Multi-Method Chronometric Constraints on the Thermal, Structural and Morphotectonic Evolution of the Eastern and Western Sierras Pampeanas with Special Emphasis on K-Ar Dating of Fault Gouges

Die hier präsentierte Studie umfasst detaillierte Untersuchungen zur thermochronologischen, strukturellen sowie morphologischen Entwicklung der Östlichen und Westlichen Sierras Pampeanas in Argentinien, zwischen 26°S to 34°S südlicher Breite. Kapitel 3 diskutiert thermochronologische Daten (Apatit Spaltspuren, Zirkon und Apatit (U-Th)/He) sowie K-Ar Illit-Datierung an Störungsletten aus der Sierra de Comechingones sowie Ar-Ar Alter an Vulkaniten des vulkanischen Gürtels von San Luis (Östliche Sierras Pampeanas). K-Ar Illitalter belegen den Beginn spröder Deformation vor etwa 340 Ma. Thermochronologische Daten dokumentieren geringe Exhumationsraten seit dem späten Paläozoikum sowie eine maximale Exhumierung von etwa 2,3 km seit der späten Kreidezeit. Ar-Ar Datierungen an vulkanischen Gesteinen des San Luis Vulkanischen Gürtels ergeben Alter zwischen 7,54 Ma und 1,91 Ma. Dies belegt ein ostwärts gerichtetes Fortschreiten der magmatischen Front, welches mit einer Verflachung des Subduktionswinkels der Nazca Platte unter die Südamerikanische Platte vor etwa 11.2 Ma assoziiert wird. Darüber hinaus deuten die hier präsentierten thermochronologischen Daten an, dass der Anteil Andiner Exhumation und Hebung an der Gesamthebung und Exhumation der Sierras Pampeanas von geringer ist als gemeinhin angenommen. Kapitel 4 präsentiert Ergebnisse von Niedrig-Temperatur thermochronologischen Untersuchungen sowie K-Ar Alter retrograd gewachsener Illite aus spröden Störungszonen der Sierra de San Luis (Östliche Sierras Pampeanas). K-Ar Illitalter belegen eine lang andauernde Aktivität spröder Deformation welche unmittelbar nach dem Ende der Chanic Phase der Famatinischen Orogenese vor etwa 320 Ma einsetzte und zeitlich mit dem Übergang von duktilen zu spröden Deformationsmechanismen übereinstimmt. Jüngste Illitlater liegen zwischen 222-172 Ma. Diese können als Abkühlalter des Grundgebirges unter die zur Illitbildung benötigten Temperaturen interpretiert werden, jedoch nicht als Ende der spröden Deformation. Diese Interpretation wird von den Ergebnissen thermochronologischer Untersuchungen bestätigt. (U-Th)/He Datierungen an Apatiten und Zirkonen, sowie Apatit Spaltspuranalysen dokumentieren die Exhumation seit dem Perm, welche möglicherweise in Verbindung zur San Rafael Orogenese steht. Die ermittelten Abkühlalter belegen geringe Exhumationsraten sowie die damit einhergehende lange Verweildauer der Proben in den Temperaturbereichen der partial annealing bzw. parial retention zone von Apatit und Zirkon (PRZA, PRZZ und PAZA). Die finale Abkühlung auf Oberflächentemperaturen fand im Verlauf des Jura und der späten Kreide statt. Die Abkühlgeschichten der Sierra de San Luis und Sierra de Comechingones werden in einem Entwicklungsmodel zusammengefasst, welches signifikante Unterschiede in der thermischen Entwicklung beider Gebirgszüge offenbart. Kapitel 5 diskutiert die thermochronologische Entwicklung der Sierra de Pie de Palo, einem ausgeprägten Höhenzug in den Westlichen Sierras Pampeanas. Thermochronologische Untersuchungen zeigen das die strukturelle Entwicklung der Sierra Pie de Palo bereits im späten Paläozoikum einsetzte und von jeher durch tektonisch kontrollierte Erosion geprägt wurde, welche sich im Verlauf des Mesozoikums aufgrund extensionaler Tektonik zwar verlangsamte, jedoch andauerte. Die heutige Topographie des Gebirgszuges bildete sich im Zuge Andiner Kompression im Verlauf des Späten Mesozoikums und Paläogens durch die Hebung und damit einhergehender Denudation einzelner Grundgebirgsblöcke. Die mit der Hebung assoziierte Deformation schritt dabei von Ost nach West voran. Der Gesamtbetrag vertikaler Hebung seit dem frühen Paläozoikum kann auf ca. 3,7-4,3 km eingegrenzt werden, wobei die Gesamtexhumation etwa 1,7-2,2 km bei einer Exhumationsrate von 0,03-0,04 mm/a beträgt. Kapitel 6 stellt eine Methode zur Interpretation von K-Ar Illit Feinfraktionsaltern aus Störungsletten aus nichtsedimentären Gesteinen vor. Gemäß der vorgestellten Methode werden die ermittelten K Ar Illitalter in Kombination mit den Untersuchungsergebnissen unabhängiger Parameter, z.B. Illitkristallinität, Illit-Polytypie und Polytyp-Quantifizierung, Korngröße, Tonmineralogie, K-Ar Abkühlaltern des Nebengesteins sowie mit Ergebnissen thermochronologischer Untersuchungen (AHe, ZHe, AFT) evaluiert. Dieser Interpretationsansatz wird im Rahmen einer regionalen Studie innerhalb der Östlichen Sierras Pampeanas exemplarisch angewandt. Im Zuge dessen wurde eine große Zahl von Störungsletten systematisch beprobt und analysiert. Ermittelte K-Ar Illitalter decken die Zeitspanne vom Devon bis in die Kreidezeit und dokumentieren eine lang anhaltende Phase bruchhafter Deformation in der Region. Alter >320 Ma sind synchron mit einer Periode kompressiver intra-Platten Tektonik, während Permische und Triassische Alter mit einer Periode flacher Subduktion der Farallon Platte unter die Südamerikansche Platte assoziiert werden können. Darüber hinaus belegen die K-Ar Illitalter ein von Nord nach Süd Fortschreiten der spröden Deformation in den Sierras de San Luis und Comechingones. Die Integrität und Konsistenz der analysierten Daten belegt die Leistungsfähigkeit und tektonische Signifikanz der hier vorgestellten Methode, welche somit einen bedeutenden Beitrag zur Entschlüsselung komplexer Abkühlungs- und Deformationsereignisse bieten kann. Jedoch kann gezeigt werden, dass die Aussagekraft der hier vorgestellten Methode stark von der Abkühlgeschichte des Untersuchungsgebietes abhängt. Kapitel 7 präsentiert thermochronologische Daten aus den gesamten Sierras Pampeanas. Darüber hinaus werden alle verfügbaren thermochronologischen und geochronologischen Daten zur Abkühlgeschichte der Sierras Pampeanas diskutiert und in ein Abkühlmodell zusammengefasst. Die Daten belegen eine Abkühlung unter 200°C im Verlauf des Karbons. Im Verlauf des Perms und der Trias schritt die Abkühlung von West nach Ost fort, räumlich und zeitlich einhergehend mit dem fortschreiten eines flachen Subduktionsereignisses der Farallon-Platte unter die heutige Südamerikanische Platte. Mesozoische Riftereignisse und damit einhergehende Sedimentation und Versenkung zeigen nur lokal Einfluss auf die ermittelten Abkühlalter. Dies deutet darauf hin, dass die zum Verlust der Altersinformation der thermochronologischen Systeme notwenige Versenkungstiefen nur entlang der schmalen, räumlich eingeschränkten Kretazischen Riftbecken erreicht werden. Die finale Abkühlung auf Oberflächentemperaturen verlief diachron in den nördlichen und südlichen Sierras Pampeanas. So können im Norden Neogene Alter beobachtet werden, während die südlichen und westlichen Sierras Pampeanas spätestens seit der Kreide bzw. frühen Paleogens auf Oberflächentemperaturen abgekühlt waren. Letzteres deutet auf die Existenz einer positiven Topographie in den südlichen Sierras Pampeanas, bereits vor dem Einsetzen Cenozoischen Andinen Kompression und der im Neogenen einsetzenden flachen Subduktion der Nazca-Platte hin. Dies wiederum wiederspricht der allgemein akzeptierten Hypothese, dass die Exhumation und Hebung der Sierras Pampeanas allein mit der Neogenen flachen Subduktion der Nazca-Platte in Verbindung stehen. Im Gegensatz dazu wird vorgeschlagen, dass diese Neogenen Prozesse lediglich zu einer Überprägung und Akzentuierung des bereits existierenden Reliefs führten. Diese Vermutung kann durch die Berechnung auffallend niedriger Denudationsraten in den Östlichen und Westlichen Sierras Pampeanas von 0,010 0,024 km/a gestützt werden, welche auf stabile Bedingungen, zumindest seit der späten Kreidezeit, hindeuten

Dissolved noble gases and stable isotopes as tracers of preferential fluid flow along faults in the Lower Rhine Embayment, Germany

Groundwater in shallow unconsolidated sedimentary aquifers close to the Bornheim fault in the Lower Rhine Embayment (LRE), Germany, has relatively low δ2H and δ18O values in comparison to regional modern groundwater recharge, and 4He concentrations up to 1.7 × 10−4 cm3 (STP) g–1 ± 2.2 % which is approximately four orders of magnitude higher than expected due to solubility equilibrium with the atmosphere. Groundwater age dating based on estimated in situ production and terrigenic flux of helium provides a groundwater residence time of ∼107 years. Although fluid exchange between the deep basal aquifer system and the upper aquifer layers is generally impeded by confining clay layers and lignite, this study’s geochemical data suggest, for the first time, that deep circulating fluids penetrate shallow aquifers in the locality of fault zones, implying  that sub-vertical fluid flow occurs along faults in the LRE. However, large hydraulic-head gradients observed across many faults suggest that they act as barriers to lateral groundwater flow. Therefore, the geochemical data reported here also substantiate a conduit-barrier model of fault-zone hydrogeology in unconsolidated sedimentary deposits, as well as corroborating the concept that faults in unconsolidated aquifer systems can act as loci for hydraulic connectivity between deep and shallow aquifers. The implications of fluid flow along faults in sedimentary basins worldwide are far reaching and of particular concern for carbon capture and storage (CCS) programmes, impacts of deep shale gas recovery for shallow groundwater aquifers, and nuclear waste storage sites where fault zones could act as potential leakage pathways for hazardous fluids

A novel pathogenic CACNA1A variant causing episodic ataxia type 2 (EA2) spectrum phenotype in four family members and a novel combined therapy

Objective!#!The safety and efficacy of surgical microvascular decompression (MVD) in elderly patients with trigeminal neuralgia (TN) is controversially discussed in the literature. A widespread reluctance to expose this cohort to major intracranial surgery persists. Our aim was to compare the efficacy and safety between older and younger patients with TN.!##!Methods!#!In this cross-sectional study, 139 MVD procedures (103 patients < 70 and 36 patients ≥ 70) were included. Surgical fitness was assessed by the American Society of Anesthesiology (ASA) grade. The pain-free interval was evaluated using Kaplan-Meier analysis only in patients with a recent follow-up visit. Independent risk factors for recurrence in patients with a minimum 12-month follow-up were determined.!##!Results!#!Patients ≥ 70 showed a significantly higher number of comorbidities. Pain intensity, affection of trigeminal branches and symptom duration was similar between groups. No significant difference in treatment associated complications and permanent neurological deficits was shown. There was no treatment-related mortality. A tendency towards a lower recurrence rate in patients < 70 did not reach statistical significance (17.6% vs. 28.6%, P = 0.274). Pain-free interval was not different between both cohorts (78.7 vs. 73.5 months, P = 0.391).!##!Conclusion!#!Despite a higher prevalence of comorbidities in elderly patients, complication rates and neurological deficits after MVD were comparable to younger patients. Rates of immediate and long-term pain relief compared favorably to previous studies and were similar between elderly and younger patients. These data endorse MVD as a safe and effective first-line surgical procedure for elderly patients with TN and neurovascular conflict on MRI

Transcriptional effects of copy number alterations in a large set of human cancers

Copy number alterations (CNAs) can promote tumor progression by altering gene expression levels. Due to transcriptional adaptive mechanisms, however, CNAs do not always translate proportionally into altered expression levels. By reanalyzing >34,000 gene expression profiles, we reveal the degree of transcriptional adaptation to CNAs in a genome-wide fashion, which strongly associate with distinct biological processes. We then develop a platform-independent method-transcriptional adaptation to CNA profiling (TACNA profiling)-that extracts the transcriptional effects of CNAs from gene expression profiles without requiring paired CNA profiles. By applying TACNA profiling to >28,000 patient-derived tumor samples we define the landscape of transcriptional effects of CNAs. The utility of this landscape is demonstrated by the identification of four genes that are predicted to be involved in tumor immune evasion when transcriptionally affected by CNAs. In conclusion, we provide a novel tool to gain insight into how CNAs drive tumor behavior via altered expression levels

Using Distributed Temperature Sensing to monitor field scale dynamics of ground surface temperature and related substrate heat flux

We present one of the first studies of the use of Distributed Temperature Sensing (DTS) along fibre-optic cables to purposely monitor spatial and temporal variations in ground surface temperature (GST) and soil temperature, and provide an estimate of the heat flux at the base of the canopy layer and in the soil. Our field site was at a groundwater-fed wet meadow in the Netherlands covered by a canopy layer (between 0-0.5 m thickness) consisting of grass and sedges. At this site, we ran a single cable across the surface in parallel 40 m sections spaced by 2 m, to create a 40×40 m monitoring field for GST. We also buried a short length (≈10 m) of cable to depth of 0.1±0.02 m to measure soil temperature. We monitored the temperature along the entire cable continuously over a two-day period and captured the diurnal course of GST, and how it was affected by rainfall and canopy structure. The diurnal GST range, as observed by the DTS system, varied between 20.94 and 35.08◦C; precipitation events acted to suppress the range of GST. The spatial distribution of GST correlated with canopy vegetation height during both day and night. Using estimates of thermal inertia, combined with a harmonic analysis of GST and soil temperature, substrate and soil-heat fluxes were determined. Our observations demonstrate how the use of DTS shows great promise in better characterising area-average substrate/soil heat flux, their spatiotemporal variability, and how this variability is affected by canopy structure. The DTS system is able to provide a much richer data set than could be obtained from point temperature sensors. Furthermore, substrate heat fluxes derived from GST measurements may be able to provide improved closure of the land surface energy balance in micrometeorological field studies. This will enhance our understanding of how hydrometeorological processes interact with near-surface heat fluxes

Distributed temperature sensing as a down-hole tool in hydrogeology

Distributed Temperature Sensing (DTS) technology enables down-hole temperature monitoring to study hydrogeological processes at unprecedentedly high frequency and spatial resolution. DTS has been widely applied in passive mode in site investigations of groundwater flow, in-well flow, and subsurface thermal property estimation. However, recent years have seen the further development of the use of DTS in an active mode (A-DTS) for which heat sources are deployed. A suite of recent studies using A-DTS down-hole in hydrogeological investigations illustrate the wide range of different approaches and creativity in designing methodologies. The purpose of this review is to outline and discuss the various applications and limitations of DTS in down-hole investigations for hydrogeological conditions and aquifer geological properties. To this end, we first review examples where passive DTS has been used to study hydrogeology via down-hole applications. Secondly, we discuss and categorize current A-DTS borehole methods into three types. These are thermal advection tests, hybrid cable flow logging, and heat pulse tests. We explore the various options with regards to cable installation, heating approach, duration, and spatial extent in order to improve their applicability in a range of settings. These determine the extent to which each method is sensitive to thermal properties, vertical in well flow, or natural gradient flow. Our review confirms that the application of DTS has significant advantages over discrete point temperature measurements, particularly in deep wells, and highlights the potential for further method developments in conjunction with other emerging fiber optic based sensors such as Distributed Acoustic Sensing. This article is protected by copyright. All rights reserved

Effect of volcanic dykes on coastal groundwater flow and saltwater intrusion : a field-scale multiphysics approach and parameter evaluation

Acknowledgments This research was primarily based on research grant‐aided by the Irish Department of Communications, Energy and Natural Resources under the National Geoscience Programme 2007–2013. It also benefited from complementary funding from the Scottish Alliance for Geoscience, Environment and Society (SAGES). We acknowledge the contribution in data acquisition of the MSc students in Environmental Engineering at Queen's University Belfast, the landowner for access to the inland fields and the Department of Geography, Archaeology and Paleoecology at QUB for provision of the tidal model of Belfast Lough. The data used are listed in the references, tables, and figures and are available from the corresponding author upon demand. We acknowledge the constructive comments by the Associate Editor and three reviewers, which helped in improving the final manuscript.Peer reviewedPublisher PD

Cyclin E expression is associated with high levels of replication stress in triple-negative breast cancer

Replication stress entails the improper progression of DNA replication. In cancer cells, including breast cancer cells, an important cause of replication stress is oncogene activation. Importantly, tumors with high levels of replication stress may have different clinical behavior, and high levels of replication stress appear to be a vulnerability of cancer cells, which may be therapeutically targeted by novel molecularly targeted agents. Unfortunately, data on replication stress is largely based on experimental models. Further investigation of replication stress in clinical samples is required to optimally implement novel therapeutics. To uncover the relation between oncogene expression, replication stress, and clinical features of breast cancer subgroups, we immunohistochemically analyzed the expression of a panel of oncogenes (Cyclin E, c-Myc, and Cdc25A,) and markers of replication stress (phospho-Ser33-RPA32 and γ-H2AX) in breast tumor tissues prior to treatment (n = 384). Triple-negative breast cancers (TNBCs) exhibited the highest levels of phospho-Ser33-RPA32 (P < 0.001 for all tests) and γ-H2AX (P < 0.05 for all tests). Moreover, expression levels of Cyclin E (P < 0.001 for all tests) and c-Myc (P < 0.001 for all tests) were highest in TNBCs. Expression of Cyclin E positively correlated with phospho-RPA32 (Spearman correlation r = 0.37, P < 0.001) and γ-H2AX (Spearman correlation r = 0.63, P < 0.001). Combined, these data indicate that, among breast cancers, replication stress is predominantly observed in TNBCs, and is associated with expression levels of Cyclin E. These results indicate that Cyclin E overexpression may be used as a biomarker for patient selection in the clinical evaluation of drugs that target the DNA replication stress response

Functional genomic mRNA profiling of a large cancer data base demonstrates mesothelin overexpression in a broad range of tumor types

The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays. This technique was used in a database comprising 19,746 tumors to identify for 41 tumor types the percentage of samples with an overexpression of MSLN compared to a normal background. A literature search was performed to compare the FGM profiling data with studies reporting IHC MSLN tumor expression. FGM profiling showed MSLN overexpression in gastrointestinal (12-36%) and gynecological tumors (20-66%), non-small cell lung cancer (21%) and synovial sarcomas (30%). The overexpression found in thyroid cancers (5%) and renal cell cancers (10%) was not yet reported with IHC analyses. We observed that MSLN amplification rate within esophageal cancer depends on the histotype (31% for adenocarcinomas versus 3% for squamous-cell carcinomas). Subset analysis in breast cancer showed MSLN amplification rates of 28% in triple-negative breast cancer (TNBC) and 33% in basal-like breast cancer. Further subtype analysis of TNBCs showed the highest amplification rate (42%) in the basal-like 1 subtype and the lowest amplification rate (9%) in the luminal androgen receptor subtype