Growth description for vessel wall adaptation: a thick-walled mixture model of abdominal aortic aneurysm evolution

(1) Background: Vascular tissue seems to adapt towards stable homeostatic mechanical conditions, however, failure of reaching homeostasis may result in pathologies. Current vascular tissue adaptation models use many ad hoc assumptions, the implications of which are far from being fully understood; (2) Methods: The present study investigates the plausibility of different growth kinematics in modeling Abdominal Aortic Aneurysm (AAA) evolution in time. A structurally motivated constitutive description for the vessel wall is coupled to multi-constituent tissue growth descriptions; Constituent deposition preserved either the constituent’s density or its volume, and Isotropic Volume Growth (IVG), in-Plane Volume Growth (PVG), in-Thickness Volume Growth (TVG) and No Volume Growth (NVG) describe the kinematics of the growing vessel wall. The sensitivity of key modeling parameters is explored, and predictions are assessed for their plausibility; (3) Results: AAA development based on TVG and NVG kinematics provided not only quantitatively, but also qualitatively different results compared to IVG and PVG kinematics. Specifically, for IVG and PVG kinematics, increasing collagen mass production accelerated AAA expansion which seems counterintuitive. In addition, TVG and NVG kinematics showed less sensitivity to the initial constituent volume fractions, than predictions based on IVG and PVG; (4) Conclusions: The choice of tissue growth kinematics is of crucial importance when modeling AAA growth. Much more interdisciplinary experimental work is required to develop and validate vascular tissue adaption models, before such models can be of any practical use

Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis

Chemoresistance is one of the barriers for the development of bladder cancer treatments. Previously, we showed that glycoprotein-130 (GP130) is overexpressed in chemoresistant bladder cancer cells and that knocking down GP130 expression reduced cell viability. In our current work, we showed that down-regulation of GP130 sensitized bladder cancer cells to cisplatin-based chemotherapy by activating DNA repair signaling. We performed immunohistochemistry and demonstrated a positive correlation between the levels of Ku70, an initiator of canonical non-homologous end joining repair (c-NHEJ) and suppressor of apoptosis, and GP130 in human bladder cancer specimens. GP130 knockdown by SC144, a small molecule inhibitor, in combination with cisplatin, increased the number of DNA lesions, specifically DNA double-stranded breaks, with a subsequent increase in apoptosis and reduced cell viability. Furthermore, GP130 inhibition attenuated Ku70 expression in bladder and breast cancer cells as well as in transformed kidney cells. In addition, we fabricated a novel polymer-lipid hybrid delivery system to facilitate GP130 siRNA delivery that had a similar efficiency when compared with Lipofectamine, but induced less toxicity

Analytical and numerical analyses of the micromechanics of soft fibrous connective tissues

State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting, close form expressions, are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method these predictions are compared with corresponding 3-D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations

Dilemmas in doing insider research in professional education

This article explores the dilemmas I encountered when researching social work education in England as an insider researcher who was simultaneously employed as an educator in the host institution. This was an ethnographic project deploying multiple methods and generating rich case study material which informed the student textbook Becoming a Social Worker the four-year period of the project. First, ethical dilemmas emerged around informed consent and confidentiality when conducting surveys of students and reading their portfolios. Second, professional dilemmas stemmed from the ways in which my roles as a researcher, academic tutor, social worker and former practice educator converged and collided. Third, political dilemmas pertained to the potential for the project to crystallize and convey conflicts among stakeholders in the university and community. Since the majority of research in social work education is conducted by insiders, we have a vital interest in making sense of such complexity

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

Position of the Third Na+ Site in the Aspartate Transporter GltPh and the Human Glutamate Transporter, EAAT1

Glutamate transport via the human excitatory amino acid transporters is coupled to the co-transport of three Na+ ions, one H+ and the counter-transport of one K+ ion. Transport by an archaeal homologue of the human glutamate transporters, GltPh, whose three dimensional structure is known is also coupled to three Na+ ions but only two Na+ ion binding sites have been observed in the crystal structure of GltPh. In order to fully utilize the GltPh structure in functional studies of the human glutamate transporters, it is essential to understand the transport mechanism of GltPh and accurately determine the number and location of Na+ ions coupled to transport. Several sites have been proposed for the binding of a third Na+ ion from electrostatic calculations and molecular dynamics simulations. In this study, we have performed detailed free energy simulations for GltPh and reveal a new site for the third Na+ ion involving the side chains of Threonine 92, Serine 93, Asparagine 310, Aspartate 312, and the backbone of Tyrosine 89. We have also studied the transport properties of alanine mutants of the coordinating residues Threonine 92 and Serine 93 in GltPh, and the corresponding residues in a human glutamate transporter, EAAT1. The mutant transporters have reduced affinity for Na+ compared to their wild type counterparts. These results confirm that Threonine 92 and Serine 93 are involved in the coordination of the third Na+ ion in GltPh and EAAT1

Peer norm guesses and self-reported attitudes towards performance-related pay

Due to a variety of reasons, people see themselves differently from how they see others. This basic asymmetry has broad consequences. It leads people to judge themselves and their own behavior differently from how they judge others and others’ behavior. This research, first, studies the perceptions and attitudes of Greek Public Sector employees towards the introduction of Performance-Related Pay (PRP) systems trying to reveal whether there is a divergence between individual attitudes and guesses on peers’ attitudes. Secondly, it is investigated whether divergence between own self-reported and peer norm guesses could mediate the acceptance of the aforementioned implementation once job status has been controlled for. This study uses a unique questionnaire of 520 observations which was designed to address the questions outlined in the preceding lines. Our econometric results indicate that workers have heterogeneous attitudes and hold heterogeneous beliefs on others’ expectations regarding a successful implementation of PRP. Specifically, individual perceptions are less skeptical towards PRP than are beliefs on others’ attitudes. Additionally, we found that managers are significantly more optimistic than lower rank employees regarding the expected success of PRP systems in their jobs. However, they both expect their peers to be more negative than they themselves are