Hybridized Discontinuous Galerkin/Hybrid Mixed Methods for a Multiple Network Poroelasticity Model with Application in Biomechanics

The quasi-static multiple-network poroelastic theory (MPET) model, first introduced in the context of geomechanics [G. Barenblatt, G. Zheltov, and I. Kochina, J. Appl. Math. Mech., 24 (1960), pp. 1286-1303], has recently found new applications in biomechanics. In practice, the parameters in the MPET equations can vary over several orders of magnitude which makes their stable discretization and fast solution a challenging task. Here, a new efficient parameter-robust hybridized discontinuous Galerkin method, which also features fluid mass conservation, is proposed for the MPET model. Its stability analysis, crucial for the well-posedness of the discrete problem, is performed, and cost-efficient parameter-robust preconditioners are derived. We present a series of numerical computations for a four-network MPET model of a human brain which demonstrate the performance of the new algorithms.</p

Pathways and genes differentially expressed in the motor cortex of patients with sporadic amyotrophic lateral sclerosis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by the progressive degeneration of motoneurons in brain and spinal cord. Despite identification of disease-linked mutations, the diversity of processes involved and the ambiguity of their relative importance in ALS pathogenesis still represent a major impediment to disease models as a basis for effective therapies. Moreover, the human motor cortex, although critical to ALS pathology and physiologically altered in most forms of the disease, has not been screened systematically for therapeutic targets. RESULTS: By whole-genome expression profiling and stringent significance tests we identify genes and gene groups de-regulated in the motor cortex of patients with sporadic ALS, and interpret the role of individual candidate genes in a framework of differentially expressed pathways. Our findings emphasize the importance of defense responses and cytoskeletal, mitochondrial and proteasomal dysfunction, reflect reduced neuronal maintenance and vesicle trafficking, and implicate impaired ion homeostasis and glycolysis in ALS pathogenesis. Additionally, we compared our dataset with publicly available data for the SALS spinal cord, and show a high correlation of changes linked to the diseased state in the SALS motor cortex. In an analogous comparison with data for the Alzheimer's disease hippocampus we demonstrate a low correlation of global changes and a moderate correlation for changes specifically linked to the SALS diseased state. CONCLUSION: Gene and sample numbers investigated allow pathway- and gene-based analyses by established error-correction methods, drawing a molecular portrait of the ALS motor cortex that faithfully represents many known disease features and uncovers several novel aspects of ALS pathology. Contrary to expectations for a tissue under oxidative stress, nuclear-encoded mitochondrial genes are uniformly down-regulated. Moreover, the down-regulation of mitochondrial and glycolytic genes implies a combined reduction of mitochondrial and cytoplasmic energy supply, with a possible role in the death of ALS motoneurons. Identifying candidate genes exclusively expressed in non-neuronal cells, we also highlight the importance of these cells in disease development in the motor cortex. Notably, some pathways and candidate genes identified by this study are direct or indirect targets of medication already applied to unrelated illnesses and point the way towards the rapid development of effective symptomatic ALS therapies

Ein optimierter Versorgungsprozess bei Patienten mit schlafbezogenen Atmungsstörungen – Pilotstudie

Background: To date, patients have been instructed in diagnostic polygraphy (PG) by a trained specialist. This process is time- and cost-intensive. In a pilot study, we tested an innovative procedure in sleep-disordered breathing (SDB) to achieve faster diagnoses and more effective referral for treatment. For this purpose, study participants had a PG device delivered at home directly from the provider. Methods: Patients self-administered the PGs independently using a manual, and, if necessary, received telephone support. After the night of recording, the device was sent back to the supplier. Diagnosis by a physician was done online via an encrypted portal. In addition, subjective satisfaction with the process was assessed using a questionnaire and PG results were compared with polysomnography (PSG) within a narrow timescale. Results: Fifty patients middle-aged (50.5 ± 13.7 years), male = 30/female = 20, with suspected SDB were included in the study. The study participants had a similar mean Apnea-Hypopnea Index (AHI; PSG) of M = 20.8 (SD 23.2) and a mean AHI measured using PG of M = 20.2 (SD 18.9) under both measurement methods. At AHI values between ≥15–30/h showed sensitivity of 88% and specificity of 91%. Conclusion: In assessing whether clinically relevant sleep apnea occurred, we found a weak to moderate match between the individual diagnostic categories of the measuring process, with the most frequent matches occurring in the highest and lowest diagnosis groups. However, these results do not allow for a prediction of feasibility in a general or multimorbid patient population because of the selective sample.Hintergrund: Die Einweisung der Patienten in die diagnostische Polygraphie wird bisher von einer medizinisch ausgebildeten Fachkraft durchgeführt. Dieser Prozess ist zeit- und ressourcenintensiv. In dieser Pilotstudie wurde ein innovativer Versorgungsweg bei schlafbezogenen Atmungsstörungen (SBAS) untersucht, um eine beschleunigte Diagnostik und effektivere Therapiezuweisung zu erreichen. Hierfür wurde den Studienteilnehmern ein Polygrafie (PG)-Gerät direkt von der versorgenden Firma nach Hause geliefert. Methodik: Der Patient legte die PG selbstständig nach einer Bedienungsanleitung an und erhielt bei Bedarf telefonische Unterstützung. Nach der Untersuchungsnacht wurde das Gerät zurückgesendet. Die ärztliche Befundung erfolgte online über ein verschlüsseltes Portal. Zusätzlich erfolgte eine Befragung zur subjektiven Zufriedenheit mit dem Ablaufprozess sowie ein Vergleich der PG-Ergebnisse mit einer zeitnahen Polysomnografie (PSG). Ergebnisse: Es wurden 50 Patienten (m = 30/w = 20) mit Verdacht auf SBAS im mittleren Alter von 50,5 ± 13,7 Jahren eingeschlossen. Die Probanden wiesen unter beiden Messverfahren einen ähnlichen mittleren Apnoe-Hypopnoe-Index (AHI) (PSG) von M = 20,8 (SD 23,2) und AHI (PG) von M = 20,2 (SD 18,9) auf. Bei AHI-Werten zwischen ≥15–30/h lag die Sensitivität bei 88 % und die Spezifität bei 91 %. Diskussion: In der Beurteilung, ob eine klinisch relevante Schlafapnoe vorliegt, zeigte sich eine eher schwache, moderate Übereinstimmung zwischen den einzelnen Diagnosekategorien der Messverfahren, wobei sich die häufigsten Übereinstimmungen in den höchsten und niedrigsten Diagnosegruppen zeigten. Die Ergebnisse lassen jedoch aufgrund der selektiven Stichprobe keine Prognosen hinsichtlich der Durchführbarkeit in einer allgemeinen oder multimorbiden Patientengruppe zu

Impact of newly measured 26Al(n, p)26Mg and 26Al(n, α)23Na reaction rates on the nucleosynthesis of 26Al in stars

The cosmic production of the short-lived radioactive nuclide 26Al is crucial for our understanding of the evolution of stars and galaxies. However, simulations of the stellar sites producing 26Al are still weakened by significant nuclear uncertainties. We re-evaluate the 26Al(n, p)26Mg, and 26Al(n, α)23Na ground state reactivities from 0.01 GK to 10 GK, based on the recent n TOF measurement combined with theoretical predictions and a previous measurement at higher energies, and test their impact on stellar nucleosynthesis. We computed the nucleosynthesis of low- and high-mass stars using the Monash nucleosynthesis code, the NuGrid mppnp code, and the FUNS stellar evolutionary code. Our low-mass stellar models cover the 2-3 M☉ mass range with metallicities between Z = 0.01 and 0.02, their predicted 26Al/27Al ratios are compared to 62 meteoritic SiC grains. For high-mass stars, we test our reactivities on two 15 M☉ models with Z = 0.006 and 0.02. The new reactivities allow low-mass AGB stars to reproduce the full range of 26Al/27Al ratios measured in SiC grains. The final 26Al abundance in high-mass stars, at the point of highest production, varies by a factor of 2.4 when adopting the upper, or lower limit of our rates. However, stellar uncertainties still play an important role in both mass regimes. The new reactivities visibly impact both low- and high-mass stars nucleosynthesis and allow a general improvement in the comparison between stardust SiC grains and low-mass star models. Concerning explosive nucleosynthesis, an improvement of the current uncertainties between T9∼0.3 and 2.5 is needed for future studies

Legal situation and current practice of waste incineration bottom ash utilisation in Europe

Almost 500 municipal solid waste incineration plants in the EU, Norway, and Switzerland generate about 17.6 Mt/a of incinerator bottom ash (IBA). IBA contains minerals and metals. Metals are mostly separated and sold to the scrap market and minerals are either disposed of in landfills or utilised in the construction sector. Since there is no uniform regulation for IBA utilisation at EU level, countries developed own rules with varying requirements for utilisation. As a result from a cooperation network between European experts an up-to-date overview of documents regulating IBA utilisation is presented. Furthermore, this work highlights the different requirements that have to be considered. Overall, 51 different parameters for the total content and 36 different parameters for the emission by leaching are defined. An analysis of the defined parameter reveals that leaching parameters are significantly more to be considered compared to total content parameters. In order to assess the leaching behaviour nine different leaching tests, including batch tests, up-flow percolation tests and one diffusion test (monolithic materials) are in place. A further discussion of leaching parameters showed that certain countries took over limit values initially defined for landfills for inert waste and adopted them for IBA utilisation. The overall utilisation rate of IBA in construction works is approximately 54 wt.%. It is revealed that the rate of utilisation does not necessarily depend on how well regulated IBA utilisation is, but rather seems to be a result of political commitment for IBA recycling and economically interesting circumstances

Monitoring of selected skin- and breath-borne volatile organic compounds emitted from the human body using gas chromatography ion mobility spectrometry (GC-IMS)

ISSN:1873-376XISSN:1570-0232ISSN:1572-6495ISSN:1387-227

Dynamics of an Oligotrophic Bacterial Aquifer Community during Contact with a Groundwater Plume Contaminated with Benzene, Toluene, Ethylbenzene, and Xylenes: an In Situ Mesocosm Study{dagger}

An in situ mesocosm system was designed to monitor the in situ dynamics of the microbial community in polluted aquifers. The mesocosm system consists of a permeable membrane pocket filled with aquifer material and placed within a polypropylene holder, which is inserted below groundwater level in a monitoring well. After a specific time period, the microcosm is recovered from the well and its bacterial community is analyzed. Using this system, we examined the effect of benzene, toluene, ethylbenzene, and xylene (BTEX) contamination on the response of an aquifer bacterial community by denaturing gradient gel electrophoresis analysis of PCR-amplified 16S rRNA genes and PCR detection of BTEX degradation genes. Mesocosms were filled with nonsterile or sterile aquifer material derived from an uncontaminated area and positioned in a well located in either the uncontaminated area or a nearby contaminated area. In the contaminated area, the bacterial community in the microcosms rapidly evolved into a stable community identical to that in the adjacent aquifer but different from that in the uncontaminated area. At the contaminated location, bacteria with tmoA- and xylM/xylE1-like BTEX catabolic genotypes colonized the aquifer, while at the uncontaminated location only tmoA-like genotypes were detected. The communities in the mesocosms and in the aquifer adjacent to the wells in the contaminated area consisted mainly of Proteobacteria. At the uncontaminated location, Actinobacteria and Proteobacteria were found. Our results indicate that communities with long-term stability in their structures follow the contamination plume and rapidly colonize downstream areas upon contaminatio

Rapid and Sensitive Assessment of Globin Chains for Gene and Cell Therapy of Hemoglobinopathies

The β-hemoglobinopathies sickle cell anemia and β-thalassemia are the focus of many gene-therapy studies. A key disease parameter is the abundance of globin chains because it indicates the level of anemia, likely toxicity of excess or aberrant globins, and therapeutic potential of induced or exogenous β-like globins. Reversed-phase high-performance liquid chromatography (HPLC) allows versatile and inexpensive globin quantification, but commonly applied protocols suffer from long run times, high sample requirements, or inability to separate murine from human β-globin chains. The latter point is problematic for in vivo studies with gene-addition vectors in murine disease models and mouse/human chimeras. This study demonstrates HPLC-based measurements of globin expression (1) after differentiation of the commonly applied human umbilical cord blood-derived erythroid progenitor-2 cell line, (2) in erythroid progeny of CD34+ cells for the analysis of clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of the globin regulator BCL11A, and (3) of transgenic mice holding the human β-globin locus. At run times of 8 min for separation of murine and human β-globin chains as well as of human γ-globin chains, and with routine measurement of globin-chain ratios for 12 nL of blood (tested for down to 0.75 nL) or of 300,000 in vitro differentiated cells, the methods presented here and any variant-specific adaptations thereof will greatly facilitate evaluation of novel therapy applications for β-hemoglobinopathies

Women Scientists Who Made Nuclear Astrophysics

Female role models reduce the impact on women of stereotype threat, i.e., of being at risk of conforming to a negative stereotype about one's social, gender, or racial group [1,2]. This can lead women scientists to underperform or to leave their scientific career because of negative stereotypes such as, not being as talented or as interested in science as men. Sadly, history rarely provides role models for women scientists; instead, it often renders these women invisible [3]. In response to this situation, we present a selection of twelve outstanding women who helped to develop nuclear astrophysics