Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

Amtshaftung bei Bauführung im Hochwassergebiet; fehlerhafter Flächenwidmungsplan; Nachforschungspflichten der Gemeinde

Bestehen ausreichende Anhaltspunkte für die Hochwassergef?hrdung, ist die Gemeinde verpflichtet, sich durch Nachforschungen Gewissheit über das Vorliegen oder Nichtvorliegen eines Hochwasserabflussgebietes gem § 38 Abs 3 WRG zu verschaffen. Liegt ein solches vor, hat sie gem § 12 Abs 1 Z 2 krnt GplG dieses im Fl?chenwidmungsplan ersichtlich zu machen. Erteilt die Gemeinde eine Baubewilligung ohne diese von der Erteilung einer wasserrechtlichen Bewilligung abh?ngig zu machen, haftet sie für die Kosten der Bauführung, die bei gesetzes-konformer Vorgangsweise unterlassen worden w?re.     

Entropy Based Approach to Data Loss Reparation Through the Indeterminate Fine-Grained Parallel Computation

The new method of a gap recovery in symbol sequences is presented. A covering is combined from the suitable reasonably short strings of the parts of a sequence available for observation. Two criteria are introduced to choose the best covering. It must yield the maximum of entropy of a frequency dictionary developed over the sequence obtained due to the recovery, if an overlapping combined from the copies of strings from the available parts of the sequence exists. The second criterion identifies the best covering in case when one has to use any string to cover the gap; here the best covering must yield the minimum of specific entropy of the frequency dictionary developed over the available parts of the sequence against the one developed over the entire sequence obtained due to the recovery. Kirdin kinetic machine which is the ideal fine-grained structureless computer has been used to resolve the problem of the reconstruction of a gap in symbol sequence.     

Robust channel prediction technique for decision directed RAKEreceivers

The authors describe a robust channel prediction technique for a direct sequence spread spectrum (DS-SS) system in a fast fading environment. Coherent diversity reception is employed for improved performance. To estimate the channel response, an FIR type linear prediction filter is employed for each RAKE tap. The stability of the decision directed receiver is achieved through differential encoding of the data bits. It is demonstrated through simulations that the performance of the proposed decision directed receiver is better than a receiver which relies on a pilot signal     

Instrumentation and techniques in equine fracture fixation

In recent years fracture fixation in the horse has changed significantly. New devices, mainly adapted from the human field, have been successfully introduced into large animal surgery. Examples of such implants include the DCS/DHS implant system, the self-tapping screw, the cannulated screw, and the pinless external fixator. However, new devices have also been developed exclusively for equine fracture management, including the interlocking intramedullary nail and the external skeletal fixation device. With these devices the surgeon has more options for repairing fractures in horses. Nevertheless, many problems are still unsolved. Indications exist that during the next few years new, exciting fracture fixation systems will be developed, providing further advancements in the quest for the ideal implant for horses. However, the development stages of these devices are such that mentioning the possibilities here is premature.     

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics.     

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell–cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.     

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.