530 research outputs found
PACS and SPIRE range spectroscopy of cool, evolved stars
Context: At the end of their lives AGB stars are prolific producers of dust
and gas. The details of this mass-loss process are still not understood very
well. Herschel PACS and SPIRE spectra offer a unique way of investigating
properties of AGB stars in general and the mass-loss process in particular.
Methods: The HIPE software with the latest calibration is used to process the
available PACS and SPIRE spectra of 40 evolved stars. The spectra are convolved
with the response curves of the PACS and SPIRE bolometers and compared to the
fluxes measured in imaging data of these sources. Custom software is used to
identify lines in the spectra, and to determine the central wavelengths and
line intensities. Standard molecular line databases are used to associate the
observed lines. Because of the limited spectral resolution of the spectrometers
several known lines are typically potential counterparts to any observed line.
To help identifications the relative contributions in line intensity of the
potential counterpart lines are listed for three characteristic temperatures
based on LTE calculations and assuming optically thin emission. Result: The
following data products are released: the reduced spectra, the lines that are
measured in the spectra with wavelength, intensity, potential identifications,
and the continuum spectra, i.e. the full spectra with all identified lines
removed. As simple examples of how this data can be used in future studies we
have fitted the continuum spectra with three power laws and find that the few
OH/IR stars seem to have significantly steeper slopes than the other oxygen-
and carbon-rich objects in the sample. As another example we constructed
rotational diagrams for CO and fitted a two-component model to derive
rotational temperatures.Comment: A&A accepte
Regulation of thrombin formation via the protein C pathway in normal and hypercoagulable states
Human factor Va<sub>1</sub> and factor Va<sub>2</sub>:Properties in the procoagulant and anticoagulant pathways
Screening Outside the Catalytic Site: Inhibition of Macromolecular Inter-actions Through Structure-Based Virtual Ligand Screening Experiments
During these last 15 years, drug discovery strategies have essentially focused on identifying small molecules able to inhibit catalytic sites. However, other mechanisms could be targeted. Protein-protein interactions play crucial roles in a number of biological processes, and, as such, their disruption or stabilization is becoming an area of intense activity. Along the same line, inhibition of protein-membrane could be of major importance in several disease indications. Despite the many challenges associated with the development of such classes of interaction modulators, there has been considerable success in the recent years. Importantly, through the existence of protein hot-spots and the presence of druggable pockets at the macromolecular interfaces or in their vicinities, it has been possible to find small molecule effectors using a variety of screening techniques, including combined virtual ligand-in vitro screening strategy. Indeed such in silico-in vitro protocols emerge as the method of choice to facilitate our quest of novel drug-like compounds or of mechanistic probes aiming at facilitating the understanding of molecular reactions involved in the Health and Disease process. In this review, we comment recent successes of combined in silico-in vitro screening methods applied to modulating macromolecular interactions with a special emphasis on protein-membrane interactions
A prothrombinase-based assay for detection of resistance to activated protein C
In this paper we present a new method for the detection of resistance to activated protein C (APC) that is based on direct measurement of the effect of APC an the cofactor activity of plasma factor Va. The factor V present in a diluted plasma sample was activated with thrombin and its sensitivity towards APC was subsequently determined by incubation with phospholipids and APC; The loss of factor Va cofactor activity was quantified in a prothrombinase system containing purified prothrombin. factor Xa and phospholipid vesicles and using a chromogenic assay for quantitation of thrombin formation. The reaction conditions were optimized in order to distinguish normal, heterozygous and homozygous APC-resistant plasmas. Maximal differences in the response of these plasmas towards ATC were observed when factor Va was inactivated by APC in the absence of protein S and when the: cofactor activity of factor Va was determined at a low factor Xa concentration (0.3 nM).Addition of 0.2 nM APC and 20 mu M phospholipid vesicles to a 1000-fold diluted sample of thrombin-activated normal plasma resulted in loss of mon than 85% of the cofactor activity factor Va within 6 min. Under the same conditions, APC inactivated similar to 60% and similar to 20% of the factor Va present in plasma samples from APC-resistant individuals that were heterozygous or homozygous for the mutation Arg(506)-->Gln in factor V, respectively. Discrimination between the plasma samples from normal and heterozygous and homozygous APC-resistant individuals was facilitated by introduction of the so-called APC-sensitivity ratio (APC-sr). The APC-sr was defined as the ratio of the factor Va cofactor activities determined in thrombin-activated plasma samples after 6 min incubation with or without 0.2 nM APC and was multiplied by as 100 to obtain integers (APC-sr = {factor Va(+APC)/factor Va(-APC)} x 100). Clear differences were observed between the APC-sr of plasmas from normal healthy volunteers (APC-sr: 8-20, n = 33) and from individuals that were heterozygous (APC-sr: 35-50, n = 17) or homozygous APC resistant (APC-sr: 82-88, n = 7). There was no mutual overlap between the APC-sr of normal plasmas and plasmas from heterozygous or homozygous APC resistant individuals (p < 0.0001), In all cases our test gave the same result as the DNA-based assay. Since the test is performed on a highly diluted plasma sample there is no interference by conditions that affect APC resistance tests that are based on clotting time determinations (e.g. coagulation factor deficiencies, oral anticoagulation, heparin treatment. the presence of lupus anticoagulants, pregnancy or the use of oral contraceptives). Furthermore, we show that part of the factor Va assay can be performed on an autoanalyzer which increases the number of plasma samples that can be handled simultaneously
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