Impact of endostatin gene therapy on myeloid-derived suppressor cells from a metastatic renal cell carcinoma

Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b⁺Gr⁻1⁺ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b⁺Gr⁻1⁺ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b⁺Gr⁻1⁺ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b⁺Gr⁻1⁺ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment

Characterizing Width Uniformity by Wave Propagation

This work describes a novel image analysis approach to characterize the uniformity of objects in agglomerates by using the propagation of normal wavefronts. The problem of width uniformity is discussed and its importance for the characterization of composite structures normally found in physics and biology highlighted. The methodology involves identifying each cluster (i.e. connected component) of interest, which can correspond to objects or voids, and estimating the respective medial axes by using a recently proposed wavefront propagation approach, which is briefly reviewed. The distance values along such axes are identified and their mean and standard deviation values obtained. As illustrated with respect to synthetic and real objects (in vitro cultures of neuronal cells), the combined use of these two features provide a powerful description of the uniformity of the separation between the objects, presenting potential for several applications in material sciences and biology.Comment: 14 pages, 23 figures, 1 table, 1 referenc

Partitioning Complex Networks via Size-constrained Clustering

The most commonly used method to tackle the graph partitioning problem in practice is the multilevel approach. During a coarsening phase, a multilevel graph partitioning algorithm reduces the graph size by iteratively contracting nodes and edges until the graph is small enough to be partitioned by some other algorithm. A partition of the input graph is then constructed by successively transferring the solution to the next finer graph and applying a local search algorithm to improve the current solution. In this paper, we describe a novel approach to partition graphs effectively especially if the networks have a highly irregular structure. More precisely, our algorithm provides graph coarsening by iteratively contracting size-constrained clusterings that are computed using a label propagation algorithm. The same algorithm that provides the size-constrained clusterings can also be used during uncoarsening as a fast and simple local search algorithm. Depending on the algorithm's configuration, we are able to compute partitions of very high quality outperforming all competitors, or partitions that are comparable to the best competitor in terms of quality, hMetis, while being nearly an order of magnitude faster on average. The fastest configuration partitions the largest graph available to us with 3.3 billion edges using a single machine in about ten minutes while cutting less than half of the edges than the fastest competitor, kMetis

Evaluation of high-concentrate diets that vary in physically effective neutral detergent fibre for finishing lambs

The objective of this research was to evaluate lamb diets with a high proportion of concentrate and various levels of physically effective neutral detergent fibre (NDF) using tropical ingredients. Four diets were formulated: D1 with 16.5% physically effective NDF (peNDF), D2 with 21.4% peNDF, D3 with 23.3% peNDF, and D4 with 24.6% peNDF. Twenty male Santa Inês lambs at four months old with an average liveweight (LW) of 18.6 ± 3.4 kg were fed for 49 days. There were no differences (P >0.05) among the diets in dry matter (DM) intake. Crude protein (CP) intake, relative to either LW or metabolic live weight (LW0.75) or LW, was greater (P ≤0.05) for D2 and D3 than for D1 or D4. Lower (P ≤0.05) NDF intake, relative to LW0.75 or LW, was lower for D1 than for the other diets. Selection indexes (SIs) were similar (P >0.05) among diets. Animals that consumed D1 had less (P ≤0.05) rumination time per bolus. Meaningful variations were not observed in performance and efficiency of finishing lambs that were related to differences in peNDF among the diets. Santa Inês lambs were able to adapt to diets with low levels of peNDF by increasing rumination time as a consequence of increased fibre consumption and greater particle size selection

Dynamics and thermodynamics of the spherical frustrated Blume-Emery-Griffiths model

We introduce a spherical version of the frustrated Blume-Emery-Griffiths model and solve exactly the statics and the Langevin dynamics for zero particle-particle coupling (K=0). In this case the model exhibits an equilibrium transition from a disordered to a spin glass phase which is always continuous for nonzero temperature. The same phase diagram results from the study of the dynamics. Furthermore, we notice the existence of a nonequilibrium time regime in a region of the disordered phase, characterized by aging as occurs in the spin glass phase. Due to a finite equilibration time, the system displays in this region the pattern of interrupted aging.Comment: 19 pages, 8 figure

Probing the Statistical Properties of Unknown Texts: Application to the Voynich Manuscript

While the use of statistical physics methods to analyze large corpora has been useful to unveil many patterns in texts, no comprehensive investigation has been performed on the interdependence between syntactic and semantic factors. In this study we propose a framework for determining whether a text (e.g., written in an unknown alphabet) is compatible with a natural language and to which language it could belong. The approach is based on three types of statistical measurements, i.e. obtained from first-order statistics of word properties in a text, from the topology of complex networks representing texts, and from intermittency concepts where text is treated as a time series. Comparative experiments were performed with the New Testament in 15 different languages and with distinct books in English and Portuguese in order to quantify the dependency of the different measurements on the language and on the story being told in the book. The metrics found to be informative in distinguishing real texts from their shuffled versions include assortativity, degree and selectivity of words. As an illustration, we analyze an undeciphered medieval manuscript known as the Voynich Manuscript. We show that it is mostly compatible with natural languages and incompatible with random texts. We also obtain candidates for keywords of the Voynich Manuscript which could be helpful in the effort of deciphering it. Because we were able to identify statistical measurements that are more dependent on the syntax than on the semantics, the framework may also serve for text analysis in language-dependent applications

Relating water deficiency to berry texture, skin cell wall composition and expression of remodeling genes in two Vitis vinifera varieties

The cell wall (CW) is a dynamic structure that responds to stress. Water shortage (WS) impacts grapevine berry composition and its sensorial quality. In the present work, berry texture, skin CW composition, and expression of remodeling genes were investigated in two V. vinifera varieties, Touriga Nacional (TN) and Trincadeira (TR), under two water regimes, Full Irrigation (FI) and No Irrigation (NI). The global results allowed an evident separation between both varieties and the water treatments. WS resulted in increased anthocyanin contents in both varieties, reduced amounts in cellulose and lignin at maturation, but an increase in arabinose-containing polysaccharides more tightly bound to the CW in TR. In response to WS, the majority of the CW related genes were down-regulated in a variety dependent pattern. The results support the assumption that WS affects grape berries by stiffening the CW through alteration in pectin structure, supporting its involvement in responses to environmental conditions

Andrological, pathologic, morphometric, and ultrasonographic findings in rams experimentally infected with Brucella ovis

AbstractBrucella ovis is considered the most important infectious cause of reproductive disorders in sheep. The disease is characterized by epididymitis, subfertility and infertility in rams. B. ovis occasionally results in abortion in ewes, as well. The aim of this study was to evaluate kinetic changes in the reproductive organs of rams experimentally infected with B. ovis. Nine rams were experimentally inoculated intrapreputially with 2mL of a suspension containing 1.2×109CFU (colony-forming units)/mL of B. ovis (strain ATCC25840). In addition, 50μL of a suspension containing 1.2×1010CFU/mL of the same B. ovis strain was inoculated into each conjunctival sac, resulting in 3.6×109CFU total per ram. Six of nine infected rams had developed clinical changes in the tail of the epididymis at 30 days post-infection (dpi), but these changes regressed in 50% of these rams. Ultrasound demonstrated an increase in the area of the tail of the epididymis (P<0.001), reduction in the area of the testes (P<0.001), and an increased length and width of the seminal vesicles (P<0.001) during the course of infection. A sperm granuloma was diagnosed on the basis of ultrasonography findings. Microscopically, there was epididymitis, testicular degeneration, and seminal vesiculitis. Inflammatory cells were detected in the semen even before the development of epididymitis. Moreover, inflammatory cells were also found in the semen of asymptomatic rams, indicating that the presence of leukocytes in the ejaculate is a valuable method for screening potential carriers of infections in the genital tract