IV-VI resonant cavity enhanced photodetectors for the midinfrared

A resonant-cavity enhanced detector operating in the mid-infrared at a wavelength around 3.6 micron is demonstrated. The device is based on a narrow-gap lead salt heterostructure grown by molecular beam epitaxy. Below 140 K, the photovoltage clearly shows a single narrow cavity resonance, with a relative line width of only 2 % at 80 K.Comment: 2 figure

Fragility and compressibility at the glass transition

Isothermal compressibilities and Brillouin sound velocities from the literature allow to separate the compressibility at the glass transition into a high-frequency vibrational and a low-frequency relaxational part. Their ratio shows the linear fragility relation discovered by x-ray Brillouin scattering [1], though the data bend away from the line at higher fragilities. Using the concept of constrained degrees of freedom, one can show that the vibrational part follows the fragility-independent Lindemann criterion; the fragility dependence seems to stem from the relaxational part. The physical meaning of this finding is discussed. [1] T. Scopigno, G. Ruocco, F. Sette and G. Monaco, Science 302, 849 (2003)Comment: 4 pages, 2 figures, 2 tables, 33 references. Slightly changed after refereein

Optimizing the parameters for hydro-jet dissection in fatty tissue — A morphological Ex Vivo analysis

Summary: Background: The advantage of water-jet dissection is the preservation of vessels and nerves. Especially in liver surgery, blood loss can be significantly decreased. The use of water-jet dissectors in other fields of surgery is currently under investigation. The preparation of vessels in fatty tissue is of special interest for plastic surgeons. The optimal technical parameters were investigated. Methods: Abdominal fat tissue of fresh cadavers was cut under standardized conditions with different parameters of the water-jet dissector. Results: One single pass at a cutting pressure between 20 and 60 Bar makes an incision of 8 mm. Deeper cuts can be achieved by repeated application on the same cut. Five passes at 40 Bar results in a depth of 1.7 cm without vessel damage. If the applied pressure is 50 or 60 Bar, up to 7% damaged vessels can be found. The water-jet dissection leads to a water uptake of the cut tissue. Conclusions: The optimal pressure for water-jet dissection of fatty tissue lies between 30 and 40 Bar. The effect of the mechanical irritation of the vessels has to be investigatedin vivo before using the water-jet dissector for preparation of blood vessels in humans, e.g. for flap dissectio

Understanding the ATP hydrolysis mechanism in myosin using computer simulation techniques

Molecular motors are proteins that convert energy from nucleoside triphosphate hydrolysis into mechanical work. A prominent example is myosin which drives muscle contraction and a large number of additional cellular transport phenomena in all living organisms. While hydrolyzing ATP, myosin translocates along an actin filament. The catalytic cycle for ATP hydrolysis and the mechanical motor cycle are closely coupled. Although a large number of studies have been devoted to understanding the functioning of myosin since its isolation in the 19th century, the details of the chemical mechanism underlying ATP hydrolysis and its coupling to the necessary conformational changes of myosin are poorly understood. In this thesis, theoretical methods are developed and used to gain a detailed understanding of the mechanism of ATP hydrolysis in myosin and of mechanical events that immediately follow hydrolysis. Three different possible reaction routes are investigated using combined quantum mechanical and molecular mechanical (QM/MM) reaction path simulations. To include solvent screening effects in the calculations, a new approximate method "Non-Uniform Charge Scaling" (NUCS) was developed which scales the partial atomic charges on the molecular mechanical atoms so as to optimally reproduce electrostatic interaction energies between groups of protein atoms and the QM region as determined from an initial continuum solvent analysis with a simple Coulomb potential and scaled charges. NUCS is a generally-applicable method that is particularly useful in cases where an explicit treatment of water molecules is not feasible and interfaces to implicit solvent models are lacking, as is the case for current QM/MM calculations. Path optimizations were done using Hartree-Fock calculations with 3-21G(d) and 6-31G(d,p) basis sets, followed by point energy calls using density-functional theory B3LYP/6-31+G(d,p). Despite the inaccuracies inherent in this method, the present calculations currently represent the most accurate QM/MM theoretical investigation of an enzyme-catalyzed phosphoanhydride hydrolysis reaction. Possible methodological improvements for future investigations are discussed. The three pathways studied are isoenergetic within error and are thus equally likely to be populated. The 6-31G(d,p) basis set proved to be reliable in describing the geometries during the phosphate hydrolysis reactions, whereas the 3-21G(d) basis set was found to be too inaccurate. Although the energies were not sufficiently accurate, a number of structural conclusions on the mechanism of ATP hydrolysis can be drawn and related to experimental findings from isotope exchange and mutation studies. All three paths investigated follow a single-step associative-like mechanism (see movies at http://www.iwr.uni-heidelberg.de/groups/biocomp/fischer) and show very similar heavy-atom positions in the transition states regardless of the positions of the protons. In the product states, the coordination bond between Mg2+ and Ser237 (and thus the switch-1 loop) is broken. This indicates that product release is likely to occur via an exit route that opens by complete opening of the switch-1 loop ("trap door" mechanism). Moreover, the coordination distance between Mg2+ and inorganic phosphate (Pi) is extended. This indicates that after hydrolysis this bond may be completely cleaved as an early event necessary for phosphate exit. Inspired by the simulation results, a Network Hypothesis on the mechanism of ATP hydrolysis in myosin is put forward that combines previous mechanistic proposals and that is consistent with experimental data available from mutational and isotope exchange studies. Moreover, a mechanism is suggested to explain how the catalytic cycle is coupled to the motor activity of myosin

Mechanical Relaxation in Glasses and at the Glass Transition

The Gilroy-Phillips model of relaxational jumps in asymmetric double-well potentials, developed for the Arrhenius-type secondary relaxations of the glass phase, is extended to a formal description of the breakdown of the shear modulus at the glass transition, the flow process.Comment: 13 pages, 11 figures, 49 ref

The long non-coding {RNA} {H19} suppresses carcinogenesis and chemoresistance in hepatocellular carcinoma

The long non-coding RNA (lncRNA) H19 represents a maternally expressed and epigenetically regulated imprinted gene product and is discussed to have either tumor-promoting or tumor-suppressive actions. Recently, H19 was shown to be regulated under inflammatory conditions. Therefore, aim of this study was to determine the function of H19 in hepatocellular carcinoma (HCC), an inflammation-associated type of tumor. In four different human HCC patient cohorts H19 was distinctly downregulated in tumor tissue compared to normal or non-tumorous adjacent tissue. We therefore determined the action of H19 in three different human hepatoma cell lines (HepG2, Plc/Prf5, and Huh7). Clonogenicity and proliferation assays showed that H19 overexpression could suppress tumor cell survival and proliferation after treatment with either sorafenib or doxorubicin, suggesting chemosensitizing actions of H19. Since HCC displays a highly chemoresistant tumor entity, cell lines resistant to doxorubicin or sorafenib were established. In all six chemoresistant cell lines H19 expression was significantly downregulated. The promoter methylation of the H19 gene was significantly different in chemoresistant cell lines compared to their sensitive counterparts. Chemoresistant cells were sensitized after H19 overexpression by either increasing the cytotoxic action of doxorubicin or decreasing cell proliferation upon sorafenib treatment. An H19 knockout mouse model (H19Δ3) showed increased tumor development and tumor cell proliferation after treatment with the carcinogen diethylnitrosamine (DEN) independent of the reciprocally imprinted insulin-like growth factor 2 (IGF2). In conclusion, H19 suppresses hepatocarcinogenesis, hepatoma cell growth, and HCC chemoresistance. Thus, mimicking H19 action might be a potential target to overcome chemoresistance in future HCC therapy

Cellular Ca2+ signals generate defined pH signatures in plants

Calcium ions (Ca2+) play a key role in cell signaling across organisms. The question of how a simple ion can mediate specificity has spurred research into the role of Ca2+ signatures and their encoding and decoding machinery. Such studies have frequently focussed on Ca2+ alone and our understanding of how Ca2+ signalling is integrated with other responses remains poorly understood. Using in vivo imaging with different genetically-encoded fluorescent sensors in Arabidopsis cells we show that Ca2+ transients do not occur in isolation but are accompanied by pH changes in the cytosol. We estimate the degree of cytosolic acidification at up to 0.25 pH units in response to external ATP in seedling root tips. We validated this pH-Ca2+ link for distinct stimuli. Our data suggest that the association with pH may be a general feature of Ca2+ transients that depends on the transient characteristics and the intracellular compartment. These findings suggest a fundamental link between Ca2+ and pH dynamics in plant cells, generalizing previous observations of their association in growing pollen tubes and root hairs. Ca2+ signatures act in concert with pH signatures, possibly providing an additional layer of cellular signal transduction to tailor signal specificity