Permeability and Groundwater Flow Dynamics in Deep‐Reaching Orogenic Faults Estimated From Regional‐Scale Hydraulic Simulations

Numerical modeling is used to understand the regional scale flow dynamics of the fault-hosted orogenic geothermal system at the Grimsel Mountain Pass in the Swiss Alps. The model is calibrated against observations from thermal springs discharging in a tunnel some 250 m underneath Grimsel Pass to derive estimates for the bulk permeability of the fault. Simulations confirm that without the fault as a hydraulic conductor the thermal springs would not exist. Regional topography alone drives meteoric water in a single pass through the fault plane where it penetrates to depths exceeding 10 km and acquires temperatures in excess of 250°C. Thermal constraints from the thermal springs at Grimsel Pass suggest bulk fault permeabilities in the range of 2e−15 m2–4.8e−15 m2. Reported residence times of >30,000 and 7 years for the deep geothermal and shallow groundwater components in the thermal spring water, respectively, suggest fault permeabilities of around 2.5e−15 m2. We show that the long residence time of the deep geothermal water is likely a consequence of low recharge rates during the last glaciation event in the Swiss Alps, which started some 30,000 years ago. Deep groundwater discharging at Grimsel Pass today thus infiltrated the Grimsel fault prior to the last glaciation event. The range of permeabilities estimated from observational constraints is fully consistent with a subcritical single-pass flow system in the fault plane

Effect of Glacial/Interglacial Recharge Conditions on Flow of Meteoric Water Through Deep Orogenic Faults: Insights Into the Geothermal System at Grimsel Pass, Switzerland

Many meteoric-recharged, fault-hosted geothermal systems in amagmatic orogenic belts have been active through the Pleistocene glacial/interglacial climate fluctuations. The effects of climate-induced recharge variations on fluid flow patterns and residence times of the thermal waters are complex and may influence how the geothermal and mineralization potential of the systems are evaluated. We report systematic thermal-hydraulic simulations designed to reveal the effects of recharge variations, using a model patterned on the orogenic geothermal system at Grimsel Pass in the Swiss Alps. Previous studies have shown that fault-bounded circulation of meteoric water is driven to depths of ∼10 km by the high alpine topography. Simulations suggest that the current single-pass flow is typical of interglacial periods, during which (a) meteoric recharge into the fault is high (above tens of centimeters per year), (b) conditions are at or somewhat below the critical Rayleigh number, and (c) hydraulic connectivity along the fault plane is extensive (an extent of at least 10 km into increasingly higher terrain is required to explain the 10 km penetration depth). The subcritical condition constrains the bulk fault permeability to <1e-14 m2. In contrast, the limited recharge during the numerous Pleistocene glaciation events likely induced a layered flow system, with single-pass flow confined to shallow depths while non-Rayleigh convection occurred deeper in the fault. The same layering can be observed at low aspect ratios (length/depth) of the fault plane, when the available recharge area limits flux through the fault

Reaction Mechanism and Water/Rock Ratios Involved in Epidosite Alteration of the Oceanic Crust

Epidosites are a prominent type of subseafloor hydrothermal alteration of basalts in ophiolites and greenstone belts, showing an end-member mineral assemblage of epidote + quartz + titanite + Fe-oxide. Epidosites are known to form within crustal-scale upflow zones and their fluids have been proposed as deep equivalents of black-smoker seafloor vent fluids. Proposals of the mass of fluid per mass of rock (W/R ratio) needed to form epidosites are contradictory, varying from 20 (Sr isotopes) to > 1,000 (Mg mobility). To test these proposals we have conducted a petrographic, geochemical and reactive-transport numerical simulation study of the chemical reaction that generates km3-size epidosite zones within the lavas and sheeted dike complex of the Samail ophiolite, Oman. At 250–400°C the modeled epidosite-forming fluid has near-neutral pH (∼ 5.2), high fO2, low sulfur and very low Fe (10−6 mol/kg) contents. These features argue against a genetic link with black-smoker fluids. Chemical buffering by the epidosite fluid enriches the precursor spilites in Ca and depletes them in Na and Mg. Completion of the spilite-to-epidosite reaction requires enormous W/R ratios of 700–∼40,000, depending on initial Mg content and temperature. Collectively, the variably altered rocks in the Samail epidosite zones record flow of ∼1015 kg of fluid through each km3 of precursor spilite rock. This fluid imposed on the epidosite an Sr-isotope signature inherited from the previous rock-buffered chemical evolution of the fluid through the oceanic crust, thereby explaining the apparently contradictory low W/R ratios based on Sr isotopes

Observation of open scattering channels

The existence of fully transmissive eigenchannels ("open channels") in a random scattering medium is a counterintuitive and unresolved prediction of random matrix theory. The smoking gun of such open channels, namely a bimodal distribution of the transmission efficiencies of the scattering channels, has so far eluded experimental observation. We observe an experimental distribution of transmission efficiencies that obeys the predicted bimodal Dorokhov-Mello-Pereyra-Kumar distribution. Thereby we show the existence of open channels in a linear optical scattering system. The characterization of the scattering system is carried out by a quantum-optical readout method. We find that missing a single channel in the measurement already prevents detection of the open channels, illustrating why their observation has proven so elusive until now. Our work confirms a long-standing prediction of random matrix theory underlying wave transport through disordered systems.Comment: 9 pages including methods and supplementary materials. 3 figure

Resolving mechanisms of immune-mediated disease in primary CD4 T cells

ABSTRACT Deriving mechanisms of immune-mediated disease from GWAS data remains a formidable challenge, with attempts to identify causal variants being frequently hampered by linkage disequilibrium. To determine whether causal variants could be identified via their functional effects, we adapted a massively-parallel reporter assay for use in primary CD4 T-cells, key effectors of many immune-mediated diseases. Using the results to guide further study, we provide a generalisable framework for resolving disease mechanisms from non-coding associations – illustrated by a locus linked to 6 immune-mediated diseases, where the lead functional variant causally disrupts a super-enhancer within an NF-κB-driven regulatory circuit, triggering unrestrained T-cell activation

The Expansion of the PRAME Gene Family in Eutheria

The PRAME gene family belongs to the group of cancer/testis genes whose expression is restricted primarily to the testis and a variety of cancers. The expansion of this gene family as a result of gene duplication has been observed in primates and rodents. We analyzed the PRAME gene family in Eutheria and discovered a novel Y-linked PRAME gene family in bovine, PRAMEY, which underwent amplification after a lineage-specific, autosome-to-Y transposition. Phylogenetic analyses revealed two major evolutionary clades. Clade I containing the amplified PRAMEYs and the unamplified autosomal homologs in cattle and other eutherians is under stronger functional constraints; whereas, Clade II containing the amplified autosomal PRAMEs is under positive selection. Deep-sequencing analysis indicated that eight of the identified 16 PRAMEY loci are active transcriptionally. Compared to the bovine autosomal PRAME that is expressed predominantly in testis, the PRAMEY gene family is expressed exclusively in testis and is up-regulated during testicular maturation. Furthermore, the sense RNA of PRAMEY is expressed specifically whereas the antisense RNA is expressed predominantly in spermatids. This study revealed that the expansion of the PRAME family occurred in both autosomes and sex chromosomes in a lineage-dependent manner. Differential selection forces have shaped the evolution and function of the PRAME family. The positive selection observed on the autosomal PRAMEs (Clade II) may result in their functional diversification in immunity and reproduction. Conversely, selective constraints have operated on the expanded PRAMEYs to preserve their essential function in spermatogenesis

Intrapersonal and interpersonal dimensions of cancer perception: a confirmatory factor analysis of the cancer experience and efficacy scale (CEES)

Purpose Sociocultural factors influence psychological adjustment to cancer in Asian patients in two major ways: Prioritization of relationships over individual orientations and belief in the efficacy of interpersonal cooperation. We derived and validated among Chinese colorectal cancer (CRC) patients an instrument assessing cancer perceptions to enable the study of the sociocultural processes. Patients and methods Qualitative interviews (n=16) derived 15 items addressing interpersonal experience in Chinese CRC patients' adjustment. These 15 items and 18 corresponding self-referent items were administered to 166 Chinese CRC survivors and subjected to exploratory factor analysis (EFA) to establish the initial scale structure and reliability. The final 29 items, together with other psychometric measures, were administered to a second cohort of 215 CRC patients and subjected to confirmatory factor analysis (CFA). Results EFA (63.35% of the total variance) extracted six factors: Personal strain, socioeconomic strain, emotional strain, personal efficacy, collective efficacy, and proxy efficacy. CFA confirmed the psychometric structure [?2(df)=702.91 (368); Comparative Fit Index=0.95; Nonnormed Fit Index= 0.94; Incremental Fit Index=0.95; standardized root mean square residual=0.08] of the six factors by using a model with two latent factors: Experience and efficacy. All subscales were reliable (a=0.76-0.92). Appropriate correlations with adjustment outcomes (symptom distress, psychological morbidity, and subjective well-being), optimistic personalities, and social relational quality indicated its convergent and divergent validity. Known group comparisons (i.e., age, active treatment, and colostomy) showed its clinical utility. Conclusion The cancer experience and efficacy scale is a valid multidimensional instrument for assessing intrapersonal and interpersonal dimensions of cancer experience in Asian patients, potentiating existing patient-reported outcome measures. © Springer-Verlag 2009.published_or_final_versionSpringer Open Choice, 01 Dec 201

The ETS Family Member TEL Binds to Nuclear Receptors RAR and RXR and Represses Gene Activation

Retinoic acid receptor (RAR) signaling is important for regulating transcriptional activity of genes involved in growth, differentiation, metabolism and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a member of the ETS family of transcription factors, is a DNA-binding transcriptional repressor. Here, we identify TEL as a transcriptional repressor of RAR signaling by its direct binding to both RAR and its dimerisation partner, the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in two isoforms, created by the use of an alternative startcodon at amino acid 43. Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form of TEL represses RAR signaling much more efficiently. Binding studies revealed that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have shown that repression by TEL does not involve recruitment of histone deacetylases and suggest that polycomb group proteins participate in the process