Analysis of ⁸⁵Kr: a comparison at the 10-14 level using micro-liter samples

The isotopic abundance of 85Kr in the atmosphere, currently at the level of 10−11, has increased by orders of magnitude since the dawn of nuclear age. With a half-life of 10.76 years, 85Kr is of great interest as tracers for environmental samples such as air, groundwater and ice. Atom Trap Trace Analysis (ATTA) is an emerging method for the analysis of rare krypton isotopes at isotopic abundance levels as low as 10−14 using krypton gas samples of a few micro-liters. Both the reliability and reproducibility of the method are examined in the present study by an inter-comparison among different instruments. The 85Kr/Kr ratios of 12 samples, in the range of 10−13 to 10−10, are measured independently in three laboratories: a low-level counting laboratory in Bern, Switzerland, and two ATTA laboratories, one in Hefei, China, and another in Argonne, USA. The results are in agreement at the precision level of 5%.

Measurements of Production Properties of K0S mesons and Lambda hyperons in Proton-Carbon Interactions at 31 GeV/c

Spectra of K0S mesons and Λ hyperons were measured in p+C interactions at 31 GeV/c with the large acceptance NA61/SHINE spectrometer at the CERN SPS. The data were collected with an isotropic graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections, charged pion spectra, and charged kaon spectra were previously measured using the same data set. Results on K0S and Λ production in p+C interactions serve as reference for the understanding of the enhancement of strangeness production in nucleus-nucleus collisions. Moreover, they provide important input for the improvement of neutrino flux predictions for the T2K long baseline neutrino oscillation experiment in Japan. Inclusive production cross sections for K0S and Λ are presented as a function of laboratory momentum in intervals of the laboratory polar angle covering the range from 0 up to 240 mrad. The results are compared with predictions of several hadron production models. The K0S mean multiplicity in production processes and the inclusive cross section for K0S production were measured and amount to 0.127 ± 0.005 (stat) ± 0.022 (sys) and 29.0 ± 1.6 (stat) ± 5.0 (sys) mb, respectively.

Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV/hepatitis C virus-coinfected patients

OBJECTIVES: The efficacy of current hepatitis C virus (HCV) triple therapy, including a protease inhibitor, is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response (SVR) during triple therapy and cannot wait for next-generation anti-HCV drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with silibinin before triple therapy in difficult-to-treat patients. METHODS: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon-ribavirin treatment. Intervention was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment. RESULTS: We examined six HIV/HCV-coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24. CONCLUSIONS: A lead-in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult-to-treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous failure of peginterferon-ribavirin.

The dating of dipterocarp tree rings: establishing a record of carbon cycling and climatic change in the tropics

In a first step to obtain a proxy record of past climatic events (including the El Ni (n) over tildeo-Southern Oscillation) in the normally aseasonal tropical environment of Sabah, a radial segment from a recently fallen dipterocarp (Shorea Superba) was radiocarbon dated and subjected to carbon isotope analysis. The high-precision radiocarbon results fell into the ambiguous modern plateau where several calibrated dates can exist for each sample. Dating was achieved by wiggle matching using a Bayesian approach to calibration. Using the defined growth characteristics of Shorea superba, probability density distributions were calculated and improbable dates rejected. It was found that the tree most likely started growing around AD 1660-1685. A total of 173 apparent growth increments were measured and, therefore, it could be determined that the tree formed one ring approximately every two years. Stable carbon isotope values were obtained from resin-extracted wholewood from each ring. Carbon cycling is evident in the `juvenile effect', resulting from the assimilation of respired carbon dioxide and lower light levels below the canopy, and in the `anthropogenic effect' caused by increased industrial activity in the late-nineteenth and twentieth centuries. This study demonstrates that palaeoenvironmental information can be obtained from trees growing in aseasonal environments, where climatic conditions prevent the formation of well-defined annual rings.

Dating polygenetic metamorphic assemblages along a transect across the Western Alps

Multichronometric analyses were performed on samples from a transect in the French-Italian Western Alps crossing nappes derived from the Briançonnais terrane and the Piemonte-Liguria Ocean, in an endeavour to constrain the high-pressure (HP) metamorphism and the retrogression history. 12 samples of white mica were analysed by 39Ar-40Ar stepwise heating, complemented by 2 samples from the Monte Rosa 100 km to the NE and also attributed to the Briançonnais terrane. One Sm-Nd and three Lu-Hf garnet ages from eclogites were also obtained. White mica ages decrease from ca. 300 Ma in the westernmost samples (Zone Houillère), reaching ca. 300 °C during Alpine metamorphism, to < 48 Ma in the internal units to the East, which reached ca. 500 °C during Alpine orogeny. The conventional “thermochronological” interpretation postulates Cretaceous Eo-Alpine HP metamorphism and younger “cooling ages” in the higher-temperature samples. However, Eocene Lu-Hf and Sm-Nd ages from the same samples cannot be interpreted as post-metamorphic cooling ages, which makes a Cretaceous eclogitization untenable. The age date from this transect require instead to replace conventional “thermochronology” by an approach combining age dating with detailed geochemical, petrological and microstructural investigations. Petrology reveals important mineralogical differences along the transect. Samples from the Zone Houillère mostly contain detrital mica. White mica with Si > 6.45 atoms per formula unit becomes more abundant eastward. Across the whole traverse, HP phengitic mica forms the D1 foliation. Syn-D2 mica is Si-poorer and associated with nappe stacking, exhumation, and hydrous retrogression under greenschist facies conditions. D1 phengite is very often corroded, overgrown or intergrown by syn-D2 muscovite. Most importantly, syn-D2 recrystallization is not limited to S2 schistosity domains; microchemical fingerprinting shows that it also can form pseudomorphs after crystals that could be mistaken to have formed during D1 based on microstructural arguments alone. Thereby the Cl concentration in white mica is a useful discriminator, since D2 retrogression was associated with a less saline fluid than eclogitization. Once the petrological stage is set, geochronology is straightforward. All samples contain mixtures of detrital, syn-D1 and syn-D2 mica, and retrogression phases (D3) in greatly varying proportions according to local pressure-temperature-fluid activity-deformation conditions. The correlation of age vs. Cl/K clearly identifies 47 ± 1 Ma as the age of formation of syn-D1 mica along the entire transect, including the Monte Rosa nappe samples. The inferred age of the greenschist-facies low-Si syn-D2 mica generation ranges within 39-43 Ma, with local variations. Coexistence of D1 and D2 ages, and the constancy of non-reset D1 ages along the entire transect, are strong evidence that the D1 white mica ages are very close to formation ages. Volume diffusion of Ar in white mica (activation energy E = 250 kJ/mol; pressure-adjusted diffusion coefficient D’0 < 0.03 cm2 s-1) has a subordinate effect on mineral ages compared to both prograde and retrograde recrystallization in most samples. Eocene Lu-Hf and Sm-Nd garnet ages are prograde and predate the HP peak.

Interaction of Plectin with Keratins 5 and 14: Dependence on Several Plectin Domains and Keratin Quaternary Structure.

Plectin, a cytolinker of the plakin family, anchors the intermediate filament (IF) network formed by keratins 5 and 14 (K5/K14) to hemidesmosomes, junctional adhesion complexes in basal keratinocytes. Genetic alterations of these proteins cause epidermolysis bullosa simplex (EBS) characterized by disturbed cytoarchitecture and cell fragility. The mechanisms through which mutations located after the documented plectin IF-binding site, composed of the plakin-repeat domain (PRD) B5 and the linker, as well as mutations in K5 or K14, lead to EBS remain unclear. We investigated the interaction of plectin C terminus, encompassing four domains, the PRD B5, the linker, the PRD C, and the C extremity, with K5/K14 using different approaches, including a rapid and sensitive fluorescent protein-binding assay, based on enhanced green fluorescent protein-tagged proteins (FluoBACE). Our results demonstrate that all four plectin C-terminal domains contribute to its association with K5/K14 and act synergistically to ensure efficient IF binding. The plectin C terminus predominantly interacted with the K5/K14 coil 1 domain and bound more extensively to K5/K14 filaments compared with monomeric keratins or IF assembly intermediates. These findings indicate a multimodular association of plectin with K5/K14 filaments and give insights into the molecular basis of EBS associated with pathogenic mutations in plectin, K5, or K14 genes.Journal of Investigative Dermatology advance online publication, 10 July 2014; doi:10.1038/jid.2014.255.

14C Analysis and Sample Preparation at the New Bern Laboratory for the Analysis of Radiocarbon with AMS (LARA)

The University of Bern has set up the new Laboratory for the Analysis of Radiocarbon with AMS (LARA) equipped with an accelerator mass spectrometer (AMS) MICADAS (MIni CArbon Dating System) to continue its long history of 14C analysis based on conventional counting. The new laboratory is designated to provide routine 14C dating for archaeology, climate research, and other disciplines at the University of Bern and to develop new analytical systems coupled to the gas ion source for 14C analysis of specific compounds or compound classes with specific physical properties. Measurements of reference standards and wood samples dated by dendrochronology demonstrate the quality of the 14C analyses performed at the new laboratory.

Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study

BackgroundNiemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.MethodsClinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.ResultsThe shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4¿5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.ConclusionA neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

All-Cause Mortality and Liver-Related Outcomes Following Successful Antiviral Treatment for Chronic Hepatitis C

BACKGROUND: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited. AIM: The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic. METHODS: This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma. RESULTS: A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events. CONCLUSIONS: Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years.