Development and evaluation of surface treatments to enhance the fiber-matrix adhesion in PAN-based carbon fiber/liquid crystal polymer composites. Part I: Coupling agent and amine surface treatments

Several surface treatments, using both commercially available coupling agents and reagents containing multiple amines, were applied to commingled continuous as-received AS4 carbon reinforcing fiber/liquid crystal polymer (LCP) matrix fibers. Unidirectional composites (normally 60 vol% carbon fiber) were prepared from as-received and treated commingled fibers and characterized. To estimate the effect the effect of the treatments on fiber-matrix adhesion, short beam shear (SBS) tests were conducted, the failure surfaces were examined, and spectroscopic studies wee performed. The mean SBS strength of the as-received unidirectional AS4 carbon fiber/LCP matrix composite system was 49 MPa. The best coupling agent and amine treatments yielded increases in composite shear strength of ∼ 10 to 20%, relative to the as-received AS4/LCP system. For the amine treatments, ESCA and FTIR analyses suggested of both the carbon and LCP fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers (both with coupling agents and amines) showed that strong fiber-matrix adhesion was present. That is, failure occurred in the LCP matrix material.     

Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review

Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD.     

Immature Vascular Smooth Muscle Cells in Healthy Murine Arteries and Atherosclerotic Plaques: Localization and Activity

The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis.     

The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.     

Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

Molecular Cross-Talk between Gravity- and Light-Sensing Mechanisms in Euglena gracilis

Euglena gracilis is a photosynthetic flagellate. To acquire a suitable position in its surrounding aquatic environment, it exploits light and gravity primarily as environmental cues. Several physiological studies have indicated a fine-tuned relationship between gravity sensing (gravitaxis) and light sensing in E. gracilis. However, the underlying molecular mechanism is largely unknown. The photoreceptor photoactivated adenylyl cyclase (PAC) has been studied for over a decade. Nevertheless, no direct/indirect interaction partner (upstream/downstream) has been reported for PAC. It has been shown that a specific protein, kinase A (PKA), showed to be involved in phototaxis and gravitaxis. The current study reports the localization of the specific PKA and its relationship with PAC.     

Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing.     

From expert-driven to user-oriented communication of infection control guidelines

Currently, infection control guidelines in hospitals and other health care institutions are more expert-driven than user-oriented. In order to enhance the usability of the expert-driven guideline format, we developed a website for the communication of existing guidelines that better fit the practical information needs of health care workers (HCWs). We employed a user-centered design process that involved two studies.In the initial study, 28 HCWs were asked to solve tasks using existing, paper-based infection control guidelines. In order to detect their strategies and problems, the participants were asked to think aloud. Usability problems occurred due to poorly structured information, insufficient quality of information, and a mismatch between experts’ and HCWs’ vocabulary. To overcome these shortcomings, three design principles were applied for communicating infection control guidelines: better navigation (the guidelines should be searchable in several ways); multimodality (the guidelines should not be presented as text only), and action-orientation (the guidelines should be presented as HCWs’ behaviors). A website was developed to meet these principles.In the second study, the same 28 HCWs completed tasks identical to those of the first study while thinking aloud, but this time using the website. The percentage of correctly completed tasks increased and the mean time for task completion decreased significantly. Also, respondents were more satisfied with the website than the paper-based guidelines. The number of problems due to poor information quality and a mismatch in vocabulary declined, although the number of structural problems increased. This can probably be explained by the fact that the navigation structure was user-generated (using Card Sort), in contrast to a standardized answer format based on common usability principles.Overall, we found that involving HCWs in the development process is important to create a sense of ownership and to foster the implementation of the guidelines, which might eventually result in compliance and reduce health care-associated infections. This paper outlines concrete steps for how to involve HCWs in the design process.     

Tensile modulus modeling of carbon‐filled nylon 6,6 and polycarbonate‐based resins

Electrically and thermally conductive resins can be produced by adding conductive fillers to insulating polymers. Mechanical properties, such as tensile modulus, are also important. This research focused on performing compounding runs followed by injection molding and tensile testing of carbon‐filled nylon 6,6 and polycarbonate‐based resins. The three carbon fillers investigated included an electrically conductive carbon black, synthetic graphite particles, and a milled pitch–based carbon fiber. For each polymer, resins were produced and tested that contained varying amounts of these single‐carbon fillers. In addition, combinations of fillers were investigated by conducting a full 2³ factorial design and a complete replicate in each polymer. These tensile modulus experimental results were then compared to results predicted by several different models. For the composites containing only one filler type, the Nielsen model with the modified Ψ term provided the best prediction of the actual experimental values. For the composites containing more than one filler type, a new parameter, which includes the vibrated bulk density (VBD) of the fillers, was incorporated into the Nielsen model with the modified Ψ term. This model with the new VBD parameter provided the best estimate of experimental tensile modulus for composites containing multiple‐filler types. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1716–1728, 2003