Identifying ideal stratigraphic cycles using a quantitative optimization method

The ideal cycle concept is poorly defined yet implicit and potentially useful in many stratigraphic analyses. A new method allows quantitative definition of ideal cycles and provides a simple but robust method to analyze stratal order and quantify stratigraphic interpretations. The method calculates transition probability (TP) matrices from a vertical succession of strata for all possible permutations of facies-class row numbering in the matrices. The ordering of facies classes that gives highest transition probabilities along diagonals of the TP matrix can be taken as a quantitative definition of an ideal cycle for the strata being analyzed. Application to a synthetic example shows how an ideal cycle can be identified, even in noisy strata, without any assumptions about or prior knowledge of cyclicity. Application to two outcrop examples shows how it can be useful to define the most optimal cycle and determine how much evidence is present for ordered and cyclical facies successions

A Big Fan of Signals? Exploring Autogenic and Allogenic Process and Product In a Numerical Stratigraphic Forward Model of Submarine-Fan Development

Distinguishing an allogenic signal from trends and patterns produced by autogenic processes is a critical element in interpreting, understanding, and predicting strata. Lobyte3D is a new reduced-complexity model of dispersive flow over an evolving topography on fan systems that produces surprisingly complex potentially hierarchical strata despite a simple formulation. Two submarine-fan model scenarios are run, one with constant sediment input, and one with a sinusoidal variation in sediment input with an oscillation period of 25 ky and a peak-to-trough 80% volume change. Both model scenarios show that flows cluster to produce lobes which migrate and can rapidly switch location. Runs tests that can detect thickening and thinning bed trends and spectral analysis that detects the frequency of any signal present suggest that strata can be ordered even in the absence of any allogenic signal, with cycles and trends in bed thickness, but no single characteristic frequency. In the oscillating-supply scenario, an allogenic signal is present in places, particularly in the axial mid fan, but may be difficult to distinguish from the autogenic signal with only limited outcrop data, and without knowing a priori how the allogenic signal is likely to be preserved in complex and incomplete strata. Based on these limited model results we hypothesize that analysis of mid-fan vertical sections, using simple power-spectrum analysis and counting of the significant peaks present across a range of frequencies, may allow identification of a “signal bump” that could be evidence of the presence and nature of allocyclic forcing. Further Lobyte3D modeling work will explore if and how the “signal bump” is preserved with input signals across a range of frequencies and amplitudes, to guide further data collection and interpretation in outcrop and subsurface strata

How To Interpret, Understand, and Predict Stratal Geometries Using Stratal-Control Spaces and Stratal-Control-Space Trajectories

Interpreting and predicting basin-margin stratal geometries requires understanding of controls such as variations in supply and accommodation, ideally based on independent quantitative evidence. Stratal-control spaces are a new tool to analyze controls on strata. A stratal-control space is an area, volume, or perhaps a higher-dimensional space, defined by a range of values of the controlling processes subsidence, sediment supply, and eustasy. A three-dimensional stratal-control volume with axes of subsidence, sediment supply, and eustatic rates of change can be populated with probabilities derived from analysis of time series of subsidence, supply, and eustasy. These empirical or theoretical probabilities indicate the likelihood of occurrence of any particular combination of control rates defined by any point in the volume. The stratal-control volume can then be analyzed to determine which parts of the volume represent relative sea-level fall and rise, where in the volume particular stacking patterns will occur, and how probable those stacking patterns are. For outcrop and subsurface analysis, using a stratal-control area with eustasy and subsidence combined on a relative sea-level axis allows similar analysis, and may be preferable. A stratal-control trajectory is a history of supply and accommodation rates, interpreted from outcrop or subsurface data, or observed in analogue and numerical experiments, and plotted as a series of linked points forming a trajectory through a stratal-control space. Two theoretical and one actual outcrop example are presented to demonstrate how stratal-control trajectories can be analyzed to determine which controls are dominant. The accommodation supply trajectory range ratio (ASTRR) is a useful metric to characterize trajectory geometry. Trajectories with ASTRR > 1 can be considered accommodation-dominated, and ASTRR < 1 indicates a supply-dominated trajectory. Calculating the range of stratal-control probabilities along the trajectory indicates the probability of the rates of change of subsidence, supply, and eustasy required to form the interpreted stratal geometry. Both types of stratal-control-trajectory analyses can provide important additional understanding and prediction of how, why, and where stratal geometries form

The stability paradox : why expansion of education for women has not delayed age at first union or childbearing in Latin America

Despite substantial improvements in women's education, the age atwhich Latin American women marry (cohabit) or become mothers for the first time has barely decreased over the past four decades. We refer to this as the "stability paradox." We examine the relationship between years of schooling and transitions to first union or child, analyzing retrospective information from 50 cohorts of women born between 1940 and 1989 in 12 Latin American countries. Absolute and relative measures of schooling are compared. Data is drawn from 38 Demographic Health Surveys (DHS) conducted between 1986 and 2012 in these countries. Results show that expected postponement in family transitions due to educational expansion was offset by a rise in union formation and childbearing within strata of absolute education, but stayed approximately constant within strata of relative education. The relative measure of education retains the stratifying power of education but neutralizes any effect attached to a specific number of years of schooling and the learning skills associated with them. This is consistent with the idea that access to education in Latin America reproduces existing patterns of socioeconomic advantage, rather than creating a more equitable distribution of learning opportunities and outcomes

LF-15 &amp; T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease

Background: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its antiangiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the aVb3 integrin. Methods: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined using a murine model of chronic OVA-induced allergic airways disease. Results: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. Conclusion: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo. © 2014 Grafton et al

Fibulin-1c regulates transforming growth factor–β activation in pulmonary tissue fibrosis

Copyright: © 2019, American Society for Clinical Investigation. Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice and stabilizes collagen formation. Here we discovered that Fbln1c was increased in the lung tissues of patients with IPF and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (Fbln1c–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target

Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation

STAT3 regulates the onset of oxidant-induced senescence in lung fibroblasts

Copyright © 2019 by the American Thoracic Society. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause with a median survival of only 3 years. Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics of senescent cells, and that dysregulated activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) correlates with IPF progression. The question of whether STAT3 activation is involved in fibroblast senescence remains unanswered. We hypothesized that inhibiting STAT3 activation after oxidantinduced senescence would attenuate characteristics of the senescent phenotype. We aimed to characterize a model of oxidant-induced senescence in human lung fibroblasts and to determine the effect of inhibiting STAT3 activity on the development of senescence. Exposing human lung fibroblasts to 150 μM hydrogen peroxide (H2O2) resulted in increased senescence-associated β-galactosidase content and expression of p21 and IL-6, all of which are features of senescence. The shift into senescence was accompanied by an increase of STAT3 translocation to the nucleus and mitochondria. Additionally, Seahorse analysis provided evidence of increased mitochondrial respiration characterized by increased basal respiration, proton leak, and an associated increase in superoxide (O2-) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated b-galactosidase accumulation, and restored normalmitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated

Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c

Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c–/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c–/– mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd