Progressive Closure Research Articles

The Multiple Faces of Integrin-ECM Interactions in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) comprises a series of chronic and relapsing intestinal diseases, with Crohn’s disease and ulcerative colitis being the most common. The abundant and uncontrolled deposition of extracellular matrix, namely fibrosis, is one of the major hallmarks of IBD and is responsible for the progressive narrowing and closure of the intestine, defined as stenosis. Although fibrosis is usually considered the product of chronic inflammation, the substantial failure of anti-inflammatory therapies to target and reduce fibrosis in IBD suggests that fibrosis might be sustained in an inflammation-independent manner. Pharmacological therapies targeting integrins have recently shown great promise in the treatment of IBD. The efficacy of these therapies mainly relies on their capacity to target the integrin-mediated recruitment and functionality of the immune cells at the damage site. However, by nature, integrins also act as mechanosensitive molecules involved in the intracellular transduction of signals and modifications originating from the extracellular matrix. Therefore, understanding integrin signaling in the context of IBD may offer important insights into mechanisms of matrix remodeling, which are uncoupled from inflammation and could underlie the onset and persistency of intestinal fibrosis. In this review, we present the currently available knowledge on the role of integrins in the etiopathogenesis of IBD, highlighting their role in the context of immune-dependent and independent mechanisms.

Elastic anisotropic behaviour related to crack distributions in two gneisses

Stress-strain response of foliated rocks shows that mechanical behaviour and degree of anisotropy are influenced by the spatial arrangement of phyllosilicates. But the anisotropy of these rocks is essentially due to the characteristics and distribution of cracks aligned with mica beds. At the laboratory scale, the elastic symmetry can be represented by the transverse isotropy, with the lowest elastic modulus perpendicular to the plane of aligned microcracks. These issues are discussed with reference to experimental data obtained for two gneisses of the same geological formation. The gneisses show a quite similar strength behaviour, but very different deformabilities. The measures of dynamic and static deformabilities under loading prove the influence of the progressive closure of open cracks on the compliance tensors of both gneisses. The relationship between the elastic parameters and the characteristics of the crack distributions is discussed in the framework of non-interacting crack models. Assuming the presence of two different sets of cracks, crack densities have been estimated. The different deformabilities of the two gneisses can be ascribed to their different microcrack distributions. The degree of anisotropy due to cracks reduces as stresses increase, differently for the two gneisses.

The Mesozoic exhumation history of the Karatau-Talas range, western Tian Shan, Kazakhstan-Kyrgyzstan

The Tian Shan mountain range maintains high topography across the Eurasian continent despite being distal to any modern plate boundary. Previous studies of the Tian Shan have revealed a history of mountain building in response to India-Asia collision which has overprinted much of its Mesozoic history. The Karatau and Talas ranges in the north-western Tian Shan represent a unique opportunity to investigate the erosional response to the Mesozoic tectonics of Central Asia. In this study, we present medium-to-low temperature thermochronology and thermal history modelling from a series of Neoproterozoic to Permian sedimentary and granitoid samples taken from the Karatau and Talas ranges. Our results identify three phases of late Paleozoic-Mesozoic deformation and exhumation: (1) a regional orogenic event in the Permian–Early Triassic (ca. 280–240 Ma) related to the final amalgamation of the Central Asian Orogenic Belt, (2) Late Triassic–Early Jurassic (ca. 230–190 Ma) reactivation in response to the collision of the Qiangtang block with the Eurasian margin, and a (3) phase of rapid basement cooling during the Late Jurassic–Early Cretaceous (ca. 160–140 Ma), associated with the closure of the Meso-Tethys Ocean. These results suggest that the Karatau and Talas ranges preserves extensive Mesozoic erosional signatures, which developed in response to Eurasian amalgamation of Central Asia and progressive closure of the Tethys Ocean.

Dracorhodin perchlorate enhances wound healing via β-catenin, ERK/p38, and AKT signaling in human HaCaT keratinocytes.

Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco. Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro, with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of β-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing.

Pressure Decline Analysis in Fractured Horizontal Wells: Comparison between Diagnostic Fracture Injection Test, Flowback, and Main Stage Falloff

SummaryThe pressure decline data after the end of a hydraulic fracture stage are sometimes monitored for an extended period of time. However, to the best of our knowledge, these data are not analyzed and are often ignored or underappreciated because of a lack of suitable models for the closure of propped fractures. In this study, we present a new approach to model and analyze pressure decline data that are available in unconventional horizontal wells with multistage, transverse hydraulic fracturing. The methods presented in this study allow us to quantify closure stress and average pore pressure inside the stimulated reservoir volume (SRV) and to infer the uniformity of proppant distribution without additional data acquisition costs. For the first time, field data of diagnostic fracture injection test (DFIT), flowback, and pressure decline of main fracturing stages from the same well are compared and analyzed. We found that the early-time main fracturing stage pressure decline trend is controlled by fracture tip extension, followed by progressive hydraulic fracture closure on the proppant pack, whereas late-time pressure decline reflects linear flow. When DFIT data are not available, pressure decline analysis of a main hydraulic fracturing stage can be a substitution if it can be monitored for an extended period to allow fracture closure on proppants and asperities.

Nanotechnology: A New Strategy to Treat Dental Hypersensitivity

Dental Hypersensitivity is the most commonly encountered dental problems associated with short, sharp painrising from exposed dentine in response to stimuli such as tactile, osmotic and chemical. Hypersensitivitymay present on several teeth, in one area of the mouth, or on one specific tooth. DHS should be differentiatedfrom another tooth sensitivity which may elicit from other clinical conditions such as dental caries,microleakage, cracked tooth or fractured restorations. Several treatment strategies such as desensitizationof nerve endings, masking of dentin tubules, occlusion of dentin tubules, and iontophoresis, are prevalentin clinical practices. Stannous ions, most commonly used in toothpastes as stannous fluoride, have beendemonstrated to occlude dentine tubules in vitro. SnF2 toothpaste formulations have been used for severaldecades and are widely accepted as an effective DH treatment. Recently advanced nanotechnology has takena wide leap in improving the various measures in the treatment of hypersensitivity by its nano particles.Nano structures have superior hardness, elasticity and flexural strength leading to its better application.Biomimetic particles desensitizing effect of nanocrystals which is caused by the progressive closure of thetubular openings of the dentine with plugs. These advancements have progressed the growth in the treatmentof Dental Hypersensitivity and have evoked a great amount of attention for improving disease prevention.

Case Report: Two-stage surgical resolution of Cantrell’s Pentalogy

BACKGROUND: Cantrell’s pentalogy includes the presence of five birth defects that represent a great challenge for surgeons. Abnormalities of the heart, pericardium, diaphragm, sternumand anterior abdominal wall are the main findings. Its incidence is low, however, it is essential to identify Cantrell´s pentalogy timely to adopt an adequate therapy for all specific defects, since it has high mortality. CASE REPORT: The patient was a full- term male newborn, with a history of abdominal wall defect compatible with an omphalocele detected by prenatal ultrasound. After the caesarean section, the abdominal wall defect was notable, the left liver lobe, intestines and heart emerged through it, the sternum also had a low fissure. The echocardiogram revealed a permeable oval foramen, mild tricuspid regurgitation, and severe pulmonary hypertension. EVOLUTION: Immediate surgical management was decided. Silo was placed, with progressive closure of the midline in 7 days. During the second surgical procedure, the diaphragmatic and pericardial defect was corrected with a bovine pericardial prosthesis. Despite the adequate evolution after surgery, at day 28 he presented with sudden cyanosis and didn’t respond to cardiopulmonary resuscitation and died. CONCLUSIONS: Cantrell’s Pentalogy is a rare disease, with peculiar clinical, anatomical and embryological characteristics, it represents a unique challenge for surgeons. Early diagnosis, as well as follow-up during pregnancy, planning a cesarean section in a high-level center and immediate surgical approach with a multidisciplinary team, are the key components in the management of patients with Cantrell’s Pentalogy. KEY WORDS: PENTALOGY OF CANTRELL, ECTOPIA CORDIS, UMBILICAL HERNIA. CONGENITAL.

Elastic properties of a reservoir sandstone: a broadband inter‐laboratory benchmarking exercise

ABSTRACTLow‐frequency forced‐oscillation methods applied to a reservoir sandstone allowed determination of the Young's modulus and Poisson's ratio (from axial loading), bulk modulus (by oscillation of the confining pressure) and shear modulus (from torsional‐forced oscillations) for comparison with conventional ultrasonic data. All tests were performed on a common sandstone core sample from an oil reservoir offshore West Africa. The results show a steady increase in ultrasonic velocities and shear modulus of the dry specimen as functions of pressure, which suggests a progressive closure of the inter‐granular contacts. An increase of bulk and Young's moduli and Poisson's ratio is observed on decane saturation of the sample when tested with a sufficiently small dead volume. This observation, consistent with Gassmann's theory, suggests that such measurements probe undrained (saturated isobaric) conditions. Diminution or absence of such fluid‐related stiffening for low‐frequency measurements with dead volumes comparable with the pore volume of the specimen indicates partially drained conditions and highlights the critical role of experimental boundary conditions. Directly measured bulk and shear moduli are consistent with those derived from Young's modulus and Poisson's ratio. These results of the inter‐laboratory testing using different measurement devices are consistent in terms of the effect of frequency and fluid saturation for the reservoir sandstone specimen. Such broad consistency illustrates the validity of forced‐oscillation techniques and constitutes an important benchmarking of laboratory testing of the elastic properties of a porous medium.

Sarmatian biostratigraphy of a marginal sea in northern Croatia based on calcareous nannofossils

Calcareous nannofossils of the Serravallian/Tortonian transition, known as the Sarmatian in the Paratethys were obtained from northern Croatia, Central Paratethys. The nannofossil biostratigraphy of the studied area included early Sarmatian biohorizons; the reliability of these and previous biohorizons was tested, and the known biostratigraphic and magnetostratigraphic datums of the Paratethys were compared with those from the adjacent Mediterranean and beyond. Six out of sixteen bioevents were selected to define five subzones (PNN6d-PNN8b) and crossover for the Badenian/Sarmatian boundary. Variations in the index fossil datums between the Paratethys and Tethys provide a broad perspective on local versus regional and global impacts on the nannofloras. The Paratethys/Tethys gateways (PTGs), and their progressive geodynamical closure, exerted a fundamental control on the salinity, circulation patterns and climate of the area. The global regression at the end of the Badenian, and the tectonic events associated with the Badenian/Sarmatian transition, also restricted the PTGs, initiating acmes of Calcidiscus pataecus and Reticulofenestra pseudoumbilicus, causing a small, early Sarmatian extinction event that occurred in coastal environments, which are the most affected by short-term environmental fluctuations. Stronger connections through the PTGs during the early/mid-Sarmatian transition induced a transgression that brought deep-dwelling Discoaster species into the area. The final closure of the PTG with the Mediterranean, which had been placed at the Badenian/Sarmatian boundary, actually occurred in the late Sarmatian as a result of tectonic movements that caused shallowing and a drastic reduction in nannofossil biodiversity. The PTG with the Indian Ocean existed until the early Tortonian, which allowed an early, but brief, occurrence of small, warm-water ceratoliths.

Intravascular lithotripsy in the treatment of peripheral artery disease

Peripheral artery disease (PAD) is an atherosclerotic process leading to narrowing of the major distal arteries in relation to the aortic arch. The progressive closure of the artery leads to its narrowing, reduced blood flow and the appearance of intermittent claudication - the most common symptom among patients. Standard methods of management include drug treatment and lifestyle modification. In severe cases, surgical treatment is used, including intravascular lithotripsy (IVL). The aim of the study is to analyze the available data on the treatment of peripheral arterial disease with IVL. The work uses the latest data published on the PubMed platform. The efficacy of lithotripsy in the treatment of PAD has been confirmed in numerous publications. The therapeutic effect was obtained both using the lithotripsy procedure alone as well as in combination with other methods modifying atherosclerotic plaque. IVL is a safe method, the number of observed complications was negligable. After the patient is properly qualified for the procedure, IVL may become the therapy of choice in the treatment of PAD.

Detrital zircon U-Pb ages of Middle–Late Permian sedimentary rocks from the southwestern margin of the North China Craton: Implications for provenance and tectonic evolution

The southwestern margin of the North China Craton (NCC) is located between the Alxa Terrane to the northwest, the North Qilian Orogen to the west and the North Qinling Orogen to the south. However, the paleogeographic and tectonic evolution for the southwestern part of the NCC in the Late Paleozoic is still poorly constrained. In order to constrain the Late Paleozoic tectonic evolution of the southwestern NCC, we carried out detailed field work and detrital zircon U-Pb geochronological research on Middle–Late Permian sedimentary rocks at the southwestern margin of the NCC. The U-Pb age spectra of detrital zircons from six samples are similar, showing four populations of 2.6–2.4 Ga, 2.0–1.7 Ga, 500–360 Ma and 350–250 Ma. Moreover, on the basis of the weighted-mean age of the youngest detrital zircons (257 ± 4 Ma), combined with the published results and volcanic interlayers, we propose that the Shangshihezi Formation formed during the Middle–Late Permian. Our results and published data indicate that the detrital zircons with age groups of 2.6–2.4 Ga and 2.0–1.7 Ga were likely derived from the Khondalite Belt and Yinshan Block in the northwestern NCC. The junction part between the North Qinling and North Qilian Orogen may provide the 500–360 Ma detrital zircons for the study area. The 350–250 Ma detrital zircons were probably derived from the northwestern part of the NCC. The majority of materials from Shangshihezi Formation within the study area were derived from the northwestern part of the NCC, indicating that the northwestern part of the NCC was strongly uplifted possibly resulting from the progressive subduction and closure of the Paleo-Asian Ocean. A small amount of materials were sourced from southwestern part of the NCC, indicating that the North Qinling Orogen experienced a minor uplift resulting from the northward subduction of the South Qinling terrane.

SPONTANEOUS LAMELLAR MACULAR HOLES CLOSURE.

To report two cases of spontaneous closure of lamellar macular holes with epiretinal proliferation (ERP). Observational cases report. Two patients affected with lamellar macular hole showed progressive and spontaneous closure of the hole associated with ERP development. At presentation, both patients presented with irregular foveal contour, and foveal cavitation with apparent loss of retinal tissue. In both cases, ERP, also called "lamellar hole-associated epiretinal proliferation", was present and increased in size over time. This proliferation progressively developed across the hole with apparent restoration of the foveal contour and preservation of visual acuity. This report describes two cases of lamellar macular hole in which ERP increased over time, resulting in lamellar macular hole closure. Such observations may suggest a spontaneous healing process driven by glial cell proliferation.

Modeling the Effect of Pressure on the Moduli Dispersion in Fluid‐Saturated Rocks

AbstractLaboratory experiments of ultrasonic velocities of fluid‐saturated rocks are often much higher than the predictions of the Gassmann theory. This difference is usually attributed to the velocity dispersion caused by fluid pressure relaxation between pores of different shapes and orientation. This paper proposes a simple model to characterize pressure and frequency effects on the elastic moduli of fluid‐saturated rocks in a broad frequency range. The proposed model incorporates micromechanics of wave‐induced fluid pressure relaxation at grain contacts (between crack‐like contacts and stiff pores) into pressure dependency of elastic moduli. Previously, the pressure dependency of the velocities or elastic moduli was ascribed to the progressive closure of cracks with the increasing effective pressure and expressed as an integral of crack compliance over the range of aspect ratios. For isolated cracks, this compliance is a function of crack geometry only. For cracks hydraulically connected to stiff pores, this crack compliance can be replaced by a frequency‐dependent solution of the micromechanical problem of fluid pressure relaxation between a single crack and surrounding pores. The resulting equation expresses the bulk and shear moduli of the fluid‐saturated rock as functions of both pressure and frequency. Furthermore, if pressure‐dependent moduli of both dry and fluid‐saturated moduli are known, the aspect ratio distribution can be obtained from the pressure dependency of the dry moduli, and then the saturated moduli can be computed with no adjustable parameters. The model predictions show reasonable agreement with laboratory data measured using ultrasonic and forced oscillation techniques.

Requirement for Crk and CrkL during postnatal lens development

The Crk and CrkL adaptor proteins have SH2 and SH3 domains and play essential overlapping, as well as distinct, roles in many biological processes, ranging from cell structure and motility to proliferation. Conditional ablation of both Crk and CrkL in neuronal progenitor cells, using a Nestin-Cre transgene, resulted in severe defects in postnatal eye development, including progressive eye closure, lens rupture, and retinal malformation. These phenotypes were not observed in the presence of a single wild-type allele of either Crk or CrkL. We found that the lens in knockout mice started to rupture and disintegrate between postnatal days 7 and 12, although the structure of the retina was relatively well maintained. As the lens deteriorated further, the outer nuclear layer in the posterior of the retina enlarged and developed ruffles. Cre recombination occurred in the lens and retina of the knockout mice. Furthermore, the posterior lens capsule of the knockout mouse was thinner at postnatal days 0.5 and 3, suggesting that the defective lens capsule caused rupturing of the lens near the posterior pole. These results indicate that Crk and CrkL play essential overlapping roles in postnatal lens development.

High pressure effect on the short- and intermediate-range structure of depolymerized soda lime silicate glass: Insights from micro-Raman spectroscopy

The network structure pressure dependence of a modified soda lime silicate glass, containing CaF2 and lower SiO2 content, was investigated by micro-Raman spectroscopy. The glass structure was first analyzed under normal pressure conditions in terms of network depolymerization, by comparing with commercial soda lime glass. Using calculation of non-bridging oxygens per tetrahedron (NBO/T), it was found that while commercial soda lime glasses have Q4 and Q3 units, the studied glass system presents a depolymerized structure and it is composed, on average, of Qn with n = 3 and 2. Changes due to high hydrostatic pressure were evaluated by using a diamond anvil cell up to 19 GPa. Raman scattering was used to calculate Si–O–Si angular population according to the network central force, which showed a progressive angle closure with pressure. The Raman spectrum of recovered sample, after compression/decompression cycle, showed negligible changes, suggesting that initial amorphous phase of modified glass is highly stable. The glass showed very high incompressibility, compared to aluminates, silicates, lanthanum borogermanate, or even regular soda lime glasses, suggesting that its bulk modulus is relative high. Polymerized glasses have great space vacancies within the network structure, on the contrary it was observed that the studied glass presents a densely packed structure reflecting on high incompressibility, which decreased the magnitude of permanent densification.

Two-stage pancreatic head resection after previous damage control surgery in trauma: two rare case reports

BackgroundThis study describes the successful treatment of two clinical settings of grade V pancreaticoduodenal blunt trauma only possible due to the prompt collaboration of a peripheral trauma hospital and a central hepatobiliary and pancreatic unit.Case presentationWe reviewed the clinical records of two male patients aged 17 and 47 years old who underwent a two-stage pancreaticoduodenectomy after a previous Damage-Control Surgery (DCS). Both patients were transferred to our Hepatobiliopancreatic Unit 2 days after immediate DCS with haemostasis, debridement, duodenostomy, gastroenterostomy, external drainage and laparostomy. One day after, they both underwent a two-stage Whipple’s procedure with external cannulation of the main bile duct and the main pancreatic duct with seized calibre silicone drains through the skin. The reconstructive phase was performed two weeks later. The first patient had an uneventful post-operative course and was discharged on post-operative day 8. The second patient developed a high debt biliary fistula on post-operative day 5 being submitted to a relaparotomy with extensive peritoneal lavage. After conservative measures the fistula underwent a progressive closure in 15 days, and the patient was discharged at post-operative day 50 without any limitations.ConclusionsPancreaticoduodenectomy is a life-saving operation in selected grade V pancreaticoduodenal trauma lesions. DCS is a salvage approach, often performed in peripheral hospitals, making an early referral to an hepatobiliopancreatic centre mandatory to achieve survival in these severely injured patients. A two-staged Whipple’s operation for severe duodenal / pancreatic trauma can be performed safely and may represent a life-saving option under these very unusual circumstances.

Past Hydrological Conditions in a Fluvial Valley: Records from C-O Isotope Signatures of Holocene Sediments in the Loire River (France)

Multi-proxy indices (grainsize distribution, mineralogy, δ18O, δ13C) in sediments from a meander infill in the Middle Loire alluvial plain of central France are used to highlight some aspects of the basin evolution over the period from 0 to 10,000 years BP. During the Late-Glacial and Holocene period, the lacustrine carbonate substratum of the alluvial plain was incised by the Loire River, creating numerous oxbows and channels related to meander migration. The channel fills consist mainly of fine clayey sediments deposited during flooding of the river, with an almost total absence of coarse-clastic and sandy material, except in the basal part. The record of isotope ratio variations together with the distribution of particle sizes allows the evolution of the river dynamics to be constrained. The strong decrease of carbonate δ13C in the upper part of the record is ascribed to a progressive closure of the meander and, thus, an increasing control of the C-isotope signature by biological activity in a local environment. Variations in carbonate δ18O, rather, reflect paleohydrological/paleoclimatic changes at the basin scale. The isotope record of the river dynamics also agrees with the variations in clay mineralogy.

Estimation of gas record alteration in very low-accumulation ice cores

Abstract. We measured the methane mixing ratios of enclosed air in five ice core sections drilled on the East Antarctic Plateau. Our work aims to study two effects that alter the recorded gas concentrations in ice cores: layered gas trapping artifacts and firn smoothing. Layered gas trapping artifacts are due to the heterogeneous nature of polar firn, where some strata might close early and trap abnormally old gases that appear as spurious values during measurements. The smoothing is due to the combined effects of diffusive mixing in the firn and the progressive closure of bubbles at the bottom of the firn. Consequently, the gases trapped in a given ice layer span a distribution of ages. This means that the gas concentration in an ice layer is the average value over a certain period of time, which removes the fast variability from the record. Here, we focus on the study of East Antarctic Plateau ice cores, as these low-accumulation ice cores are particularly affected by both layering and smoothing. We use high-resolution methane data to test a simple trapping model reproducing the layered gas trapping artifacts for different accumulation conditions typical of the East Antarctic Plateau. We also use the high-resolution methane measurements to estimate the gas age distributions of the enclosed air in the five newly measured ice core sections. It appears that for accumulations below 2 cm ice equivalent yr−1 the gas records experience nearly the same degree of smoothing. We therefore propose to use a single gas age distribution to represent the firn smoothing observed in the glacial ice cores of the East Antarctic Plateau. Finally, we used the layered gas trapping model and the estimation of glacial firn smoothing to quantify their potential impacts on a hypothetical 1.5-million-year-old ice core from the East Antarctic Plateau. Our results indicate that layering artifacts are no longer individually resolved in the case of very thinned ice near the bedrock. They nonetheless contribute to slight biases of the measured signal (less than 10 ppbv and 0.5 ppmv in the case of methane using our currently established continuous CH4 analysis and carbon dioxide, respectively). However, these biases are small compared to the dampening experienced by the record due to firn smoothing.

Dullard-mediated Smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation.

The establishment of separated pulmonary and systemic circulation in vertebrates, via cardiac outflow tract (OFT) septation, is a sensitive developmental process accounting for 10% of all congenital anomalies. Neural Crest Cells (NCC) colonising the heart condensate along the primitive endocardial tube and force its scission into two tubes. Here, we show that NCC aggregation progressively decreases along the OFT distal-proximal axis following a BMP signalling gradient. Dullard, a nuclear phosphatase, tunes the BMP gradient amplitude and prevents NCC premature condensation. Dullard maintains transcriptional programs providing NCC with mesenchymal traits. It attenuates the expression of the aggregation factor Sema3c and conversely promotes that of the epithelial-mesenchymal transition driver Twist1. Altogether, Dullard-mediated fine-tuning of BMP signalling ensures the timed and progressive zipper-like closure of the OFT by the NCC and prevents the formation of a heart carrying the congenital abnormalities defining the tetralogy of Fallot.

Pressure-dependent bulk compressibility of a porous granular material modeled by improved contact mechanics and micromechanical approaches: Effects of surface roughness of grains

The change of the mechanical properties of granular materials with pressure is an important topic associated with many industrial applications. In this paper we investigate the influence of hydrostatic pressure (Pe) on the effective bulk compressibility (Ceff) of a granular material by applying two modified theoretical approaches that are based on contact mechanics and micromechanics, respectively. For a granular material composed of rough grains, an extended contact model is developed to elucidate the effect of roughness of grain surfaces on bulk compressibility. At relatively low pressures, the model predicts that the decrease of bulk compressibility with pressure may be described by a power law with an exponent of -1/2 (i.e., Ceff ∝Pe−1/2), but deviates at intermediate pressures. At elevated pressures beyond full contact, bulk compressibility remains almost unchanged, which may be roughly evaluated by continuum contact mechanics. As an alternative explanation of pressure-dependent bulk compressibility, we suggest a micromechanical model that accounts for effects of different types of pore space present in granular materials. Narrow and compliant inter-granular cracks are approximated by three-dimensional oblate spheroidal cracks with rough surfaces, whereas the equant and stiff pores surrounded by three and four neighboring grains are modeled as tubular pores with cross sections of three and four cusp-like corners, respectively. In this model, bulk compressibility is strongly reduced with increasing pressure by progressive closure of rough-walled cracks. At pressures exceeding crack closure pressure, deformation of the remaining equant pores is largely insensitive to pressure, with almost no further change in bulk compressibility. To validate these models, we performed hydrostatic compression tests on Bentheim sandstone (a granular rock consisting of quartz with high porosity) under a wide range of pressure. The relation between observed microstructures and measured pressure-dependent bulk compressibility is well explained by both suggested models.