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•We explore THM coupled processes in a new TBM tunnel in the Opalinus Clay shale.•We present the evolution of in-situ state variables acquired over four years.•Radial total pressures ...(RTP) on the tunnel support are heterogeneous.•RTP reflect construction activities and long-term tunnel climate variations.•RTP reveal swelling, gap grout yielding, and are consistent with lab swelling tests.
The old Belchen tunnel tubes in the Swiss Jura Mountains were excavated with drill-and-blast in swellable sedimentary rocks, i.e., anhydrite-rich marls (Gipskeuper) and Opalinus Clay shale (OPA). Already during construction in the 1960s both rock formations caused substantial damage to the tunnel support through high swelling pressures and heave, and in later years the tubes had to be refurbished again. Important maintenance and repair prompted the construction of a new, third Belchen tunnel tube (2016–2021) with a tunnel-boring machine (TBM).
In this study we present in-situ datasets acquired to investigate the stress evolution and controlling mechanisms over more than four years at a monitoring section located in a strongly faulted OPA section of the new Belchen tunnel tube. The main datasets include time series of total radial pressure, radial strain, rock water content, rock and concrete temperatures, as well as details of the geological structures obtained from analyses of borehole logs and three-dimensional photogrammetric excavation face models. Finally, a series of idealised numerical simulations explore the impact of measured temperature variations on the measured total pressures, which confirm a strong temperature effect on radial pressures related to the setting of concrete and seasonal climatic variations.
We find that in our monitoring section radial pressures on the tunnel support are very heterogeneous, i.e., they range between 0.5 MPa and 1.5 MPa, and still gently increasing 4 years after excavation. The measured pressures are 2–5 times greater than measured in the old Belchen tunnel tubes and similar in magnitude to swelling pressures obtained in laboratory tests. EDZ permeability measurements, water content evolution, and radial strain data from the tunnel invert suggest that swelling processes contribute to the long term radial pressure build-up. Thermo-elastic deformation and swelling might be superimposed by local reactivation of tectonic faults and gap grout cracking at crack-initiation stress levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Low-level laser therapy and light-emitting diodes (LED) are increasingly used in phototherapy. Their therapeutic effects are at least partly mediated by light-induced vasodilation. The aim ...of this study was to determine the effect of different light sources on coronary arteries. Methods Porcine left coronary arteries were cut into 4-mm rings that were irradiated either by a semiconductor nonthermal gallium-arsenide diode laser or a noncoherent athermic red light source both with the same energy density up to 16 J/cm2 . After precontraction with 9, 11-dideoxy-11α, 9α-epoxymethano-prostaglandin F2 α, respective relaxation responses were evaluated. The role of endothelium as well as intracellular pathways was investigated. Results Maximum vasodilation after exposure to laser was observed at 10 J/cm2 (56.8% ± 1.2%) and decreased to 43.9% ± 2.8% at 16 J/cm2 ( p < 0.003). After adjusting exposure time to achieve equivalent energy densities in the LED group, vessel segments revealed photorelaxation of 52.9% ± 6.5% and 47.5% ± 0.6%, respectively. Vasodilations achieved by either light source were comparable at 10 J/cm2 ( p < 0.574) and 16 J/cm2 ( p < 0.322). Furthermore, vasodilation could be inhibited by administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide scavenger) and 1H-1,2,4oxadiazolo4,3-aquinoxalin-1-one (guanocyclase inhibitor) but not with L-nitro-arginine methyl ester or deendothelialization. Conclusions Vessels exposed to either light source showed a remarkable as well as comparable photorelaxation at definite energy densities. This effect is mediated by an intracellular nitric oxide–dependent mechanism. As LED sources are of small size, simple, and inexpensive build-up, they may be used during routine coronary artery bypass surgery to ease suturing of anastomosis by target vessel vasodilation.
Education researchers and the US Department of Education interpret chronic absentee data as supporting a causal relationship between absenteeism and negative outcomes later in life (Frydenlund, 2022; ...Berkowitz et al., 2017; Hopson & Lee, 2011; Thapa et al., 2013). As school absence rates continue to reflect disparities among students of color and students who are economically disadvantaged (Kearney et al., 2022), the response to absences are often based on deficit-based assumptions that are supported by compulsory attendance laws: students are not where they are required to be (Frydenlund, 2022). This study addressed three research questions focused on investigating how leaders develop perceptions of the chronically absent and practices for attendance intervention (RQ1), how site leader describe their practices towards chronically absent youth (RQ2), and the role that site leaders believe they place in creating a sense of belonging and self-determination among chronically absent youth (RQ3). This is a qualitative study that involved semi-structured interviews with 17 site leaders from a central coast school district in California with an intentional attendance intervention system, community partnerships, and significant resources allocated for supporting positive attendance. Key findings include: (1) organizational culture is critical to creating conditions that humanize students or perpetuate enclosures and judgments on students and families who do not comply with institutional expectations, (2) deficit-based perceptions of chronically absent students guide leaders to focus on outcomes and changes in behavior as they assess the effectiveness of their practices and interventions, (3) brain-based, culturally responsive perceptions of chronically absent students guide leaders to humanize their students and to focus on repairing relationships between the family and the school, (4) leaders who have experienced the impact of not belonging prioritized and defended the importance of belonging, especially for the chronically absent student, (5) leaders who have not had the opportunity to experience being marginalized viewed belonging as another educational initiative that could be addressed through systemic programming and good intentions. The findings of this study reveal the influence of leaders’ positionalities and perceptions on their practice and the areas of opportunities to focus on well-being and the survivance of marginalized learning community members. The findings of this study offer recommendations for creating conditions that support a brain-based, culturally responsive approach to supporting students who are identified as chronically absent.
Inflow data from 23 tunnels and galleries, 136 km in length and located in the Aar and Gotthard massifs of the Swiss Alps, have been analyzed with the objective (1) to understand the 3-dimensional ...spatial distribution of groundwater flow in crystalline basement rocks, (2) to assess the dependency of tunnel inflow rate on depth, tectonic overprint, and lithology, and (3) to derive the distribution of fracture transmissivity and effective hydraulic conductivity at the 100-m scale. Brittle tectonic overprint is shown to be the principal parameter regulating inflow rate and dominates over depth and lithology. The highest early time inflow rate is 1,300 l/s and has been reported from a shallow hydropower gallery intersecting a 200-m wide cataclastic fault zone. The derived lognormal transmissivity distribution is based on 1,361 tunnel intervals with a length of 100 m. Such interval transmissivities range between 10⁻⁹ and 10⁻¹ m²/s within the first 200-400 m of depth and between 10⁻⁹ and 10⁻⁴ m²/s in the depth interval of 400-1,500 m below ground surface. Outside brittle fault zones, a trend of decreasing transmissivity/hydraulic conductivity with increasing depth is observed for some schistous and gneissic geological units, whereas no trend is identified for the granitic units.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Glycated albumin (GA) is an important glycemic control marker for diabetes mellitus. This study aimed to develop a highly sensitive disposable enzyme sensor strip for GA measurement by using an ...interdigitated electrode (IDE) as an electrode platform. The superior characteristics of IDE were demonstrated using one microelectrode of the IDE pair as the working electrode (WE) and the other as the counter electrode, and by measuring ferrocyanide/ferricyanide redox couple. The oxidation current was immediately reached at the steady state when the oxidation potential was applied to the WE. Then, an IDE enzyme sensor strip for GA measurement was prepared. The measurement of fructosyl lysine, the protease digestion product of GA, exhibited a high, steady current immediately after potential application, revealing the highly reproducible measurement. The sensitivity (2.8 nA µM
) and the limit of detection (1.2 µM) obtained with IDE enzyme sensor strip were superior compared with our previously reported sensor using screen printed electrode. Two GA samples, 15 or 30% GA, corresponding to healthy and diabetic levels, respectively, were measured after protease digestion with high resolution. This study demonstrated that the application of an IDE will realize the development of highly sensitive disposable-type amperometric enzyme sensors with high reproducibility.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Alzheimer’s disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. In addition to the amyloid plaques, tau tangles, ...and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD. However, the involvement of the peripheral immune system in the neurodegenerative cascade leading to AD is poorly understood. Furthermore, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. It is currently unknown whether dysfunction in the peripheral immune system is associated with neuronal inflammation and cognitive decline.
Method
In our ongoing work, we are longitudinally characterizing resting peripheral immune system cells by flow cytometry and here present data from a subset of those with AD (n = 19) or no dementia (ND, n = 93) whom we have followed for >1 year.
Result
We have identified an increase in B cells (percent all lymphocytes, AD 6.4 (SD 8.6) vs ND 4.0 (SD 2.4) p = 0.031) and CD4
+
/CD62L
+
naïve T cells (percent CD4
+
lymphocytes, AD 33.4 (SD 18.4) vs ND 25.4 (SD 14.1) p = 0.034) among AD patients. Among the population of AD patients experiencing cognitive decline (n = 4) determined by increasing ADAS‐Cog score >6 points over one year compared to stable scores (n = 11), we have discovered a decrease in CD4
+
/CD62L
+
naïve T cells (percent CD4
+
lymphocytes, stable 33.9 (SD 14.5) vs declining 20.5 (SD 16.1) p = 0.049), increase in effector memory CD4
+
T cells (percent CD4
+
lymphocytes, stable 28.2 (SD 4.8) vs declining 47.0 (SD 6.5) p<0.001), and increase in B cells (percent all lymphocytes, stable 2.6 (SD 1.5) vs declining 5.3 (SD 1.8) p = 0.010), when compared to older adults with AD and stable cognitive status.
Conclusion
This longitudinal clinical study identifies changes in resting peripheral B and T cell populations in AD patients and among AD patients with cognitive decline.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential ...molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations deterministic solvers or the Smoldyn stochastic simulator.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVEStandardization of palmar plate osteosynthesis in order to consequently achieve physiologic anatomy of the distal radius end.INDICATIONSUnstable dorsally displaced distal radius fractures or ...fractures that should be treated functionally.CONTRAINDICATIONSSevere intraarticular joint depression that cannot be reduced with either a palmar or arthroscopic assisted approach.SURGICAL TECHNIQUEPatient in supine position with the forearm supinated on arm table. Radiopalmar incision along the radial border of the flexor carpi radialis tendon. Detachment of the pronator quadratus muscle from radial to ulnar. Gross reduction with eventual correction of a dorsal or radial shift. Placement of the angular stable plate and preliminary fixation with a nonangular stable cortical screw in the long hole at the radius shaft. Fluoroscopic control of axial alignment in the anteroposterior view and of correct distal position of the plate in the lateral view under reduction condition. Placement of one or two angular stable screws at the shaft. Under subtle reduction with flexion, ulnar deviation and axial traction placement of two K‑wires via the holes at the distal edge of the plate. These wires mostly keep reduction maintained while reduction maneuver can be paused. Fluoroscopic control in two planes. Replacement of the wires by distal angular stable screws with the help of the wires as an orientation. In case of insufficient reduction, reduction maneuver can be repeated while the first angular stable screw is locked. Final fluoroscopic control in two planes and ulnar deviation, eventually also in tangential view and clinical testing for stability of the distal radioulnar joint. Wound closure only by skin suture. Application of a sterile dressing and a palmar cast.POSTOPERATIVE MANAGEMENTArm consequently in upright position and active and complete movement of fingers. Palmar below-elbow cast for 2 weeks, then movement of wrist without exertion. After regular radiographic control 4-5 weeks postoperatively, increase of axial load to normal and, if needed, physiotherapy. Clinical control for irritation of tendons by plate or screws after 1 year and eventual plate removal.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of ...organelles and vesicles in an asymmetric fashion. The mechanisms underlying centrosome polarization are not fully understood. Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. Upon lymphocyte activation, Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse. This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. Therefore, F-actin nucleation at the centrosome--regulated by the availability of the Arp2/3 complex--determines its capacity to polarize in response to external stimuli.
Eps15 homology (EH) domains are universal interaction domains to establish networks of protein–protein interactions in the cell. These networks mainly coordinate cellular functions including ...endocytosis, actin remodeling, and other intracellular signaling pathways. They are well characterized in structural terms, except for the internal EH domain from human γ‐synergin (EHγ). Here, we complete the family of EH domain structures by determining the solution structure of the EHγ domain. The structural ensemble follows the canonical EH domain fold and the identified binding site is similar to other known EH domains. But EHγ differs significantly in the N‐ and C‐terminal regions. The N‐terminal α‐helix is shortened compared to known homologues, while the C‐terminal one is fully formed. A significant proportion of the remaining N‐ and C‐terminal regions are well structured, a feature not seen in other EH domains. Single mutations in both the N‐terminal and the C‐terminal structured extensions lead to the loss of the distinct three‐dimensional fold and turn EHγ into a molten globule like state. Therefore, we propose that the structural extensions in EHγ function as a clamp and are undoubtedly required to maintain its tertiary fold.
PDB Code(s): 2MX7;
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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