Nuclear targeting of the serine protease granzyme A (fragmentin-1)

Cytolytic granule-mediated target cell killing is effected in part through synergistic action of the membrane-acting protein perforin and serine proteases such as granzymes A (GrA) or B (GrB). In the present study we examine GrA cellular entry and nuclear uptake in intact mouse myeloid FDC-P1 cells exposed to perforin using confocal laser scanning microscopy, as well as reconstitute GrA nuclear uptake in vitro. GrA alone was found to be able to enter the cytoplasm of intact cells but did not accumulate in nuclei. In the presence of perforin, it specifically accumulated in the cell nuclei, with maximal levels about 2.5 times those in the cytoplasm after 2. 5 hours. In vitro, GrA accumulated in the nucleus and nucleolus maximally to levels that were four- and sixfold, respectively, those in the cytoplasm. In contrast, the active form of the apoptotic cysteine protease CPP32 did not accumulate in nuclei in vitro. Nuclear/nucleolar import of GrA in vitro was independent of ATP and not inhibitable by the non-hydrolyzable GTP analog GTPgammaS, but was dependent on exogenously added cytosol. Importantly, GrA was found to be able to accumulate in the nucleus of semi-intact cells in the presence of the nuclear envelope-permeabilizing detergent CHAPS, implying that the mechanism of nuclear accumulation was through binding to insoluble factors in the nucleus. GrB was found for the first time to be similar in this regard. The results support the contention that GrA and GrB accumulate in the nucleus through a novel nuclear import pathway, and that this is integral to induction of the nuclear changes associated with cytolytic granule-mediated apoptosis.David A. Jans, Lyndall J. Briggs, Patricia Jans, Christopher J. Froelich, Gayathri Parasivam, Sharad Kumar, Vivien R. Sutton and Joseph A. Trapan

Upgrading glass melting technology by model-based processing

[no abstract available

The influence of taphonomy on histological and isotopic analyses of treated and untreated buried modern human bone

The chemical (e.g., preservation/embalming) treatment of skeletal remains can reduce overall DNA quality and quantity. The histological and stable isotope examination of treated and untreated human remains improves our understanding of how chemical preservatives impact bone diagenesis and will determine if chemical treatment adversely affects stable isotope ratio analysis of collagen. Fidelity in the application(s) of stable isotope interpretations requires that the isotope delta (δ) values have not been altered postmortem. Re-associated antimeres and refits of chemically treated and untreated rib and long bones from eight casualties [thin-sectioned human bone (n = 43) and collagen extraction/stable isotope analysis (n = 42)] from the World War II Battle of Tarawa were examined to compare skeletal elements from the same individual that had different taphonomic histories. Histological analyses included scoring upon the Oxford Histological Index (OHI) and Birefringence scale, recording microbial invasion, and general observations. The collected data were analyzed via simple descriptive statistics and paired samples t-tests. Treated remains scored higher on the OHI and for Birefringence, indicating that bone quality was good to excellent. The untreated samples scored lower on the OHI and Birefringence scales suggesting poorer preservation than the treated remains. Histology results were supported by the isotope sample preparation results: the collagen % yield was higher for treated bone than untreated bone. Additionally, chemical preservation had no meaningful impact on isotope δ values of treated and untreated remains from the same element or pair-matched elements. Overall, treated remains exhibited good preservation while untreated remains exhibit poorer preservation with significant microfocal destruction to the extent that little histological analyses can be applied. Stable isotope ratio analysis is viable for both treated and untreated remains indicating this testing modality likely can be used for most treated remains, regardless of origin

A Tri-National program for estimating the link between snow resources and hydrological droughts

To evaluate how summer low flows and droughts are affected by the winter snowpack, a Tri-National effort will analyse data from three catchments: Alpbach (Prealps, central Switzerland), Gudjaretis-Tskali (Little Caucasus, central Georgia), and Kamenice (Jizera Mountains, northern Czech Republic). Two GIS-based rainfall-runoff models will simulate over 10 years of runoff in streams based on rain and snowfall measurements, and further meteorological variables. The models use information on the geographical settings of the catchments together with knowledge of the hydrological processes of runoff generation from rainfall, looking particularly at the relationship between spring snowmelt and summer droughts. These processes include snow accumulation and melt, evapotranspiration, groundwater recharge in spring that contributes to (the) summer runoff, and will be studied by means of the environmental isotopes 18O and 2H. Knowledge about the isotopic composition of the different water sources will allow to identify the flow paths and estimate the residence time of snow meltwater in the subsurface and its contribution to the stream. The application of the models in different nested or neighbouring catchments will explore their potential for further development and allow a better early prediction of low-flow periods in various mountainous zones across Europe. The paper presents the planned activities including a first analysis of already available dataset of environmental isotopes, discharge, snow water equivalent and modelling experiments of the (already) available datasets

Investigation of the Exclusive 3He(e,e'pp)n Reaction

Cross sections for the 3He(e,e'pp)n reaction were measured over a wide range of energy and three- momentum transfer. At a momentum transfer q=375 MeV/c, data were taken at transferred energies omega ranging from 170 to 290 MeV. At omega=220 MeV, measurements were performed at three q values (305, 375, and 445 MeV/c). The results are presented as a function of the neutron momentum in the final-state, as a function of the energy and momentum transfer, and as a function of the relative momentum of the two-proton system. The data at neutron momenta below 100 MeV/c, obtained for two values of the momentum transfer at omega=220 MeV, are well described by the results of continuum-Faddeev calculations. These calculations indicate that the cross section in this domain is dominated by direct two-proton emission induced by a one-body hadronic current. Cross section distributions determined as a function of the relative momentum of the two protons are fairly well reproduced by continuum-Faddeev calculations based on various realistic nucleon-nucleon potential models. At higher neutron momentum and at higher energy transfer, deviations between data and calculations are observed that may be due to contributions of isobar currents.Comment: 14 pages, 1 table, 17 figure

Biomass production in plantations: Land constraints increase dependency on irrigation water

Integrated assessment model scenarios project rising deployment of biomass‐using energy systems in climate change mitigation scenarios. But there is concern that bioenergy deployment will increase competition for land and water resources and obstruct objectives such as nature protection, the preservation of carbon‐rich ecosystems, and food security. To study the relative importance of water and land availability as biophysical constraints to bioenergy deployment at a global scale, we use a process‐detailed, spatially explicit biosphere model to simulate rain‐fed and irrigated biomass plantation supply along with the corresponding water consumption for different scenarios concerning availability of land and water resources. We find that global plantation supplies are mainly limited by land availability and only secondarily by freshwater availability. As a theoretical upper limit, if all suitable lands on Earth, besides land currently used in agriculture, were available for bioenergy plantations (“Food first” scenario), total plantation supply would be in the range 2,010–2,300 EJ/year depending on water availability and use. Excluding all currently protected areas reduces the supply by 60%. Excluding also areas where conversion to biomass plantations causes carbon emis- sions that might be considered unacceptably high will reduce the total plantation supply further. For example, excluding all areas where soil and vegetation carbon stocks exceed 150 tC/ha (“Carbon threshold savanna” scenario) reduces the supply to 170–290 EJ/year. With decreasing land availability, the amount of water available for irrigation becomes vitally important. In the least restrictive land availability scenario (“Food first”), up to 77% of global plantation biomass supply is obtained without additional irrigation. This share is reduced to 31% for the most restrictive “Carbon threshold savanna” scenario. The results highlight the critical —and geographically varying—importance of co‐managing land and water resources if substantial contributions of bioenergy are to be reached in mitigation portfolios

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed

Performance of the LHCb Vertex Detector Alignment Algorithm determined with Beam Test Data

LHCb is the dedicated heavy flavour experiment at the Large Hadron Collider at CERN. The partially assembled silicon vertex locator (VELO) of the LHCb experiment has been tested in a beam test. The data from this beam test have been used to determine the performance of the VELO alignment algorithm. The relative alignment of the two silicon sensors in a module and the relative alignment of the modules has been extracted. This alignment is shown to be accurate at a level of approximately 2 micron and 0.1 mrad for translations and rotations, respectively in the plane of the sensors. A single hit precision at normal track incidence of about 10 micron is obtained for the sensors. The alignment of the system is shown to be stable at better than the 10 micron level under air to vacuum pressure changes and mechanical movements of the assembled system.Comment: accepted for publication in NIM