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The paper proposes a new data-flow based approach for the identification of backbones in infinite clusters on 2-D percolation site lattices of dimension L × L . The infinite cluster is identified first, then a multi step algorithm is applied for the reduction of the infinite cluster to its backbone. Algorithm performances are evaluated theoretically and experimentally. The algorithm is local and can therefore be efficiently implemented on data-flow parallel platforms in Θ ( L ) time if applied on percolation lattices near the critical percolation probability or in Θ ( L 2 ) in the worst case. The proposed methodology could resolve the problem of stack overflow at large systems that can appear with classical graph based algorithms, and has potential for a higher execution speed-up on parallel architectures. [ABSTRACT FROM AUTHOR]

Processes within porous building materials, water-filled soils pores and many other porusmedias modeled by the cellular automation (CA). We propose an algorithm for counting isolated objects in random generate granular systems. The algorithm is based on a Leviald's cellular automation (CA). We use regular two dimensional network in which a pore is presented with uniform distribution. The algorithm is tested on various networks which are generated near the percolation threshold. [ABSTRACT FROM AUTHOR]

Abstract: The initial use of immunosuppressive therapy (IST) in severe aplastic anemia (sAA) or reapplication of IST-centered methods following disease relapse is successful only in well-selected patients. The potential treatment by autologous stem cell (SC) transplant in sAA is still an innovative/pioneering therapeutic approach. To our best knowledge, this is the second published case of autologous SC transplant in sAA. The aim of this work was to optimize mobilization and timing for SC harvesting – using our own controlled-rate cryopreservation – with higher CD34+/CD90+ subset yield and recovery in order to obtain complete and long-term hematopoietic reconstitution following autologous SC transplant. We report a 35year-old sAA male patient who initially underwent IST using rabbit ATG and Cyclosporine A (CsA). He was supportive transfusion dependent for the whole period of IST-phase. After the second IST-cycle, polymorphonuclear (PMN) cell count increase (>2.0×109/L) was observed, when SC mobilization, two large volume leukapheresis procedures and following autologous transplant were performed. The yields of harvested CD34+ and CD34+/CD90+ cells were 5.75×106/kgbm and 1.7×106/kgbm, respectively. The quantity of applied CD34+ and CD34+/CD90+ cells in autologous SC transplant were 5.45×106/kgbm (7-AADCD34 + viability =95.42%) and 1.63×106/kgbm (7-AADCD34 + /CD90 + viability =95.42%), respectively. Hematopoietic reconstitution registered due to second month after autologous SC transplant and he is 24months in complete medullar, hematological and clinical remission, with normal cytogenetic status – applying only continuous CsA therapy. The results obtained strongly confirm that in sAA, with no allogeneic SC donor, autologous transplant can result in a successful clinical outcome. We suggest that CD34+/CD90+ subset count in peripheral blood and/or cell-harvest could be more valuable predictive factor than total CD34+ quantity of optimized collection-timing and superior treatment efficacy of autologous SC transplant in sAA. [Copyright &y& Elsevier]

Disturbance of the tight junction (TJ) complexes between brain endothelial cells leads to increased paracellular permeability, allowing leukocyte entry into inflamed brain tissue and also contributing to edema formation. The current study dissects the mechanisms by which a chemokine, CCL2, induces TJ disassembly. It investigates the potential role of selective internalization of TJ transmembrane proteins (occludin and claudin-5) in increased permeability of the brain endothelial barrier in vitro. To map the internalization and intracellular fate of occiudin and claudin-5, green fluorescent protein fusion proteins of these TJ proteins were generated and imaged by fluorescent microscopy with simultaneous measurement of transendothelial electrical resistance. During CCL2-induced reductions in transendothelial electrical resistance, claudin-5 and occludin became internalized via caveolae and further processed to early (EEA1+) and recycling (Rab4+) endosomes but not to late endosomes. Western blot analysis of fractions collected from a sucrose gradient showed the presence of claudin-5 and occludin in the same fractions that contained caveolin-1. For the first time, these results suggest an underlying molecular mechanism by which the pro-inflammatory chemokine CCL2 mediates brain endothelial barrier disruptionduring CNS inflammation. [ABSTRACT FROM AUTHOR]

Monocyte chemoattractant protein-1 (MCP-1 or CCL2) regulates blood-brain barrier permeability by inducing morphological and biochemical alterations in the tight junction (TJ) complex between brain endothelial cells. The present study used cultured brain endothelial cells to examine the signaling networks involved in the redistribution of TJ proteins (occludin, ZO-1, ZO-2, claudin-5) by CCL2. The CCL2-induced alterations in the brain endothelial barrier were associated with de novo Ser/Thr phosphorylation of occludin, ZO-1, ZO-2, and claudin-5. The phosphorylated TJ proteins were redistributed/localized in Triton X-100-soluble as well as Triton X-100-insoluble cell fractions. Two protein kinase C (PKC) isoforms, PKCα and PKCζ, had a significant impact on this event. Inhibition of their activity using dominant negative mutants PKCα-DN and PKCζ-DN diminished CCL2 effects on brain endothelial permeability. Previous data indicate that Rho/Rho kinase signaling is involved in CCL2 regulation of brain endothelial permeability. The interactions between the PKC and Rho/Rho kinase pathways were therefore examined. Rho, PKCα, and PKCζ activities were knocked down using dominant negative mutants (T17Rho, PKCα-DN, and PKCζ-DN, respectively). PKCα and Rho, but not PKCζ and Rho, interacted at the level of Rho, with PKCα being a downstream target for Rho. Double transfection experiments using dominant negative mutants confirmed that this interaction is critical for CCL2-induced redistribution of TJ proteins. Collectively these data suggest for the first time that CCL2 induces brain endothelial hyperpermeability via Rho/PKCα signal pathway interactions. [ABSTRACT FROM AUTHOR]

The imperative of sustainability demands that every decision-making process in building and designing a hydro power system, analyzes the environmental, political, historical, cultural and other social impacts, besides the normal technical and economical concerns. Presently, most design processes incorporate impacts as non-technical criteria, through environmental and social impact assessment studies. These latter studies are mainly descriptive texts, conducted after all the technical optimizations of the design were completed and not always included within the optimization calculation. The main goal of this paper is to present the possibility for incorporating all the non-technical criteria as fuzzy mathematical functions in the optimization and decision-making process, right from the very first planning step, simultaneously and equally with other relevant, numerically presented, technical criteria. The idea was developed and tested on a practical example: the hydropower utilization of the Drina River between Foca and Gorazde, two towns in Bosnia and Herzegovina, a region with extreme environmental, political, historical, cultural and other social conflict. In spite of the restrictive environment, this part of the river has very high hydro potential, which is a renewable resource. Consideration of both the technical and non-technical criteria in the fuzzy optimized model, as presented in the paper, leads to novel project solutions. The final design consisting of three almost uniform dams plants: Sadba 362, Ustikolina 373 and Paunci 384, was proven to be sustainable for development as well as very similar to experts’ reasoning. The chosen optimal solution for hydro power development is a cascade consisting of three hydro power plants, instead of a single high dam, which might affect the environment and strongly disturb local communities. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5–90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0–50.0 min with SC and 130.0–300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1–3 IV → cycles 4–6 SC: 77.5% → 72.5%; cycles 1–3 SC → cycles 4–6 IV: 77.5% → 63.8%). Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion. [Display omitted] • PHranceSCa showed that most patients strongly preferred PH FDC SC over P + H IV. • PH FDC SC was generally well tolerated. • There were no new safety signals, even when switching. • PH FDC SC offers a quicker alternative to IV infusion. [ABSTRACT FROM AUTHOR]