The primary reaction dynamics of channelrhodopsin-2 was investigated using femtosecond vis-pump/mid-IR probe spectroscopy. Due to the fast deactivation of the excited state in channelrhodopsin-2, it ...is possible to observe the direct impact of retinal isomerization on the protein surrounding. We show that the dominant negative band at 1665 cm–1 tentatively assigned to an amide I vibration is developed with a time constant of 0.5 ps. Also a variety of side-chain vibrations are formed or intensified on this time scale. The comparison of the light-induced FT-IR spectra of channelrhodopsin-2 in H2O and D2O at 80 K enabled us to tentatively identify the contribution of Arg side chain(s). The subsequently observed decay of nearly the whole difference pattern has a particularly high impact on the CC and CN stretching vibrations of the retinal. This suggests that the underlying mechanism describes a cooling process in which the excess energy is redirected toward the retinal surrounding, e.g., the protein and functional water molecules. The pronounced protein contributions in comparison to other rhodopsins point to a very efficient energy redistribution in channelrhodopsin-2.
•Thermal behavior and sorption characteristics of the CaCl2-CH3OH system are studied by TGA/DSC.•SCPs and COPs are derived from thermogravimetric data.•Cyclic reversibility is estimated in repeated ...methanolation/demethanolation cycles.•Constant CH3OH sorption and evolution of heat energy over cycling are observed.•The working pair CaCl2-CH3OH possesses a good cyclability and reversible cooling output over 18 cycles.
Addition compounds of CaCl2 and CH3OH are promising thermochemical materials for thermal energy storage and conversion. Achievable evaporation temperatures lie within the operating range of standard building and industrial refrigeration applications. In heterogeneous gas–solid reactions the cooling power of the respective reaction pair is mainly dependent on the uptake rate of the gaseous reactant. In this paper, a comprehensive study on the influence of various procedural parameters and thermal cycling on the cooling efficiency performance of CaCl2 methanolates was carried out at material scale to provide insights on application design principles. SCPs and cooling COPs were calculated from experimental data obtained by simultaneous TGA/DSC. SCPs, averaged over a methanolation time of 60 min, varied between 157 W/kg and 366 W/kg, whereas maximum SCPs reached values between 232 W/kg and 1029 W/kg depending on methanol partial pressure. The results indicate possible applications with evaporator temperatures around 10 °C, as for the cooling of buildings. COPs were within the range of 0.59 and 0.76. Results showed that thermodynamic conditions and thermophysical properties of the material had a great impact on the methanolation/demethanolation reaction kinetics. Under periodic conditions a slight attenuation of the maximum cooling power was observed, whilst the more practically relevant average SCP was stable over a number of 18 cycles. With respect to application design, different regeneration (demethanolation) temperatures as well as the impact of the thermal history of the material were investigated. The reaction pair can also be used with regeneration temperatures of ≤100 °C.
Salvage radiation therapy (SRT) can be offered to patients with relapsing glioblastoma multiforme (GBM). Here we report our experience with a schedule extending the treatment time of SRT with the aim ...to prolong the cytotoxic effect of ionizing radiation while minimizing the cytotoxic hazards for the surrounding brain.
From 2009 until 2017, 124 of 218 patients received radical resection, adjuvant chemo-radiation with photons and temozolomide (TMZ) followed by adjuvant TMZ. Re-irradiation was performed in 26 patients due to local relapse. Treatment schedules varied. Survival and molecular markers were assessed.
The median survival was respectively 12 months (9-14.5) of the 124 patients treated with tri-modal therapy and 19.2 months (14.9-24.6) for the 26 patients retreated with SRT (
=0.038). Patients who received daily fractions of 1,6 to 1,65 Gy to a total dose of >40 Gy had a median survival time of 24,6 months compared to patients treated with higher daily doses or a total dose of <40 Gy (p= 0.039), consistent with the observation that patients treated with 21-28 fractions had a median survival of 21,9 months compared to 15,8 months of patients who received 5-20 fractions (p=.0.05). Patients with Ki-67 expression of >30% seemed to perform better than patients with expression levels of ≤20% (
=0.03). MGMT methylation status, TERT promoter or ATRX mutations, overexpression of p53, p16, PD-L1, and EGFR were not prognostic.
Re-irradiation of relapsing GBM is a highly valid treatment option. Our observation challenges hypofractionated stereotactic radiotherapy for retreatment and controlled trials on the fractionation dose for SRT are needed. Robust predictive molecular markers could be beneficial in the selection of patients for SRT.
Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation ...after cetuximab treatment, but clinical data are not sufficient to date.
We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment.
Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found.
Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.
Despite some popularity of hamsters as pets and laboratory animals there is no reliable phylogeny of the subfamily Cricetinae available so far. Contradicting views exist not only about the actual ...number of species but also concerning the validity of several genera. We used partial DNA sequences of two mitochondrial (cytochrome
b, 12S rRNA) and one partial nuclear gene (von Willebrand Factor exon 28) to provide a first gene tree of the Cricetinae based on 15 taxa comprising six genera. According to our data, Palaearctic hamsters fall into three distinct phylogenetic groups:
Phodopus,
Mesocricetus, and
Cricetus-related species which evolved during the late Miocene about 7–12
MY ago. Surprisingly, the genus
Phodopus, which was previously thought to have appeared during the Pleistocene, forms the oldest clade. The largest number of extant hamster genera is found in a group of
Cricetus-related hamsters. The genus
Cricetulus itself proved to be not truly monophyletic with
Cricetulus migratorius appearing more closely related to
Tscherskia,
Cricetus, and
Allocricetulus. We propose to place the species within a new monotypic genus. Molecular clock calculations are not always in line with the dating of fossil records. DNA based divergence time estimates as well as taxonomic relationships demand a reevaluation of morphological characters previously used to identify fossils and extant hamsters.
We present a comparative study using femtosecond pump/probe spectroscopy in the visible and infrared of the early photodynamics of solubilized proteorhodopsin (green absorbing variant) in D2O with ...deprotonated (pD 9.2) and protonated (pD 6.4) primary proton acceptor Asp-97. The vis-pump/vis-probe experiments show a kinetic isotope effect that is more pronounced for alkaline conditions, thus decreasing the previously reported pH-dependence of the primary reaction of proteorhodopsin in H2O. This points to a pH dependent H-bonding network in the binding pocket of proteorhodopsin, that directly influences the primary photo-induced dynamics. The vis-pump/IR-probe experiments were carried out in two different spectral regions and allowed to monitor the retinal CC (1500cm−1–1580cm−1) and CN stretching vibration as well as the amide I mode of the protein (1590cm−1–1680cm−1). Like the FTIR spectra of the K intermediate (PRK–PR difference spectra) in this spectral range, the kinetic parameters and also the quantum efficiency of photo-intermediate formation are found to be virtually independent of the pD value.
Femtosecond spectroscopy and quantum chemical calculations provide detailed insights into the specificities of the uncaging mechanism of CO2 from ortho‐, meta‐, and para‐nitrophenylacetate (see ...figure). The emerging general principles allow a rational design of improved ortho‐nitrophenyl cages for chemical and biological applications.
Eines der beiden wichtigsten Ziele des Risikostrukturausgleichs (RSA) ist die Herstellung von Chancengleichheit im Wettbewerb. Das bedeutet, dass die Kassen nach Bereinigung um ihre spezifische ...Managementleistung eine vergleichbare Deckungsquote haben sollen. Um festzustellen, ob der heutige RSA fair ist, muss daher die Managementleistung beurteilt werden. Der Artikel diskutiert, wie ein solches Verfahren funktionieren kann. Das Ergebnis ist ein methodischer Vorschlag zur Beurteilung der Zielgenauigkeit des RSA.
Femtosecond time‐resolved spectroscopy in the visible and IR range was utilized to study the primary reaction dynamics of the proteorhodopsin (PR) D97N mutant in comparison with wild type PR at ...different pH values. The analysis of the data obtained in the mid‐IR closely resembles the results for wild type PR. The observation of the first ground state intermediate K is initially obscured by a complex reaction scheme of vibrational relaxation and heating effects, but its spectral signature clearly emerges at long delay times. In the visible range, a biexponential decay of the excited state within 30 ps and the formation of the K photoproduct is observed. The decay time constants derived for the D97N mutant in D2O are slightly larger than in H2O due to H/D exchange. This kinetic isotope effect is even less pronounced than for wild type PR at pH 6. These results support the current notion of a pH dependent hydrogen bonding network in the retinal binding pocket of PR and a weaker interaction between the retinal Schiff base and the counter ion complex compared to bacteriorhodopsin.
A lab-scale thermochemical heat storage reactor was developed in the European project “thermal battery” to obtain information on the characteristics of a closed heat storage system, based on ...thermochemical reactions. The present type of storage is capable of re-using waste heat from cogeneration system to produce useful heat for space heating. The storage material used was SrBr2·6H2O. Due to agglomeration or gel-like problems, a structural element was introduced to enhance vapour and heat transfer. Honeycomb heat exchanger was designed and tested. 13 dehydration-hydration cycles were studied under low-temperature conditions (material temperatures < 100 °C) for storage. Discharging was realized at water vapour pressure of about 42 mbar. Temperature evolution inside the reactor at different times and positions, chemical conversion, thermal power and overall efficiency were analysed for the selected cycles. Experimental system thermal capacity and efficiency of 65 kWh and 0.77 are respectively obtained with about 1 kg of SrBr2·6H2O. Heat transfer fluid recovers heat at a short span of about 43 °C with an average of 22 °C during about 4 h, acceptable temperature for the human comfort (20 °C on day and 16 °C at night). System performances were obtained for a salt bed energy density of 213 kWh·m3. The overall heat transfer coefficient of the honeycomb heat exchanger has an average value of 147 W m−2 K−1. Though promising results have been obtained, ameliorations need to be made, in order to make the closed thermochemical heat storage system competitive for space heating.
•Lab-scale thermochemical heat storage is designed, constructed and tested.•The use of honeycomb heat exchanger as a heat and vapour process enhancement.•Closed system (1 kg SrBr2·6H2O) able to give back 3/4 of initial thermal waste energy.•System storage capacity and thermal efficiency are respectively 65 kWh and 0.77.•System capable of re-using waste heat from cogeneration to supply space heating.
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