Regulation of cargo transfer between ESCRT-0 and ESCRT-I complexes by flotillin-1 during endosomal sorting of ubiquitinated cargo

Ubiquitin-dependent sorting of membrane proteins in endosomes directs them to lysosomal degradation. In the case of receptors such as the epidermal growth factor receptor (EGFR), lysosomal degradation is important for the regulation of downstream signalling. Ubiquitinated proteins are recognised in endosomes by the endosomal sorting complexes required for transport (ESCRT) complexes, which sequentially interact with the ubiquitinated cargo. Although the role of each ESCRT complex in sorting is well established, it is not clear how the cargo is passed on from one ESCRT to the next. We here show that flotillin-1 is required for EGFR degradation, and that it interacts with the subunits of ESCRT-0 and -I complexes (hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and Tsg101). Flotillin-1 is required for cargo recognition and sorting by ESCRT-0/Hrs and for its interaction with Tsg101. In addition, flotillin-1 is also required for the sorting of human immunodeficiency virus 1 Gag polyprotein, which mimics ESCRT-0 complex during viral assembly. We propose that flotillin-1 functions in cargo transfer between ESCRT-0 and -I complexes

Effects of prolonged anoxia on electrical activity of the heart in Crucian carp (Carassius carassius)

The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored. Heart rate variability greatly increased under anoxia, and completely recovered under re-oxygenation. The RT interval increased from 2.8±0.34 s in normoxia to 5.8±0.44 s under anoxia (P<0.05), which reflects a doubling of the ventricular action potential (AP) duration. Acclimatisation to winter induced extensive changes in gene expression relative to summer-acclimatised fish, including depression in those coding for the sarcoplasmic reticulum calcium pump (Serca2-q2) and ATP-sensitive K(+) channels (Kir6.2) (P<0.05). Genes of delayed rectifier K(+) (kcnh6) and Ca(2+) channels (cacna1c) were up-regulated in winter fish (P<0.05). In contrast, the additional challenge of anoxia caused only minor changes in gene expression, e.g. depressed expression of Kir2.2b K(+) channel gene (kcnj12b), whereas expression of Ca(2+) (cacna1a, -c and -g) and Na(+) channel genes (scn4a and scn5a) were not affected. These data suggest that low temperature pre-conditions the Crucian carp heart for winter anoxia, whereas sustained anoxic bradycardia and prolongation of AP duration are directly induced by oxygen shortage without major changes in gene expression

Calculated beam quality correction factors for ionization chambers in MV photon beams

The beam quality correction factor, , which corrects for the difference in the ionization chamber response between the reference and clinical beam quality, is an integral part of radiation therapy dosimetry. The uncertainty of is one of the most significant sources of uncertainty in the dose determination. To improve the accuracy of available data, four partners calculated factors for 10 ionization chamber models in linear accelerator beams with accelerator voltages ranging from 6 MV to 25 MV, including flattening-filter-free (FFF) beams. The software used in the calculations were EGSnrc and PENELOPE, and the ICRU report 90 cross section data for water and graphite were included in the simulations. Volume averaging correction factors were calculated to correct for the dose averaging in the chamber cavities. A comparison calculation between partners showed a good agreement, as did comparison with literature. The values from TRS-398 were higher than our values for each chamber where data was available. The values for the FFF beams did not follow the same , relation as beams with flattening filter (values for 10 MV FFF beams were below fits made to other data on average by 0.3%), although our FFF sources were only for Varian linacs.Peer reviewe

Balancing profitability of energy production, societal impacts and biodiversity in offshore wind farm design

The global demand for renewable energy is on the rise. Expansion of onshore wind energy is in many parts of the world limited by societal acceptance, and also ecological impacts are a concern. Here, pragmatic methods are developed for the integration of high-dimensional spatial data in offshore wind energy planning. Over 150 spatial data layers are created, which either oppose or support offshore wind energy development, and represent ecological, societal, and economic factors. The method is tested in Finland, where interest in developing offshore wind energy is growing. Analyses were done using a spatial prioritization approach, originally developed for the prioritization of high dimensional ecological data, and rarely used in planning offshore wind energy. When all criteria are integrated, it is possible to find a balanced solution where offshore wind farms cause little disturbance to biodiversity and society, while at the same time yielding high profitability for wind energy production. Earlier proposed areas for offshore wind farms were also evaluated. They were generally well suited for wind power, with the exception of a couple of areas with comparatively high environmental impacts. As an outcome, new areas well suited for large scale wind power deployment were recognized, where construction costs would be moderate and disturbance to biodiversity, marine industries and people limited. A novel tradeoff visualization method was also developed for the conflicts and synergies of offshore energy deployment, which could ease the dialogue between different stakeholders in a spatial planning context. Overall, this study provides a generic and transparent approach for well-informed analysis of offshore wind energy development potential when conflict resolution between biodiversity, societal factors and economic profits is needed. The proposed approach is replicable elsewhere in the world. It is also structurally suitable for the planning of impact avoidance and conflict resolution in the context of other forms of construction or resource extraction.Peer reviewe

Vacuum Rabi splitting and strong coupling dynamics for surface plasmon polaritons and Rhodamine 6G molecules

We report on strong coupling between surface plasmon polaritons (SPP) and Rhodamine 6G (R6G) molecules, with double vacuum Rabi splitting energies up to 230 and 110 meV. In addition, we demonstrate the emission of all three energy branches of the strongly coupled SPP-exciton hybrid system, revealing features of system dynamics that are not visible in conventional reflectometry. Finally, in analogy to tunable-Q microcavities, we show that the Rabi splitting can be controlled by adjusting the interaction time between waveguided SPPs and R6G deposited on top of the waveguide. The interaction time can be controlled with sub-fs precision by adjusting the length of the R6G area with standard lithography methods.Comment: 4 pages, 4 figure

First-principles simulation of intrinsic collision cascades in KCl and NaCl to test interatomic potentials at energies between 5 and 350 eV

Theoretical interatomic potentials for KCl and NaCl are tested at energies 5–350 eV against experimental data from intrinsic collision cascades. The collisional scattering of Cl with Cl, K, and Na atoms was observed from Doppler-shifted γ rays depopulating an excited state in recoiling Cl36 produced through the thermal neutron capture Cl35(n,γ)36Cl. The collisional scattering was simulated with molecular dynamics. Interatomic potentials from the present Iab initioP atomic cluster calculations are proposed for the Cl-Cl, Cl-K, and Cl-Na interactions in KCl and NaCl.Peer reviewe

Improving the surface structure of high quality Sr2FeMoO6 thin films for multilayer structures

Two sets of Sr2FeMoO6 thin films were prepared with pulsed laser deposition and the effect of the laserfluence and the deposition temperature was investigated. The Sr2FeMoO6 thin films showed clear evi-dence of impurity phases when the laser fluence was altered. Phase pure films resulted through thewhole temperature range between 900 ◦C and 1050 ◦C when a proper laser fluence was used. Films fabri-cated at lower deposition temperatures resulted with smaller surface roughnesses around 5 nm, higherCurie temperatures and with relatively high saturation magnetization values. The Curie temperaturewas determined from the minimum of the first order derivative and results showed the highest values of350 K and above. The films with the highest Curie temperature reached zero magnetization above 400 K.The results indicate that both high microstructural and high magnetic quality Sr2FeMoO6 thin films canbe obtained with a deposition temperature between 900 ◦C and 950 ◦C. This provides better fabricationparameters for the upcoming SFMO multilayer structures.</p

Radiation Hardness Studies in a CCD with High-Speed Column Parallel Readout

Charge Coupled Devices (CCDs) have been successfully used in several high energy physics experiments over the past two decades. Their high spatial resolution and thin sensitive layers make them an excellent tool for studying short-lived particles. The Linear Collider Flavour Identification (LCFI) collaboration is developing Column-Parallel CCDs (CPCCDs) for the vertex detector of the International Linear Collider (ILC). The CPCCDs can be read out many times faster than standard CCDs, significantly increasing their operating speed. The results of detailed simulations of the charge transfer inefficiency (CTI) of a prototype CPCCD are reported and studies of the influence of gate voltage on the CTI described. The effects of bulk radiation damage on the CTI of a CPCCD are studied by simulating the effects of two electron trap levels, 0.17 and 0.44 eV, at different concentrations and operating temperatures. The dependence of the CTI on different occupancy levels (percentage of hit pixels) and readout frequencies is also studied. The optimal operating temperature for the CPCCD, where the effects of the charge trapping are at a minimum, is found to be about 230 K for the range of readout speeds proposed for the ILC. The results of the full simulation have been compared with a simple analytic model.Comment: 3 pages, 6 figures; presented at IEEE'07, ALCPG'07, ICATPP'0

Characterization of 19A-like 19F pneumococcal isolates from Papua New Guinea and Fiji.

Molecular identification of Streptococcus pneumoniae serotype 19F is routinely performed by PCR targeting the wzy gene of the capsular biosynthetic locus. However, 19F isolates with genetic similarity to 19A have been reported in the United States and Brazil. We screened 78 pneumococcal carriage isolates and found six 19F wzy variants that originated from children in Papua New Guinea and Fiji. Isolates were characterized using multilocus sequence typing and opsonophagocytic assays. The 19F wzy variants displayed similar susceptibility to anti-19F IgG antibodies compared to standard 19F isolates. Our findings indicate that these 19F variants may be more common than previously believed