Porosity and permeability determination of organic-rich Posidonia shales based on 3-D analyses by FIB-SEM microscopy

The goal of this study is to better understand the porosity and permeability in shales to improve modelling fluid and gas flow related to shale diagenesis. Two samples (WIC and HAD) were investigated, both mid-Jurassic organic-rich Posidonia shales from Hils area, central Germany of different maturity (WIC R0 0.53 % and HAD R0 1.45 %). The method for image collection was focused ion beam (FIB) microscopy coupled with scanning electron microscopy (SEM). For image and data analysis Avizo and GeoDict was used. Porosity was calculated from segmented 3-D FIB based images and permeability was simulated by a Navier Stokes–Brinkman solver in the segmented images. Results show that the quantity and distribution of pore clusters and pores (≥  40 nm) are similar. The largest pores are located within carbonates and clay minerals, whereas the smallest pores are within the matured organic matter. Orientation of the pores calculated as pore paths showed minor directional differences between the samples. Both samples have no continuous connectivity of pore clusters along the axes in the x, y, and z direction on the scale of 10 to 20 of micrometer, but do show connectivity on the micrometer scale. The volume of organic matter in the studied volume is representative of the total organic carbon (TOC) in the samples. Organic matter does show axis connectivity in the x, y, and z directions. With increasing maturity the porosity in organic matter increases from close to 0 to more than 5 %. These pores are small and in the large organic particles have little connection to the mineral matrix. Continuous pore size distributions are compared with mercury intrusion porosimetry (MIP) data. Differences between both methods are caused by resolution limits of the FIB-SEM and by the development of small pores during the maturation of the organic matter. Calculations show no permeability when only considering visible pores due to the lack of axis connectivity. Adding the organic matter with a background permeability of 1 × 10−21 m2 to the calculations, the total permeability increased by up to 1 order of magnitude for the low mature and decreases slightly for the overmature sample from the gas window. Anisotropy of permeability was observed. Permeability coefficients increase by 1 order of magnitude if simulations are performed parallel to the bedding. Our results compare well with experimental data from the literature suggesting that upscaling may be possible in the future as soon as maturity dependent organic matter permeability coefficients can be determined

Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C

Long-term cellular and regional specificity of the photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina

This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the ventral retina and visual streak. In damaged regions, the outer nuclear layer was reduced in thickness or eliminated entirely, with a concomitant loss of immunoreactivity for rhodopsin. However, the magnitude of the effect varied between animals with the same IAA dose and survival time, suggesting individual differences in the bioavailability of the toxin. In all eyes, the inner retina remained intact, as judged by the thickness of the inner nuclear layer, and by the pattern of immunoreactivity for protein kinase C-α (rod bipolar cells) and calbindin D-28 (horizontal cells). Müller cell stalks became immunoreactive for glial fibrillary acidic protein (GFAP) even in IAA-treated retinae that had no signs of cell loss, indicating a response of the retina to the toxin. However, no marked hypertrophy or proliferation of Müller cells was observed with either GFAP or vimentin immunohistochemistry. Thus the selective, long lasting damage to the photoreceptors produced by this toxin did not lead to a reorganization of the surviving cells, at least with survival as long as 6 months, in contrast to the remodeling of the inner retina that is observed in inherited retinal degenerations such as retinitis pigmentosa and retinal injuries such as retinal detachmen

Connected pathway relative permeability from pore-scale imaging of imbibition

Pore-scale images obtained from a synchrotron-based X-ray computed micro-tomography (µCT) imbibition experiment in sandstone rock were used to conduct Navier–Stokes flow simulations on the connected pathways of water and oil phases. The resulting relative permeability was compared with steady-state Darcy-scale imbibition experiments on 5 cm large twin samples from the same outcrop sandstone material. While the relative permeability curves display a large degree of similarity, the endpoint saturations for the µCT data are 10% in saturation units higher than the experimental data. However, the two datasets match well when normalizing to the mobile saturation range. The agreement is particularly good at low water saturations, where the oil is predominantly connected. Apart from different saturation endpoints, in this particular experiment where connected pathway flow dominates, the discrepancies between pore-scale connected pathway flow simulations and Darcy-scale steady-state data are minor overall and have very little impact on fractional flow. The results also indicate that if the pore-scale fluid distributions are available and the amount of disconnected non-wetting phase is low, quasi-static flow simulations may be sufficient to compute relative permeability. When pore-scale fluid distributions are not available, fluid distributions can be obtained from a morphological approach, which approximates capillary-dominated displacement. The relative permeability obtained from the morphological approach compare well to drainage steady state whereas major discrepancies to the imbibition steady-state experimental data are observed. The morphological approach does not represent the imbibition process very well and experimental data for the spatial arrangement of the phases are required. Presumably for modeling imbibition relative permeability an approach is needed that captures moving liquid-liquid interfaces, which requires viscous and capillary forces simultaneously

Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

Spinal muscular atrophy (SMA) is an autosomal recessive disorder causing progressive proximal muscular, respiratory, and bulbar weakness. We present outcome data on motor function, ventilation, nutrition, and language development of SMA patients treated with nusinersen in Switzerland. This multicenter, observational study included 44 patients. At treatment initiation, after 2 months and then every 4 months we assessed motor function with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale expanded (HFMSE) and 6-Minute Walk Test (6MWT). At treatment initiation, patients were 0.1-44.6 years old, treatment duration ranged from 6 to 41 months. All 11 SMA type 1 children achieved higher CHOP-INTEND scores at the last assessment compared to treatment initiation, 4 acquired stable sitting. Six type 1 children were <18 months-old at treatment initiation. Two of them did not need ventilation or nutritional support at the last assessment; three had delayed language development and 3 articulation difficulties. 5/21 SMA type 2 patients achieved higher HFMSE scores. All ambulant type 3 patients showed a gain in the 6MWT. Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults

Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder causing progressive proximal muscular, respiratory, and bulbar weakness. We present outcome data on motor function, ventilation, nutrition, and language development of SMA patients treated with nusinersen in Switzerland. This multicenter, observational study included 44 patients. At treatment initiation, after 2 months and then every 4 months we assessed motor function with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale expanded (HFMSE) and 6-Minute Walk Test (6MWT). At treatment initiation, patients were 0.1-44.6 years old, treatment duration ranged from 6 to 41 months. All 11 SMA type 1 children achieved higher CHOP-INTEND scores at the last assessment compared to treatment initiation, 4 acquired stable sitting. Six type 1 children were <18 months-old at treatment initiation. Two of them did not need ventilation or nutritional support at the last assessment; three had delayed language development and 3 articulation difficulties. 5/21 SMA type 2 patients achieved higher HFMSE scores. All ambulant type 3 patients showed a gain in the 6MWT. Nusinersen is an effective treatment, with gains in motor function occurring particularly in children and SMA type 1, but also in type 2 and 3, adolescents and adults

The origin of non-thermal fluctuations in multiphase flow in porous media

Core flooding experiments to determine multiphase flow in properties of rock such as relative permeability can show significant fluctuations in terms of pressure, saturation, and electrical conductivity. That is typically not considered in the Darcy scale interpretation but treated as noise. However, in recent years, flow regimes that exhibit spatio-temporal variations in pore scale occupancy related to fluid phase pressure changes have been identified. They are associated with topological changes in the fluid configurations caused by pore-scale instabilities such as snap-off. The common understanding of Darcy-scale flow regimes is that pore-scale phenomena and their signature should have averaged out at the scale of representative elementary volumes (REV) and above. In this work, it is demonstrated that pressure fluctuations observed in centimeter-scale experiments commonly considered Darcy-scale at fractional flow conditions, where wetting and non-wetting phases are co-injected into porous rock at small (<10−6) capillary numbers are ultimately caused by pore-scale processes, but there is also a Darcy-scale fractional flow theory aspect. We compare fluctuations in fractional flow experiments conducted on samples of few centimeters size with respective experiments and in-situ micro-CT imaging at pore-scale resolution using synchrotron-based X-ray computed micro-tomography. On that basis we can establish a systematic causality from pore to Darcy scale. At the pore scale, dynamic imaging allows to directly observe the associated breakup and coalescence processes of non-wetting phase clusters, which follow “trajectories” in a “phase diagram” defined by fractional flow and capillary number and can be used to categorize flow regimes. Connected pathway flow would be represented by a fixed point, whereas processes such as ganglion dynamics follow trajectories but are still overall capillary-dominated. That suggests that the origin of the pressure fluctuations observed in centimeter-sized fractional flow experiments are capillary effects. The energy scale of the pressure fluctuations corresponds to 105-106 times the thermal energy scale. This means the fluctuations are non-thermal. At the centimeter scale, there are non-monotonic and even oscillatory solutions permissible by the fractional flow theory, which allow the fluctuations to be visible and—depending on exact conditions—significant at centimeter scale, within the viscous limit of classical (Darcy scale) fractional flow theory. That also means that the phenomenon involves both capillary aspects from the pore or cluster scale and viscous aspects of fractional flow and occurs right at the transition, where the physical description concept changes from pore to Darcy scale