Anisotropic material properties of the human uterus

The mechanical function of the uterus is crucial for the protection of the fetus during a healthy pregnancy. Early contractile activation of uterine tissue can lead to preterm labor and birth (PTB). In 2014, 9.56 percent of pregnancies ended in PTB; it is also the leading cause of death in children under five years of age. Characterizing the material properties of uterine tissue is important for understanding the mechanical failures of the uterus and the causes of PTB. In this study, a workflow of experiments and data processing techniques were employed. 78 uterine specimens were collected from consenting 28 patients who underwent hysterectomy. A four-level ramp-hold indentation test was performed. IFEA was performed to fit four material parameters to the experimental data: Young's Modulus E, Poisson’s ratio v, the fiber stiffness factor ksi, and the fiber angle concentration b. Within each uterus, significant differences in Young’s Modulus E and Poisson’s ratio n were observed at different locations and different layers, indicating the heterogeneity of the human uterine material properties. However, the fitted values for fiber stiffness x and angle concentration b exhibited a wide spread with no significant differences observed across comparison groups. There were also no obvious differences between patients with different parities, as suggested in previous studies

Quantitative Evaluation of Collagen Crosslinks and Corresponding Tensile Mechanical Properties in Mouse Cervical Tissue during Normal Pregnancy

The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31–0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle

Background Currently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect. We have previously shown that three anoctamin 1 (ANO1) antagonists mediate potent relaxation of precontracted human uterine smooth muscle (USM). In this study, we aimed to determine whether a combination of sub-relaxatory doses of tocolytic drugs in current clinical use [the L-type voltage-gated calcium channel (VGCC) blocker, nifedipine (NIF); and the β2-adrenergic (β2AR) agonist, terbutaline (TRB)] will potentiate USM relaxation with two ANO1 antagonists [benzbromarone (BB) and MONNA (MN)]. Objective This study sought to examine the synergistic potency and mechanistic basis of two ANO1 antagonists with currently available tocolytic drugs. Functional endpoints assessed included relaxation of pre-contracting pregnant human USM tissue, inhibition of intracellular calcium release, and reduction of spontaneous transient inward current (STIC) recordings in human uterine smooth muscle cells. Methods Human myometrial strips and primary human USM cells were used in organ bath and calcium flux experiments with different combinations of sub-threshold doses of ANO1 antagonists and terbutaline or nifedipine to determine if ANO1 antagonists potentiate tocolytic drugs. Results The combination of sub-threshold doses of two ANO1 antagonists and current tocolytic drugs demonstrate a significant degree of synergy to relax human pregnant USM compared to the effects achieved when these drugs are administered individually. Conclusion A combination of sub-threshold doses of VGCC blocker and β2AR agonist with ANO1 antagonists potentiates relaxation of oxytocin-induced contractility and calcium flux in human USM ex vivo. Our findings may serve as a foundation for novel tocolytic drug combinations

The T Tauri star RY Tau as a case study of the inner regions of circumstellar dust disks

We study the inner region of the circumstellar disk around the TTauri star RY Tau. Our aim is to find a physical description satisfying the available interferometric data, obtained with the mid-infrared interferometric instrument at the Very Large Telescope Interferometer, as well as the spectral energy distribution. We also compare the findings with the results of similar studies, including those of intermediate-mass stars. Our analysis is done within the framework of a passive circumstellar disk, which is optionally supplemented by the effects of accretion and an added envelope. To achieve a more consistent and realistic model, we used our continuum transfer code MC3D. In addition, we studied the shape of the 10um silicate emission feature in terms of the underlying dust population, both for single-dish and for interferometric measurements. We show that a modestly flaring disk model with accretion can explain both the observed spectral energy distribution and the mid-infrared visibilities obtained with the mid-infrared infrared instrument. We found an interesting ambiguity: a circumstellar active disk model with an added envelope, and a lower accretion rate than in the active disk model without envelope, could represent the observations equally as well. This type of model with the envelope should be considered a viable alternative in future models of other TTauri stars. The approach of a disk with a puffed-up inner rim wall and the influence of a stellar companion is also discussed. From the study of the silicate emission feature we see evidence for dust evolution in a TTauri star, with a decreasing fraction of small amorphous and an increasing fraction of crystalline particles closer to the star.Comment: 19 pages, 23 figures; accepted by Astronomy & Astrophysic

Reading between the lines:Disk emission, wind, and accretion during the Z CMa NW outburst

(Abridged) We use optical spectroscopy to investigate the disk, wind, and accretion during the 2008 ZCMa NW outburst. Over 1000 optical emission lines reveal accretion, a variable, multi-component wind, and double-peaked lines of disk origin. The variable, non-axisymmetric, accretion-powered wind has slow ($\sim$0 km s$^{-1}$), intermediate ($\sim -$100 km s$^{-1}$) and fast ($\geq -$400 km s$^{-1}$) components. The fast components are of stellar origin and disappear in quiescence, while the slow component is less variable and could be related to a disk wind. The changes in the optical depth of the lines between outburst and quiescence are consistent with increased accretion being responsible for the observed outburst. We derive an accretion rate of 10$^{-4}$ M$_\odot$/yr in outburst. The Fe I and weak Fe II lines arise from an irradiated, flared disk at $\sim$0.5-3 $\times$M$_*$/16M$_\odot$ au with asymmetric upper layers, revealing that the energy from the accretion burst is deposited at scales below 0.5 au. Some line profiles have redshifted asymmetries, but the system is unlikely sustained by magnetospheric accretion, especially in outburst. The accretion-related structures extend over several stellar radii and, like the wind, are likely non-axisymmetric. The stellar mass may be $\sim$6-8 M$_\odot$, lower than previously thought ($\sim$16 M$_\odot$). Emission line analysis is found to be a powerful tool to study the innermost regions and accretion in stars within a very large range of effective temperatures. The density ranges in the disk and accretion structures are higher than in late-type stars, but the overall behavior, including the innermost disk emission and variable wind, is very similar independently of the spectral type. Our work suggests a common outburst behavior for stars with spectral types ranging from M-type to intermediate-mass stars.Comment: Accepted by A&A, 21 pages plus online appendix. Version 2: Minor typos corrected. Version 3: Note on DIBs added, typos correcte

Effective monitoring of freshwater fish

Freshwater ecosystems constitute only a small fraction of the planet’s water resources, yet support much of its diversity, with freshwater fish accounting for more species than birds, mammals, amphibians, or reptiles. Fresh waters are, however, particularly vulnerable to anthropogenic impacts, including habitat loss, climate and land use change, nutrient enrichment, and biological invasions. This environmental degradation, combined with unprecedented rates of biodiversity change, highlights the importance of robust and replicable programmes to monitor freshwater fish assemblages. Such monitoring programmes can have diverse aims, including confirming the presence of a single species (e.g. early detection of alien species), tracking changes in the abundance of threatened species, or documenting long-term temporal changes in entire communities. Irrespective of their motivation, monitoring programmes are only fit for purpose if they have clearly articulated aims and collect data that can meet those aims. This review, therefore, highlights the importance of identifying the key aims in monitoring programmes, and outlines the different methods of sampling freshwater fish that can be used to meet these aims. We emphasise that investigators must address issues around sampling design, statistical power, species’ detectability, taxonomy, and ethics in their monitoring programmes. Additionally, programmes must ensure that high-quality monitoring data are properly curated and deposited in repositories that will endure. Through fostering improved practice in freshwater fish monitoring, this review aims to help programmes improve understanding of the processes that shape the Earth's freshwater ecosystems, and help protect these systems in face of rapid environmental change

Michael Fernandez Direct Measurement of the Permeability of Human Cervical Tissue

The mechanical integrity of the uterine cervix is critical for a pregnancy to successfully reach full term. It must be strong to retain the fetus throughout gestation and then undergo a remodeling and softening process before labor for delivery of the fetus. It is believed that cervical insufficiency (CI), a condition in pregnancy resulting in preterm birth (PTB), is related to a cervix with compromised mechanical strength which cannot resist deformation caused by external forces generated by the growing fetus. Such PTBs are responsible for infant developmental problems and in severe cases infant mortality. To understand the etiologies of CI, our overall research goal is to investigate the mechanical behavior of the cervix. Permeability is a mechanical property of hydrated collagenous tissues that dictates the time-dependent response of the tissue to mechanical loading. The goal of this study was to design a novel soft tissue permeability testing device and to present direct hydraulic permeability measurements of excised nonpregnant (NP) and pregnant (PG) human cervical tissue from women with different obstetric histories. Results of hydraulic permeability testing indicate repeatability for specimens from single patients, with an order of magnitude separating the NP and PG group means (2:1 6 1:4 Â 10 À14 and 3:2 6 4:8 Â 10 À13 m 4 =N Á s, respectively), and large variability within the NP and PG sample groups. Differences were found between samples with similar obstetric histories, supporting the view that medical history may not be a good predictor of permeability (and therefore mechanical behavior) and highlighting the need for patient-specific measurements of cervical mechanical properties. The permeability measurements from this study will be used in future work to model the constitutive material behavior of cervical tissue and to develop in vivo diagnostic tools to stage the progression of labor