Development of Synthetic Platelet‐Activating Hydrogel Matrices to Induce Local Hemostasis

Several hemostatic strategies rely on the use of blood components such as fibrinogen and thrombin, which suffer from high cost and short shelf‐life. Here, a cost‐effective synthetic biomaterial is developed for rapid local hemostasis. Instead of using thrombin, thrombin‐receptor‐agonist‐peptide‐6 (TRAP6) is covalently engineered in polyvinyl alcohol (PVA) hydrogels. Soluble PVA‐TRAP6 is first prepared by covalent attachment of cysteine‐containing TRAP6 onto the backbone of PVA‐norbornenes (PVA‐NB) through photoconjugation. Cytotoxicity studies using C2C12 myoblasts indicate that PVA‐NB and PVA‐TRAP6 are nontoxic. Thromboelastography reveals that hemostatic activity of TRAP6 is retained in conjugated form, which is comparable to free TRAP6 solutions with equal concentrations. A 0.1% PVA‐TRAP6 solution can shorten the clotting time (CT) to ca. 45% of the physiological CT. High platelet‐activating efficiency is further confirmed by platelet aggregation assay and flow cytometry (FACS). For potential clinical applications, TRAP6‐presenting hydrogel particulates (PVA‐TRAP6‐P) are developed for local platelet activation and hemostasis. PVA‐TRAP6‐P is prepared by biofunctionalization of photopolymerized PVA‐NB hydrogel particulates (PVA‐NB‐P) with TRAP6. It is demonstrated that PVA‐TRAP6‐P can effectively shorten the CT to ca. 50%. FACS shows that PVA‐TRAP6‐P can activate platelets to a comparable extent as soluble TRAP6 control. Altogether, PVA‐TRAP6‐P represents a promising class of biomaterials for safe hemostasis and wound healing.     

Optimized Hash Tree for Authentication in Sensor Networks

Authentication based on the Merkle tree has been proposed as an energy efficient approach in a resource constrained sensor network environment. It replaces complicated certificate verification with more power efficient hash computations. While previous works assumed complete binary Merkle tree structures, which can be used efficiently only in sensor networks with a specific number of sensor nodes, we investigate incomplete Merkle trees to support any number of sensors. For the incomplete Merkle tree, we demonstrate that an optimal structure can be found through mathematical analysis and simulation. A novel tree indexing scheme is also proposed to reduce communication overhead and save sensors resources during authentication     

Crystallization of poly(ethylene terephthalate)/polycarbonate blends. I. Unreinforced systems

The crystallization and transition temperatures of poly(ethylene terephthalate) (PET) in blends with polycarbonate (PC) is considered using thermal analysis. Additives typically used in commercial polyester blends, transesterification inhibitor and antioxidant, are found to enhance the crystallization rate of PET. Differential scanning calorimetry (DSC) reveals two glass transition temperatures in PET/PC blends, consistent with an immiscible blend. Optical microscopy observations are also consistent with an immiscible blend. Small shifts observed in the T_g of each component may be due to interactions between the phases. The degree of crystallinity of PET in PET/PC blends is significantly depressed for high PC contents. Also, in blends with PC content greater than 60 wt %, two distinct crystallization exotherms are observed in dynamic crystallization from the melt. The isothermal crystallization kinetics of PET, PET modified with blend additives, and PET in PET/PC blends have been evaluated using DSC and the data analyzed using the Avrami model. The crystallization of PET in these systems is found to deviate from the Avrami prediction in the later stages of crystallization. Isothermal crystallization data are found to superimpose when plotted as a function of time divided by crystallization half-time. A weighted series Avrami model is found to describe the crystallization of PET and PET/PC blends during all stages of crystallization. © 1996 John Wiley & Sons, Inc.     

Attaching of flexible chains to novolacs on the basis of bisphenol A

Networks containing both flexible segments and rigid structures were synthesized on the basis of bisphenol A novolacs and diglycidylether of butanediol using imidazole as an accelerator. A stoichiometric ratio between epoxy groups and phenolic groups of the novolacs leads to networks with methylene bridges as network junctions. In contrast to this, the same reaction with bisphenol A leads to completely soluble products. The glass transition temperature of this soluble material is considerably lower than the glass transition temperature of the networks. Increasing content of methylene bridges in the novolacs leads to an increase of the glass transition temperature of the networks and to a decrease of the δc_p value at the glass transition. Furthermore, epoxy excess leads to networks with rubber-structure of the bisphenol A novolac used in the reaction with the diglycidylether. It was found that conformations with intramolecular hydrogen bondings exist between phenolic hydroxyl groups, which considerably influence the reactivity of the novolac with the epoxy group. © 1996 John Wiley & Sons, Inc.     

Calcined Hydroxyapatite with Collagen I Foam Promotes Human MSC Osteogenic Differentiation

Collagen I-based foams were modified with calcined or noncalcined hydroxyapatite or calcium phosphates with various particle sizes and pores to monitor their effect on cell interactions. The resulting scaffolds thus differed in grain size, changing from nanoscale to microscopic, and possessed diverse morphological characteristics and resorbability. The materials’ biological action was shown on human bone marrow MSCs. Scaffold morphology was identified by SEM. Using viability test, qPCR, and immunohistochemical staining, we evaluated the biological activity of all of the materials. This study revealed that the most suitable scaffold composition for osteogenesis induction is collagen I foam with calcined hydroxyapatite with a pore size of 360 ± 130 µm and mean particle size of 0.130 µm. The expression of osteogenic markers RunX2 and ColI mRNA was promoted, and a strong synthesis of extracellular protein osteocalcin was observed. ColI/calcined HAP scaffold showed significant osteogenic potential, and can be easily manipulated and tailored to the defect size, which gives it great potential for bone tissue engineering applications.     

Monooxime‐monocarbamoyl Bispyridinium Xylene‐Linked Reactivators of Acetylcholinesterase—Synthesis,In vitro and Toxicity Evaluation,and Docking Studies

Acetylcholinesterase (AChE) reactivators are crucial antidotes to organophosphate intoxication. A new series of 26 monooxime‐monocarbamoyl xylene‐linked bispyridinium compounds was prepared and tested in vitro, along with known reactivators (pralidoxime, HI‐6, obidoxime, trimedoxime, methoxime, K107, K108 and K203), on a model of tabun‐ and paraoxon‐, methylparaoxon‐ and DFP‐inhibited human erythrocyte AChE. Although their ability to reactivate tabun‐inhibited AChE did not exceed that of the previously known compounds, some newly prepared compounds showed promising reactivation of pesticide‐inhibited AChE. The acute toxicity of the novel compounds was also determined. Docking studies using tabun‐inhibited AChE were performed for three compounds of interest. The structure–activity relationship (SAR) study confirmed the apparent influence of the xylene linkage and carbamoyl moiety on the reactivation ability and toxicity of the agents.     

Gap Junctional Communication via Connexin43 between Purkinje Fibers and Working Myocytes Explains the Epicardial Activation Pattern in the Postnatal Mouse Left Ventricle

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.     

Influence of addition of nanosize barium cerate on the microstructure and properties of top-seeded melt growth YBCO bulk superconductors

Barium cerate (BaCeO₃) is one of the possible additions to bulk YBa₂Cu₃O₇ single-grain superconductors to suppress the growth of Y₂BaCuO₅ (Y211) particles. This paper investigates the synthesis of barium cerate powder and its use in YBa₂Cu₃O₇ bulk superconductors. Crystalline barium cerate was synthesized by solid-state reaction, by co-precipitation of oxalates and by sol-gel method. Final calcination was held in air or in vacuum. It is shown that the most efficient in refining Y211 is nanocrystalline barium cerate prepared by sol-gel method calcined in vacuum. The effective refinement of Y211 particles occurred over the entire interval of nanocrystalline BaCeO₃ addition from 0.38 to 1.90 wt%. The optimal concentration of nanosize barium cerate was determined, microstructure and superconducting properties were characterized. The effect of Y211 content on trapped field in YBCO bulks with addition of nanocrystalline barium cerate is shown.     

Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.