Plasmin-Induced Activation of Human Platelets Is Modulated by Thrombospondin-1, Bona Fide Misfolded Proteins and Thiol Isomerases

Inflammatory processes are triggered by the fibrinolytic enzyme plasmin. Tissue-type plasminogen activator, which cleaves plasminogen to plasmin, can be activated by the cross-β-structure of misfolded proteins. Misfolded protein aggregates also represent substrates for plasmin, promoting their degradation, and are potent platelet agonists. However, the regulation of plasmin-mediated platelet activation by misfolded proteins and vice versa is incompletely understood. In this study, we hypothesize that plasmin acts as potent agonist of human platelets in vitro after short-term incubation at room temperature, and that the response to thrombospondin-1 and the bona fide misfolded proteins Eap and SCN⁻-denatured IgG interfere with plasmin, thereby modulating platelet activation. Plasmin dose-dependently induced CD62P surface expression on, and binding of fibrinogen to, human platelets in the absence/presence of plasma and in citrated whole blood, as analyzed by flow cytometry. Thrombospondin-1 pre-incubated with plasmin enhanced these plasmin-induced platelet responses at low concentration and diminished them at higher dose. Platelet fibrinogen binding was dose-dependently induced by the C-terminal thrombospondin-1 peptide RFYVVMWK, Eap or NaSCN-treated IgG, but diminished in the presence of plasmin. Blocking enzymatically catalyzed thiol-isomerization decreased plasmin-induced platelet responses, suggesting that plasmin activates platelets in a thiol-dependent manner. Thrombospondin-1, depending on the concentration, may act as cofactor or inhibitor of plasmin-induced platelet activation, and plasmin blocks platelet activation induced by misfolded proteins and vice versa, which might be of clinical relevance.     

Novel cold chemical lamination bonding technique—A simple LTCC thermistor-based flow sensor

The LTCC technique enables fabrication of microfluidic devices. The structures consist of channels, chambers and screen-printed passives. The lamination is a quality-determining process in the manufacture of the fluidic modules. The commonly used bonding method is thermocompression. The tapes are joined together at high pressure (up to 30 MPa) and temperature (up to 80 °C) for 2–15 min. Although these parameters allow good LTCC module encapsulation, the quality of the chamber geometry is strongly affected by high pressure and temperature. The cold chemical lamination (CCL) technique presented in this paper, a solvent-based method, largely avoids these problems. A film of a special solvent is deposited on the green tape, and softens the surface. The tape layers are then stacked and compressed at low pressure, below 100 kPa, at room temperature. The fabrication of a simple LTCC thermistor-based flow sensor is presented here to compare both lamination methods. The test device consists of one buried thermistor screen printed on a bridge hanging in a gas/liquid channel. The basic sensor parameters (measurement range, working temperature, output signal, working pressure and measurement error) are analyzed.     

Low-pressure,thermo-compressive lamination

Lamination of green ceramic tapes is one of the most important technological processes in multilayer ceramic technology. Lamination affects the quality of all 3D structures (e.g., channels, chambers, membranes, etc.). Novel chemical methods of lamination reduce the deformation of 3D structures. However, these methods are useless in the fabrication of thin membranes and structures with thick-film electronic components or electric vias. Therefore, thermo-compressive lamination is still the best solution for the lamination of green ceramic tapes. Low-pressure thermo-compressive lamination with an insert material is presented in this paper. The influence of pressure and Low Temperature Cofired Ceramics (LTCC) material on the compressibility and shrinkage of LTCC, as well as the influence of the insert material on deflection and distortion of the membranes are presented and discussed in this paper.     

Structure-activity relationship studies on the immune stimulatory effects of base-modified CpG toll-like receptor 9 agonists

Synthetic oligodeoxynucleotides containing unmethylated deoxycytidylyl-deoxyguanosine dinucleotide (CpG) motifs are able to stimulate potent immune responses through a signaling pathway involving Toll-like receptor 9 (TLR9). We have investigated the structure-activity relationship (SAR) of base-modified CpG oligonucleotides with TLR9 by measuring TLR9 activation by 20-mer oligonucleotides having just a single human recognition motif (5'-GTCGTT-3') in functional cell-based TLR9 assays. Substitution of guanine by hypoxanthine and 6-thioguanine resulted in activity similar to the unmodified parent molecule, whereas purine, 2-aminopurine, 2,6-diaminopurine, and 8-oxo-7,8-dihydroguanine substitution resulted in approximately 40-60 % reduction in activity, and 7-deazaguanine substitution led to the strongest (80 %) reduction in TLR9 stimulation. Furthermore, none of the investigated modifications at C5 and N4 of cytosine were well tolerated with respect to human TLR9 stimulation. Our results are compatible with a SAR model in which guanine is recognized by the Hoogsteen site, and C5 is most critical for recognition of cytosine. In addition, we found significant species-specific differences between human and murine TLR9 recognition, which demonstrates the importance of choosing appropriate assay systems for SAR studies.     

Oberflächenenergetische Charakterisierung

Surface Energetic Characterization of Nanoscale Fillers and Elastomers Almost any technically used rubber material is filled with particles in nanometer size, by which the properties of the material can be specific controlled. In modern car tires the used fillers have crucial influence on driving security (wet grip and ice grip), on fuel consumption (rolling resistance) and on the cost‐effectiveness (life time of the tire) [1].The first fillers used in rubber application were carbon blacks; actually in passenger car tires mostly surface modified silica is applied. The implementation of novel filler systems like organophilic modified layered silicates (organo‐clays) or carbon nanotubes is subject of intense research [2,3]. Surface energy and –polarity of the filler surface is a crucial, but often underestimated determining factor. All surface properties of rubber and filler have to be well balanced to get the nanoscale filler particles finely dispersed in the rubber matrix and also to obtain a good adhesion between polymer and filler surface.     

Hygrothermisches Verhalten eingebetteter Holzbalkenköpfe im innnengedämmten Außenmauerwerk: Heizungstechnisch gestützte Innendämmung bei Holzbalkendecken

The hygrothermic performance of wooden beam ends embedded in an inside insulated outside wall considering a heating system. Heating pipe aided inside thermal insulation in case of a timber joist floor. An improvement of the hygrothermal performance of worth preserving facades by means of an inside insulation is proved correct for crucial projects also, using capillary activ thermal insulation materials or a vapor retarder dependent on the relative humididy. On the other hand in case of embedded wooden beam ends there are controversial discussions The experts suggest proposals from an airthight construction and the using of fungicides and the sorptive binding of moisture up to a beam end completely open for air flow rate. This paper is focused to the hygric problems of the wooden beam ends. A lot of measurements are carried out in situ under condition of use in testhouses and by means of a teststand in the Building Physics testing floor of the FHL. In each cases the experiments are supported by a numerical simulation of the coupled heat and mass transfer. Apart from the seasonal process of the wooden moisture content and the hygrothermal state of the air gaps of the beam heads area the results quantify also the effect of local heat transfer by means of heating channels near the floor board area and through so‐called passive and active heat bars within the wooden beam ends.     

Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis

Curcumin is a natural bioactive component derived from the turmeric plant Curcuma longa, which exhibits a range of beneficial activities on human cells. Previously, an inhibitory effect of curcumin on platelets was demonstrated. However, it is unknown whether this inhibitory effect is due to platelet apoptosis or procoagulant platelet formation. In this study, curcumin did not activate caspase 3-dependent apoptosis of human platelets, but rather induced the formation of procoagulant platelets. Interestingly, curcumin at low concentration (5 µM) potentiated, and at high concentration (50 µM) inhibited ABT-737-induced platelet apoptosis, which was accompanied by inhibition of ABT-737-mediated thrombin generation. Platelet viability was not affected by curcumin at low concentration and was reduced by 17% at high concentration. Furthermore, curcumin-induced autophagy in human platelets via increased translocation of LC3I to LC3II, which was associated with activation of adenosine monophosphate (AMP) kinase and inhibition of protein kinase B activity. Because curcumin inhibits P-glycoprotein (P-gp) in cancer cells and contributes to overcoming multidrug resistance, we showed that curcumin similarly inhibited platelet P-gp activity. Our results revealed that the platelet inhibitory effect of curcumin is mediated by complex processes, including procoagulant platelet formation. Thus, curcumin may protect against or enhance caspase-dependent apoptosis in platelets under certain conditions.     

Dynamic behavior of short aramid fiber‐filled elastomer composites

Short fiber reinforcement is a suitable way to improve the tribological properties of elastomers. However, rubbers products are often exposed to highly dynamic mechanical loadings. Hereby it is crucial to study the change in dynamic behavior due to the addition of short fibers. Therefore, these properties were investigated in terms of dynamic mechanical thermal analysis, heat build‐up (HBU), and fatigue crack growth resistance under cyclic loadings for two different rubber compounds. A peroxide cured ethylene–propylene–diene rubber (EPDM) and a sulfur cured natural rubber (NR) compound were chosen and reinforced with two types of short aramid fibers. It was found that the short fibers could contribute to the improvement in the crack growth resistance, HBU, and the dynamic mechanical behavior of the composites depending on the testing conditions. POLYM. ENG. SCI., 54:2958–2964, 2014. © 2014 Society of Plastics Engineers     

Contribution of physico-chemical properties of interfaces on dispersibility, adhesion and flocculation of filler particles in rubber

Reinforcing fillers are added to elastomeric compounds to improve and adjust several mechanical, dynamical, tribological, etc. properties with respect to different applications, i.e. for automotive tires, or technical rubber goods. Carbon black and precipitated silica are widely used as rubber reinforcing fillers; however, some new classes of nanosized substances like organophilic modified clay or carbon nanotubes are presently intensive studied as possible future filler systems in combination with carbon black or silica.An important parameter for the dispersibility and compatibility of the filler in the polymer matrix of rubber compounds is the surface energy and surface polarity of the solid filler particles. Therefore, we systematically measured and compared the dynamic contact angles of a collection of different filler types (carbon blacks, silica, carbon nanotubes and organoclays) using the Wilhelmy method, whereby the particles were fixed as a thin layer at a double-sided adhesive tape. From the contact angle values the polar and disperse part of the surface energies of the filler particles were calculated by fitting Fowkes formula. For an estimation of the compatibility of the fillers with different types of rubber polymers we additionally analyzed the surface energy and polarity of the gum (unfilled) elastomers. From the evaluated surface energies and polarities, thermodynamic predictors for the dispersibility (enthalpy of immersion), the adhesion between filler particles and polymer matrix in the nanocomposite, and for the flocculation behaviour of the particles in a rubber matrix (difference in the works of adhesion) were derived. These thermodynamic predictors improve considerably the compounding process of novel rubber nanocomposites with respect to target-oriented adjustment of rubber properties.     

Rubber composites based on graphene nanoplatelets,expanded graphite,carbon nanotubes and their combination: A comparative study

Solution styrene butadiene rubber (S-SBR) composites reinforced with graphene nanoplatelets (GnPs), expanded graphite (EG), and multiwalled carbon nanotubes (MWCNTs) were prepared and the electrical and various mechanical properties were compared to understand the specific dispersion and reinforcement behaviours of these nanostructured fillers. The electrical resistivity of the rubber composite gradually decreased with the increase of filler amount in the composite. The electrical percolation behaviour was found to be started at 15 phr (parts per hundred rubber) for GnP and 20 phr for EG filled systems, whereas a sharp drop was found at 5 phr for MWCNT based composites. At a particular filler loading, dynamic mechanical analysis and tensile test showed a significant improvement of the mechanical properties of the composites comprised of MWCNT followed by GnP and then EG. The high aspect ratio of MWCNT enabled to form a network at low filler loading and, consequently, a good reinforcement effect was observed. To investigate the effect of hybrid fillers, MWCNT (up to 5 phr) were added in a selected composition of EG based compounds. The formation of a mixed filler network showed a synergistic effect on the improvement of electrical as well as various mechanical properties.