Unloading joints in the central Aar granite of the Schöllenen Gorge (canton Uri, Switzerland)

Zusammenfassung: Talklüfte können im Zusammenhang mit Strasseneinschnitten, Wasserkraftanlagen und geologischen Massenbewegungen in steilen Talflanken eine wichtige Rolle spielen. Die Schöllenenschlucht im Reusstal (zentrale Schweizer Alpen) bildet ein ideales Untersuchungsgebiet für das Studium der Eigenschaften und Entstehungsmechanismen solcher Talklüfte. Die Schöllenen- Schlucht liegt am Südrand des Zentralen Aaregranits, welcher vor rund 300Mio. Jahren intrudierte, während der Alpenbildung nur lokal duktil deformiert und anschliessend an die Oberfläche gehoben wurde. Die bis zu 600 m tiefe Schlucht bietet einen idealen Einblick in das komplexe Trennflächengefüge des Plutons. Einen Einblick in das Berginnere erlauben zudem die Stollen des Kraftwerks Göschenen. Die Kartierungsarbeit führte zur Unterscheidung von zwei vermutlich alpin-syntektonischen Kluftfamilien (S- und Q-Klüfte) sowie drei Generationen von Entlastungsklüften (subhorizontale Dehnungsklüfte (L-Klüfte) und zwei Generationen von mittelsteilen bis steilen Talklüften (T1- und T2- Klüfte)). Die zahlreichen S-Klüfte verlaufen meistens parallel zur alpinen Schieferung, d. h. ungefähr E-W streichend und steil gegen Süden einfallend. Die weniger häufigen Q-Klüfte fallen steil gegen SW ein, der Winkel zwischen den beiden Kluftfamilien beträgt 60 bis 80 Grad. Die räumliche Lage der verschiedenen Entlastungsklüfte wurde primär in Querprofilen durch die Schöllenen erfasst. Die ersten Entlastungsklüfte verlaufen horizontal, sie bildeten sich unabhängig von der Topographie möglicherweise während einer spätalpinen miocänen Hebung des Aarmassivs. Eine erste Generation von Talklüften (T1) fällt mit 30-45 Grad beidseitig talwärts ein und wurde vermutlich während einer frühen pleistozänen Eintalung gebildet. Die jüngsten Talklüfte (T2) sind parallel zur heutigen Taloberfläche der Schöllenenschlucht orientiert, d. h. sie liegen parallel zu den mit spätpleistozänen Gletscherschliffen markierten Felsoberflächen. Die Frequenz sowie die Grösse dieser Klüfte nehmen zumindest in einem Stollen gegen das Berginnere ab und konnten bis rund 150 Meter ins Berginnere nachgewiesen werden. Fraktographische Untersuchungen, d. h. die Untersuchung von Bruchstrukturen auf Kluftoberflächen (hauptsächlich Federmarken mit einer Grösse von 5 bis 10 m) bestätigten diese relative Alterabfolge. Ebenso konnten dadurch jeweils der Ursprungspunkt einer Kluft und die Bruchfortpflanzungsrichtung bestimmt werden. Es zeigte sich dabei stets, dass grosse Talklüfte (bis über hundert Meter Länge) aus mehreren 5-10 Meter grossen Extensionsklüften bestehen, welche durch primär subhorizontale stabile Rissausbreitung entstanden sind. Grosse Talklüfte bilden sich bevorzugt in Graniten mit nur geringer alpin-tektonischer überprägung. Die Talklüfte der Schöllenen bilden sich nicht als Scherbrüche, wie dies von früheren Autoren angenommen wurde, sondern als Extensionsrisse in einem kompressiven Spannungsfeld. Das räumliche Auftreten und die beobachteten Grössen der Talklüfte können teilweise mit quantitativen Bruchkriterien, wie sie für hohlraumnahe Extensionsrisse in Tunnelwerken entwickelt wurden, erklärt werden. Wesentlich für den Ort und die Grösse der Talklüfte sind neben den Deviatorspannungen und Zugspannungen auch die σ3/σ1 Hauptspannungsverhältnisse. Erste numerische Modellrechnungen zu einer mehrphasigen glazialen Eintalung vermögen die beobachteten Bildungsbereiche und Eigenschaften der Talklüfte grob abzubilde

Economic evaluation of oral versus parenteral iron therapy for iron deficiency without anemia

The Swiss Federal Office of Public Health (SFOPH) commissioned a Health Technology Assessment (HTA) regarding iron therapy in symptomatic patients with iron deficiency without anemia (iron deficiency no anemia, IDNA) to the Basel Institute for Clinical Epidemiology and Biostatistics (CEB) and the Winterthur Institute of Health Economics (WIG). The scope, which describes the background of the HTA and elucidates the general approach, has been published on the SFOPH homepage. This HTA followed a step-wise approach. The aim of the first step was to assess the clinical effectiveness of iron therapy in symptomatic patients with IDNA, and to identify symptomatic populations that benefit from the therapy. In this first step, the clinical effectiveness of iron therapy was assessed in comparison to any other non-iron treatment or placebo, irrespective of the route of iron administration. This step was conducted by CEB, and the results are summarized in chapter 2 of this document. In the second step, which will be conducted by WIG, the economic evaluation shall compare parenteral versus oral iron therapy for those populations, for which a significant treatment effect of iron therapy (parenteral or oral) versus control could be identified during the first step. Based on the effectiveness results, the scope of the economic evaluation is outlined in chapter 4. Section 4.1 defines the objective of the economic evaluation. Section 4.2 defines the population, the intervention, the comparator, and the outcome (PICO) which will be evaluated. A screening of health economic literature and publicly available HTAs for economic studies comparing parenteral with oral iron therapy is presented in section 4.3, and section 4.4 concludes with the outline of the research methodology of the economic evaluation

Measurement of the 58Ni(α, γ) 62Zn reaction and its astrophysical impact

Funding Details: PHY 08-22648, NSF, National Science Foundation; PHY 0969058, NSF, National Science Foundation; PHY 1102511, NSF, National Science FoundationCross section measurements of the 58Ni(α,γ)62Zn reaction were performed in the energy range Eα=5.5to9.5 MeV at the Nuclear Science Laboratory of the University of Notre Dame, using the NSCL Summing NaI(Tl) detector and the γ-summing technique. The measurements are compared to predictions in the statistical Hauser-Feshbach model of nuclear reactions using the SMARAGD code. It is found that the energy dependence of the cross section is reproduced well but the absolute value is overestimated by the prediction. This can be remedied by rescaling the α width by a factor of 0.45. Stellar reactivities were calculated with the rescaled α width and their impact on nucleosynthesis in type Ia supernovae has been studied. It is found that the resulting abundances change by up to 5% when using the new reactivities. © 2014 American Physical Society.Peer reviewe

Super-high-resolution Earth observation datasets of North American permafrost landscapes

While temperatures are increasing on the global scale, the Arctic regions are especially vulnerable to this changing climate and landscapes underlain by permafrost experience increased thaw and degradation. The enhanced warming of organic-rich frozen ground can have severe consequences on infrastructure and ecosystems and is projected to become a highly relevant driver of greenhouse gas fluxes into the atmosphere. Degrading permafrost landscapes occur extensively in vast areas of the North American Arctic, directly affecting communities and ecosystems. To identify and quantify these widespread degradation phenomena over vast areas, we require highest-resolution Earth observation dataset that we collect during aerial imaging campaigns. We here report on observations and first results from three airborne campaigns in 2018, 2019 and 2021. We performed large-scale monitoring of permafrost-affected areas in northern Canada and Alaska, focusing on sites that experienced disturbances in the past or recently. This included sites with vulnerable settlements, coastal erosion, thaw slumping, lake expansion and drainage, ice-wedge degradation and thaw subsidence, fire scars, pingos, methane seeps, and sites affected by beaver activities. All surveys were flown with the Alfred Wegener Institute's Polar-5 and -6 scientific airplanes at 500-1500 m altitude above terrain. The onboard sensor, the Modular Aerial Camera System (MACS), a very-high-resolution multispectral camera developed by the German Aerospace Center, operated in the visible (RGB) and near-infrared (NIR) domain. From the comprehensive collection of multiple TB of gathered data, super-high-resolution (up to 7 cm/px) RGB+NIR image mosaics and stereophotogrammetric digital surface models were derived. By presenting the data and first analyses, we would like to invite the community to discuss best use for maximized benefit of the data, in order to substantially contribute to our understanding of permafrost thaw dynamics

A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: application to acetaminophen

International audienceObesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations of insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5 mM) or high (20 mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicit

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therap

Individual Effector/Regulator T Cell Ratios Impact Bone Regeneration

There is increasing evidence that T lymphocytes play a key role in controlling endogenous regeneration. Regeneration appears to be impaired in case of local accumulation of CD8+ effector T cells (TEFF), impairing endogenous regeneration by increasing a primary "useful" inflammation toward a damaging level. Thus, rescuing regeneration by regulating the heightened pro-inflammatory reaction employing regulatory CD4+ T (TReg) cells could represent an immunomodulatory option to enhance healing. Hypothesis was that CD4+ TReg might counteract undesired effects of CD8+ TEFF. Using adoptive TReg transfer, bone healing was consistently improved in mice possessing an inexperienced immune system with low amounts of CD8+ TEFF. In contrast, mice with an experienced immune system (high amounts of CD8+ TEFF) showed heterogeneous bone repair with regeneration being dependent upon the individual TEFF/TReg ratio. Thus, the healing outcome can only be improved by an adoptive TReg therapy, if an unfavorable TEFF/TReg ratio can be reshaped; if the individual CD8+ TEFF percentage, which is dependent on the individual immune experience can be changed toward a favorable ratio by the TReg transfer. Remarkably, also in patients with impaired fracture healing the TEFF/TReg ratio was higher compared to uneventful healers, validating our finding in the mouse osteotomy model. Our data demonstrate for the first time the key-role of a balanced TEFF/TReg response following injury needed to reach successful regeneration using bone as a model system. Considering this strategy, novel opportunities for immunotherapy in patients, which are at risk for impaired healing by targeting TEFF cells and supporting TReg cells to enhance healing are possible

A status report on the observability of cosmic bubble collisions

In the picture of eternal inflation as driven by a scalar potential with multiple minima, our observable universe resides inside one of many bubbles formed from transitions out of a false vacuum. These bubbles necessarily collide, upsetting the homogeneity and isotropy of our bubble interior, and possibly leading to detectable signatures in the observable portion of our bubble, potentially in the Cosmic Microwave Background or other precision cosmological probes. This constitutes a direct experimental test of eternal inflation and the landscape of string theory vacua. Assessing this possibility roughly splits into answering three questions: What happens in a generic bubble collision? What observational effects might be expected? How likely are we to observe a collision? In this review we report the current progress on each of these questions, improve upon a few of the existing results, and attempt to lay out directions for future work.Comment: Review article; comments very welcome. 24 pages + 4 appendices; 19 color figures. (Revised version adds two figures, minor edits.

Cryo-EM structural studies of the agonist complexed human TRPV4 ion-channel reveals novel structural rearrangements resulting in an open-conformation

The human transient receptor potential vanilloid 4 (hTRPV4) ion channel plays a critical role in a variety of biological processes. Whilst the activation of hTRPV4 gating properties has been reported for a broad spectrum of stimuli, including synthetic 4α-phorbols, the molecular basis of the activation is poorly understood. Here we report the novel cryo-EM structure of the hTRPV4 determined in the presence of the archetypical phorbol acid agonist, 4α-PDD. Complementary mutagenesis experiments support the EM-identified binding site as well as allowing rationalization of disruptive mutants located outside of the 4α-PDD binding site. This work represents the first structural information of hTRPV4 in a ligand-induced open conformation. Together, our data reveal the underlying molecular mechanisms resulting in the opening of the central pore and ion-channel activation and provide a structural template for designing inhibitors targeting the open-state conformation of hTRPV4