS)

Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

2014-02-01

The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

Increased kinin levels and decreased responsiveness to kinins during aging.

PubMed

Pérez, Viviana; Velarde, Victoria; Acuña-Castillo, Claudio; Gómez, Christian; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

2005-08-01

Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals.

Wolves in sheep's clothing: Is non-profit status used to signal quality?

PubMed

Jones, Daniel B; Propper, Carol; Smith, Sarah

2017-09-01

Why do many firms in the healthcare sector adopt non-profit status? One argument is that non-profit status serves as a signal of quality when consumers are not well informed. A testable implication is that an increase in consumer information may lead to a reduction in the number of non-profits in a market. We test this idea empirically by exploiting an exogenous increase in consumer information in the US nursing home industry. We find that the information shock led to a reduction in the share of non-profit homes, driven by a combination of home closure and sector switching. The lowest quality non-profits were the most likely to exit. Our results have important implications for the effects of reforms to increase consumer provision in a number of public services. Copyright © 2017. Published by Elsevier B.V.

SKN-1-independent transcriptional activation of glutathione S-transferase 4 (GST-4) by EGF signaling

PubMed Central

Van de Walle, Pieter; Schoofs, Liliane

2016-01-01

ABSTRACT In C. elegans research, transcriptional activation of glutathione S-transferase 4 (gst-4) is often used as a read-out for SKN-1 activity. While many heed an assumed non-exclusivity of the GFP reporter signal driven by the gst-4 promoter to SKN-1, this is also often ignored. We here show that gst-4 can also be transcriptionally activated by EOR-1, a transcription factor mediating effects of the epidermal growth factor (EGF) pathway. Along with enhancing exogenous oxidative stress tolerance, EOR-1 inde-pendently of SKN-1 increases gst-4 transcription in response to augmented EGF signaling. Our findings caution researchers within the C. elegans community to always rely on sufficient experimental controls when assaying SKN-1 transcriptional activity with a gst-4p::gfp reporter, such as SKN-1 loss-of-function mutants and/or additional target genes next to gst-4. PMID:28090393

Unconventional repertoire profile is imprinted during acute chikungunya infection for natural killer cells polarization toward cytotoxicity.

PubMed

Petitdemange, Caroline; Becquart, Pierre; Wauquier, Nadia; Béziat, Vivien; Debré, Patrice; Leroy, Eric M; Vieillard, Vincent

2011-09-01

Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance.

Structural basis for activity of highly efficient RNA mimics of green fluorescent protein

PubMed Central

Warner, Katherine Deigan; Chen, Michael C.; Song, Wenjiao; Strack, Rita L.; Thorn, Andrea; Jaffrey, Samie R.; Ferré-D’Amaré, Adrian R.

2014-01-01

Green fluorescent protein (GFP) and its derivatives revolutionized the study of proteins. Spinach is a recently reported in vitro evolved RNA mimic of GFP, which as genetically encoded fusions, makes possible live-cell, real-time imaging of biological RNAs, without resorting to large RNA-binding protein-GFP fusions. To elucidate the molecular basis of Spinach fluorescence, we have solved its co-crystal structure bound to its cognate exogenous chromophore, revealing that Spinach activates the small molecule by immobilizing it between a base triple, a G-quadruplex, and an unpaired guanine. Mutational and NMR analyses indicate that the G-quadruplex is essential for Spinach fluorescence, is also present in other fluorogenic RNAs, and may represent a general strategy for RNAs to induce fluorescence of chromophores. The structure has guided the design of a miniaturized 'Baby Spinach', and provides the foundation for structure-driven design and tuning of fluorescent RNAs. PMID:25026079

Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation

PubMed Central

Kim, Kyoung Min; Wagle, Sajeev; Moon, Young Jae; Wang, Sung Il; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul

2018-01-01

Synovitis of the affected joint is a common in avascular osteonecrosis (AVN). Increased levels of pro-inflammatory cytokine interleukin-6 (IL-6) have been reported in AVN, but the mechanism of this increase remains unclear. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, inhibits the release of inflammatory cytokines. Interferon β (IFN-β) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-β treatment on AVN and to evaluate the specific signal pathway relating to IL-6 and SIRT1 affected during AVN. Using a dissection microscope, AVN was surgically induced in the distal femurs of mice. Exogenous IFN-β was administered to the model mice. The effects of exogenous IFN-β on AVN model mice were assessed using hematoxylin eosin and safranin-O staining, and bone resorption activity was measured using tartrate-resistant acid phosphatase (TRAP) and CD68 staining. Western blots, real-time RT-PCR, and immunohistochemical staining were performed to evaluate the production of SIRT1 and IL-6 in tissues. The RAW 264.7 cell line and bone marrow derived osteoclasts treated with exogenous IFN-β. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-β treated mice compared with mice in the AVN group. Treatment with IFN-β increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-β decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-β could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN. PMID:29423066

Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation.

PubMed

Kim, Kyoung Min; Wagle, Sajeev; Moon, Young Jae; Wang, Sung Il; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul

2018-01-09

Synovitis of the affected joint is a common in avascular osteonecrosis (AVN). Increased levels of pro-inflammatory cytokine interleukin-6 (IL-6) have been reported in AVN, but the mechanism of this increase remains unclear. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, inhibits the release of inflammatory cytokines. Interferon β (IFN-β) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-β treatment on AVN and to evaluate the specific signal pathway relating to IL-6 and SIRT1 affected during AVN. Using a dissection microscope, AVN was surgically induced in the distal femurs of mice. Exogenous IFN-β was administered to the model mice. The effects of exogenous IFN-β on AVN model mice were assessed using hematoxylin eosin and safranin-O staining, and bone resorption activity was measured using tartrate-resistant acid phosphatase (TRAP) and CD68 staining. Western blots, real-time RT-PCR, and immunohistochemical staining were performed to evaluate the production of SIRT1 and IL-6 in tissues. The RAW 264.7 cell line and bone marrow derived osteoclasts treated with exogenous IFN-β. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-β treated mice compared with mice in the AVN group. Treatment with IFN-β increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-β decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-β could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN.

Genetic and functional studies of the intervertebral disc: a novel murine intervertebral disc model.

PubMed

Pelle, Dominic W; Peacock, Jacqueline D; Schmidt, Courtney L; Kampfschulte, Kevin; Scholten, Donald J; Russo, Scott S; Easton, Kenneth J; Steensma, Matthew R

2014-01-01

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.

Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

PubMed Central

Pelle, Dominic W.; Peacock, Jacqueline D.; Schmidt, Courtney L.; Kampfschulte, Kevin; Scholten, Donald J.; Russo, Scott S.; Easton, Kenneth J.; Steensma, Matthew R.

2014-01-01

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration. PMID:25474689

Protective effect of exogenous hydrogen sulfide on pulmonary artery endothelial cells by suppressing endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease.

PubMed

Ding, Hai-Bo; Liu, Kai-Xiong; Huang, Jie-Feng; Wu, Da-Wen; Chen, Jun-Ying; Chen, Qing-Shi

2018-06-13

Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder characterized by inflammation, representing a significant leading cause of chronic morbidity and mortality. Reports have implicated hydrogen sulfide (H 2 S) in both the pathology and treatment of COPD. The present study aimed to explore the effects involved with exogenous H 2 S on endoplasmic reticulum stress (ERS) and pulmonary artery endothelial cells (PAECs) in a rat model of COPD. Rat models of COPD were successfully established by means of passive smoke exposure and intratracheal injection with lipopolysaccharide (LPS). Pulmonary function tests were performed and histopathological changes were observed. The expression of ERS markers, glucose-regulated protein-78 (GRP78), and C/EBP homologous protein (CHOP) and caspase-12, associated with ERS-induced apoptosis, were determined by western blot and immunohistochemistry methods. TUNEL assay was applied to determine the apoptosis index (AI) in PAECs. Treatment with NaHS was followed by the exhibition of markedly increased forced expiratory volume over 0.3 s (FEV0.3)/forced vital capacity (FVC) and dynamic lung compliance as well as integral optical density (IOD), with decreased RI among COPD rats. Western blot analysis, immunohistochemistry and TUNEL assay results revealed there to be reduced expressions of GRP78, CHOP and caspase-12 in the lung tissues and AI of PAECs, post NaHS treatment. The key findings of the current study highlight ERS in COPD rats, as well as well as reduced apoptosis in PAECs in connection with exogenous H 2 S by suppressing ERS. Copyright © 2018. Published by Elsevier Masson SAS.

Laser surgery of zebrafish (Danio rerio) embryos using femtosecond laser pulses: Optimal parameters for exogenous material delivery, and the laser's effect on short- and long-term development

PubMed Central

Kohli, Vikram; Elezzabi, Abdulhakem Y

2008-01-01

Background Femtosecond (fs) laser pulses have recently received wide interest as an alternative tool for manipulating living biological systems. In various model organisms the excision of cellular components and the intracellular delivery of foreign exogenous materials have been reported. However, the effect of the applied fs laser pulses on cell viability and development has yet to be determined. Using the zebrafish (Danio rerio) as our animal model system, we address both the short- and long-term developmental changes following laser surgery on zebrafish embryonic cells. Results An exogenous fluorescent probe, fluorescein isothiocyanate (FITC), was successfully introduced into blastomere cells and found to diffuse throughout all developing cells. Using the reported manipulation tool, we addressed whether the applied fs laser pulses induced any short- or long-term developmental effects in embryos reared to 2 and 7 days post-fertilization (dpf). Using light microscopy and scanning electron microscopy we compared key developmental features of laser-manipulated and control samples, including the olfactory pit, dorsal, ventral and pectoral fins, notochord, pectoral fin buds, otic capsule, otic vesicle, neuromast patterning, and kinocilia of the olfactory pit rim and cristae of the lateral wall of the ear. Conclusion In our study, no significant differences in hatching rates and developmental morphologies were observed in laser-manipulated samples relative to controls. This tool represents an effective non-destructive technique for potential medical and biological applications. PMID:18230185

Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease.

PubMed

Wang, Ellian; Chiou, Yuan-Yow; Jeng, Wen-Yih; Lin, Hsiu-Kuan; Lin, Hsi-Hui; Chin, Hsian-Jean; Leo Wang, Chi-Kuang; Yu, Shang-Shiuan; Tsai, Shih-Chieh; Chiang, Chih-Ying; Cheng, Po-Hao; Lin, Hong-Jie; Jiang, Si-Tse; Chiu, Sou-Tyau; Hsieh-Li, Hsiu Mei

2017-02-01

Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1 L3/L3 ): Pkd1 L3/L3 (with endogenous Ngal), Pkd1 L3/L3 ; Ngal Tg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1 L3/L3 ; Ngal -/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Maternal Supply of Cas9 to Zygotes Facilitates the Efficient Generation of Site-Specific Mutant Mouse Models

PubMed Central

Cebrian-Serrano, Alberto; Zha, Shijun; Hanssen, Lars; Biggs, Daniel; Preece, Christopher

2017-01-01

Genome manipulation in the mouse via microinjection of CRISPR/Cas9 site-specific nucleases has allowed the production time for genetically modified mouse models to be significantly reduced. Successful genome manipulation in the mouse has already been reported using Cas9 supplied by microinjection of a DNA construct, in vitro transcribed mRNA and recombinant protein. Recently the use of transgenic strains of mice overexpressing Cas9 has been shown to facilitate site-specific mutagenesis via maternal supply to zygotes and this route may provide an alternative to exogenous supply. We have investigated the feasibility of supplying Cas9 genetically in more detail and for this purpose we report the generation of a transgenic mice which overexpress Cas9 ubiquitously, via a CAG-Cas9 transgene targeted to the Gt(ROSA26)Sor locus. We show that zygotes prepared from female mice harbouring this transgene are sufficiently loaded with maternally contributed Cas9 for efficient production of embryos and mice harbouring indel, genomic deletion and knock-in alleles by microinjection of guide RNAs and templates alone. We compare the mutagenesis rates and efficacy of mutagenesis using this genetic supply with exogenous Cas9 supply by either mRNA or protein microinjection. In general, we report increased generation rates of knock-in alleles and show that the levels of mutagenesis at certain genome target sites are significantly higher and more consistent when Cas9 is supplied genetically relative to exogenous supply. PMID:28081254

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

Estimation of the total daily oral intake of NDMA attributable to drinking water.

PubMed

Fristachi, Anthony; Rice, Glenn

2007-09-01

Disinfection with chlorine and chloramine leads to the formation of many disinfection by-products including N-Nitrosodimethylamine (NDMA). Because NDMA is a probable human carcinogen, public health officials are concerned with its occurrence in drinking water. The goal of this study was to estimate NDMA concentrations from exogenous (i.e., drinking water and food) and endogenous (i.e., formed in the human body) sources, calculate average daily doses for ingestion route exposures and estimate the proportional oral intake (POI) of NDMA attributable to the consumption of drinking water relative to other ingestion sources of NDMA. The POI is predicted to be 0.02% relative to exogenous and endogenous NDMA sources combined. When only exogenous sources are considered, the POI was predicted to be 2.7%. The exclusion of endogenously formed NDMA causes the POI to increase dramatically, reflecting its importance as a potentially major source of exposure and uncertainty in the model. Although concentrations of NDMA in foods are small and human exposure to NDMA from foods is quite low, the contribution from food is predicted to be high relative to that of drinking water. The mean concentration of NDMA in drinking water would need to increase from 2.1 x 10(-3) microg/L to 0.10 microg/L, a 47-fold increase, for the POI to reach 1%, relative to all sources of NDMA considered in our model, suggesting that drinking water consumption is most likely a minor source of NDMA exposure.

Exogenous nitric oxide can control SIRS and downregulate NFkappaB.

PubMed

Lozano, Francisco S; Barros, Marcello B; García-Criado, Francisco J; Gomez-Alonso, Alberto

2005-03-01

Nitric oxide (NO) participates in inflammation and affects almost all steps of its development. Several experimental studies have unveiled the beneficial effects of NO through modulation of the Systemic Inflammatory Response Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the beneficial effects of exogenous NO and its levels of action (biochemical and cellular) in a model of SIRS induced by two sequential insults. Dacron graft implantation (first insult) and subsequent administration of Zymosan A (second insult) in Wistar rats. The animals were divided into four groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations: Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB. The model established (Control) induced a mortality rate of 20%. Also, it significantly increased the levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and NFkappaB levels (P <0.05). The exogenous administration of NO before the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA) and at cellular level (transcription) in a lasting manner. The cascade-like interrelationship of both levels and the study design do not allow us the pinpoint the key to its modulation.

A unique role of endogenous visual-spatial attention in rapid processing of multiple targets

PubMed Central

Guzman, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

2012-01-01

Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions). We report that endogenous attention uniquely contributes to processing of multiple targets. For speeded visual discrimination, response times are faster for multiple redundant targets than for single targets due to probability summation and/or signal integration. This redundancy gain was unaffected when attention was exogenously diverted from the targets, but was completely eliminated when attention was endogenously diverted. This was not due to weaker manipulation of exogenous attention because our exogenous and endogenous cues similarly affected overall response times. Thus, whereas exogenous attention is superior for processing single targets, endogenous attention plays a unique role in allocating resources crucial for rapid concurrent processing of multiple targets. PMID:21517209

[Effect of cadmium stress on physiological characteristics of garlic seedlings and the alleviation effects of exogenous calcium].

PubMed

Li, He; Lian, Hai-feng; Liu, Shi-qi; Yu, Xin-hui; Sun, Ya-li; Guo, Hui-ping

2015-04-01

In the experiment, the effects of exogenous cadmium (Cd2+) and calcium (Ca2+) in nutrient solution on growth, photosynthetic characteristics, enzymes activities, main mineral elements absorption of garlic seedlings were studied. The results showed that cadmium could obviously inhibit the growth of garlic seedlings, decrease the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves, reduced the enzymes (SOD, POD, CAT) activities and increase the MDA content of leaves, and also could reduce the N, P, K, Ca, Mg contents and increase the Cd content of roots. The growth was promoted after adding exogenous calcium to garlic seedlings under cadmium stress, which reflected that the morphological indexes were increased at first and then decreased with the increase of exogenous calcium concentrations, and were maximized when the exogenous calcium was 2 or 3 mmol x L(-1). At the same time, the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves showed a similar tendency with the morphological indexes, and they were the highest when the exogenous calcium was 2 or 3 mmol x L(-1). In addition, adding exogenous calcium to garlic seedlings under cadmium stress enhanced the enzymes (SOD, POD, CAT) activities and decreased the MDA content of leaves, also added the N, P, K, Ca, Mg contents and reduced the Cd content of roots, and the effect was best when the exogenous calcium concentration was 2 or 3 mmol x L(-1).

Elongator Plays a Positive Role in Exogenous NAD-Induced Defense Responses in Arabidopsis.

PubMed

An, Chuanfu; Ding, Yezhang; Zhang, Xudong; Wang, Chenggang; Mou, Zhonglin

2016-05-01

Extracellular NAD is emerging as an important signal molecule in animal cells, but its role in plants has not been well-established. Although it has been shown that exogenous NAD(+) activates defense responses in Arabidopsis, components in the exogenous NAD(+)-activated defense pathway remain to be fully discovered. In a genetic screen for mutants insensitive to exogenous NAD(+) (ien), we isolated a mutant named ien2. Map-based cloning revealed that IEN2 encodes ELONGATA3 (ELO3)/AtELP3, a subunit of the Arabidopsis Elongator complex, which functions in multiple biological processes, including histone modification, DNA (de)methylation, and transfer RNA modification. Mutations in the ELO3/AtELP3 gene compromise exogenous NAD(+)-induced expression of pathogenesis-related (PR) genes and resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326, and transgenic expression of the coding region of ELO3/AtELP3 in elo3/Atelp3 restores NAD(+) responsiveness to the mutant plants, demonstrating that ELO3/AtELP3 is required for exogenous NAD(+)-induced defense responses. Furthermore, mutations in genes encoding the other five Arabidopsis Elongator subunits (ELO2/AtELP1, AtELP2, ELO1/AtELP4, AtELP5, and AtELP6) also compromise exogenous NAD(+)-induced PR gene expression and resistance to P. syringae pv. maculicola ES4326. These results indicate that the Elongator complex functions as a whole in exogenous NAD(+)-activated defense signaling in Arabidopsis.

Object-centered representations support flexible exogenous visual attention across translation and reflection.

PubMed

Lin, Zhicheng

2013-11-01

Visual attention can be deployed to stimuli based on our willful, top-down goal (endogenous attention) or on their intrinsic saliency against the background (exogenous attention). Flexibility is thought to be a hallmark of endogenous attention, whereas decades of research show that exogenous attention is attracted to the retinotopic locations of the salient stimuli. However, to the extent that salient stimuli in the natural environment usually form specific spatial relations with the surrounding context and are dynamic, exogenous attention, to be adaptive, should embrace these structural regularities. Here we test a non-retinotopic, object-centered mechanism in exogenous attention, in which exogenous attention is dynamically attracted to a relative, object-centered location. Using a moving frame configuration, we presented two frames in succession, forming either apparent translational motion or in mirror reflection, with a completely uninformative, transient cue presented at one of the item locations in the first frame. Despite that the cue is presented in a spatially separate frame, in both translation and mirror reflection, behavioralperformance in visual search is enhanced when the target in the second frame appears at the same relative location as the cue location than at other locations. These results provide unambiguous evidence for non-retinotopic exogenous attention and further reveal an object-centered mechanism supporting flexible exogenous attention. Moreover, attentional generalization across mirror reflection may constitute an attentional correlate of perceptual generalization across lateral mirror images, supporting an adaptive, functional account of mirror images confusion. Copyright © 2013 Elsevier B.V. All rights reserved.

Object-centered representations support flexible exogenous visual attention across translation and reflection

PubMed Central

Lin, Zhicheng

2013-01-01

Visual attention can be deployed to stimuli based on our willful, top-down goal (endogenous attention) or on their intrinsic saliency against the background (exogenous attention). Flexibility is thought to be a hallmark of endogenous attention, whereas decades of research show that exogenous attention is attracted to the retinotopic locations of the salient stimuli. However, to the extent that salient stimuli in the natural environment usually form specific spatial relations with the surrounding context and are dynamic, exogenous attention, to be adaptive, should embrace these structural regularities. Here we test a non-retinotopic, object-centered mechanism in exogenous attention, in which exogenous attention is dynamically attracted to a relative, object-centered location. Using a moving frame configuration, we presented two frames in succession, forming either apparent translational motion or in mirror reflection, with a completely uninformative, transient cue presented at one of the item locations in the first frame. Despite that the cue is presented in a spatially separate frame, in both translation and mirror reflection, human performance in visual search is enhanced when the target in the second frame appears at the same relative location as the cue location than at other locations. These results provide unambiguous evidence for non-retinotopic exogenous attention and further reveal an object-centered mechanism supporting flexible exogenous attention. Moreover, attentional generalization across mirror reflection may constitute an attentional correlate of perceptual generalization across lateral mirror images, supporting an adaptive, functional account of mirror images confusion. PMID:23942348

Ontology-Driven Business Modelling: Improving the Conceptual Representation of the REA Ontology

NASA Astrophysics Data System (ADS)

Gailly, Frederik; Poels, Geert

Business modelling research is increasingly interested in exploring how domain ontologies can be used as reference models for business models. The Resource Event Agent (REA) ontology is a primary candidate for ontology-driven modelling of business processes because the REA point of view on business reality is close to the conceptual modelling perspective on business models. In this paper Ontology Engineering principles are employed to reengineer REA in order to make it more suitable for ontology-driven business modelling. The new conceptual representation of REA that we propose uses a single representation formalism, includes a more complete domain axiomatizat-ion (containing definitions of concepts, concept relations and ontological axioms), and is proposed as a generic model that can be instantiated to create valid business models. The effects of these proposed improvements on REA-driven business modelling are demonstrated using a business modelling example.

Integrating a Detailed Agricultural Model in a Global Economic Framework: New methods for assessment of climate mitigation and adaptation opportunities

NASA Astrophysics Data System (ADS)

Thomson, A. M.; Izaurralde, R. C.; Calvin, K.; Zhang, X.; Wise, M.; West, T. O.

2010-12-01

Climate change and food security are global issues increasingly linked through human decision making that takes place across all scales from on-farm management actions to international climate negotiations. Understanding how agricultural systems can respond to climate change, through mitigation or adaptation, while still supplying sufficient food to feed a growing global population, thus requires a multi-sector tool in a global economic framework. Integrated assessment models are one such tool, however they are typically driven by historical aggregate statistics of production in combination with exogenous assumptions of future trends in agricultural productivity; they are not yet capable of exploring agricultural management practices as climate adaptation or mitigation strategies. Yet there are agricultural models capable of detailed biophysical modeling of farm management and climate impacts on crop yield, soil erosion and C and greenhouse gas emissions, although these are typically applied at point scales that are incompatible with coarse resolution integrated assessment modeling. To combine the relative strengths of these modeling systems, we are using the agricultural model EPIC (Environmental Policy Integrated Climate), applied in a geographic data framework for regional analyses, to provide input to the global economic model GCAM (Global Change Assessment Model). The initial phase of our approach focuses on a pilot region of the Midwest United States, a highly productive agricultural area. We apply EPIC, a point based biophysical process model, at 60 m spatial resolution within this domain and aggregate the results to GCAM agriculture and land use subregions for the United States. GCAM is then initialized with multiple management options for key food and bioenergy crops. Using EPIC to distinguish these management options based on grain yield, residue yield, soil C change and cost differences, GCAM then simulates the optimum distribution of the available management options to meet demands for food and energy over the next century. The coupled models provide a new platform for evaluating future changes in agricultural management based on food demand, bioenergy demand, and changes in crop yield and soil C under a changing climate. This framework can be applied to evaluate the economically and biophysically optimal distribution of management under future climates.

Message survival and decision dynamics in a class of reactive complex systems subject to external fields

NASA Astrophysics Data System (ADS)

Rodriguez Lucatero, C.; Schaum, A.; Alarcon Ramos, L.; Bernal-Jaquez, R.

2014-07-01

In this study, the dynamics of decisions in complex networks subject to external fields are studied within a Markov process framework using nonlinear dynamical systems theory. A mathematical discrete-time model is derived using a set of basic assumptions regarding the convincement mechanisms associated with two competing opinions. The model is analyzed with respect to the multiplicity of critical points and the stability of extinction states. Sufficient conditions for extinction are derived in terms of the convincement probabilities and the maximum eigenvalues of the associated connectivity matrices. The influences of exogenous (e.g., mass media-based) effects on decision behavior are analyzed qualitatively. The current analysis predicts: (i) the presence of fixed-point multiplicity (with a maximum number of four different fixed points), multi-stability, and sensitivity with respect to the process parameters; and (ii) the bounded but significant impact of exogenous perturbations on the decision behavior. These predictions were verified using a set of numerical simulations based on a scale-free network topology.

The Endogenous-Exogenous Partition in Attribution Theory

ERIC Educational Resources Information Center

Kruglanski, Arie W.

1975-01-01

Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

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

Coevolution of farming and private property during the early Holocene.

PubMed

Bowles, Samuel; Choi, Jung-Kyoo

2013-05-28

The advent of farming around 12 millennia ago was a cultural as well as technological revolution, requiring a new system of property rights. Among mobile hunter-gatherers during the late Pleistocene, food was almost certainly widely shared as it was acquired. If a harvested crop or the meat of a domesticated animal were to have been distributed to other group members, a late Pleistocene would-be farmer would have had little incentive to engage in the required investments in clearing, cultivation, animal tending, and storage. However, the new property rights that farming required--secure individual claims to the products of one's labor--were infeasible because most of the mobile and dispersed resources of a forager economy could not cost-effectively be delimited and defended. The resulting chicken-and-egg puzzle might be resolved if farming had been much more productive than foraging, but initially it was not. Our model and simulations explain how, despite being an unlikely event, farming and a new system of farming-friendly property rights nonetheless jointly emerged when they did. This Holocene revolution was not sparked by a superior technology. It occurred because possession of the wealth of farmers--crops, dwellings, and animals--could be unambiguously demarcated and defended. This facilitated the spread of new property rights that were advantageous to the groups adopting them. Our results thus challenge unicausal models of historical dynamics driven by advances in technology, population pressure, or other exogenous changes. Our approach may be applied to other technological and institutional revolutions such as the 18th- and 19th-century industrial revolution and the information revolution today.

Coevolution of farming and private property during the early Holocene

PubMed Central

Bowles, Samuel; Choi, Jung-Kyoo

2013-01-01

The advent of farming around 12 millennia ago was a cultural as well as technological revolution, requiring a new system of property rights. Among mobile hunter–gatherers during the late Pleistocene, food was almost certainly widely shared as it was acquired. If a harvested crop or the meat of a domesticated animal were to have been distributed to other group members, a late Pleistocene would-be farmer would have had little incentive to engage in the required investments in clearing, cultivation, animal tending, and storage. However, the new property rights that farming required—secure individual claims to the products of one’s labor—were infeasible because most of the mobile and dispersed resources of a forager economy could not cost-effectively be delimited and defended. The resulting chicken-and-egg puzzle might be resolved if farming had been much more productive than foraging, but initially it was not. Our model and simulations explain how, despite being an unlikely event, farming and a new system of farming-friendly property rights nonetheless jointly emerged when they did. This Holocene revolution was not sparked by a superior technology. It occurred because possession of the wealth of farmers—crops, dwellings, and animals—could be unambiguously demarcated and defended. This facilitated the spread of new property rights that were advantageous to the groups adopting them. Our results thus challenge unicausal models of historical dynamics driven by advances in technology, population pressure, or other exogenous changes. Our approach may be applied to other technological and institutional revolutions such as the 18th- and 19th-century industrial revolution and the information revolution today. PMID:23671111

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

PubMed Central

Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

2015-01-01

During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering

PubMed Central

Havlicek, Martin; Friston, Karl J.; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D.

2011-01-01

This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain. PMID:21396454

City-scale expansion of human thermoregulatory costs.

PubMed

Hill, Richard W; Muhich, Timothy E; Humphries, Murray M

2013-01-01

The physiological maintenance of a stable internal temperature by mammals and birds - the phenomenon termed homeothermy - is well known to be energetically expensive. The annual energy requirements of free-living mammals and birds are estimated to be 15-30 times higher than those of similar-size ectothermic vertebrates like lizards. Contemporary humans also use energy to accomplish thermoregulation. They are unique, however, in having shifted thermoregulatory control from the body to the occupied environment, with most people living in cities in dwellings that are temperature-regulated by furnaces and air conditioners powered by exogenous energy sources. The energetic implications of this strategy remain poorly defined. Here we comparatively quantify energy costs in cities, dwellings, and individual human bodies. Thermoregulation persists as a major driver of energy expenditure across these three scales, resulting in energy-versus-ambient-temperature relationships remarkably similar in shape. Incredibly, despite the many and diversified uses of network-delivered energy in modern societies, the energy requirements of six North American cities are as temperature-dependent as the energy requirements of isolated, individual homeotherms. However, the annual per-person energy cost of exogenously powered thermoregulation in cities and dwellings is 9-28 times higher than the cost of endogenous, metabolic thermoregulation of the human body. Shifting the locus of thermoregulatory control from the body to the dwelling achieves climate-independent thermal comfort. However, in an era of amplifying climate change driven by the carbon footprint of humanity, we must acknowledge the energetic extravagance of contemporary, city-scale thermoregulation, which prioritizes heat production over heat conservation.

City-Scale Expansion of Human Thermoregulatory Costs

PubMed Central

Hill, Richard W.; Muhich, Timothy E.; Humphries, Murray M.

2013-01-01

The physiological maintenance of a stable internal temperature by mammals and birds – the phenomenon termed homeothermy – is well known to be energetically expensive. The annual energy requirements of free-living mammals and birds are estimated to be 15–30 times higher than those of similar-size ectothermic vertebrates like lizards. Contemporary humans also use energy to accomplish thermoregulation. They are unique, however, in having shifted thermoregulatory control from the body to the occupied environment, with most people living in cities in dwellings that are temperature-regulated by furnaces and air conditioners powered by exogenous energy sources. The energetic implications of this strategy remain poorly defined. Here we comparatively quantify energy costs in cities, dwellings, and individual human bodies. Thermoregulation persists as a major driver of energy expenditure across these three scales, resulting in energy-versus-ambient-temperature relationships remarkably similar in shape. Incredibly, despite the many and diversified uses of network-delivered energy in modern societies, the energy requirements of six North American cities are as temperature-dependent as the energy requirements of isolated, individual homeotherms. However, the annual per-person energy cost of exogenously powered thermoregulation in cities and dwellings is 9–28 times higher than the cost of endogenous, metabolic thermoregulation of the human body. Shifting the locus of thermoregulatory control from the body to the dwelling achieves climate-independent thermal comfort. However, in an era of amplifying climate change driven by the carbon footprint of humanity, we must acknowledge the energetic extravagance of contemporary, city-scale thermoregulation, which prioritizes heat production over heat conservation. PMID:24143181

Organic carbon sources and controlling processes on aquifer arsenic cycling in the Jianghan Plain, central China.

PubMed

Yu, Kai; Gan, Yiqun; Zhou, Aiguo; Liu, Chongxuan; Duan, Yanhua; Han, Li; Zhang, Yanan

2018-05-30

Groundwater arsenic contamination is a common environmental problem that threatens the health of over 100 million people globally. Apparent seasonal fluctuations in groundwater arsenic concentrations have been reported in various locations worldwide, including the Jianghan Plain, central China. This phenomenon has been attributed to shifts in redox conditions induced by seasonal incursions of surface water. However, it is not clear what processes during the incursion lead to changes in the redox conditions and what is the source of the organic carbon driving these processes. Therefore, we conducted a long-term investigation of stable carbon isotopic compositions in surface water and groundwater, as well as long-term monitoring of hydraulic gradients and geochemical compositions at the Jianghan Plain. Results indicated that a series of biogeochemical processes occurred during surface water incursion, including aerobic microbial respiration, nitrate and sulfate reduction. Groundwater arsenic was removed by adsorption on iron oxyhydroxides produced during oxidation of ferrous iron, resulting in dramatic decreases in arsenic concentrations during surface water recharge seasons. These processes were likely driven by organic carbon vertically transported from surface water and released from the surficial aquitard above 15 m. Groundwater pumping may accelerate the vertical infiltration of oxidizing recharge water and drive exogenous organic carbon to depth. Findings of this study advance the understandings of the mechanisms that cause temporal variations in groundwater As and the importance of exogenous organic carbon that may influence the temporal behavior of arsenic in groundwater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke.

PubMed

Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Hassanzadeh, Gholamreza; Zendedel, Adib

2017-01-01

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.

The hyperthermophilic α-amylase from Thermococcus sp. HJ21 does not require exogenous calcium for thermostability because of high-binding affinity to calcium.

PubMed

Cheng, Huaixu; Luo, Zhidan; Lu, Mingsheng; Gao, Song; Wang, Shujun

2017-05-01

The hyperthermophilic α-amylase from Thermococcus sp. HJ21 does not require exogenous calcium ions for thermostability, and is a promising alternative to commercially available α-amylases to increase the efficiency of industrial processes like the liquefaction of starch. We analyzed the amino acid sequence of this α-amylase by sequence alignments and structural modeling, and found that this α-amylase closely resembles the α-amylase from Pyrococcus woesei. The gene of this α-amylase was cloned in Escherichia coli and the recombinant α-amylase was overexpressed and purified with a combined renaturation-purification procedure. We confirmed thermostability and exogenous calcium ion independency of the recombinant α-amylase and further investigated the mechanism of the independency using biochemical approaches. The results suggested that the α-amylase has a high calcium ion binding affinity that traps a calcium ion that would not dissociate at high temperatures, providing a direct explanation as to why the addition of calcium ions is not required for thermostability. Understanding of the mechanism offers a strong base on which to further engineer properties of this α-amylase for better potential applications in industrial processes.

Electromagnetic Properties Analysis on Hybrid-driven System of Electromagnetic Motor

NASA Astrophysics Data System (ADS)

Zhao, Jingbo; Han, Bingyuan; Bei, Shaoyi

2018-01-01

The hybrid-driven system made of permanent-and electromagnets applied in the electromagnetic motor was analyzed, equivalent magnetic circuit was used to establish the mathematical models of hybrid-driven system, based on the models of hybrid-driven system, the air gap flux, air-gap magnetic flux density, electromagnetic force was proposed. Taking the air-gap magnetic flux density and electromagnetic force as main research object, the hybrid-driven system was researched. Electromagnetic properties of hybrid-driven system with different working current modes is studied preliminary. The results shown that analysis based on hybrid-driven system can improve the air-gap magnetic flux density and electromagnetic force more effectively and can also guarantee the output stability, the effectiveness and feasibility of the hybrid-driven system are verified, which proved theoretical basis for the design of hybrid-driven system.

A model of strength

USGS Publications Warehouse

Johnson, Douglas H.; Cook, R.D.

2013-01-01

In her AAAS News & Notes piece "Can the Southwest manage its thirst?" (26 July, p. 362), K. Wren quotes Ajay Kalra, who advocates a particular method for predicting Colorado River streamflow "because it eschews complex physical climate models for a statistical data-driven modeling approach." A preference for data-driven models may be appropriate in this individual situation, but it is not so generally, Data-driven models often come with a warning against extrapolating beyond the range of the data used to develop the models. When the future is like the past, data-driven models can work well for prediction, but it is easy to over-model local or transient phenomena, often leading to predictive inaccuracy (1). Mechanistic models are built on established knowledge of the process that connects the response variables with the predictors, using information obtained outside of an extant data set. One may shy away from a mechanistic approach when the underlying process is judged to be too complicated, but good predictive models can be constructed with statistical components that account for ingredients missing in the mechanistic analysis. Models with sound mechanistic components are more generally applicable and robust than data-driven models.

Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

ERIC Educational Resources Information Center

McKillip, Jack

Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

Improved exogenous DNA uptake in bovine spermatozoa and gene expression in embryos using membrane destabilizing agents in ICSI-SMGT.

PubMed

Sánchez-Villalba, Esther; Arias, María Elena; Zambrano, Fabiola; Loren, Pía; Felmer, Ricardo

2018-02-01

Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical biotechnological tool for producing transgenic animals. However, transgene expression with this technique in bovine embryos is still inefficient due to low uptake and binding of exogenous DNA in spermatozoa. The present study evaluated the effects of sperm membrane destabilization on the binding capacity, location and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)-SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa including the control. Spermatozoa treated with different membrane destabilizing agents bound the exogenous DNA throughout the head and tail of spermatozoa, compared with the control, in which binding occurred mainly in the post-acrosomal region and tail. The amount of exogenous DNA bound to spermatozoa was much higher for the different sperm treatments than the control (P < 0.05), most likely due to the damage induced by these treatments to the plasma and acrosomal membranes. Exogenous gene expression in embryos was also improved by these treatments. These results demonstrated that sperm membrane destabilization could be a novel strategy in bovine SMGT protocols for the generation of transgenic embryos by ICSI.

Structural principles within the human-virus protein-protein interaction network

PubMed Central

Franzosa, Eric A.; Xia, Yu

2011-01-01

General properties of the antagonistic biomolecular interactions between viruses and their hosts (exogenous interactions) remain poorly understood, and may differ significantly from known principles governing the cooperative interactions within the host (endogenous interactions). Systems biology approaches have been applied to study the combined interaction networks of virus and human proteins, but such efforts have so far revealed only low-resolution patterns of host-virus interaction. Here, we layer curated and predicted 3D structural models of human-virus and human-human protein complexes on top of traditional interaction networks to reconstruct the human-virus structural interaction network. This approach reveals atomic resolution, mechanistic patterns of host-virus interaction, and facilitates systematic comparison with the host’s endogenous interactions. We find that exogenous interfaces tend to overlap with and mimic endogenous interfaces, thereby competing with endogenous binding partners. The endogenous interfaces mimicked by viral proteins tend to participate in multiple endogenous interactions which are transient and regulatory in nature. While interface overlap in the endogenous network results largely from gene duplication followed by divergent evolution, viral proteins frequently achieve interface mimicry without any sequence or structural similarity to an endogenous binding partner. Finally, while endogenous interfaces tend to evolve more slowly than the rest of the protein surface, exogenous interfaces—including many sites of endogenous-exogenous overlap—tend to evolve faster, consistent with an evolutionary “arms race” between host and pathogen. These significant biophysical, functional, and evolutionary differences between host-pathogen and within-host protein-protein interactions highlight the distinct consequences of antagonism versus cooperation in biological networks. PMID:21680884

Impaired postprandial releases/syntheses of ghrelin and PYY(3-36) and blunted responses to exogenous ghrelin and PYY(3-36) in a rodent model of diet-induced obesity.

PubMed

Xu, Junying; McNearney, Terry A; Chen, J D Z

2011-04-01

This study investigated the effects of peripheral administration of ghrelin and PYY(3-36) on food intake and plasma and tissue fasting and postprandial ghrelin and PYY(3-36) levels in normal-weight (NW) and diet-induced-obese (DIO) rats. In experiment one, NW and DIO rats received a single intraperitoneal injection of saline, PYY(3-36) or ghrelin; food intake was measured for 4 h. In experiment two, total plasma ghrelin and PYY(3-36), gastric fundus ghrelin, and ascending colon PYY(3-36) were measured either after a 20-h fast or 2 h after refeeding in NW and DIO rats by radioimmunoassay. Compared to the NW rats, findings in the DIO rats revealed: (i) a reduced sensitivity to both the anorectic effect of exogenous PYY(3-36) and the orexigenic effect of exogenous ghrelin; (ii) the postprandial plasma ghrelin levels were significantly higher; and (iii) refeeding decreased endogenous plasma ghrelin levels by 53% in the NW rats and 39% in DIO rats. Refeeding increased the plasma PYY(3-36) level by 58% in the NW rats versus 9% in the DIO rats (P=0.003). Compared with regular rats, DIO rats exhibit blunted responses in food intake to exogenous ghrelin and PYY(3-36). Although endogenous ghrelin and PYY(3-36) in DIO rats are not altered in the fasting state, their responses to food ingestion are blunted in comparison with regular rats. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

PubMed Central

Nahata, M; Saegusa, Y; Sadakane, C; Yamada, C; Nakagawa, K; Okubo, N; Ohnishi, S; Hattori, T; Sakamoto, N; Takeda, H

2014-01-01

Background Physical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice. Methods Fasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress. Key Results Mice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist. Conclusions & Inferences Plasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress. PMID:24684160

Different specificities of two aldehyde dehydrogenases from Saccharomyces cerevisiae var. boulardii.

PubMed

Datta, Suprama; Annapure, Uday S; Timson, David J

2017-04-30

Aldehyde dehydrogenases play crucial roles in the detoxification of exogenous and endogenous aldehydes by catalysing their oxidation to carboxylic acid counterparts. The present study reports characterization of two such isoenzymes from the yeast Saccharomyces cerevisiae var. boulardii (NCYC 3264), one mitochondrial (Ald4p) and one cytosolic (Ald6p). Both Ald4p and Ald6p were oligomeric in solution and demonstrated positive kinetic cooperativity towards aldehyde substrates. Wild-type Ald6p showed activity only with aliphatic aldehydes. Ald4p, on the contrary, showed activity with benzaldehyde along with a limited range of aliphatic aldehydes. Inspection of modelled structure of Ald6p revealed that a bulky amino acid residue (Met 177 , compared with the equivalent residue Leu 196 in Ald4p) might cause steric hindrance of cyclic substrates. Therefore, we hypothesized that specificities of the two isoenzymes towards aldehyde substrates were partly driven by steric hindrance in the active site. A variant of wild-type Ald6p with the Met 177 residue replaced by a valine was also characterized to address to the hypothesis. It showed an increased specificity range and a gain of activity towards cyclohexanecarboxaldehyde. It also demonstrated an increased thermal stability when compared with both the wild-types. These data suggest that steric bulk in the active site of yeast aldehyde dehydrogenases is partially responsible for controlling specificity. © 2017 The Author(s).

Attention and prediction in human audition: a lesson from cognitive psychophysiology

PubMed Central

Schröger, Erich; Marzecová, Anna; SanMiguel, Iria

2015-01-01

Attention is a hypothetical mechanism in the service of perception that facilitates the processing of relevant information and inhibits the processing of irrelevant information. Prediction is a hypothetical mechanism in the service of perception that considers prior information when interpreting the sensorial input. Although both (attention and prediction) aid perception, they are rarely considered together. Auditory attention typically yields enhanced brain activity, whereas auditory prediction often results in attenuated brain responses. However, when strongly predicted sounds are omitted, brain responses to silence resemble those elicited by sounds. Studies jointly investigating attention and prediction revealed that these different mechanisms may interact, e.g. attention may magnify the processing differences between predicted and unpredicted sounds. Following the predictive coding theory, we suggest that prediction relates to predictions sent down from predictive models housed in higher levels of the processing hierarchy to lower levels and attention refers to gain modulation of the prediction error signal sent up to the higher level. As predictions encode contents and confidence in the sensory data, and as gain can be modulated by the intention of the listener and by the predictability of the input, various possibilities for interactions between attention and prediction can be unfolded. From this perspective, the traditional distinction between bottom-up/exogenous and top-down/endogenous driven attention can be revisited and the classic concepts of attentional gain and attentional trace can be integrated. PMID:25728182

Engineering antigens for in situ erythrocyte binding induces T-cell deletion.

PubMed

Kontos, Stephan; Kourtis, Iraklis C; Dane, Karen Y; Hubbell, Jeffrey A

2013-01-02

Antigens derived from apoptotic cell debris can drive clonal T-cell deletion or anergy, and antigens chemically coupled ex vivo to apoptotic cell surfaces have been shown correspondingly to induce tolerance on infusion. Reasoning that a large number of erythrocytes become apoptotic (eryptotic) and are cleared each day, we engineered two different antigen constructs to target the antigen to erythrocyte cell surfaces after i.v. injection, one using a conjugate with an erythrocyte-binding peptide and another using a fusion with an antibody fragment, both targeting the erythrocyte-specific cell surface marker glycophorin A. Here, we show that erythrocyte-binding antigen is collected much more efficiently than free antigen by splenic and hepatic immune cell populations and hepatocytes, and that it induces antigen-specific deletional responses in CD4(+) and CD8(+) T cells. We further validated T-cell deletion driven by erythrocyte-binding antigens using a transgenic islet β cell-reactive CD4(+) T-cell adoptive transfer model of autoimmune type 1 diabetes: Treatment with the peptide antigen fused to an erythrocyte-binding antibody fragment completely prevented diabetes onset induced by the activated, autoreactive CD4(+) T cells. Thus, we report a translatable modular biomolecular approach with which to engineer antigens for targeted binding to erythrocyte cell surfaces to induce antigen-specific CD4(+) and CD8(+) T-cell deletion toward exogenous antigens and autoantigens.

Long-term evolution of the western South Atlantic passive continental margin in a key area of SE Brazil revealed by thermokinematic numerical modeling using the software code Pecube

NASA Astrophysics Data System (ADS)

Stippich, Christian; Krob, Florian; Glasmacher, Ulrich A.; Hackspacher, Peter C.

2016-04-01

The aim of the research is to quantify the long-term evolution of the western South Atlantic passive continental margin (SAPCM) in SE-Brazil. Excellent onshore outcrop conditions and extensive pre-rift to post-rift archives between São Paulo and Laguna allow a high precision quantification of exhumation, and rock uplift rates, influencing physical parameters, long-term acting forces, and process-response systems. Research will integrate published1 and partly published thermochronological data from Brazil, and test lately published new concepts on causes of long-term landscape and lithospheric evolution in southern Brazil. Six distinct lithospheric blocks (Laguna, Florianópolis, Curitiba, Ilha Comprida, Peruibe and Santos), which are separated by fracture zones1 are characterized by individual thermochronological age spectra. Furthermore, the thermal evolution derived by numerical modeling indicates variable post-rift exhumation histories of these blocks. In this context, we will provide information on the causes for the complex exhumation history of the Florianópolis, and adjacent blocks. The climate-continental margin-mantle coupled process-response system is caused by the interaction between endogenous and exogenous forces, which are related to the mantle-process driven rift - drift - passive continental margin evolution of the South Atlantic, and the climate change since the Early/Late Cretaceous climate maximum. Special emphasis will be given to the influence of long-living transform faults such as the Florianopolis Fracture Zone (FFZ) on the long-term topography evolution of the SAPCM's. A long-term landscape evolution model with process rates will be achieved by thermo-kinematic 3-D modeling (software code PECUBE2,3 and FastScape4). Testing model solutions obtained for a multidimensional parameter space against the real thermochronological and geomorphological data set, the most likely combinations of parameter rates, and values can be constrained. The data and models will allow separating the exogenous and endogenous forces and their process rates. References 1. Karl, M., Glasmacher, U.A., Kollenz, S., Franco-Magalhaes, A.O.B., Stockli, D.F., Hackspacher, P., 2013. Evolution of the South Atlantic passive continental margin in southern Brazil derived from zircon and apatite (U-Th-Sm)/He and fission-track data. Tectonophysics, Volume 604, Pages 224-244. 2. Braun, J., 2003. Pecube: A new finite element code to solve the 3D heat transport equation including the effects of a time-varying, finite amplitude surface topography. Computers and Geosciences, v.29, pp.787-794. 3. Braun, J., van der Beek, P., Valla, P., Robert, X., Herman, F., Goltzbacj, C., Pedersen, V., Perry, C., Simon-Labric, T., Prigent, C. 2012. Quantifying rates of landscape evolution and tectonic processes by thermochronology and numerical modeling of crustal heat transport using PECUBE. Tectonophysics, v.524-525, pp.1-28. 4. Braun, J. and Willett, S.D., 2013. A very efficient, O(n), implicit and parallel method to solve the basic stream power law equation governing fluvial incision and landscape evolution. Geomorphology, v.180-181, 170-179.

Evaluation of regional climate simulations for air quality modelling purposes

NASA Astrophysics Data System (ADS)

Menut, Laurent; Tripathi, Om P.; Colette, Augustin; Vautard, Robert; Flaounas, Emmanouil; Bessagnet, Bertrand

2013-05-01

In order to evaluate the future potential benefits of emission regulation on regional air quality, while taking into account the effects of climate change, off-line air quality projection simulations are driven using weather forcing taken from regional climate models. These regional models are themselves driven by simulations carried out using global climate models (GCM) and economical scenarios. Uncertainties and biases in climate models introduce an additional "climate modeling" source of uncertainty that is to be added to all other types of uncertainties in air quality modeling for policy evaluation. In this article we evaluate the changes in air quality-related weather variables induced by replacing reanalyses-forced by GCM-forced regional climate simulations. As an example we use GCM simulations carried out in the framework of the ERA-interim programme and of the CMIP5 project using the Institut Pierre-Simon Laplace climate model (IPSLcm), driving regional simulations performed in the framework of the EURO-CORDEX programme. In summer, we found compensating deficiencies acting on photochemistry: an overestimation by GCM-driven weather due to a positive bias in short-wave radiation, a negative bias in wind speed, too many stagnant episodes, and a negative temperature bias. In winter, air quality is mostly driven by dispersion, and we could not identify significant differences in either wind or planetary boundary layer height statistics between GCM-driven and reanalyses-driven regional simulations. However, precipitation appears largely overestimated in GCM-driven simulations, which could significantly affect the simulation of aerosol concentrations. The identification of these biases will help interpreting results of future air quality simulations using these data. Despite these, we conclude that the identified differences should not lead to major difficulties in using GCM-driven regional climate simulations for air quality projections.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2003-02-01

that intermittent androgen ablation therapy can be enhanced by finasteride , an inhibitor of T to DHT conversion, To test our hypothesis in animal...models, it is necessary to deliver exogenous T at physiologic levels and finasteride over a long period of time, We have worked out conditions to deliver T and finasteride in nude mice, which will allow us to test our hypothesis.

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302.

PubMed

Wojtkowiak, Jonathan W; Cornnell, Heather C; Matsumoto, Shingo; Saito, Keita; Takakusagi, Yoichi; Dutta, Prasanta; Kim, Munju; Zhang, Xiaomeng; Leos, Rafael; Bailey, Kate M; Martinez, Gary; Lloyd, Mark C; Weber, Craig; Mitchell, James B; Lynch, Ronald M; Baker, Amanda F; Gatenby, Robert A; Rejniak, Katarzyna A; Hart, Charles; Krishna, Murali C; Gillies, Robert J

2015-01-01

Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clinical HAPs activity could be improved. In this study, we sought to identify non-pharmacological methods to acutely exacerbate tumor hypoxia to increase TH-302 activity in pancreatic ductal adenocarcinoma (PDAC) tumor models. Three human PDAC cell lines with varying sensitivity to TH-302 (Hs766t > MiaPaCa-2 > SU.86.86) were used to establish PDAC xenograft models. PDAC cells were metabolically profiled in vitro and in vivo using the Seahorse XF system and hyperpolarized (13)C pyruvate MRI, respectively, in addition to quantitative immunohistochemistry. The effect of exogenous pyruvate on tumor oxygenation was determined using electroparamagnetic resonance (EPR) oxygen imaging. Hs766t and MiaPaCa-2 cells exhibited a glycolytic phenotype in comparison to TH-302 resistant line SU.86.86. Supporting this observation is a higher lactate/pyruvate ratio in Hs766t and MiaPaCa xenografts as observed during hyperpolarized pyruvate MRI studies in vivo. Coincidentally, response to exogenous pyruvate both in vitro (Seahorse oxygen consumption) and in vivo (EPR oxygen imaging) was greatest in Hs766t and MiaPaCa models, possibly due to a higher mitochondrial reserve capacity. Changes in oxygen consumption and in vivo hypoxic status to pyruvate were limited in the SU.86.86 model. Combination therapy of pyruvate plus TH-302 in vivo significantly decreased tumor growth and increased survival in the MiaPaCa model and improved survival in Hs766t tumors. Using metabolic profiling, functional imaging, and computational modeling, we show improved TH-302 activity by transiently increasing tumor hypoxia metabolically with exogenous pyruvate. Additionally, this work identified a set of biomarkers that may be used clinically to predict which tumors will be most responsive to pyruvate + TH-302 combination therapy. The results of this study support the concept that acute increases in tumor hypoxia can be beneficial for improving the clinical efficacy of HAPs and can positively impact the future treatment of PDAC and other cancers.

Data-driven Modelling for decision making under uncertainty

NASA Astrophysics Data System (ADS)

Angria S, Layla; Dwi Sari, Yunita; Zarlis, Muhammad; Tulus

2018-01-01

The rise of the issues with the uncertainty of decision making has become a very warm conversation in operation research. Many models have been presented, one of which is with data-driven modelling (DDM). The purpose of this paper is to extract and recognize patterns in data, and find the best model in decision-making problem under uncertainty by using data-driven modeling approach with linear programming, linear and nonlinear differential equation, bayesian approach. Model criteria tested to determine the smallest error, and it will be the best model that can be used.

Differences in clinical ocular outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix: a systematic review of published literature.

PubMed

Ramírez Soto, Max Carlos

2017-09-28

Sporotrichosis is an implantation mycosis caused by Sporothrix species prevalent worldwide, which occasionally can also result in intraocular infection presenting as an exogenous or endogenous infection (disseminated sporotrichosis). Knowledge in its clinical recognition and management is limited. To systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix . Case reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups. From 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration. Anterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas. Sporothrix infection should be included in the differential diagnosis for ocular inflammation, regardless of the presence or absence of autoimmune comorbidities and whether the patient resides in an endemic area or not. Ophthalmologists should consider intravitreal and systemic antifungal therapy for exogenous and endogenous endophthalmitis caused by Sporothrix . © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Exogenous reinfection of tuberculosis in a low-burden area.

PubMed

Schiroli, Consuelo; Carugati, Manuela; Zanini, Fabio; Bandera, Alessandra; Di Nardo Stuppino, Silvia; Monge, Elisa; Morosi, Manuela; Gori, Andrea; Matteelli, Alberto; Codecasa, Luigi; Franzetti, Fabio

2015-12-01

Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Exogenously applied spermidine alleviates photosynthetic inhibition under drought stress in maize (Zea mays L.) seedlings associated with changes in endogenous polyamines and phytohormones.

PubMed

Li, Lijie; Gu, Wanrong; Li, Jing; Li, Congfeng; Xie, Tenglong; Qu, Danyang; Meng, Yao; Li, Caifeng; Wei, Shi

2018-05-15

Drought stress (DS) is a major environmental factor limiting plant growth and crop productivity worldwide. It has been established that exogenous spermidine (Spd) stimulates plant tolerance to DS. The effects of exogenous Spd on plant growth, photosynthetic performance, and chloroplast ultrastructure as well as changes in endogenous polyamines (PAs) and phytohormones were investigate in DS-resistant (Xianyu 335) and DS-sensitive (Fenghe 1) maize seedlings under well-watered and DS treatments. Exogenous Spd alleviated the stress-induced reduction in growth, photosynthetic pigment content, photosynthesis rate (P n ) and photochemical quenching (q P ) parameters, including the maximum photochemistry efficiency of photosystem II (PSII) (F v /F m ), PSII operating efficiency (ФPSII), and qP coefficient. Exogenous Spd further enhanced stress-induced elevation in non-photochemical quenching (NPQ) and the de-epoxidation state of the xanthophyll cycle (DEPS). Microscopic analysis revealed that seedlings displayed a more ordered arrangement of chloroplast ultrastructure upon Spd application during DS. Exogenous Spd increased the endogenous PA concentrations in the stressed plants. Additionally, exogenous Spd increased indoleacetic acid (IAA), zeatin riboside (ZR) and gibberellin A 3 (GA 3 ) and decreased salicylic acid (SA) and jasmonate (JA) concentrations under DS. These results indicate that exogenous Spd can alleviate the growth inhibition and damage to the structure and function of the photosynthetic apparatus caused by DS and that this alleviation may be associated with changes in endogenous PAs and phytohormones. This study contributes to advances in the knowledge of Spd-induced drought tolerance. Copyright © 2018. Published by Elsevier Masson SAS.

Comparison of the performance of tracer kinetic model-driven registration for dynamic contrast enhanced MRI using different models of contrast enhancement.

PubMed

Buonaccorsi, Giovanni A; Roberts, Caleb; Cheung, Sue; Watson, Yvonne; O'Connor, James P B; Davies, Karen; Jackson, Alan; Jayson, Gordon C; Parker, Geoff J M

2006-09-01

The quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data is subject to model fitting errors caused by motion during the time-series data acquisition. However, the time-varying features that occur as a result of contrast enhancement can confound motion correction techniques based on conventional registration similarity measures. We have therefore developed a heuristic, locally controlled tracer kinetic model-driven registration procedure, in which the model accounts for contrast enhancement, and applied it to the registration of abdominal DCE-MRI data at high temporal resolution. Using severely motion-corrupted data sets that had been excluded from analysis in a clinical trial of an antiangiogenic agent, we compared the results obtained when using different models to drive the tracer kinetic model-driven registration with those obtained when using a conventional registration against the time series mean image volume. Using tracer kinetic model-driven registration, it was possible to improve model fitting by reducing the sum of squared errors but the improvement was only realized when using a model that adequately described the features of the time series data. The registration against the time series mean significantly distorted the time series data, as did tracer kinetic model-driven registration using a simpler model of contrast enhancement. When an appropriate model is used, tracer kinetic model-driven registration influences motion-corrupted model fit parameter estimates and provides significant improvements in localization in three-dimensional parameter maps. This has positive implications for the use of quantitative DCE-MRI for example in clinical trials of antiangiogenic or antivascular agents.

The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia.

PubMed

He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

2015-08-25

Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca(2+) and K(+) in root cells by increasing the activity of plasma membrane (PM) H(+)-ATPase and tonoplast H(+)-ATPase and H(+)-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber.

Diagnostic utility of dermatoscopy in hydroquinone-induced exogenous ochronosis.

PubMed

Mishra, Sunil N; Dhurat, Rachita S; Deshpande, Deepal J; Nayak, Chitra S

2013-04-01

  Hydroquinone is the preferred topical bleaching agent used in the treatment of melasma. The adverse effects of its chronic use are confetti-like depigmentation and exogenous ochronosis. Exogenous ochronosis manifests clinically with gray-brown or blue-black hyperpigmentation, as well as pinpoint hyperchromic caviar-like papules over the malar region. Dermatoscopic findings of ochronosis are unique and point towards a clue for its diagnosis.   Three cases of suspected hydroquinone-induced exogenous ochronosis while treating melasma were subjected to dermatoscopy and histopathology studies.   Dermatoscopy in the areas of caviar-like hyperpigmentation revealed accentuation of the normal pseudo-rete of the facial skin with amorphous densely-pigmented structures obliterating some follicular opening and multiple thin, short arciform structures. On histopathological examination, curved ochre-colored structures, 'banana-shaped' fibers, were seen in the dermis of all patients.   Exogenous ochronosis is difficult to treat. Dermatologists should be able to differentiate it from melasma and immediately discontinue hydroquinone. Exogenous ochronosis has characteristic features on dermatoscopy which may obviate the need for an invasive procedure of biopsy for its diagnosis. © 2012 The International Society of Dermatology.

CrossTalk. The Journal of Defense Software Engineering. Volume 23, Number 6, Nov/Dec 2010

DTIC Science & Technology

2010-11-01

Model of archi- tectural design. It guides developers to apply effort to their software architecture commensurate with the risks faced by...Driven Model is the promotion of risk to prominence. It is possible to apply the Risk-Driven Model to essentially any software development process...succeed without any planned architecture work, while many high-risk projects would fail without it . The Risk-Driven Model walks a middle path

A framework to analyze emissions implications of ...

EPA Pesticide Factsheets

Future year emissions depend highly on the evolution of the economy, technology and current and future regulatory drivers. A scenario framework was adopted to analyze various technology development pathways and societal change while considering existing regulations and future uncertainty in regulations and evaluate resulting emissions growth patterns. The framework integrates EPA’s energy systems model with an economic Input-Output (I/O) Life Cycle Assessment model. The EPAUS9r MARKAL database is assembled from a set of technologies to represent the U.S. energy system within MARKAL bottom-up technology rich energy modeling framework. The general state of the economy and consequent demands for goods and services from these sectors are taken exogenously in MARKAL. It is important to characterize exogenous inputs about the economy to appropriately represent the industrial sector outlook for each of the scenarios and case studies evaluated. An economic input-output (I/O) model of the US economy is constructed to link up with MARKAL. The I/O model enables user to change input requirements (e.g. energy intensity) for different sectors or the share of consumer income expended on a given good. This gives end-users a mechanism for modeling change in the two dimensions of technological progress and consumer preferences that define the future scenarios. The framework will then be extended to include environmental I/O framework to track life cycle emissions associated

The development of a non-linear autoregressive model with exogenous input (NARX) to model climate-water clarity relationships: reconstructing a historical water clarity index for the coastal waters of the southeastern USA

NASA Astrophysics Data System (ADS)

Lee, Cameron C.; Sheridan, Scott C.; Barnes, Brian B.; Hu, Chuanmin; Pirhalla, Douglas E.; Ransibrahmanakul, Varis; Shein, Karsten

2017-10-01

The coastal waters of the southeastern USA contain important protected habitats and natural resources that are vulnerable to climate variability and singular weather events. Water clarity, strongly affected by atmospheric events, is linked to substantial environmental impacts throughout the region. To assess this relationship over the long-term, this study uses an artificial neural network-based time series modeling technique known as non-linear autoregressive models with exogenous input (NARX models) to explore the relationship between climate and a water clarity index (KDI) in this area and to reconstruct this index over a 66-year period. Results show that synoptic-scale circulation patterns, weather types, and precipitation all play roles in impacting water clarity to varying degrees in each region of the larger domain. In particular, turbid water is associated with transitional weather and cyclonic circulation in much of the study region. Overall, NARX model performance also varies—regionally, seasonally and interannually—with wintertime estimates of KDI along the West Florida Shelf correlating to the actual KDI at r > 0.70. Periods of extreme (high) KDI in this area coincide with notable El Niño events. An upward trend in extreme KDI events from 1948 to 2013 is also present across much of the Florida Gulf coast.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

PubMed

Hilker, Frank M; Allen, Linda J S; Bokil, Vrushali A; Briggs, Cheryl J; Feng, Zhilan; Garrett, Karen A; Gross, Louis J; Hamelin, Frédéric M; Jeger, Michael J; Manore, Carrie A; Power, Alison G; Redinbaugh, Margaret G; Rúa, Megan A; Cunniffe, Nik J

2017-10-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Control of the NASA Langley 16-Foot Transonic Tunnel with the Self-Organizing Feature Map

NASA Technical Reports Server (NTRS)

Motter, Mark A.

1998-01-01

A predictive, multiple model control strategy is developed based on an ensemble of local linear models of the nonlinear system dynamics for a transonic wind tunnel. The local linear models are estimated directly from the weights of a Self Organizing Feature Map (SOFM). Local linear modeling of nonlinear autonomous systems with the SOFM is extended to a control framework where the modeled system is nonautonomous, driven by an exogenous input. This extension to a control framework is based on the consideration of a finite number of subregions in the control space. Multiple self organizing feature maps collectively model the global response of the wind tunnel to a finite set of representative prototype controls. These prototype controls partition the control space and incorporate experimental knowledge gained from decades of operation. Each SOFM models the combination of the tunnel with one of the representative controls, over the entire range of operation. The SOFM based linear models are used to predict the tunnel response to a larger family of control sequences which are clustered on the representative prototypes. The control sequence which corresponds to the prediction that best satisfies the requirements on the system output is applied as the external driving signal. Each SOFM provides a codebook representation of the tunnel dynamics corresponding to a prototype control. Different dynamic regimes are organized into topological neighborhoods where the adjacent entries in the codebook represent the minimization of a similarity metric which is the essence of the self organizing feature of the map. Thus, the SOFM is additionally employed to identify the local dynamical regime, and consequently implements a switching scheme than selects the best available model for the applied control. Experimental results of controlling the wind tunnel, with the proposed method, during operational runs where strict research requirements on the control of the Mach number were met, are presented. Comparison to similar runs under the same conditions with the tunnel controlled by either the existing controller or an expert operator indicate the superiority of the method.

Exogenous estrogen as mediator of racial differences in bioactive insulin-like growth factor-I levels among postmenopausal women.

PubMed

Jung, Su Yon; Vitolins, Mara Z; Paskett, Electra D; Chang, Shine

2015-04-01

The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Model-driven Service Engineering with SoaML

NASA Astrophysics Data System (ADS)

Elvesæter, Brian; Carrez, Cyril; Mohagheghi, Parastoo; Berre, Arne-Jørgen; Johnsen, Svein G.; Solberg, Arnor

This chapter presents a model-driven service engineering (MDSE) methodology that uses OMG MDA specifications such as BMM, BPMN and SoaML to identify and specify services within a service-oriented architecture. The methodology takes advantage of business modelling practices and provides a guide to service modelling with SoaML. The presentation is case-driven and illuminated using the telecommunication example. The chapter focuses in particular on the use of the SoaML modelling language as a means for expressing service specifications that are aligned with business models and can be realized in different platform technologies.

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

PubMed

Hu, Xiaolei; Chen, Fengling

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients

PubMed Central

Hu, Xiaolei

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. PMID:29233817

Event-driven simulation in SELMON: An overview of EDSE

NASA Technical Reports Server (NTRS)

Rouquette, Nicolas F.; Chien, Steve A.; Charest, Leonard, Jr.

1992-01-01

EDSE (event-driven simulation engine), a model-based event-driven simulator implemented for SELMON, a tool for sensor selection and anomaly detection in real-time monitoring is described. The simulator is used in conjunction with a causal model to predict future behavior of the model from observed data. The behavior of the causal model is interpreted as equivalent to the behavior of the physical system being modeled. An overview of the functionality of the simulator and the model-based event-driven simulation paradigm on which it is based is provided. Included are high-level descriptions of the following key properties: event consumption and event creation, iterative simulation, synchronization and filtering of monitoring data from the physical system. Finally, how EDSE stands with respect to the relevant open issues of discrete-event and model-based simulation is discussed.

Measurement of endogenous versus exogenous formaldehyde-induced DNA-protein crosslinks in animal tissues by stable isotope labeling and ultrasensitive mass spectrometry

PubMed Central

Lai, Yongquan; Yu, Rui; Hartwell, Hadley J.; Moeller, Benjamin C.; Bodnar, Wanda M.; Swenberg, James A.

2016-01-01

DNA-protein crosslinks (DPCs) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Due to their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally-specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([13CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous (13CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues, but were absent in tissues distant to the site of contact. This observation together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde, and may inform improved disease prevention and treatment strategies. PMID:26984759

A method for tracing exogenous DNA uptake in live spermatozoa and embryos.

PubMed

Mu, Y; Jiao, M; Zhao, Y; Lv, J; Wang, J; Hao, J; Zhang, X; Kong, Q; Liu, Z

2018-03-01

Sperm-mediated gene transfer(SMGT) is a simple method for producing transgenic animals. Due to the lack of repeatability in spermatozoa binding and internalization of exogenous DNA, the efficiency of SMGT is still low. Considering this point, the present work aims to develop a method for evaluating the spermatozoa capacity of binding exogenous DNA after co-incubation with DNA. The main approach is using a Cy5-labelled DNA to trace the exogenous DNA and assess the ability of spermatozoa to take up exogenous DNA. Using this technique, we found that the percentage of spermatozoa that are binding and uptaking DNA is higher at concentration of 10 μg/mL and 100 μg/mL than 5 μg/mL, 1 μg/mL and 0 μg/mL after incubation with Cy5-DNA for 30min at 37oC. After fertilization, the DNA fluorescence signal was also detected in zygotes in groups where spermatozoa were incubated with 10 μg/mL and 100 μg/mL of Cy5-DNA. These results showed a simple and convenient method to trace the exogenous DNA in spermatozoa and zygote when compared to conventional methods of labeling DNA during fertilization, resulting in a real-time observation of the exogenous DNA in spermatozoa and zygote. Copyright© by the Polish Academy of Sciences.

Visible propagation from invisible exogenous cueing.

PubMed

Lin, Zhicheng; Murray, Scott O

2013-09-20

Perception and performance is affected not just by what we see but also by what we do not see-inputs that escape our awareness. While conscious processing and unconscious processing have been assumed to be separate and independent, here we report the propagation of unconscious exogenous cueing as determined by conscious motion perception. In a paradigm combining masked exogenous cueing and apparent motion, we show that, when an onset cue was rendered invisible, the unconscious exogenous cueing effect traveled, manifesting at uncued locations (4° apart) in accordance with conscious perception of visual motion; the effect diminished when the cue-to-target distance was 8° apart. In contrast, conscious exogenous cueing manifested in both distances. Further evidence reveals that the unconscious and conscious nonretinotopic effects could not be explained by an attentional gradient, nor by bottom-up, energy-based motion mechanisms, but rather they were subserved by top-down, tracking-based motion mechanisms. We thus term these effects mobile cueing. Taken together, unconscious mobile cueing effects (a) demonstrate a previously unknown degree of flexibility of unconscious exogenous attention; (b) embody a simultaneous dissociation and association of attention and consciousness, in which exogenous attention can occur without cue awareness ("dissociation"), yet at the same time its effect is contingent on conscious motion tracking ("association"); and (c) underscore the interaction of conscious and unconscious processing, providing evidence for an unconscious effect that is not automatic but controlled.

Endogenous versus exogenous shocks in systems with memory

NASA Astrophysics Data System (ADS)

Sornette, D.; Helmstetter, A.

2003-02-01

Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

Regularized Generalized Structured Component Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun

2009-01-01

Generalized structured component analysis (GSCA) has been proposed as a component-based approach to structural equation modeling. In practice, GSCA may suffer from multi-collinearity, i.e., high correlations among exogenous variables. GSCA has yet no remedy for this problem. Thus, a regularized extension of GSCA is proposed that integrates a ridge…

a Latent Variable Path Analysis Model of Secondary Physics Enrollments in New York State.

NASA Astrophysics Data System (ADS)

Sobolewski, Stanley John

The Percentage of Enrollment in Physics (PEP) at the secondary level nationally has been approximately 20% for the past few decades. For a more scientifically literate citizenry as well as specialists to continue scientific research and development, it is desirable that more students enroll in physics. Some of the predictor variables for physics enrollment and physics achievement that have been identified previously includes a community's socioeconomic status, the availability of physics, the sex of the student, the curriculum, as well as teacher and student data. This study isolated and identified predictor variables for PEP of secondary schools in New York. Data gathered by the State Education Department for the 1990-1991 school year was used. The source of this data included surveys completed by teachers and administrators on student characteristics and school facilities. A data analysis similar to that done by Bryant (1974) was conducted to determine if the relationships between a set of predictor variables related to physics enrollment had changed in the past 20 years. Variables which were isolated included: community, facilities, teacher experience, number of type of science courses, school size and school science facilities. When these variables were isolated, latent variable path diagrams were proposed and verified by the Linear Structural Relations computer modeling program (LISREL). These diagrams differed from those developed by Bryant in that there were more manifest variables used which included achievement scores in the form of Regents exam results. Two criterion variables were used, percentage of students enrolled in physics (PEP) and percent of students enrolled passing the Regents physics exam (PPP). The first model treated school and community level variables as exogenous while the second model treated only the community level variables as exogenous. The goodness of fit indices for the models was 0.77 for the first model and 0.83 for the second model. No dramatic differences were found between the relationship of predictor variables to physics enrollment in 1972 and 1991. New models indicated that smaller school size, enrollment in previous science and math courses and other school variables were more related to high enrollment rather than achievement. Exogenous variables such as community size were related to achievement. It was shown that achievement and enrollment were related to a different set of predictor variables.

Lightweight approach to model traceability in a CASE tool

NASA Astrophysics Data System (ADS)

Vileiniskis, Tomas; Skersys, Tomas; Pavalkis, Saulius; Butleris, Rimantas; Butkiene, Rita

2017-07-01

A term "model-driven" is not at all a new buzzword within the ranks of system development community. Nevertheless, the ever increasing complexity of model-driven approaches keeps fueling all kinds of discussions around this paradigm and pushes researchers forward to research and develop new and more effective ways to system development. With the increasing complexity, model traceability, and model management as a whole, becomes indispensable activities of model-driven system development process. The main goal of this paper is to present a conceptual design and implementation of a practical lightweight approach to model traceability in a CASE tool.

Population continuity, demic diffusion and Neolithic origins in central-southern Germany: the evidence from body proportions.

PubMed

Gallagher, A; Gunther, M M; Bruchhaus, H

2009-01-01

The transition to agro-pastoralism in central Europe has been framed within a dichotomy of "regional continuity" versus exogenous "demic diffusion". While substantial genetic support exists for a model of demographic diffusion from an ancestral source in the Near East, archaeological data furnish weak support for the "wave of advance" model. Nevertheless, archaeological evidence attests the widespread introduction of an exogenous "package" comprising ceramics, cereals, pulses and domesticated animals to central Europe at 5600calBCE. Body proportions are under strong climatic selection and evince remarkable stability within regional lineages. As such, they offer a viable and robust alternative to cranio-facial data in assessing hypothesised continuity and replacement with the transition to agro-pastoralism in central Europe. Humero-clavicular, brachial and crural indices in a large sample (n=75) of Linienbandkeramik (LBK), Late Neolithic and Early Bronze Age specimens from the middle Elbe-Saale-Werra valley (MESV) were compared with Eurasian and African terminal Pleistocene, European Mesolithic and geographically disparate recent human specimens. Mesolithic Europeans display considerable variation in humero-clavicular and brachial indices yet none approach the extreme "hyper-polar" morphology of LBK humans from the MESV. In contrast, Late Neolithic and Early Bronze Age peoples display elongated brachial and crural indices reminiscent of terminal Pleistocene and "tropically adapted" recent humans. These marked morphological changes likely reflect exogenous immigration during the terminal Fourth millennium cal BC. Population expansion and diffusion is a function of increased mobility and settlement dispersal concomitant with significant technological and subsistence changes in later Neolithic societies during the late fourth millennium cal BCE.

Lower extremity EMG-driven modeling of walking with automated adjustment of musculoskeletal geometry

PubMed Central

Meyer, Andrew J.; Patten, Carolynn

2017-01-01

Neuromusculoskeletal disorders affecting walking ability are often difficult to manage, in part due to limited understanding of how a patient’s lower extremity muscle excitations contribute to the patient’s lower extremity joint moments. To assist in the study of these disorders, researchers have developed electromyography (EMG) driven neuromusculoskeletal models utilizing scaled generic musculoskeletal geometry. While these models can predict individual muscle contributions to lower extremity joint moments during walking, the accuracy of the predictions can be hindered by errors in the scaled geometry. This study presents a novel EMG-driven modeling method that automatically adjusts surrogate representations of the patient’s musculoskeletal geometry to improve prediction of lower extremity joint moments during walking. In addition to commonly adjusted neuromusculoskeletal model parameters, the proposed method adjusts model parameters defining muscle-tendon lengths, velocities, and moment arms. We evaluated our EMG-driven modeling method using data collected from a high-functioning hemiparetic subject walking on an instrumented treadmill at speeds ranging from 0.4 to 0.8 m/s. EMG-driven model parameter values were calibrated to match inverse dynamic moments for five degrees of freedom in each leg while keeping musculoskeletal geometry close to that of an initial scaled musculoskeletal model. We found that our EMG-driven modeling method incorporating automated adjustment of musculoskeletal geometry predicted net joint moments during walking more accurately than did the same method without geometric adjustments. Geometric adjustments improved moment prediction errors by 25% on average and up to 52%, with the largest improvements occurring at the hip. Predicted adjustments to musculoskeletal geometry were comparable to errors reported in the literature between scaled generic geometric models and measurements made from imaging data. Our results demonstrate that with appropriate experimental data, joint moment predictions for walking generated by an EMG-driven model can be improved significantly when automated adjustment of musculoskeletal geometry is included in the model calibration process. PMID:28700708

Large signal-to-noise ratio quantification in MLE for ARARMAX models

NASA Astrophysics Data System (ADS)

Zou, Yiqun; Tang, Xiafei

2014-06-01

It has been shown that closed-loop linear system identification by indirect method can be generally transferred to open-loop ARARMAX (AutoRegressive AutoRegressive Moving Average with eXogenous input) estimation. For such models, the gradient-related optimisation with large enough signal-to-noise ratio (SNR) can avoid the potential local convergence in maximum likelihood estimation. To ease the application of this condition, the threshold SNR needs to be quantified. In this paper, we build the amplitude coefficient which is an equivalence to the SNR and prove the finiteness of the threshold amplitude coefficient within the stability region. The quantification of threshold is achieved by the minimisation of an elaborately designed multi-variable cost function which unifies all the restrictions on the amplitude coefficient. The corresponding algorithm based on two sets of physically realisable system input-output data details the minimisation and also points out how to use the gradient-related method to estimate ARARMAX parameters when local minimum is present as the SNR is small. Then, the algorithm is tested on a theoretical AutoRegressive Moving Average with eXogenous input model for the derivation of the threshold and a gas turbine engine real system for model identification, respectively. Finally, the graphical validation of threshold on a two-dimensional plot is discussed.

Flow cytometric sex sorting affects CD4 membrane distribution and binding of exogenous DNA on bovine sperm cells.

PubMed

Domingues, William Borges; da Silveira, Tony Leandro Rezende; Komninou, Eliza Rossi; Monte, Leonardo Garcia; Remião, Mariana Härter; Dellagostin, Odir Antônio; Corcini, Carine Dahl; Varela Junior, Antônio Sergio; Seixas, Fabiana Kömmling; Collares, Tiago; Campos, Vinicius Farias

2017-08-01

Bovine sex-sorted sperm have been commercialized and successfully used for the production of transgenic embryos of the desired sex through the sperm-mediated gene transfer (SMGT) technique. However, sex-sorted sperm show a reduced ability to internalize exogenous DNA. The interaction between sperm cells and the exogenous DNA has been reported in other species to be a CD4-like molecule-dependent process. The flow cytometry-based sex-sorting process subjects the spermatozoa to different stresses causing changes in the cell membrane. The aim of this study was to elucidate the relationship between the redistribution of CD4-like molecules and binding of exogenous DNA to sex-sorted bovine sperm. In the first set of experiments, the membrane phospholipid disorder and the redistribution of the CD4 were evaluated. The second set of experiments was conducted to investigate the effect of CD4 redistribution on the mechanism of binding of exogenous DNA to sperm cells and the efficiency of lipofection in sex-sorted bovine sperm. Sex-sorting procedure increased the membrane phospholipid disorder and induced the redistribution of CD4-like molecules. Both X-sorted and Y-sorted sperm had decreased DNA bound to membrane in comparison with the unsorted sperm; however, the binding of the exogenous DNA was significantly increased with the addition of liposomes. Moreover, we demonstrated that the number of sperm-bound exogenous DNA was decreased when these cells were preincubated with anti-bovine CD4 monoclonal antibody, supporting our hypothesis that CD4-like molecules indeed play a crucial role in the process of exogenous DNA/bovine sperm cells interaction.

Principal Dynamic Mode Analysis of the Hodgkin–Huxley Equations

PubMed Central

Eikenberry, Steffen E.; Marmarelis, Vasilis Z.

2015-01-01

We develop an autoregressive model framework based on the concept of Principal Dynamic Modes (PDMs) for the process of action potential (AP) generation in the excitable neuronal membrane described by the Hodgkin–Huxley (H–H) equations. The model's exogenous input is injected current, and whenever the membrane potential output exceeds a specified threshold, it is fed back as a second input. The PDMs are estimated from the previously developed Nonlinear Autoregressive Volterra (NARV) model, and represent an efficient functional basis for Volterra kernel expansion. The PDM-based model admits a modular representation, consisting of the forward and feedback PDM bases as linear filterbanks for the exogenous and autoregressive inputs, respectively, whose outputs are then fed to a static nonlinearity composed of polynomials operating on the PDM outputs and cross-terms of pair-products of PDM outputs. A two-step procedure for model reduction is performed: first, influential subsets of the forward and feedback PDM bases are identified and selected as the reduced PDM bases. Second, the terms of the static nonlinearity are pruned. The first step reduces model complexity from a total of 65 coefficients to 27, while the second further reduces the model coefficients to only eight. It is demonstrated that the performance cost of model reduction in terms of out-of-sample prediction accuracy is minimal. Unlike the full model, the eight coefficient pruned model can be easily visualized to reveal the essential system components, and thus the data-derived PDM model can yield insight into the underlying system structure and function. PMID:25630480

The effects of exogenous surfactant treatment in a murine model of two-hit lung injury.

PubMed

Zambelli, Vanessa; Bellani, Giacomo; Amigoni, Maria; Grassi, Alice; Scanziani, Margherita; Farina, Francesca; Latini, Roberto; Pesenti, Antonio

2015-02-01

Because pulmonary endogenous surfactant is altered during acute respiratory distress syndrome, surfactant replacement may improve clinical outcomes. However, trials of surfactant use have had mixed results. We designed this animal model of unilateral (right) lung injury to explore the effect of exogenous surfactant administered to the injured lung on inflammation in the injured and noninjured lung. Mice underwent hydrochloric acid instillation (1.5 mL/kg) into the right bronchus and prolonged (7 hours) mechanical ventilation (25 mL/kg). After 3 hours, mice were treated with 1 mL/kg exogenous surfactant (Curosurf®) (surf group) or sterile saline (NaCl 0.9%) (vehicle group) in the injured (right) lung or did not receive any treatment (hydrochloric acid, ventilator-induced lung injury). Gas exchange, lung compliance, and bronchoalveolar inflammation (cells, albumin, and cytokines) were evaluated. After a significant analysis of variance (ANOVA) test, Tukey post hoc test was used for statistical analysis. At least 8 to 10 mice in each group were analyzed for each evaluated variable. Surfactant treatment significantly increased both the arterial oxygen tension to fraction of inspired oxygen ratio and respiratory system static compliance (P = 0.027 and P = 0.007, respectively, for surf group versus vehicle). Surfactant therapy increased indices of inflammation in the acid-injured lung compared with vehicle: inflammatory cells (685 [602-773] and 216 [125-305] × 1000/mL, respectively; P < 0.001) and albumin in bronchoalveolar lavage (BAL) (1442 ± 588 and 743 ± 647 μg/mL, respectively; P = 0.027). These differences were not found (P = 0.96 and P = 0.54) in the contralateral (uninjured) lung (inflammatory cells 131 [78-195] and 119 [87-149] × 1000/mL and albumin 135 ± 100 and 173 ± 115 μg/mL). Exogenous surfactant administration to an acid-injured right lung improved gas exchange and whole respiratory system compliance. However, markers of inflammation increased in the right (injured) lung, although this result was not found in the left (uninjured) lung. These data suggest that the mechanism by which surfactant improves lung function may involve both uninjured and injured alveoli.

Exogenous and endogenous attention during perceptual learning differentially affect post-training target thresholds

PubMed Central

Mukai, Ikuko; Bahadur, Kandy; Kesavabhotla, Kartik; Ungerleider, Leslie G.

2012-01-01

There is conflicting evidence in the literature regarding the role played by attention in perceptual learning. To further examine this issue, we independently manipulated exogenous and endogenous attention and measured the rate of perceptual learning of oriented Gabor patches presented in different quadrants of the visual field. In this way, we could track learning at attended, divided-attended, and unattended locations. We also measured contrast thresholds of the Gabor patches before and after training. Our results showed that, for both exogenous and endogenous attention, accuracy in performing the orientation discrimination improved to a greater extent at attended than at unattended locations. Importantly, however, only exogenous attention resulted in improved contrast thresholds. These findings suggest that both exogenous and endogenous attention facilitate perceptual learning, but that these two types of attention may be mediated by different neural mechanisms. PMID:21282340

Alleviation of cadmium toxicity to Cole (Brassica campestris L. Cruciferae) by exogenous glutathione

NASA Astrophysics Data System (ADS)

Wang, Jun; Huang, Bin; Chen, Xin; Shi, Yi

2017-04-01

In this study, we determined the influence of exogenous GSH on cadmium toxicity to cole. GSH addition had beneficial effect on plant development and growth, especially on aboveground biomass and root length. Despite that exogenous GSH insignificantly promoted Cd uptake by the plant, it could decrease of Cd root-to-shoot transport and ameliorate Cd toxicity to the plant. At 6 mg Cd kg-1 soil, GSH addition well countered the Cd-induced significant reduction in CAT activity, but only insignificantly decreased MDA content, suggesting exogenous GSH might indirectly protect plant against oxidative stress via regulating antioxidative enzyme activities. However, at 12 mg Cd kg-1 soil, GSH application insignificantly increased the antioxidant activities but significantly decreased MDA content, indicating external GSH could directly participate in removing radical oxygen species. The results suggest exogenous GSH may have the potential of decreasing Cd accumulation in the edible parts of cultivars and alleviating Cd toxicity.

Transport of Ice on the Surface of Iapetus

NASA Astrophysics Data System (ADS)

Galuba, Götz G.

2014-11-01

The global black-and-white dichotomy as well as the dark floors and rims of equatorial craters on the Saturnian moon Iapetus can be explained by ice migration driven by a thermal feedback [1]. All icy moons in the Jovian and Saturnian systems are - with the exception of Titan - airless bodies. Yet it is unique, how these two types of surface features on Iapetus look. A physical model of the processes of absorption, sublimation and deposition was developed and a computational model that simulates ice migration of volatiles under these circumstances derived. The model tessellates the surfaces of an airless body into triangles of equal size that can each have different surface properties. These properties evolve while the model simulates a long-term development. A rate network of net migration is calculated from sublimation and redeposition under the assumptions ofa. a slowly rotating bodyb. undisturbed ballistic molecular trajectoriesc. isotropic emissiond. Maxwellian speed distributione. high sticking coefficients of the surfaces.The assumptions (b.) to (e.) are equally valid for all bigger outer solar system icy moons (except Titan). The very first assumption however is not equally valid throughout the moons of the outer solar system. Callisto being in many regards similar to Iapetus still has a five times higher rotation rate. So global effects depending on slow rotation are more profound on Iapetus. The computer model is complemented by a model for local ice migration from craters.First results show, that the global timescale of albedo change in our model is of the same order of magnitude as in the supporting material to [1] with a tendency towards slightly faster 2 Gyr instead of ~2.4 Gyr) darkening compared to the "Model B". The time rate of local crater darkening rates lies between the global darkening rate and rate of the opposing brightening effect as estimated in [2] to (τ between 10 and 100 MYr).[1] Formation of Iapetus’ Extreme Albedo Dichotomy by Exogenically Triggered Thermal Ice Migration, John R. Spencer , Tilmann Denk, Science 22, Vol. 327, January 2010.[2] Iapetus: Unique Surface Properties and a Global Color Dichotomy from Cassini Imaging T. Denk et al., Science 22, Vol. 327, January 2010.

Key variables influencing patterns of lava dome growth and collapse

NASA Astrophysics Data System (ADS)

Husain, T.; Elsworth, D.; Voight, B.; Mattioli, G. S.; Jansma, P. E.

2013-12-01

Lava domes are conical structures that grow by the infusion of viscous silicic or intermediate composition magma from a central volcanic conduit. Dome growth can be characterized by repeated cycles of growth punctuated by collapse, as the structure becomes oversized for its composite strength. Within these cycles, deformation ranges from slow long term deformation to sudden deep-seated collapses. Collapses may range from small raveling failures to voluminous and fast-moving pyroclastic flows with rapid and long-downslope-reach from the edifice. Infusion rate and magma rheology together with crystallization temperature and volatile content govern the spatial distribution of strength in the structure. Solidification, driven by degassing-induced crystallization of magma leads to the formation of a continuously evolving frictional talus as a hard outer shell. This shell encapsulates the cohesion-dominated soft ductile core. Here we explore the mechanics of lava dome growth and failure using a two-dimensional particle-dynamics model. This meshless model follows the natural evolution of a brittle carapace formed by loss of volatiles and rheological stiffening and avoids difficulties of hour-glassing and mesh-entangelment typical in meshed models. We test the fidelity of the model against existing experimental and observational models of lava dome growth. The particle-dynamics model follows the natural development of dome growth and collapse which is infeasible using simple analytical models. The model provides insight into the triggers that lead to the transition in collapse mechasnism from shallow flank collapse to deep seated sector collapse. Increase in material stiffness due to decrease in infusion rate results in the transition of growth pattern from endogenous to exogenous. The material stiffness and strength are strongly controlled by the magma infusion rate. Increase in infusion rate decreases the time available for degassing induced crystallization leading to a transition in the growth pattern, while a decrease in infusion rate results in larger crystals causing the material to stiffen leading to formation of spines. Material stiffness controls the growth direction of the viscous plug in the lava dome interior. Material strength and stiffness controled by rate of infusion influence lava dome growth more significantly than coefficient of frictional of the talus.

A modeling approach to estimate the solar disinfection of viral indicator organisms in waste stabilization ponds and surface waters.

PubMed

Kohn, Tamar; Mattle, Michael J; Minella, Marco; Vione, Davide

2016-01-01

Sunlight is known to be a pertinent factor governing the infectivity of waterborne viruses in the environment. Sunlight inactivates viruses via endogenous inactivation (promoted by absorption of solar light in the UVB range by the virus) and exogenous processes (promoted by adsorption of sunlight by external chromophores, which subsequently generate inactivating reactive species). The extent of inactivation is still difficult to predict, as it depends on multiple parameters including virus characteristics, solution composition, season and geographical location. In this work, we adapted a model typically used to estimate the photodegradation of organic pollutants, APEX, to explore the fate of two commonly used surrogates of human viruses (coliphages MS2 and ϕX174) in waste stabilization pond and natural surface water. Based on experimental data obtained in previous work, we modeled virus inactivation as a function of water depth and composition, as well as season and latitude, and we apportioned the contributions of the different inactivation processes to total inactivation. Model results showed that ϕX174 is inactivated more readily than MS2, except at latitudes >60°. ϕX174 inactivation varies greatly with both season (20-fold) and latitude (10-fold between 0 and 60°), and is dominated by endogenous inactivation under all solution conditions considered. In contrast, exogenous processes contribute significantly to MS2 inactivation. Because exogenous inactivation can be promoted by longer wavelengths, which are less affected by changes in season and latitude, MS2 exhibits smaller fluctuations in inactivation throughout the year (10-fold) and across the globe (3-fold between 0 and 60°) compared to ϕX174. While a full model validation is currently not possible due to the lack of sufficient field data, our estimated inactivation rates corresponded well to those reported in field studies. Overall, this study constitutes a step toward estimating microbial water quality as a function of spatio-temporal information and easy-to-determine solution parameters. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Model-Driven Development Method for Management Information Systems

NASA Astrophysics Data System (ADS)

Mizuno, Tomoki; Matsumoto, Keinosuke; Mori, Naoki

Traditionally, a Management Information System (MIS) has been developed without using formal methods. By the informal methods, the MIS is developed on its lifecycle without having any models. It causes many problems such as lack of the reliability of system design specifications. In order to overcome these problems, a model theory approach was proposed. The approach is based on an idea that a system can be modeled by automata and set theory. However, it is very difficult to generate automata of the system to be developed right from the start. On the other hand, there is a model-driven development method that can flexibly correspond to changes of business logics or implementing technologies. In the model-driven development, a system is modeled using a modeling language such as UML. This paper proposes a new development method for management information systems applying the model-driven development method to a component of the model theory approach. The experiment has shown that a reduced amount of efforts is more than 30% of all the efforts.

Surface tension driven flow in glass melts and model fluids

NASA Technical Reports Server (NTRS)

Mcneil, T. J.; Cole, R.; Subramanian, R. S.

1982-01-01

Surface tension driven flow has been investigated analytically and experimentally using an apparatus where a free column of molten glass or model fluids was supported at its top and bottom faces by solid surfaces. The glass used in the experiments was sodium diborate, and the model fluids were silicone oils. In both the model fluid and glass melt experiments, conclusive evidence was obtained to prove that the observed flow was driven primarily by surface tension forces. The experimental observations are in qualitative agreement with predictions from the theoretical model.

Simulating large-scale pedestrian movement using CA and event driven model: Methodology and case study

NASA Astrophysics Data System (ADS)

Li, Jun; Fu, Siyao; He, Haibo; Jia, Hongfei; Li, Yanzhong; Guo, Yi

2015-11-01

Large-scale regional evacuation is an important part of national security emergency response plan. Large commercial shopping area, as the typical service system, its emergency evacuation is one of the hot research topics. A systematic methodology based on Cellular Automata with the Dynamic Floor Field and event driven model has been proposed, and the methodology has been examined within context of a case study involving the evacuation within a commercial shopping mall. Pedestrians walking is based on Cellular Automata and event driven model. In this paper, the event driven model is adopted to simulate the pedestrian movement patterns, the simulation process is divided into normal situation and emergency evacuation. The model is composed of four layers: environment layer, customer layer, clerk layer and trajectory layer. For the simulation of movement route of pedestrians, the model takes into account purchase intention of customers and density of pedestrians. Based on evacuation model of Cellular Automata with Dynamic Floor Field and event driven model, we can reflect behavior characteristics of customers and clerks at the situations of normal and emergency evacuation. The distribution of individual evacuation time as a function of initial positions and the dynamics of the evacuation process is studied. Our results indicate that the evacuation model using the combination of Cellular Automata with Dynamic Floor Field and event driven scheduling can be used to simulate the evacuation of pedestrian flows in indoor areas with complicated surroundings and to investigate the layout of shopping mall.

Nucleic-acid-programmed Ag-nanoclusters as a generic platform for visualization of latent fingerprints and exogenous substances.

PubMed

Ran, Xiang; Wang, Zhenzhen; Zhang, Zhijun; Pu, Fang; Ren, Jinsong; Qu, Xiaogang

2016-01-11

We display a nucleic acid controlled AgNC platform for latent fingerprint visualization. The versatile emission of aptamer-modified AgNCs was regulated by the nearby DNA regions. Multi-color images for simultaneous visualization of fingerprints and exogenous components were successfully obtained. A quantitative detection strategy for exogenous substances in fingerprints was also established.

Exogenous spatial attention influences figure-ground assignment.

PubMed

Vecera, Shaun P; Flevaris, Anastasia V; Filapek, Joseph C

2004-01-01

In a hierarchical stage account of vision, figure-ground assignment is thought to be completed before the operation of focal spatial attention. Results of previous studies have supported this account by showing that unpredictive, exogenous spatial precues do not influence figure-ground assignment, although voluntary attention can influence figure-ground assignment. However, in these studies, attention was not summoned directly to a region in a figure-ground display. In three experiments, we addressed the relationship between figure-ground assignment and visuospatial attention. In Experiment 1, we replicated the finding that exogenous precues do not influence figure-ground assignment when they direct attention outside of a figure-ground stimulus. In Experiment 2, we demonstrated that exogenous attention can influence figure-ground assignment if it is directed to one of the regions in a figure-ground stimulus. In Experiment 3, we demonstrated that exogenous attention can influence figure-ground assignment in displays that contain a Gestalt figure-ground cue; this result suggests that figure-ground processes are not entirely completed prior to the operation of focal spatial attention. Exogenous spatial attention acts as a cue for figure-ground assignment and can affect the outcome of figure-ground processes.

The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia

PubMed Central

He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

2015-01-01

Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca2+ and K+ in root cells by increasing the activity of plasma membrane (PM) H+-ATPase and tonoplast H+-ATPase and H+-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber. PMID:26304855

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation.

PubMed

Imai, Jun; Otani, Mayu; Sakai, Takahiro; Hatta, Shinichi

2017-08-21

Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8 + T cells and memory CD8 + T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments. Until recently, characterizations of these endocytic compartments were limited because there were no specific molecular markers other than exogenous antigens. The method described here is a new vesicle isolation protocol, which allows for the purification of these endocytic compartments. Using this purified microsome, we reconstituted the ERAD-like transport, ubiquitination, and processing of the exogenous antigen in vitro, suggesting that the ubiquitin-proteasome system processed the exogenous antigen after export from this cellular compartment. This protocol can be further applied to other cell types to clarify the molecular mechanism of CP.

Considerations on the Use of Exogenous Fibrolytic Enzymes to Improve Forage Utilization

PubMed Central

Mendoza, Germán D.; Plata-Pérez, Fernando X.

2014-01-01

Digestion of cell wall fractions of forage in the rumen is incomplete due to the complex links which limit their degradation. It is therefore necessary to find options to optimize the use of forages in ruminant production systems. One alternative is to use exogenous enzymes. Exogenous fibrolytic enzymes are of fungal or bacterial origin and increase nutrient availability from the cell wall, which consists of three fractions in different proportions depending on the species of forage: digestible, potentially digestible, and indigestible. The response to addition of exogenous enzymes varies with the type of forage; many researchers infer that there are enzyme-forage interactions but fail to explain the biological mechanism. We hypothesize that the response is related to the proportion of the potentially digestible fraction. The exogenous enzyme activity depends on several factors but if the general conditions for enzyme action are available, the potentially digestible fraction may determine the magnitude of the response. Results of experiments with exogenous fibrolytic enzymes in domestic ruminants are inconsistent. This, coupled with their high cost, has made their use unattractive to farmers. Development of cheaper products exploring other microorganisms with fibrolytic activity, such as Fomes fomentarius or Cellulomonas flavigena, is required. PMID:25379525

An Exogenous Surfactant-Producing Bacillus subtilis Facilitates Indigenous Microbial Enhanced Oil Recovery

PubMed Central

Gao, Peike; Li, Guoqiang; Li, Yanshu; Li, Yan; Tian, Huimei; Wang, Yansen; Zhou, Jiefang; Ma, Ting

2016-01-01

This study used an exogenous lipopeptide-producing Bacillus subtilis to strengthen the indigenous microbial enhanced oil recovery (IMEOR) process in a water-flooded reservoir in the laboratory. The microbial processes and driving mechanisms were investigated in terms of the changes in oil properties and the interplay between the exogenous B. subtilis and indigenous microbial populations. The exogenous B. subtilis is a lipopeptide producer, with a short growth cycle and no oil-degrading ability. The B. subtilis facilitates the IMEOR process through improving oil emulsification and accelerating microbial growth with oil as the carbon source. Microbial community studies using quantitative PCR and high-throughput sequencing revealed that the exogenous B. subtilis could live together with reservoir microbial populations, and did not exert an observable inhibitory effect on the indigenous microbial populations during nutrient stimulation. Core-flooding tests showed that the combined exogenous and indigenous microbial flooding increased oil displacement efficiency by 16.71%, compared with 7.59% in the control where only nutrients were added, demonstrating the application potential in enhanced oil recovery in water-flooded reservoirs, in particular, for reservoirs where IMEOR treatment cannot effectively improve oil recovery. PMID:26925051

An Exogenous Surfactant-Producing Bacillus subtilis Facilitates Indigenous Microbial Enhanced Oil Recovery.

PubMed

Gao, Peike; Li, Guoqiang; Li, Yanshu; Li, Yan; Tian, Huimei; Wang, Yansen; Zhou, Jiefang; Ma, Ting

2016-01-01

This study used an exogenous lipopeptide-producing Bacillus subtilis to strengthen the indigenous microbial enhanced oil recovery (IMEOR) process in a water-flooded reservoir in the laboratory. The microbial processes and driving mechanisms were investigated in terms of the changes in oil properties and the interplay between the exogenous B. subtilis and indigenous microbial populations. The exogenous B. subtilis is a lipopeptide producer, with a short growth cycle and no oil-degrading ability. The B. subtilis facilitates the IMEOR process through improving oil emulsification and accelerating microbial growth with oil as the carbon source. Microbial community studies using quantitative PCR and high-throughput sequencing revealed that the exogenous B. subtilis could live together with reservoir microbial populations, and did not exert an observable inhibitory effect on the indigenous microbial populations during nutrient stimulation. Core-flooding tests showed that the combined exogenous and indigenous microbial flooding increased oil displacement efficiency by 16.71%, compared with 7.59% in the control where only nutrients were added, demonstrating the application potential in enhanced oil recovery in water-flooded reservoirs, in particular, for reservoirs where IMEOR treatment cannot effectively improve oil recovery.

Heterochronic developmental shift caused by thyroid hormone in larval sand dollars and its implications for phenotypic plasticity and the evolution of nonfeeding development.

PubMed

Heyland, Andreas; Hodin, Jason

2004-03-01

Recent work on a diverse array of echinoderm species has demonstrated, as is true in amphibians, that thyroid hormone (TH) accelerates development to metamorphosis. Interestingly, the feeding larvae of several species of sea urchins seem to obtain TH through their diet of planktonic algae (exogenous source), whereas nonfeeding larvae of the sand dollar Peronella japonica produce TH themselves (endogenous source). Here we examine the effects of TH (thyroxine) and a TH synthesis inhibitor (thiourea) on the development of Dendraster excentricus, a sand dollar with a feeding larva. We report reduced larval skeleton lengths and more rapid development of the juvenile rudiment in the exogenous TH treatments when compared to controls. Also, larvae treated with exogenous TH reached metamorphic competence faster at a significantly reduced juvenile size, representing the greatest reduction in juvenile size ever reported for an echinoid species with feeding larvae. These effects of TH on D. excentricus larval development are strikingly similar to the phenotypically plastic response of D. excentricus larvae reared under high food conditions. We hypothesize that exogenous (algae-derived) TH is the plasticity cue in echinoid larvae, and that the larvae use ingested TH levels as an indicator for larval nutrition, ultimately signaling the attainment of metamorphic competence. Furthermore, our experiments with the TH synthesis inhibitor thiourea indicate that D. excentricus larvae can produce some TH endogenously. Endogenous TH production might, therefore, be a shared feature among sand dollars, facilitating the evolution of nonfeeding larval development in that group. Mounting evidence on the effects of thyroid hormones in echinoderm development suggests life-history models need to incorporate metamorphic hormone effects and the evolution of metamorphic hormone production.

Fructose-1,6-Bisphospate does not preserve ATP in hypoxic-ischemic neonatal cerebrocortical slices

PubMed Central

Liu, Jia; Hirai, Kiyoshi; Litt, Lawrence

2008-01-01

Fructose-1,6-bisphosphate (FBP), an endogenous intracellular metabolite in glycolysis, was found in many preclinical studies to be neuroprotective during hypoxia-ischemia (HI) when administered exogenously. We looked for HI neuroprotection from FBP in a neonatal rat brain slice model, using 14.1 Tesla 1H /31P/13C NMR spectroscopy of perchloric acid slice extracts to ask: 1) if FBP preserves high energy phosphates during HI; and 2) if exogenous [1-13C]FBP enters cells and is glycolytically metabolized to [3-13C]lactate. We also asked: 3) if substantial superoxide production occurs during and after HI, thinking such might be treatable by exogenous FBP's antioxidant effects. Superfused P7 rat cerebrocortical slices (350μm) were treated with 2 mM FBP before and during 30 min of HI, and then given four hours of recovery with an FBP-free oxygenated superfusate. Slices were removed before HI, at the end of HI, and at 1 and 4 hours after HI. FBP did not improve high energy phosphate levels or change 1H metabolite profiles. Large increases in [3-13C]lactate were seen with 13C NMR, but the lactate fractional enrichment was always (1.1±0.5)%, implying that all of lactate's 13C was natural abundance 13C, that none was from metabolism of 13C-FBP. FBP had no effect on the fluorescence of ethidium produced from superoxide oxidation of hydroethidine. Compared to control slices, ethidium fluorescence was 25% higher during HI and 50% higher at the end of recovery. Exogenous FBP did not provide protection or enter glycolysis. Its use as an antioxidant might be worth studying at higher FBP concentrations. PMID:18725216

Exogenous transforming growth factor-β1 enhances smooth muscle differentiation in embryonic mouse jejunal explants.

PubMed

Coletta, Riccardo; Roberts, Neil A; Randles, Michael J; Morabito, Antonino; Woolf, Adrian S

2017-01-13

An ex vivo experimental strategy that replicates in vivo intestinal development would in theory provide an accessible setting with which to study normal and dysmorphic gut biology. The current authors recently described a system in which mouse embryonic jejunal segments were explanted onto semipermeable platforms and fed with chemically defined serum-free media. Over 3 days in organ culture, explants formed villi and they began to undergo spontaneous peristalsis. As defined in the current study, the wall of the explanted gut failed to form a robust longitudinal smooth muscle (SM) layer as it would do in vivo over the same time period. Given the role of transforming growth factor β1 (TGFβ1) in SM differentiation in other organs, it was hypothesized that exogenous TGFβ1 would enhance SM differentiation in these explants. In vivo, TGFβ receptors I and II were both detected in embryonic longitudinal jejunal SM cells and, in organ culture, exogenous TGFβ1 induced robust differentiation of longitudinal SM. Microarray profiling showed that TGFβ1 increased SM specific transcripts in a dose dependent manner. TGFβ1 proteins were detected in amniotic fluid at a time when the intestine was physiologically herniated. By analogy with the requirement for exogenous TGFβ1 for SM differentiation in organ culture, the TGFβ1 protein that was demonstrated to be present in the amniotic fluid may enhance intestinal development when it is physiologically herniated in early gestation. Future studies of embryonic intestinal cultures should include TGFβ1 in the defined media to produce a more faithful model of in vivo muscle differentiation. Copyright © 2017 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd. Copyright © 2017 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd.

Role of protein-glutathione contacts in defining glutaredoxin-3 [2Fe-2S] cluster chirality, ligand exchange and transfer chemistry.

PubMed

Sen, Sambuddha; Cowan, J A

2017-10-01

Monothiol glutaredoxins (Grx) serve as intermediate cluster carriers in iron-sulfur cluster trafficking. The [2Fe-2S]-bound holo forms of Grx proteins display cysteinyl coordination from exogenous glutathione (GSH), in addition to contact from protein-derived Cys. Herein, we report mechanistic studies that investigate the role of exogenous glutathione in defining cluster chirality, ligand exchange, and the cluster transfer chemistry of Saccharomyces cerevisiae Grx3. Systematic perturbations were introduced to the glutathione-binding site by substitution of conserved charged amino acids that form crucial electrostatic contacts with the glutathione molecule. Native Grx3 could also be reconstituted in the absence of glutathione, with either DTT, BME or free L-cysteine as the source of the exogenous Fe-S ligand contact, while retaining full functional reactivity. The delivery of the [2Fe-2S] cluster to Grx3 from cluster donor proteins such as Isa, Nfu, and a [2Fe-2S](GS) 4 complex, revealed that electrostatic contacts are of key importance for positioning the exogenous glutathione that in turn influences the chiral environment of the cluster. All Grx3 derivatives were reconstituted by standard chemical reconstitution protocols and found to transfer cluster to apo ferredoxin 1 (Fdx1) at rates comparable to native protein, even when using DTT, BME or free L-cysteine as a thiol source in place of GSH during reconstitution. Kinetic analysis of cluster transfer from holo derivatives to apo Fdx1 has led to a mechanistic model for cluster transfer chemistry of native holo Grx3, and identification of the likely rate-limiting step for the reaction.

Use and comparison of different internal ribosomal entry sites (IRES) in tricistronic retroviral vectors

PubMed Central

Douin, Victorine; Bornes, Stephanie; Creancier, Laurent; Rochaix, Philippe; Favre, Gilles; Prats, Anne-Catherine; Couderc, Bettina

2004-01-01

Background Polycistronic retroviral vectors that contain several therapeutic genes linked via internal ribosome entry sites (IRES), provide new and effective tools for the co-expression of exogenous cDNAs in clinical gene therapy protocols. For example, tricistronic retroviral vectors could be used to genetically modify antigen presenting cells, enabling them to express different co-stimulatory molecules known to enhance tumor cell immunogenicity. Results We have constructed and compared different retroviral vectors containing two co-stimulatory molecules (CD70, CD80) and selectable marker genes linked to different IRES sequences (IRES from EMCV, c-myc, FGF-2 and HTLV-1). The tricistronic recombinant amphotropic viruses containing the IRES from EMCV, FGF-2 or HTLV-1 were equally efficient in inducing the expression of an exogenous gene in the transduced murine or human cells, without displaying any cell type specificity. The simultaneous presence of several IRESes on the same mRNA, however, can induce the differential expression of the various cistrons. Here we show that the IRESes of HTLV-1 and EMCV interfere with the translation induced by other IRESes in mouse melanoma cells. The IRES from FGF-2 did however induce the expression of exogenous cDNA in human melanoma cells without any positive or negative regulation from the other IRESs present within the vectors. Tumor cells that were genetically modified with the tricistronic retroviral vectors, were able to induce an in vivo anti-tumor immune response in murine models. Conclusion Translation of the exogenous gene is directed by the IRES and its high level of expression not only depends on the type of cell that is transduced but also on the presence of other genetic elements within the vector. PMID:15279677

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

PubMed Central

Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.

2017-01-01

Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693

Elbow joint angle and elbow movement velocity estimation using NARX-multiple layer perceptron neural network model with surface EMG time domain parameters.

PubMed

Raj, Retheep; Sivanandan, K S

2017-01-01

Estimation of elbow dynamics has been the object of numerous investigations. In this work a solution is proposed for estimating elbow movement velocity and elbow joint angle from Surface Electromyography (SEMG) signals. Here the Surface Electromyography signals are acquired from the biceps brachii muscle of human hand. Two time-domain parameters, Integrated EMG (IEMG) and Zero Crossing (ZC), are extracted from the Surface Electromyography signal. The relationship between the time domain parameters, IEMG and ZC with elbow angular displacement and elbow angular velocity during extension and flexion of the elbow are studied. A multiple input-multiple output model is derived for identifying the kinematics of elbow. A Nonlinear Auto Regressive with eXogenous inputs (NARX) structure based multiple layer perceptron neural network (MLPNN) model is proposed for the estimation of elbow joint angle and elbow angular velocity. The proposed NARX MLPNN model is trained using Levenberg-marquardt based algorithm. The proposed model is estimating the elbow joint angle and elbow movement angular velocity with appreciable accuracy. The model is validated using regression coefficient value (R). The average regression coefficient value (R) obtained for elbow angular displacement prediction is 0.9641 and for the elbow anglular velocity prediction is 0.9347. The Nonlinear Auto Regressive with eXogenous inputs (NARX) structure based multiple layer perceptron neural networks (MLPNN) model can be used for the estimation of angular displacement and movement angular velocity of the elbow with good accuracy.

Dynamic modeling of neuronal responses in fMRI using cubature Kalman filtering.

PubMed

Havlicek, Martin; Friston, Karl J; Jan, Jiri; Brazdil, Milan; Calhoun, Vince D

2011-06-15

This paper presents a new approach to inverting (fitting) models of coupled dynamical systems based on state-of-the-art (cubature) Kalman filtering. Crucially, this inversion furnishes posterior estimates of both the hidden states and parameters of a system, including any unknown exogenous input. Because the underlying generative model is formulated in continuous time (with a discrete observation process) it can be applied to a wide variety of models specified with either ordinary or stochastic differential equations. These are an important class of models that are particularly appropriate for biological time-series, where the underlying system is specified in terms of kinetics or dynamics (i.e., dynamic causal models). We provide comparative evaluations with generalized Bayesian filtering (dynamic expectation maximization) and demonstrate marked improvements in accuracy and computational efficiency. We compare the schemes using a series of difficult (nonlinear) toy examples and conclude with a special focus on hemodynamic models of evoked brain responses in fMRI. Our scheme promises to provide a significant advance in characterizing the functional architectures of distributed neuronal systems, even in the absence of known exogenous (experimental) input; e.g., resting state fMRI studies and spontaneous fluctuations in electrophysiological studies. Importantly, unlike current Bayesian filters (e.g. DEM), our scheme provides estimates of time-varying parameters, which we will exploit in future work on the adaptation and enabling of connections in the brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlation analysis of air pollutant index levels and dengue cases across five different zones in Selangor, Malaysia.

PubMed

Thiruchelvam, Loshini; Dass, Sarat C; Zaki, Rafdzah; Yahya, Abqariyah; Asirvadam, Vijanth S

2018-05-07

This study investigated the potential relationship between dengue cases and air quality - as measured by the Air Pollution Index (API) for five zones in the state of Selangor, Malaysia. Dengue case patterns can be learned using prediction models based on feedback (lagged terms). However, the question whether air quality affects dengue cases is still not thoroughly investigated based on such feedback models. This work developed dengue prediction models using the autoregressive integrated moving average (ARIMA) and ARIMA with an exogeneous variable (ARIMAX) time series methodologies with API as the exogeneous variable. The Box Jenkins approach based on maximum likelihood was used for analysis as it gives effective model estimates and prediction. Three stages of model comparison were carried out for each zone: first with ARIMA models without API, then ARIMAX models with API data from the API station for that zone and finally, ARIMAX models with API data from the zone and spatially neighbouring zones. Bayesian Information Criterion (BIC) gives goodness-of-fit versus parsimony comparisons between all elicited models. Our study found that ARIMA models, with the lowest BIC value, outperformed the rest in all five zones. The BIC values for the zone of Kuala Selangor were -800.66, -796.22, and -790.5229, respectively, for ARIMA only, ARIMAX with single API component and ARIMAX with API components from its zone and spatially neighbouring zones. Therefore, we concluded that API levels, either temporally for each zone or spatio- temporally based on neighbouring zones, do not have a significant effect on dengue cases.

Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: Feasibility study on an agar phantom model.

PubMed

Blasco-Gimenez, Ramón; Lequerica, Juan L; Herrero, Maria; Hornero, Fernando; Berjano, Enrique J

2010-04-01

The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min(-1)). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 degrees C; (3) substantial errors (larger than 15 degrees C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 degrees C).

Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

PubMed Central

McFadden, David G.; Politi, Katerina; Bhutkar, Arjun; Chen, Frances K.; Song, Xiaoling; Pirun, Mono; Santiago, Philip M.; Kim-Kiselak, Caroline; Platt, James T.; Lee, Emily; Hodges, Emily; Rosebrock, Adam P.; Bronson, Roderick T.; Socci, Nicholas D.; Hannon, Gregory J.; Jacks, Tyler; Varmus, Harold

2016-01-01

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity. PMID:27702896

Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma.

PubMed

McFadden, David G; Politi, Katerina; Bhutkar, Arjun; Chen, Frances K; Song, Xiaoling; Pirun, Mono; Santiago, Philip M; Kim-Kiselak, Caroline; Platt, James T; Lee, Emily; Hodges, Emily; Rosebrock, Adam P; Bronson, Roderick T; Socci, Nicholas D; Hannon, Gregory J; Jacks, Tyler; Varmus, Harold

2016-10-18

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.

Investigations into the differential reactivity of endogenous and exogenous mercury species in coastal sediments.

PubMed

Bouchet, S; Rodriguez-Gonzalez, P; Bridou, R; Monperrus, M; Tessier, E; Anschutz, P; Guyoneaud, R; Amouroux, D

2013-03-01

Stable isotopic tracer methodologies now allow the evaluation of the reactivity of the endogenous (ambient) and exogenous (added) Hg to further predict the potential effect of Hg inputs in ecosystems. The differential reactivity of endogenous and exogenous Hg was compared in superficial sediments collected in a coastal lagoon (Arcachon Bay) and in an estuary (Adour River) from the Bay of Biscay (SW France). All Hg species (gaseous, aqueous, and solid fraction) and ancillary data were measured during time course slurry experiments under variable redox conditions. The average endogenous methylation yield was higher in the estuarine (1.2 %) than in the lagoonal sediment (0.5 %), although both methylation and demethylation rates were higher in the lagoonal sediment in relation with a higher sulfate-reducing activity. Demethylation was overall more consistent than methylation in both sediments. The endogenous and exogenous Hg behaviors were always correlated but the exogenous inorganic Hg (IHg) partitioning into water was 2.0-4.3 times higher than the endogenous one. Its methylation was just slightly higher (1.4) in the estuarine sediment while the difference in the lagoonal sediment was much larger (3.6). The relative endogenous and exogenous methylation yields were not correlated to IHg partitioning, demonstrating that the bioavailable species distributions were different for the two IHg pools. In both sediments, the exogenous IHg partitioning equaled the endogenous one within a week, while its higher methylation lasted for months. Such results provide an original assessment approach to compare coastal sediment response to Hg inputs.

Drought and exogenous abscisic acid alter hydrogen peroxide accumulation and differentially regulate the expression of two maize RD22-like genes.

PubMed

Phillips, Kyle; Ludidi, Ndiko

2017-08-18

Increased biosynthesis of abscisic acid (ABA) occurs in plants in response to water deficit, which is mediated by changes in the levels of reactive oxygen species such as H 2 O 2 . Water deficit and ABA induce expression of some RD22-like proteins. This study aimed to evaluate the effect of water deficit and exogenous ABA (50 µM ABA applied every 24 hours for a total of 72 hours) on H 2 O 2 content in Zea mays (maize) and to characterise genes encoding two putative maize RD22-like proteins (designated ZmRD22A and ZmRD22B). The expression profiles of the two putative maize RD22-like genes in response to water deficit and treatment with ABA were examined in leaves. In silico analyses showed that the maize RD22-like proteins share domain organisation with previously characterized RD22-like proteins. Both water deficit and exogenous ABA resulted in increased H 2 O 2 content in leaves but the increase was more pronounced in response to water deficit than to exogenous ABA. Lignin content was not affected by exogenous ABA, whereas it was decreased by water deficit. Expression of both RD22-like genes was up-regulated by drought but the ZmRD22A gene was not influenced by exogenous ABA, whereas ZmRD22B was highly responsive to exogenous ABA.

Measurement of Endogenous versus Exogenous Formaldehyde-Induced DNA-Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry.

PubMed

Lai, Yongquan; Yu, Rui; Hartwell, Hadley J; Moeller, Benjamin C; Bodnar, Wanda M; Swenberg, James A

2016-05-01

DNA-protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([(13)CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous ((13)CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues but were absent in tissues distant to the site of contact. This observation, together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined, suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for the persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde and may inform improved disease prevention and treatment strategies. Cancer Res; 76(9); 2652-61. ©2016 AACR. ©2016 American Association for Cancer Research.

Using Data-Driven Model-Brain Mappings to Constrain Formal Models of Cognition

PubMed Central

Borst, Jelmer P.; Nijboer, Menno; Taatgen, Niels A.; van Rijn, Hedderik; Anderson, John R.

2015-01-01

In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-based biases. In this paper we used model-based fMRI analysis to create a data-driven model-brain mapping for five modules of the ACT-R cognitive architecture. We then validated this mapping by applying it to two new datasets with associated models. The new mapping was at least as powerful as an existing mapping that was based on the literature, and indicated where the models were supported by the data and where they have to be improved. We conclude that data-driven model-brain mappings can provide strong constraints on cognitive models, and that model-based fMRI is a suitable way to create such mappings. PMID:25747601

Exogenous near-infrared fluorophores and their applications in cancer diagnosis: biological and clinical perspectives.

PubMed

Zhang, Hua; Uselman, Ryan R; Yee, Douglas

2011-05-01

Near-infrared fluorescent (NIRF) imaging is a rapidly growing research field which has the potential to be an important imaging modality in cancer diagnosis. Various exogenous NIR fluorophores have been developed for the technique, including small molecule fluorophores and nanoparticles. NIRF imaging has been used in animal models for the detection of cancer overthe last twenty years and has in recent years been used in human clinical trials. This article describes the types and characteristics of exogenous fluorophores available for in vivo fluorescent cancer imaging. The article also discusses the progression of NIRF cancer imaging over recent years and its future challenges, from both a biological and clinical perspective. in The review also looks at its application for lymph node mapping, tumor targeting and characterization, and tumor margin definition for surgical guidance. NIRF imaging is not in routine clinical cancer practice; yet, the authors predict that techniques using NIR fluorophores for tumor margin definition and lymph node mapping will enter clinical practice in the near future. The authors also anticipate that NIRF imaging research will lead to the development of flurophores with 'high brightness' that will overcome the limited penetration of this modality and be better suited for non invasive tumor targeting.

Genetic exchange between endogenous and exogenous LINE-1 repetitive elements in mouse cells.

PubMed Central

Belmaaza, A; Wallenburg, J C; Brouillette, S; Gusew, N; Chartrand, P

1990-01-01

The repetitive LINE (L1) elements of the mouse, which are present at about 10(5) copies per genome and share over 80% of sequence homology, were examined for their ability to undergo genetic exchange with exogenous L1 sequences. The exogenous L1 sequences, carried by a shuttle vector, consisted of an internal fragment from L1Md-A2, a previously described member of the L1 family of the mouse. Using an assay that does not require the reconstitution of a selectable marker we found that this vector, in either circular or linear form, acquired DNA sequences from endogenous L1 elements at a frequency of 10(-3) to 10(-4) per rescued vector. Physical analysis of the acquired L1 sequences revealed that distinct endogenous L1 elements acted as donors and that different subfamilies participated. These results demonstrate that L1 elements are readily capable of genetic exchange. Apart from gene conversion events, the acquisition of L1 sequences outside the region of homology suggested that a second mechanism was also involved in the genetic exchange. A model which accounts for this mechanism is presented and its potential implication on the rearrangement of L1 elements is discussed. Images PMID:1978749

Using fluorometry and ion-sensitive microelectrodes to study the functional expression of heterologously-expressed ion channels and transporters in Xenopus oocytes

PubMed Central

Musa-Aziz, Raif; Boron, Walter F.; Parker, Mark D.

2010-01-01

The Xenopus laevis oocyte is a model system for the electrophysiological study of exogenous ion transporters. Three main reasons make the oocyte suitable for this purpose: (a) it has a large cell size (~1 mm diameter), (b) it has an established capacity to produce—from microinjected mRNAs or cRNAs—exogenous ion transporters with close-to-physiological post-translational modifications and actions, and (c) its membranes contain endogenous ion-transport activities which are usually smaller in magnitude than the activities of exogenously-expressed ion transporters. The expression of ion-transporters as green-fluorescent-protein fusions allows the fluorometric assay of transporter yield in living oocytes. Monitoring of transporter-mediated movement of ions such as Cl−, H+ (and hence base equivalents like OH−1 and HCO3−), K+, and Na+ is achieved by positioning the tips of ion-sensitive microelectrodes inside the oocyte and/or at the surface of the oocyte plasma membrane. The use of ion-sensitive electrodes is critical for studying net ion-movements mediated by electroneutral transporters. The combined use of fluorometry and electrophysiology expedites transporter study by allowing measurement of transporter yield prior to electrophysiological study and correlation of relative transporter yield with transport rates. PMID:20051266

Hydrogen-driven asymmetric reduction of hydroxyacetone to (R)-1,2-propanediol by Ralstonia eutropha transformant expressing alcohol dehydrogenase from Kluyveromyces lactis.

PubMed

Oda, Takahiro; Oda, Koji; Yamamoto, Hiroaki; Matsuyama, Akinobu; Ishii, Masaharu; Igarashi, Yasuo; Nishihara, Hirofumi

2013-01-10

Conversion of industrial processes to more nature-friendly modes is a crucial subject for achieving sustainable development. Utilization of hydrogen-oxidation reactions by hydrogenase as a driving force of bioprocess reaction can be an environmentally ideal method because the reaction creates no pollutants. We expressed NAD-dependent alcohol dehydrogenase from Kluyveromyces lactis in a hydrogen-oxidizing bacterium: Ralstonia eutropha. This is the first report of hydrogen-driven in vivo coupling reaction of the alcohol dehydrogenase and indigenous soluble NAD-reducing hydrogenase. Asymmetric reduction of hydroxyacetone to (R)-1,2-propanediol, which is a commercial building block for antibacterial agents, was performed using the transformant as the microbial cell catalyst. The two enzymes coupled in vitro in vials without a marked decrease of reactivity during the 20 hr reaction because of the hydrogenase reaction, which generates no by-product that affects enzymes. Alcohol dehydrogenase was expressed functionally in R. eutropha in an activity level equivalent to that of indigenous NAD-reducing hydrogenase under the hydrogenase promoter. The hydrogen-driven in vivo coupling reaction proceeded only by the transformant cell without exogenous addition of a cofactor. The decrease of reaction velocity at higher concentration of hydroxyacetone was markedly reduced by application of an in vivo coupling system. Production of (R)-1,2-propanediol (99.8% e.e.) reached 67.7 g/l in 76 hr with almost a constant rate using a jar fermenter. The reaction velocity under 10% PH2 was almost equivalent to that under 100% hydrogen, indicating the availability of crude hydrogen gas from various sources. The in vivo coupling system enabled cell-recycling as catalysts. Asymmetric reduction of hydroxyacetone by a coupling reaction of the two enzymes continued in both in vitro and in vivo systems in the presence of hydrogen. The in vivo reaction system using R. eutropha transformant expressing heterologous alcohol dehydrogenase showed advantages for practical usage relative to the in vitro coupling system. The results suggest a hopeful perspective of the hydrogen-driven bioprocess as an environmentally outstanding method to achieve industrial green innovation. Hydrogen-oxidizing bacteria can be useful hosts for the development of hydrogen-driven microbial cell factories.

A new approach to modeling temperature-related mortality: Non-linear autoregressive models with exogenous input.

PubMed

Lee, Cameron C; Sheridan, Scott C

2018-07-01

Temperature-mortality relationships are nonlinear, time-lagged, and can vary depending on the time of year and geographic location, all of which limits the applicability of simple regression models in describing these associations. This research demonstrates the utility of an alternative method for modeling such complex relationships that has gained recent traction in other environmental fields: nonlinear autoregressive models with exogenous input (NARX models). All-cause mortality data and multiple temperature-based data sets were gathered from 41 different US cities, for the period 1975-2010, and subjected to ensemble NARX modeling. Models generally performed better in larger cities and during the winter season. Across the US, median absolute percentage errors were 10% (ranging from 4% to 15% in various cities), the average improvement in the r-squared over that of a simple persistence model was 17% (6-24%), and the hit rate for modeling spike days in mortality (>80th percentile) was 54% (34-71%). Mortality responded acutely to hot summer days, peaking at 0-2 days of lag before dropping precipitously, and there was an extended mortality response to cold winter days, peaking at 2-4 days of lag and dropping slowly and continuing for multiple weeks. Spring and autumn showed both of the aforementioned temperature-mortality relationships, but generally to a lesser magnitude than what was seen in summer or winter. When compared to distributed lag nonlinear models, NARX model output was nearly identical. These results highlight the applicability of NARX models for use in modeling complex and time-dependent relationships for various applications in epidemiology and environmental sciences. Copyright © 2018 Elsevier Inc. All rights reserved.

Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

PubMed

Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

2015-12-29

Salinity-alkalinity stress is known to adversely affect a variety of processes in plants, thus inhibiting growth and decreasing crop yield. Polyamines protect plants against a variety of environmental stresses. However, whether exogenous spermidine increases the tolerance of tomato seedlings via effects on chloroplast antioxidant enzymes and chlorophyll metabolism is unknown. In this study, we examined the effect of exogenous spermidine on chlorophyll synthesis and degradation pathway intermediates and related enzyme activities, as well as chloroplast ultrastructure, gene expression, and antioxidants in salinity-alkalinity-stressed tomato seedlings. Salinity-alkalinity stress disrupted chlorophyll metabolism and hindered uroorphyrinogen III conversion to protoporphyrin IX. These effects were more pronounced in seedlings of cultivar Zhongza No. 9 than cultivar Jinpengchaoguan. Under salinity-alkalinity stress, exogenous spermidine alleviated decreases in the contents of total chlorophyll and chlorophyll a and b in seedlings of both cultivars following 4 days of stress. With extended stress, exogenous spermidine reduced the accumulation of δ-aminolevulinic acid, porphobilinogen, and uroorphyrinogen III and increased the levels of protoporphyrin IX, Mg-protoporphyrin IX, and protochlorophyllide, suggesting that spermidine promotes the conversion of uroorphyrinogen III to protoporphyrin IX. The effect occurred earlier in cultivar Jinpengchaoguan than in cultivar Zhongza No. 9. Exogenous spermidine also alleviated the stress-induced increases in malondialdehyde content, superoxide radical generation rate, chlorophyllase activity, and expression of the chlorophyllase gene and the stress-induced decreases in the activities of antioxidant enzymes, antioxidants, and expression of the porphobilinogen deaminase gene. In addition, exogenous spermidine stabilized the chloroplast ultrastructure in stressed tomato seedlings. The tomato cultivars examined exhibited different capacities for responding to salinity-alkalinity stress. Exogenous spermidine triggers effective protection against damage induced by salinity-alkalinity stress in tomato seedlings, probably by maintaining chloroplast structural integrity and alleviating salinity-alkalinity-induced oxidative damage, most likely through regulation of chlorophyll metabolism and the enzymatic and non-enzymatic antioxidant systems in chloroplast. Exogenous spermidine also exerts positive effects at the transcription level, such as down-regulation of the expression of the chlorophyllase gene and up-regulation of the expression of the porphobilinogen deaminase gene.

Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1.

PubMed

Xu, Jiaqi; Sadahira, Takuya; Kinoshita, Rie; Li, Shun-Ai; Huang, Peng; Wada, Koichiro; Araki, Motoo; Ochiai, Kazuhiko; Noguchi, Hirofumi; Sakaguchi, Masakiyo; Nasu, Yasutomo; Watanabe, Masami

2017-11-01

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)β-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-β-catenin (activated form of β-catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/β-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/β-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/β-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/β-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-β-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-β-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-β-catenin and inhibits Wnt/β-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/β-catenin signaling.

The University Professor As a Utility Maximizer and Producer of Learning, Research, and Income

ERIC Educational Resources Information Center

Becker, William E., Jr.

1975-01-01

A professonial decision-making model is presented for the purpose of exploring alternative plans to raise teaching quality. It is demonstrated that an increase in the pecuniary return to teaching will raise teaching quality while exogenous changes in teaching and/or research technology need not. (Author/EA)

Exogenous and Endogenous Impacts into Teachers' Work Performance Sphere

ERIC Educational Resources Information Center

Nasrun

2016-01-01

By this synopsis research which conveyed of findings to unfold mutual effect between teachers' performance and incentive scheme and teachers' personal competency, and principal leadership, and work motivation, by means of explanatory research in which ex facto method was ad hock model chosen because of classified as non-experiment. The grounds…

Pre-Service Teachers' Attitude towards Information and Communication Technology Usage: A Ghanaian Survey

ERIC Educational Resources Information Center

Gyamfi, Stephen Adu

2017-01-01

This study employed the Technology Acceptance Model (TAM) to empirically investigate factors that influence Ghanaian pre-service teachers' attitudes towards Information and Communication Technology (ICT) usage. To achieve this aim, the study extended the TAM framework by adding leadership support and job relevance as exogenous variables. Data were…

Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model.

PubMed

Lv, Fengshou; Yang, Xiaopeng; Cui, Chuanju; Su, Chunhe

2017-01-01

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila. Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC). Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration. The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.

National treatment systems in global perspective.

PubMed

Klingemann, H

1999-09-01

Drug policy development is mostly viewed as emerging within the nation state. Processes of diffusion of innovative policies have been neglected to a large extent. The comparative study of public policy has demonstrated, however, that diffusion is an important predictor of early policy adaptation. Thus, the analysis asks the general question of the relative importance of endogenous and exogenous effects on the development of drug policies in various countries. Specifically it describes the Swiss debate leading to the popular initiative on 'Youth Without Drugs' as well as the international reactions regarding its liberal outcome. Results of an expert survey show two broad types of reactions. There is one set of countries where chances for the introduction of limited heroin-prescription trials during the next 5 years are considered probable and a second set of countries which seems to be strictly status quo oriented. In the concluding section a model is suggested which systematically considers endogenous as well as exogenous predictors of 'soft' or 'hard' drug policy adoption. Results of a first tentative test of the model are encouraging for future empirical research on diffusion processes of drug policies.

Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster

PubMed Central

Ogunjimi, Benson; Willem, Lander; Beutels, Philippe; Hens, Niel

2015-01-01

Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure ‘opportunities’ through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed. DOI: http://dx.doi.org/10.7554/eLife.07116.001 PMID:26259874

Exogenous administration of Substance P enhances wound healing in a novel skin-injury model.

PubMed

Delgado, Angel V; McManus, Albert T; Chambers, James P

2005-04-01

Soft tissue injury accounts for approximately 44% of all wounds in both the military and civilian populations. Following injury to soft tissue, Substance P (SP) and other neuropeptides are released by cutaneous neurons and modulate the function of immunocompetent and inflammatory cells, as well as epithelial and endothelial cells. The interaction between these components of the nervous system and multiple target cells affecting cutaneous repair is of increasing interest. In this report, we describe the effects of SP on wound repair in a novel, laser-induced, skin-wound model. Gross and histologic examination of laser-induced injury revealed that exogenously administered SP affects wound healing via neurite outgrowth, in addition to adhesion molecule and neurokinin-1 receptor involvement in vivo. All SP effects were decreased by pretreatment with Spantide II, an SP antagonist. The elucidation of SP-mediating mechanisms is crucial to firmly establishing the involvement and interaction of the peripheral nervous system and the immune system in cutaneous repair. Findings presented here suggest that SP participates in the complex network of mediators involved in cutaneous inflammation and wound healing.

Estimating Latent Variable Interactions With Non-Normal Observed Data: A Comparison of Four Approaches

PubMed Central

Cham, Heining; West, Stephen G.; Ma, Yue; Aiken, Leona S.

2012-01-01

A Monte Carlo simulation was conducted to investigate the robustness of four latent variable interaction modeling approaches (Constrained Product Indicator [CPI], Generalized Appended Product Indicator [GAPI], Unconstrained Product Indicator [UPI], and Latent Moderated Structural Equations [LMS]) under high degrees of non-normality of the observed exogenous variables. Results showed that the CPI and LMS approaches yielded biased estimates of the interaction effect when the exogenous variables were highly non-normal. When the violation of non-normality was not severe (normal; symmetric with excess kurtosis < 1), the LMS approach yielded the most efficient estimates of the latent interaction effect with the highest statistical power. In highly non-normal conditions, the GAPI and UPI approaches with ML estimation yielded unbiased latent interaction effect estimates, with acceptable actual Type-I error rates for both the Wald and likelihood ratio tests of interaction effect at N ≥ 500. An empirical example illustrated the use of the four approaches in testing a latent variable interaction between academic self-efficacy and positive family role models in the prediction of academic performance. PMID:23457417

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

PubMed Central

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation.

PubMed

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.

Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts.

PubMed

Zhang, Yang; Lin, Zhe; Foolen, Jasper; Schoen, Ingmar; Santoro, Alberto; Zenobi-Wong, Marcy; Vogel, Viola

2014-11-01

Early wound healing is associated with fibroblasts assembling a provisional fibronectin-rich extracellular matrix (ECM), which is subsequently remodeled and interlaced by type I collagen. This exposes fibroblasts to time-variant sets of matrices during different stages of wound healing. Our goal was thus to gain insight into the ECM-driven functional regulation of human foreskin fibroblasts (HFFs) being either anchored to a fibronectin (Fn) or to a collagen-decorated matrix, in the absence or presence of cyclic mechanical strain. While the cells reoriented in response to the onset of uniaxial cyclic strain, cells assembled exogenously added Fn with a preferential Fn-fiber alignment along their new orientation. Exposure of HFFs to exogenous Fn resulted in an increase in matrix metalloproteinase (MMP) expression levels, i.e. MMP-15 (RT-qPCR), and MMP-9 activity (zymography), while subsequent exposure to collagen slightly reduced MMP-15 expression and MMP-9 activity compared to Fn-exposure alone. Cyclic strain upregulated Fn fibrillogenesis and actin stress fiber formation, but had comparatively little effect on MMP activity. We thus propose that the appearance of collagen might start to steer HFFs towards homeostasis, as it decreased both MMP secretion and the tension of Fn matrix fibrils as assessed by Fluorescence Resonance Energy Transfer. These results suggest that HFFs might have a high ECM remodeling or repair capacity in contact with Fn alone (early event), which is reduced in the presence of Col1 (later event), thereby down-tuning HFF activity, a processes which would be required in a tissue repair process to finally reach tissue homeostasis. Copyright © 2014. Published by Elsevier B.V.

Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas.

PubMed

Formosa, R; Borg, J; Vassallo, J

2017-08-01

Pituitary adenomas (PA) represent the largest group of intracranial neoplasms and yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use a high-throughput screening method to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway downregulated in all PA types. This was confirmed by real-time PCR in 31 tumours. The AHR has been shown to regulate cell cycle progression in various cell types; however, its role in pituitary tissue has never been investigated. In order to validate the role of AHR in PA behaviour, further functional studies were undertaken. Over-expression of AHR in GH3 cells revealed a tumour suppressor potential independent of exogenous ligand activation by benzo α-pyrene (BαP). Cell cycle analysis and quantitative PCR of cell cycle regulator genes revealed that both unstimulated and BαP-stimulated AHR reduced E2F-driven transcription and altered expression of cell cycle regulator genes, thus increasing the percentage of cells in G 0 /G 1 phase and slowing the proliferation rate of GH3 cells. Co-immunoprecipitation confirmed the interaction between AHR and retinoblastoma (Rb1) protein supporting this as a functional mechanism for the observed reduction. Endogenous Ahr reduction using silencing RNA confirmed the tumour suppressive function of the Ahr. These data support a mechanistic pathway for the putative tumour suppressive role of AHR specifically in PA, possibly through its role as a cell cycle co-regulator, even in the absence of exogenous ligands. © 2017 The authors.

Aryl hydrocarbon receptor (AHR) is a potential tumour suppressor in pituitary adenomas

PubMed Central

Formosa, R; Borg, J

2017-01-01

Pituitary adenomas (PA) represent the largest group of intracranial neoplasms and yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use a high-throughput screening method to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway downregulated in all PA types. This was confirmed by real-time PCR in 31 tumours. The AHR has been shown to regulate cell cycle progression in various cell types; however, its role in pituitary tissue has never been investigated. In order to validate the role of AHR in PA behaviour, further functional studies were undertaken. Over-expression of AHR in GH3 cells revealed a tumour suppressor potential independent of exogenous ligand activation by benzo α-pyrene (BαP). Cell cycle analysis and quantitative PCR of cell cycle regulator genes revealed that both unstimulated and BαP-stimulated AHR reduced E2F-driven transcription and altered expression of cell cycle regulator genes, thus increasing the percentage of cells in G0/G1 phase and slowing the proliferation rate of GH3 cells. Co-immunoprecipitation confirmed the interaction between AHR and retinoblastoma (Rb1) protein supporting this as a functional mechanism for the observed reduction. Endogenous Ahr reduction using silencing RNA confirmed the tumour suppressive function of the Ahr. These data support a mechanistic pathway for the putative tumour suppressive role of AHR specifically in PA, possibly through its role as a cell cycle co-regulator, even in the absence of exogenous ligands. PMID:28649092

From endogenous to exogenous pattern formation: Invasive plant species changes the spatial distribution of a native ant.

PubMed

Li, Kevin; He, Yifan; Campbell, Susanna K; Colborn, A Shawn; Jackson, Eliot L; Martin, Austin; Monagan, Ivan V; Ong, Theresa Wei Ying; Perfecto, Ivette

2017-06-01

Invasive species are a significant threat to global biodiversity, but our understanding of how invasive species impact native communities across space and time remains limited. Based on observations in an old field in Southeast Michigan spanning 35 years, our study documents significant impacts of habitat change, likely driven by the invasion of the shrub, Elaeagnus umbellata, on the nest distribution patterns and population demographics of a native ant species, Formica obscuripes. Landcover change in aerial photographs indicates that E. umbellata expanded aggressively, transforming a large proportion of the original open field into dense shrubland. By comparing the ant's landcover preferences before and after the invasion, we demonstrate that this species experienced a significant unfavorable change in its foraging areas. We also find that shrub landcover significantly moderates aggression between nests, suggesting nests are more related where there is more E. umbellata. This may represent a shift in reproductive strategy from queen flights, reported in the past, to asexual nest budding. Our results suggest that E. umbellata may affect the spatial distribution of F. obscuripes by shifting the drivers of nest pattern formation from an endogenous process (queen flights), which led to a uniform pattern, to a process that is both endogenous (nest budding) and exogenous (loss of preferred habitat), resulting in a significantly different clustered pattern. The number and sizes of F. obscuripes nests in our study site are projected to decrease in the next 40 years, although further study of this population's colony structures is needed to understand the extent of this decrease. Elaeagnus umbellata is a common invasive shrub, and similar impacts on native species might occur in its invasive range, or in areas with similar shrub invasions. © 2017 John Wiley & Sons Ltd.

Different synaptic stimulation patterns influence the local androgenic and estrogenic neurosteroid availability triggering hippocampal synaptic plasticity in the male rat.

PubMed

Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2017-02-01

Electrophysiological recordings were used to investigate the role of the local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on synaptic long-term effects induced in the hippocampal CA1 region of male rat slices. Long-term depression (LTD) and long-term potentiation (LTP), induced by different stimulation patterns, were examined under the block of the DHT synthesis by finasteride (FIN), and the E2 synthesis by letrozole (LET). We used low frequency stimulation (LFS) for LTD, high frequency stimulation (HFS) for LTP, and intermediate patterns differing in duration or frequency. We found that FIN reverted the LFS-LTD into LTP and enhanced LTP induced by intermediate and HFSs. These effects were abolished by exogenous DHT at concentration higher than the basal one, suggesting a stimulus dependent increase in DHT availability. No effect on the synaptic responses was observed giving DHT alone. Moreover, we found that the inhibition of E2 synthesis influenced the HFS-LTP by reducing its amplitude, and the exogenous E2 either enhanced HFS-LTP or reverted the LFS-LTD into LTP. The equivalence of the E2 concentration for rescuing the full HFS-LTP under LET and reverting the LFS-LTD into LTP suggests an enhancement of the endogenous E2 availability that is specifically driven by the HFS. No effect of FIN or LET was observed on the responses to stimuli that did not induce either LTD or LTP. This study provides evidence that the E2 and DHT availability combined with specific stimulation patterns is determinant for the sign and amplitude of the long-term effects. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida▿

PubMed Central

Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

2011-01-01

Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants. PMID:21709086

GA-DELLA pathway is involved in regulation of nitrogen deficiency-induced anthocyanin accumulation.

PubMed

Zhang, Yongqiang; Liu, Zhongjuan; Liu, Jianping; Lin, Sheng; Wang, Jianfeng; Lin, Wenxiong; Xu, Weifeng

2017-04-01

DELLA proteins positively regulate nitrogen deficiency-induced anthocyanin accumulation through directly interaction with PAP1 to enhance its transcriptional activity on anthocyanin biosynthetic gene expressions. Plants can survive a limiting nitrogen supply by undergoing adaptive responses, including induction of anthocyanin production. However, the detailed mechanism is still unclear. In this study, we found that this process was impaired and enhanced, respectively, by exogenous GA 3 (an active form of GAs) and paclobutrazol (PAC, a specific GA biosynthesis inhibitor) in Arabidopsis seedlings. Consistently, the nitrogen deficiency-induced transcript levels of several key genes involved in anthocyanin biosynthesis, including F3'H, DFR, LDOX, and UF3GT, were decreased and enhanced by exogenous GA 3 and PAC, respectively. Moreover, the nitrogen deficiency-induced anthocyanin accumulation and biosynthesis gene expressions were impaired in the loss-of-function mutant gai-t6/rga-t2/rgl1-1/rgl2-1/rgl3-1 (della) but enhanced in the GA-insensitive mutant gai, suggesting that DELLA proteins, known as repressors of GA signaling, are necessary for fully induction of nitrogen deficiency-driven anthocyanin biosynthesis. Using yeast two-hybrid (Y2H) assay, pull-down assay, and luciferase complementation assay, it was found that RGA, a DELLA of Arabidopsis, could strongly interact with PAP1, a known regulatory transcription factor positively involved in anthocyanin biosynthesis. Furthermore, transient expression assays indicated that RGA and GAI could enhance the transcriptional activities of PAP1 on its downstream genes, including F3'H and DFR. Taken together, this study suggests that DELLAs are necessary regulators for nitrogen deficiency-induced anthocyanin accumulation through interaction with PAP1 and enhancement of PAP1's transcriptional activity on its target genes. GA-DELLA-involved anthocyanin accumulation is important for plant adaptation to nitrogen deficiency.

The Arabidopsis Phytocystatin AtCYS5 Enhances Seed Germination and Seedling Growth under Heat Stress Conditions.

PubMed

Song, Chieun; Kim, Taeyoon; Chung, Woo Sik; Lim, Chae Oh

2017-08-01

Phytocystatins (PhyCYSs) are plant-specific proteinaceous inhibitors that are implicated in protein turnover and stress responses. Here, we characterized a PhyCYS from Arabidopsis thaliana , which was designated AtCYS5. RT-qPCR analysis showed that the expression of AtCYS5 in germinating seeds was induced by heat stress (HS) and exogenous abscisic acid (ABA) treatment. Analysis of the expression of the β -glucuronidase reporter gene under the control of the AtCYS5 promoter showed that AtCYS5 expression during seed germination was induced by HS and ABA. Constitutive overexpression of AtCYS5 driven by the cauliflower mosaic virus 35S promoter led to enhanced HS tolerance in transgenic Arabidopsis , which was characterized by higher fresh weight and root length compared to wild-type (WT) and knockout ( cys5 ) plants grown under HS conditions. The HS tolerance of At-CYS5 -overexpressing transgenic plants was associated with increased insensitivity to exogenous ABA during both seed germination and post-germination compared to WT and cys5 . Although no HS elements were identified in the 5'-flanking region of AtCYS5 , canonical ABA-responsive elements (ABREs) were detected. AtCYS5 was upregulated in ABA-treated protoplasts transiently co-expressing this gene and genes encoding bZIP ABRE-binding factors (ABFs and AREB3). In the absence of ABA, ABF1 and ABF3 directly bound to the ABREs in the AtCYS5 promoter, which activated the transcription of this gene in the presence of ABA. These results suggest that an ABA-dependent pathway plays a positive role in the HS-responsive expression of AtCYS5 during seed germination and post-germination growth.

NARMAX model identification of a palm oil biodiesel engine using multi-objective optimization differential evolution

NASA Astrophysics Data System (ADS)

Mansor, Zakwan; Zakaria, Mohd Zakimi; Nor, Azuwir Mohd; Saad, Mohd Sazli; Ahmad, Robiah; Jamaluddin, Hishamuddin

2017-09-01

This paper presents the black-box modelling of palm oil biodiesel engine (POB) using multi-objective optimization differential evolution (MOODE) algorithm. Two objective functions are considered in the algorithm for optimization; minimizing the number of term of a model structure and minimizing the mean square error between actual and predicted outputs. The mathematical model used in this study to represent the POB system is nonlinear auto-regressive moving average with exogenous input (NARMAX) model. Finally, model validity tests are applied in order to validate the possible models that was obtained from MOODE algorithm and lead to select an optimal model.

Consentaneous Agent-Based and Stochastic Model of the Financial Markets

PubMed Central

Gontis, Vygintas; Kononovicius, Aleksejus

2014-01-01

We are looking for the agent-based treatment of the financial markets considering necessity to build bridges between microscopic, agent based, and macroscopic, phenomenological modeling. The acknowledgment that agent-based modeling framework, which may provide qualitative and quantitative understanding of the financial markets, is very ambiguous emphasizes the exceptional value of well defined analytically tractable agent systems. Herding as one of the behavior peculiarities considered in the behavioral finance is the main property of the agent interactions we deal with in this contribution. Looking for the consentaneous agent-based and macroscopic approach we combine two origins of the noise: exogenous one, related to the information flow, and endogenous one, arising form the complex stochastic dynamics of agents. As a result we propose a three state agent-based herding model of the financial markets. From this agent-based model we derive a set of stochastic differential equations, which describes underlying macroscopic dynamics of agent population and log price in the financial markets. The obtained solution is then subjected to the exogenous noise, which shapes instantaneous return fluctuations. We test both Gaussian and q-Gaussian noise as a source of the short term fluctuations. The resulting model of the return in the financial markets with the same set of parameters reproduces empirical probability and spectral densities of absolute return observed in New York, Warsaw and NASDAQ OMX Vilnius Stock Exchanges. Our result confirms the prevalent idea in behavioral finance that herding interactions may be dominant over agent rationality and contribute towards bubble formation. PMID:25029364

Note: Model-based identification method of a cable-driven wearable device for arm rehabilitation

NASA Astrophysics Data System (ADS)

Cui, Xiang; Chen, Weihai; Zhang, Jianbin; Wang, Jianhua

2015-09-01

Cable-driven exoskeletons have used active cables to actuate the system and are worn on subjects to provide motion assistance. However, this kind of wearable devices usually contains uncertain kinematic parameters. In this paper, a model-based identification method has been proposed for a cable-driven arm exoskeleton to estimate its uncertainties. The identification method is based on the linearized error model derived from the kinematics of the exoskeleton. Experiment has been conducted to demonstrate the feasibility of the proposed model-based method in practical application.

Effect of Exogenous Abscisic Acid and Methyl Jasmonate on Anthocyanin Composition, Fatty Acids, and Volatile Compounds of Cabernet Sauvignon (Vitis vinifera L.) Grape Berries.

PubMed

Ju, Yan-Lun; Liu, Min; Zhao, Hui; Meng, Jiang-Fei; Fang, Yu-Lin

2016-10-12

The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet Sauvignon grape berries. Exogenous ABA and MeJA improved the content of total anthocyanins (TAC) and individual anthocyanins. Lipoxygenase (LOX) activity also increased after treatment. Furthermore, 16 fatty acids were detected. The linoleic acid concentration gradually increased with ABA concentration. The fatty acid content decreased with increasing MeJA concentration and then increased again, with the exception of linoleic acid. After exogenous ABA and MeJA treatment, the C6 aroma content increased significantly. Interestingly, the exogenous ABA and MeJA treatments improved mainly the content of 1-hexanol, hexanal, and 2-heptanol. These results provide insight into the effect of plant hormones on wine grapes, which is useful for grape quality improvement.

Effects of exogenous salinity (NaCl) gradient on Cd release in acidified contaminated brown soil

NASA Astrophysics Data System (ADS)

Zhang, Lina; Rong, Yong; Mao, Li; Gao, Zhiyuan; Liu, Xiaoyu; Dong, Zhicheng

2018-02-01

Taking acidified Cd contaminated brown soil in Yantai as the research object, based on different exogenous salinity (NaCl) gradient (0%, 0.3%, 0.6%, 0.9%, 1.5%, 2% and 5%), indoor simulation experiments of Cd release were carried out after field investigation. Results showed that there was a significantly positive relation (r>0.90) between Cd release concentration/amount/ratio and exogenous salt (NaCl). Besides, the more exogenous salt (NaCl) was added; maximum release concentration/amount of Cd appeared the earlier. It was found that exogenous salt (NaCl) addition could obviously promote Cd release from acidified Cd contaminated brown soil. It was believed that this could be mainly due to the cation exchange between Cd2+ and Na+, together with the dissociation and/or complexation between Cl- and Cd2+. In addition, available adsorption sites reduction by exchange base in soil causing Cd changed from solid state to soil solution was also a probable reason.

Transurethral lithotripsy with holmium-YAG laser of a large exogenous prostatic calculus.

PubMed

Hasegawa, Masanori; Ohara, Rei; Kanao, Kent; Nakajima, Yosuke

2011-04-01

Prostatic calculi are classified into two types, endogenous and exogenous calculi, based on their origin. Endogenous calculi are commonly observed in elderly men; however, exogenous prostatic calculi are extremely rare. We report here the case of a 51-year-old man who suffered incontinence and pollakiuria with a giant exogenous prostatic calculus almost completely replacing the prostatic tissue. X-rays and computed tomography demonstrated a large calculus of 65 × 58 mm in the small pelvic cavity. The patient underwent a transurethral lithotripsy with a holmium-YAG laser and a total of 85 g of disintegrated stones was retrieved and chemical stone analysis revealed the presence of magnesium ammonium phosphate. The incontinence improved and the voiding volume increased dramatically, and no stone recurrence in the prostatic fossa occurred at the 2 years follow-up. The etiology of this stone formation seemed to be based on some exogenous pathways combined with urinary stasis and chronic urinary infection due to compression fracture of the lumbar vertebra.

Saccade preparation is required for exogenous attention but not endogenous attention or IOR.

PubMed

Smith, Daniel T; Schenk, Thomas; Rorden, Chris

2012-12-01

Covert attention is tightly coupled with the control of eye movements, but there is controversy about how tight this coupling is. The premotor theory of attention proposes that activation of the eye movement system is necessary to produce shifts of attention. In this study, we experimentally prevented healthy participants from planning or executing eye movements and observed the effect on exogenous attention, inhibition of return (IOR), and endogenous attention. The participants experienced a deficit of exogenous attentional facilitation that was specific to locations that were inaccessible by saccade. In contrast, their ability to endogenously orient attention was preserved, as was IOR. These results show that (a) exogenous attention depends on motor preparation, (b) IOR is independent of motor preparation and exogenous attention, and (c) endogenous attention is independent of motor preparation. Although these data are consistent with a weak version of the premotor theory, we believe they can be better explained by a biased competition account of visual attention.

Do endogenous and exogenous action control compete for perception?

PubMed

Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

2012-04-01

Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

Physiological Levels of Pik3ca H1047R Mutation in the Mouse Mammary Gland Results in Ductal Hyperplasia and Formation of ERα-Positive Tumors

PubMed Central

Tikoo, Anjali; Roh, Vincent; Montgomery, Karen G.; Ivetac, Ivan; Waring, Paul; Pelzer, Rebecca; Hare, Lauren; Shackleton, Mark; Humbert, Patrick; Phillips, Wayne A.

2012-01-01

PIK3CA, the gene coding for the p110α subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3caH1047R, into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin−; CD29lo; CD24+; CD61+) cell population. The Pik3caH1047R expressing mice eventually develop mammary tumors with 100% penetrance but with a long latency (>12 months). This is significantly longer than has been reported for transgenic models where expression of the mutant Pik3ca is driven by an exogenous promoter. Histological analysis of the tumors formed revealed predominantly ERα-positive fibroadenomas, carcinosarcomas and sarcomas. In vitro induction of Pik3caH1047R in immortalized mammary epithelial cells also resulted in tumor formation when injected into the mammary fat pad of immunodeficient recipient mice. This novel model, which reproduces the scenario of a heterozygous somatic mutation occurring in the endogenous PIK3CA gene, will thus be a valuable tool for investigating the role of Pik3caH1047R mutation in mammary tumorigenesis both in vivo and in vitro. PMID:22666336

Cardioprotective activity of placental growth factor combined with oral supplementation of l-arginine in a rat model of acute myocardial infarction.

PubMed

Luo, Liyun; Chen, Bairong; Huang, Yin; Liang, Zibin; Li, Songbiao; Yin, Yuelan; Chen, Jian; Wu, Wei

2016-01-01

Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI. Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson's staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed. Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group ( P <0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group ( P <0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group ( P <0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group ( P <0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group ( P <0.01). Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l-arginine have a more pronounced, synergistic protective effect on myocardial protection compared with that of exogenous PlGF therapy alone.

Evaluation of the efficacy of laparoscopic resection for the management of exogenous cesarean scar pregnancy.

PubMed

Wang, Guangwei; Liu, Xiaofei; Bi, Fangfang; Yin, Lili; Sa, Rina; Wang, Dandan; Yang, Qing

2014-05-01

To retrospectively analyze the clinical data of 71 patients with exogenous cesarean scar pregnancy (CSP) treated in our hospital in the past 2 years, to compare the outcomes of exogenous CSP treated with different methods, and to evaluate the safety and feasibility of laparoscopic resection of exogenous CSP. Comparative observational study. Tertiary medical centers. 71 women with exogenous cesarean scar pregnancy. Hysteroscopic resection of CSP, and laparoscopic resection of CSP. Operation time, intraoperative blood loss, postoperative drainage of the uterine cavity, postoperative days in hospital, time for β-human chorionic gonadotropin (β-hCG) to return to normal levels, absorption time of the mass. For the laparoscopic group, the time for serum β-hCG to return normal levels and the postoperative drainage of the uterine cavity were significantly lower than in the patients who had undergone hysteroscopic resection. We found no statistically significant difference in the intraoperative blood loss and postoperative days in hospital between the two groups, but the operation time was longer in laparoscopic group. Laparoscopic surgery for a cesarean scar pregnancy has the advantages of a high success rate, fewer complications, and a shorter time for β-hCG levels to normalize. This procedure is especially suitable for the treatment of exogenous CSP. Copyright © 2014. Published by Elsevier Inc.

[Effects of exogenous spermidine on Cucumis sativus L. seedlings photosynthesis under root zone hypoxia stress].

PubMed

Wang, Tian; Wang, Suping; Guo, Shirong; Sun, Yanjun

2006-09-01

With water culture, this paper studied the effects of exogenous spermidine (Spd) on the net photosynthetic rate (Pn), intercellular CO2 concentrations (Ci), stomatal conductance (Gs), transpiration rate (Tr), apparent quantum yield (phi c), and carboxylation efficiency (CE) of cucumber seedlings tinder hypoxia stress. The results showed that the Pn decreased gradually under hypoxia stress, and reached the minimum 10 days after by 63. 33% of the control. Compared with that of hypoxia-stressed plants, the Pn after 10 days application of exogenous Spd increased 1.25 times. A negative correlation (R2 = 0.4730 - 0.7118) was found between Pn and Ci. Gs and Tr changed in wider ranges, which decreased under hypoxia-stress, but increased under hypoxia-stress plus exogenous Spd application. There was a significant positive correlation between Gs and Tr (R2 = 0.7821 - 0.9458), but these two parameters had no significant correlation with Pn; Hypoxia stress induced a decrease of phi c and CE by 63.01% and 72.33%, respectively, while hypoxia stress plus exogenous Spd application made phi c and CE increase by 23% and 14%, respectively. The photo-inhibition of cucumber seedlings under hypoxia stress was mainly caused by non-stomatal limitation, while exogenous Spd alleviated the hypoxia stress by repairing photosynthesis system.

Role of Exogenous Progesterone in the Treatment of Men and Women with Substance Use Disorders: A Narrative Review.

PubMed

Peltier, MacKenzie R; Sofuoglu, Mehmet

2018-05-14

Substance use disorders (SUDs) remain problematic as many individuals are untreated or do not benefit from the currently available interventions. Thus, there is an urgent need to develop novel pharmacological interventions to treat SUDs. Evidence suggests that the female sex hormone, progesterone, attenuates the craving for and the euphoric effects of drugs of abuse. Research to date has demonstrated that progesterone may modulate responses to drugs of abuse and may have utility as a novel treatment for SUDs. A literature search was conducted to identify and examine studies that administered exogenous progesterone. Sixteen publications were identified, exploring the utility of exogenous progesterone or its metabolite, allopregnanolone, among a range of substances, including amphetamines (one study), benzodiazepines (one study), cocaine (nine studies), and tobacco/nicotine (five studies). Results indicated that exogenous progesterone and, its metabolite allopregnanolone, demonstrated preliminary efficacy as a treatment for substance use in both men and women. Notably, progesterone appears to target negative affect and augment cognitive functioning, especially among female substance users. Additional research is needed to explore the potential use of exogenous progesterone and allopregnanolone in the treatment of SUDs, including that associated with alcohol and opioids, but considering the current promising findings, exogenous progesterone and allopregnanolone may have utility as novel pharmacological treatments for SUDs.

BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy

PubMed Central

Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

2015-01-01

Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell’s response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF+ DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells. PMID:25991860

Dance partner or dance floor?: exogenous factors resulting in accidents in professional dancers.

PubMed

Wanke, Eileen M; Mill, Helmgard; Wanke, Alice; Davenport, Jaqueline; Checcetti, Fistd; Koch, Franziska; Groneberg, David A

2013-09-01

Injury prevention in professional dancers is very important due to the high risk for acute injuries posing a threat to dancers' careers. Causative factors of acute injuries in professional dance can be divided into exogenous and endogenous factors. Although both are known in professional dance, there is still a lack of data to have a differentiated view. The aim of this study is to analyze exogenous factors resulting in work accidents of professional dancers. The data for the evaluation were obtained from work accident reports (n = 1,438, female 722, male 716) from six Berlin Theatres. Evaluation and descriptive statistics were conducted by SPSS 18 and Excel 2007. About half (48.5%, n = 698) of all work accidents are caused by exogenous factors. The "dance partner" is the most common exogenous factor (39.9%), followed by the dance floor (28.24%) and props (13.6%). The lower extremity is the most frequent structure injured in either sex (male 47.3%, female 61.3%), followed by the upper extremity in females (14.6%) and spine in male dancers (19.8%). The stage is the most common injury location in both genders (males 63.9%, females 56.8%). Acute injuries caused by exogenous factors were particularly sustained during performances (males 58.8%, females 50.5%) and during rehearsals (males 33%, females 39.9%). This study shows the key significance of exogenous factors in acute injuries in professional dance. Preserving the dancers' health and preventing injuries takes top priority, and therefore, interventions in the artistic work cannot be ruled out when preventive measures are implemented.

Differences between endogenous and exogenous emotion inhibition in the human brain.

PubMed

Kühn, Simone; Haggard, Patrick; Brass, Marcel

2014-05-01

The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.

PubMed

Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

2015-06-02

Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell's response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells.

Exogenous Application of GABA Improves PEG-Induced Drought Tolerance Positively Associated with GABA-Shunt, Polyamines, and Proline Metabolism in White Clover.

PubMed

Yong, Bin; Xie, Huan; Li, Zhou; Li, Ya-Ping; Zhang, Yan; Nie, Gang; Zhang, Xin-Quan; Ma, Xiao; Huang, Lin-Kai; Yan, Yan-Hong; Peng, Yan

2017-01-01

In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ 1 -pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism.

Exogenous Application of GABA Improves PEG-Induced Drought Tolerance Positively Associated with GABA-Shunt, Polyamines, and Proline Metabolism in White Clover

PubMed Central

Yong, Bin; Xie, Huan; Li, Zhou; Li, Ya-Ping; Zhang, Yan; Nie, Gang; Zhang, Xin-Quan; Ma, Xiao; Huang, Lin-Kai; Yan, Yan-Hong; Peng, Yan

2017-01-01

In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ1-pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism. PMID:29312009

Integrated modeling and analysis of the multiple electromechanical couplings for the direct driven feed system in machine tools

NASA Astrophysics Data System (ADS)

Yang, Xiaojun; Lu, Dun; Liu, Hui; Zhao, Wanhua

2018-06-01

The complicated electromechanical coupling phenomena due to different kinds of causes have significant influences on the dynamic precision of the direct driven feed system in machine tools. In this paper, a novel integrated modeling and analysis method of the multiple electromechanical couplings for the direct driven feed system in machine tools is presented. At first, four different kinds of electromechanical coupling phenomena in the direct driven feed system are analyzed systematically. Then a novel integrated modeling and analysis method of the electromechanical coupling which is influenced by multiple factors is put forward. In addition, the effects of multiple electromechanical couplings on the dynamic precision of the feed system and their main influencing factors are compared and discussed, respectively. Finally, the results of modeling and analysis are verified by the experiments. It finds out that multiple electromechanical coupling loops, which are overlapped and influenced by each other, are the main reasons of the displacement fluctuations in the direct driven feed system.

Proteomic and physiological analyses reveal the role of exogenous spermidine on cucumber roots in response to Ca(NO3)2 stress.

PubMed

Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng

2018-05-01

The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.

The NTeQ ISD Model: A Tech-Driven Model for Digital Natives (DNs)

ERIC Educational Resources Information Center

Williams, C.; Anekwe, J. U.

2017-01-01

Integrating Technology for enquiry (NTeQ) instructional development model (ISD), is believed to be a technology-driven model. The authors x-rayed the ten-step model to reaffirm the ICT knowledge demand of the learner and the educator; hence computer-based activities at various stages of the model are core elements. The model also is conscious of…

Performance Analysis of a Ring Current Model Driven by Global MHD

NASA Astrophysics Data System (ADS)

Falasca, A.; Keller, K. A.; Fok, M.; Hesse, M.; Gombosi, T.

2003-12-01

Effectively modeling the high-energy particles in Earth's inner magnetosphere has the potential to improve safety in both manned and unmanned spacecraft. One model of this environment is the Fok Ring Current Model. This model can utilize as inputs both solar wind data, and empirical ionospheric electric field and magnetic field models. Alternatively, we have a procedure which allows the model to be driven by outputs from the BATS-R-US global MHD model. By using in-situ satellite data we will compare the predictive capability of this model in its original stand-alone form, to that of the model when driven by the BATS-R-US Global Magnetosphere Model. As a basis for comparison we use the April 2002 and May 2003 storms where suitable LANL geosynchronous data are available.

Pharmacokinetic Model of the Transport of Fast-Acting Insulin From the Subcutaneous and Intradermal Spaces to Blood.

PubMed

Lv, Dayu; Kulkarni, Sandip D; Chan, Alice; Keith, Stephen; Pettis, Ron; Kovatchev, Boris P; Farhi, Leon S; Breton, Marc D

2015-07-01

Pharmacokinetic (PK) models describing the transport of insulin from the injection site to blood assist clinical decision making and are part of in silico platforms for developing and testing of insulin delivery strategies for treatment of patients with diabetes. The ability of these models to accurately describe all facets of the in vivo insulin transport is therefore critical for their application. Here, we propose a new model of fast-acting insulin analogs transport from the subcutaneous and intradermal spaces to blood that can accommodate clinically observed biphasic appearance and delayed clearance of injected insulin, 2 phenomena that are not captured by existing PK models. To develop the model we compare 9 insulin transport PK models which describe hypothetical insulin delivery pathways potentially capable of approximating biphasic appearance of exogenous insulin. The models are tested with respect to their ability to describe clinical data from 10 healthy volunteers which received 1 subcutaneous and 2 intradermal insulin injections on 3 different occasions. The optimal model, selected based on information and posterior identifiability criteria, assumes that insulin is delivered at the administrative site and is then transported to the bloodstream via 2 independent routes (1) diffusion-like process to the blood and (2) combination of diffusion-like processes followed by an additional compartment before entering the blood. This optimal model accounts for biphasic appearance and delayed clearance of exogenous insulin. It agrees better with the clinical data as compared to commonly used models and is expected to improve the in silico development and testing of insulin treatment strategies, including artificial pancreas systems. © 2015 Diabetes Technology Society.

Consistent data-driven computational mechanics

NASA Astrophysics Data System (ADS)

González, D.; Chinesta, F.; Cueto, E.

2018-05-01

We present a novel method, within the realm of data-driven computational mechanics, to obtain reliable and thermodynamically sound simulation from experimental data. We thus avoid the need to fit any phenomenological model in the construction of the simulation model. This kind of techniques opens unprecedented possibilities in the framework of data-driven application systems and, particularly, in the paradigm of industry 4.0.

Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy

PubMed Central

Garcia-Diaz, Beatriz; Garone, Caterina; Barca, Emanuele; Mojahed, Hamed; Gutierrez, Purification; Pizzorno, Giuseppe; Tanji, Kurenai; Arias-Mendoza, Fernando; Quinzii, Caterina M.

2014-01-01

Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogastrointestinal encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe reductions of thymidine phosphorylase activity; marked elevations of the pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and somatic multiple deletions, depletion and site-specific point mutations of mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double knockout mice recapitulated several features of these patients including thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine in tissues, mitochondrial DNA depletion, respiratory chain defects and white matter changes. However, in contrast to patients with this disease, mutant mice showed mitochondrial alterations only in the brain. To test the hypothesis that elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed double knockout mice with exogenous thymidine and deoxyuridine, and assessed clinical, neuroradiological, histological, molecular, and biochemical consequences. Mutant mice treated with exogenous thymidine and deoxyuridine showed reduced survival, body weight, and muscle strength, relative to untreated animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the disease, was enhanced and the small intestine showed a reduction of smooth muscle cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only in the brain but also in the small intestine, and deoxyribonucleoside triphosphate imbalance was observed in the brain. The relative proportion, rather than the absolute amount of deoxyribonucleoside triphosphate, was critical for mitochondrial DNA maintenance. Thus, our results demonstrate that stress of exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our knockout mice. Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches. PMID:24727567

The Sociophonetic and Acoustic Vowel Dynamics of Michigan's Upper Peninsula English

NASA Astrophysics Data System (ADS)

Rankinen, Wil A.

The present sociophonetic study examines the English variety in Michigan's Upper Peninsula (UP) based upon a 130-speaker sample from Marquette County. The linguistic variables of interest include seven monophthongs and four diphthongs: 1) front lax, 2) low back, and 3) high back monophthongs and 4) short and 5) long diphthongs. The sample is stratified by the predictor variables of heritage-location, bilingualism, age, sex and class. The aim of the thesis is two fold: 1) to determine the extent of potential substrate effects on a 71-speaker older-aged bilingual and monolingual subset of these UP English speakers focusing on the predictor variables of heritage-location and bilingualism, and 2) to determine the extent of potential exogenous influences on an 85-speaker subset of UP English monolingual speakers by focusing on the predictor variables of heritage-location, age, sex and class. All data were extracted from a reading passage task collected during a sociolinguistic interview and measured instrumentally. The findings of this apparent-time data reveal the presence of lingering effects from substrate sources and developing effects from exogenous sources based upon American and Canadian models of diffusion. The linguistic changes-in-progress from above, led by middle-class females, are taking shape in the speech of UP residents of whom are propagating linguistic phenomena typically associated with varieties of Canadian English (i.e., low-back merger, Canadian shift, and Canadian raising); however, the findings also report resistance of such norms by working-class females. Finally, the data also reveal substrate effects demonstrating cases of dialect leveling and maintenance. As a result, the speech spoken in Michigan's Upper Peninsula can presently be described as a unique variety of English comprised of lingering substrate effects as well as exogenous effects modeled from both American and Canadian English linguistic norms.

Effect of exogenous progesterone on embryo size and ewe uterine gene expression in an ovine 'dam size' model of maternal constraint.

PubMed

Fermin, Lisanne M; Pain, Sarah J; Morel, Patrick C H; Gedye, Kristene R; Kenyon, Paul R; Blair, Hugh T

2017-11-21

Progesterone (P4), acting via its receptor, regulates uterine function and histotroph production, which are crucial to embryo growth. This study aimed to examine exogenous P4 effects on embryo size and differential endometrial gene expression at Day 19 of gestation using a 'dam size' sheep model of maternal constraint. Purebred Suffolk (S, genotypically large) embryos were transferred into recipient groups of Cheviot (C, genotypically small) or Suffolk ewes that had, or had not, been pre-treated with P4 from Days 0 to 6 of pregnancy. At Day 19S embryos were collected from four experimental groups: P4 pretreated S ewes (SP4; n=5), untreated S ewes (SnP4; n=15), P4 pretreated C ewes (CP4; n=7) and untreated C ewes (CnP4; n=21). Day-19 embryos from CP4 ewes were larger (P<0.05) than those from CnP4 ewes and similar in size (P>0.05) to embryos from SnP4 and SP4 ewes. Expression of mucin 1 (MUC1) and prostaglandin-endoperoxide synthase 2 (PTGS2) was upregulated in uterine horns ipsilateral to the corpus luteum from CP4 ewes. Prostaglandin receptor (PGR), MUC1 and PTGS2 expression was upregulated, whilst cathepsin L (CTSL) and radical S-adenosyl methionine domain-containing 2 (RSAD2) expression was downregulated in the ipsilateral horn of SP4 ewes. This suggests that pretreating ewes with exogenous P4 may alleviate early pregnancy maternal constraint via mechanisms that alter uterine function. However, further research is required to investigate the timing of P4 administration and its impact on conception rates.

Exploring the effects of overburden on the sublimation and transport of H2O on Iapetus

NASA Astrophysics Data System (ADS)

Rivera-Valentin, Edgard G.; Blackburn, David G.; Ulrich, Richard K.

2012-08-01

It has been shown through both measurements and simulations that there exists a measurable ice-free, porous, overburden overlaying water ice on Cassini Regio. Mass transfer through this porous media in a vacuum would occur in the Knudsen regime, which provides sublimation rates orders of magnitude smaller than Hertz-Langmuir sublimation. The availability of water ice for transport from this region is thus currently controlled by mass transfer through the dark material overburden. Thermal segregation suggests that Iapetus' polar regions have been brightened via ballistic transport of water and its subsequent cold trapping since exogenic deposition models predict dark high latitudes on the leading hemisphere. The limiting effect of the dark material on transport of water ice may thus greatly impact the current mass balance at the poles. The effects of the overburden on the global stability and transport of H2O is addressed in order to gain insight into its influence on the polar albedo distribution and current state of thermal segregation within the dark terrain. Results indicate that thermal segregation is currently an inactive or weak process within Cassini Regio, though it is an ongoing process at the inter-terrain regions. Modeling of polar accumulation suggests that even accounting for the current dark material cover within Cassini Regio there exists sufficient ballistically inbound water to overcome exogenic darkening mechanisms. Topographic effects on local albedo differences are also simulated to provide a more complete water stability study of Iapetus. Results suggest that topographically induced changes in heat flux may be sufficient to create the observed local albedo contrasts and also support ongoing dark exogenic deposition within Cassini Regio to explain the lack of bright slopes deep within the dark terrain.

Intramuscular injection of exogenous leptin induces adiposity, glucose intolerance and fatty liver by repressing the JAK2-STAT3/PI3K pathway in a rat model.

PubMed

Wu, Lihong; Chen, Guoxiong; Liu, Wen; Yang, Xuechao; Gao, Jie; Huang, Liwen; Guan, Hongbing; Li, Zhengmao; Zheng, Zhichao; Li, Meiling; Gu, Weiwang; Ge, Linhu

2017-10-01

Obesity, diabetes and fatty liver disease are extremely common in leptin-resistant patients. Dysfunction of leptin or its receptor is associated with obesity. The present study aimed to assess the effects of intramuscular injection of exogenous leptin or its receptor on fat deposition and leptin-insulin feedback regulation. Forty-five 40-day old female Sprague Dawley (SD) rats were injected thrice with leptin or its receptor intramuscularly. Adiposity and fat deposition were assessed by assessing the Lee's index, body weight, food intake, and total cholesterol, high density lipoprotein, low density lipoprotein, and triglyceride levels, as well as histological properties (liver and adipose tissue). Serum glucose, leptin, and insulin amounts were evaluated, and glucose tolerance assessed to monitor glucose metabolism in SD rats; pancreas specimens were analyzed immunohistochemically. Hypothalamic phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and phosphatidylinositol-3-kinase (PI3K) signaling, and hepatic sterol regulatory element binding protein-1 (SREBP-1) were qualified by Western blotting. Leptin receptor immunogen reduced fat deposition, increased appetite, and lowered serum leptin levels, enhancing STAT3 signaling in hypothalamus and down-regulating hepatic SREBP-1. In contrast, SD rats administered leptin immunogen displayed significantly increased body weight and fat deposition, with up-regulated SREBP-1, indicating adiposity occurrence. SD rats administered leptin immunogen also showed glucose intolerance, β- cell reduction in the pancreas, and deregulation of JAK2-STAT3/PI3K signaling, indicating that Lep rats were at risk of diabetes. In conclusion, intramuscular injection of exogenous leptin or its receptor, a novel rat model approach, can be used in obesity pathogenesis and therapeutic studies. Copyright © 2017. Published by Elsevier Inc.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

PubMed

Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

2009-06-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.