Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Although tissue factor (TF), the principial initiator of physiological coagulation and pathological thrombosis, has recently been proposed to be present in human blood, the functional significance and location of the intravascular TF is unknown. In the plasma portion of blood, we found TF to be mainly associated with circulating microvesicles. By cell sorting with the specific marker CD42b, platelet-derived microvesicles were identified as a major location of the plasma TF. This was confirmed by the presence of full-length TF in microvesicles acutely shedded from the activated platelets. TF was observed to be stored in the α-granules and the open canalicular system of resting platelets and to be exposed on the cell surface after platelet activation. Functional competence of the blood-based TF was enabled when the microvesicles and platelets adhered to neutrophils, as mediated by P-selectin and neutrophil counterreceptor (PSGL-1, CD18 integrins) interactions. Moreover, neutrophil-secreted oxygen radical species supported the intravascular TF activity. The pools of platelet and microvesicle TF contributed additively and to a comparable extent to the overall blood TF activity, indicating a substantial participation of the microvesicle TF. Our results introduce a new concept of TF-mediated coagulation crucially dependent on TF associated with microvesicles and activated platelets, which principally enables the entire coagulation system to proceed on a restricted cell surface

Finite-Elemente-Modellierung des Risswachstums an 3-Punktbiegeproben

Das Verhalten einer 3-Punkt-Biegeprobe mit Anriss unter Belastung kann mittels eines Finite-Element-Modells nachgebildet werden. Das Modell ermöglicht die Berücksichtigung von elastisch-plastischem Materialverhalten entsprechend der jeweiligen materialspezifischen Spannungs-Dehnungs-Kurve, welche mit dem Ansatz der multilinearen kinematischen Verfestigung (MKIN) umgesetzt wird. Weiterhin gestattet das Modell die Einbeziehung der realen Rollenkinematik beim Biegevorgang. Für die Beschreibung des Bruchkriteriums wird ein spezielles Damage-Modell verwendet, mit dem man in der Lage ist, das Risswachstums in geeigneter Weise wiederzugeben. Mit diesem Modell lässt sich auch das Teilentlastungs-Compliance-Verfahren nachbilden. Diese Simulation ermöglicht die Einschätzung von Korrekturansätzen zur experimentellen Risslängenbestimmung über die Compliance-Methode

Spectroscopic studies of the chlorophyll d containing photosystem I from the cyanobacterium, Acaryochloris marina

AbstractAbsorbance difference spectroscopy and redox titrations have been applied to investigate the properties of photosystem I from the chlorophyll d containing cyanobacterium Acaryochloris marina. At room temperature, the (P740+−P740) and (FA/B−−FA/B) absorbance difference spectra were recorded in the range between 300 and 1000 nm while at cryogenic temperatures, (P740+A1−−P740A1) and (3P740−P740) absorbance difference spectra have been measured. Spectroscopic and kinetic evidence is presented that the cofactors involved in the electron transfer from the reduced secondary electron acceptor, phylloquinone (A1−), to the terminal electron acceptor and their structural arrangement are virtually identical to those of chlorophyll a containing photosystem I. The oxidation potential of the primary electron donor P740 of photosystem I has been reinvestigated. We find a midpoint potential of 450±10 mV in photosystem I-enriched membrane fractions as well as in thylakoids which is very similar to that found for P700 in chlorophyll a dominated organisms. In addition, the extinction difference coefficient for the oxidation of the primary donor has been determined and a value of 45,000±4000 M−1 cm−1 at 740 nm was obtained. Based on this value the ratio of P740 to chlorophyll is calculated to be 1:~200 chlorophyll d in thylakoid membranes. The consequences of our findings for the energetics in photosystem I of A. marina are discussed as well as the pigment stoichiometry and spectral characteristics of P740

Gene expression and activity of specific opioid-degrading enzymes in different brain regions of the AA and ANA lines of rats

AbstractThere is increasing evidence that alcoholism runs in families suggesting that genetic factors may play a role. In support of this hypothesis, the alcohol-preferring (AA) and the alcohol-avoiding (ANA) rat lines have been developed through selective outbreeding. Numerous studies indicate that the endogenous opioid system may be involved in controlling ethanol consumption. Changes in opioid peptides and opioid receptors have been described after ethanol intake. But, the influence of ethanol on peptidolytic degradation of opioid peptides has been largely ignored, although the peptidase-mediated metabolism of neuropeptides is known as an important regulatory site of peptidergic transmission. Neutral endopeptidase 24.11 (NEP) and angiotensin-converting enzyme (ACE) degrade neuropeptides, including enkephalin and are expressed in the brain. Furthermore, a good correspondence between the regional distribution of NEP and opioid receptors in rat brain has already been reported pointing to a possible role of NEP in regulating opioid peptides. For both enzymes studied, the gene expression pattern was found to be in good agreement with the corresponding enzyme activities in the brain regions investigated, showing the highest levels for both specific mRNAs and enzyme activities in the striatum. Differences in both measured parameters were detected in distinct brain regions of AA and ANA rats. Furthermore, in some brain regions discrepancies between ACE and NEP mRNA levels and the corresponding enzyme activities were observed. For example, in olfactory bulb and striatum such discrepancies were found for both enzymes studied. In tegmentum/colliculi a higher NEP gene expression in AA rats was associated with a higher NEP enzyme activity compared to the amounts found in ANA rats

Annotation of negotiation processes in joint-action dialogues

Situated dialogic corpora are invaluable resources for understanding the complex relationship between language, perception, and action as they are based on naturalistic dialogue situations in which the interactants are given shared goals to be accomplished in the real world. In such situations, verbal interactions are intertwined with actions, and shared goals can only be achieved via dynamic negotiation processes based on common ground constructed from discourse history as well as the interactants' knowledge about the status of actions. In this paper, we propose four major dimensions of collaborative tasks that affect the negotiation processes among interactants, and, hence, the structure of the dialogue. Based on a review of available dialogue corpora and annotation manuals, we show that existing annotation schemes so far do not adequately account for the complex dialogue processes in situated task-based scenarios. We illustrate the effects of specific features of a scenario using annotated samples of dialogue taken from the literature as well as our own corpora, and end with a brief discussion of the challenges ahead

Rocking Devices and the Role of Vestibular Stimulation on Sleep—A Systematic Review

Rocking devices are widely used across different age groups to facilitate sleep. This review discusses the current literature on rocking devices and how passive vestibular stimulation influences sleep architecture, sleep oscillations, and cognitive performance. We included eight studies that conducted research with rocking devices in humans (7) and mice (1) during daytime naps and/or nighttime sleep, respectively. Overall, vestibular stimulation during sleep induced faster sleep onset, coupled with more N2 in daytime naps or N3 in nighttime sleep. Vestibular stimulation also led to more sleep spindles and better memory consolidation. Optimal stimulation intensity was around 25 cm/s2, and lower intensities led to smaller effects. The findings suggest a sweet spot for vestibular stimulation intensity, promoting deeper sleep at the cost of wakefulness or N1 sleep without compromising REM sleep. While further studies are needed to thoroughly investigate the motion parameters that drive the impact on sleep and cognitive performance, rocking devices may present a promising therapeutic tool for people with disrupted sleep patterns

Electronic transient spectroscopy from the deep UV to the NIR: unambiguous disentanglement of complex processes

Complex multi-stage relaxation and reaction pathways after the optical excitation of molecules makes the disentanglement of the underlying mechanisms challenging. We present four examples that a new transient spectrometer with excitation fully tunable from the deep UV to the IR and 225 to 1700 nm probing allows for an analysis with greatly reduced ambiguity. The temporal resolution of about 50 fs allows us to resolve all relevant processes. For each example there is a new twist in the sequence of relaxation steps that had previously been overlooked. In malachite green it appears that the importance of the phenyl twisting has been overemphasized and rather a charge transfer state should be considered. In TINUVIN-P the predicted twisting as the driving motion for the ultrafast IC is confirmed and leads to a resolution of the earlier puzzle that the sub-5 ps regime shows kinetics deviating from a pure cooling process despite the sub-ps proton transfer cycle. For the bond cleavage of Ph2CH-Cl and Ph2CH-Br the degree of electron transfer within the radical pair can now be determined quantitatively and leads to a profound understanding of the long term cation yield. For the first time coherent wavepacket motion in the photoproducts is reported. Last but not least the measurement of the GSB recovery in the deep UV allows for the surprising result, that even after S-2 excitation of cyclopentenones the triplet states are reached with near unity probability within a few picoseconds