Integration of Exploration and Search: A Case Study of the M3 Model

International audienceEffective support for multimedia analytics applications requires exploration and search to be integrated seamlessly into a single interaction model. Media metadata can be seen as defining a multidimensional media space, casting multimedia analytics tasks as exploration, manipulation and augmentation of that space. We present an initial case study of integrating exploration and search within this multidimensional media space. We extend the M3 model, initially proposed as a pure exploration tool, and show that it can be elegantly extended to allow searching within an exploration context and exploring within a search context. We then evaluate the suitability of relational database management systems, as representatives of today’s data management technologies, for implementing the extended M3 model. Based on our results, we finally propose some research directions for scalability of multimedia analytics

Signal-Regulated Pre-mRNA Occupancy by the General Splicing Factor U2AF

Alternative splicing of transcripts in a signal-dependent manner has emerged as an important concept to ensure appropriate expression of splice variants under different conditions. Binding of the general splicing factor U2AF to splice sites preceding alternatively spliced exons has been suggested to be an important step for splice site recognition. For splicing to proceed, U2AF has to be replaced by other factors. We show here that U2AF interacts with the signal-dependent splice regulator Sam68 and that forced expression of Sam68 results in enhanced binding of the U2AF65 subunit to an alternatively spliced pre-mRNA sequence in vivo. Conversely, the rapid signal-induced and phosphorylation-dependent interference with Sam68 binding to RNA was accompanied by reduced pre-mRNA occupancy of U2AF in vivo. Our data suggest that Sam68 can affect splice site occupancy by U2AF in signal-dependent splicing. We propose that the induced release of U2AF from pre-mRNA provides a regulatory step to control alternative splicing

Ion-Transfer Voltammetric Behavior of Propranolol at Nanoscale Liquid-Liquid Interface Arrays

In this work, the ion-transfer voltammetric detection of the protonated β-blocker propranolol was explored at arrays of nanoscale interfaces between two immiscible electrolyte solutions (ITIES). Silicon nitride nanoporous membranes with 400 pores in a hexagonal arrangement, with either 50 or 17 nm radius pores, were used to form regular arrays of nanoITIES. It was found that the aqueous-to-organic ion-transfer current continuously increased steadily rather than reaching a limiting current plateau after the ion-transfer wave; the slope of this limiting current region was concentration dependent and associated with the high ion flux at the nanointerfaces. Electrochemical data were examined in terms of an independent nanointerface approach and an equivalent microdisc approach, supported by finite element simulation. In comparison to the larger interface configuration (50 nm radius), the array of 17 nm radius nanoITIES exhibited a 6.5-times higher current density for propranolol detection due to the enhanced ion flux arising from the convergent diffusion to smaller electrochemical interfaces. Both nanoITIES arrays achieved the equivalent limits of detection, 0.8 μM, using cyclic voltammetry. Additionally, the effect of scan rate on the charging and faradaic currents at these nanoITIES arrays, as well as their stability over time, was investigated. The results demonstrate that arrays of nanoscale liquid–liquid interfaces can be applied to study electrochemical drug transfer, and provide the basis for the development of miniaturized and integrated detection platforms for drug analysis

CD44v4 Is a Major E-Selectin Ligand that Mediates Breast Cancer Cell Transendothelial Migration

BACKGROUND: Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: By assessing migration of various breast cancer cells across TNF-alpha pre-activated human umbilical vein endothelial cells (HUVECs), we found that breast cancer cells migrated across HUVEC monolayers differentially and that transmigration was E-selectin dependent. Cell surface labeling with the E-selectin extracellular domain/Fc chimera (exE-selectin/Fc) showed that the transmigration capacity of breast cancer cells was correlated to both the expression level and localization pattern of E-selectin binding protein(s) on the tumor cell surface. The exE-selectin/Fc strongly bound to metastatic MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells, but not non-metastatic MCF-7 and T47D cells. Binding of exE-selectin/Fc was abolished by removal of tumor cell surface sialyl lewis x (sLe(x)) moieties. Employing an exE-selectin/Fc affinity column, we further purified the counterreceptor of E-selectin from metastatic breast cancer cells. The N-terminal protein sequence and cDNA sequence identified this E-selectin ligand as a approximately 170 kD human CD44 variant 4 (CD44v4). Purified CD44v4 showed a high affinity for E-selectin via sLe(x) moieties and, as expected, MDA-MB-231 cell adhesion to and migration across HUVEC monolayers were significantly reduced by down-regulation of tumor cell CD44v4 via CD44v4-specific siRNA. CONCLUSIONS/SIGNIFICANCE: We demonstrated, for the first time, that breast cancer cell CD44v4 is a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers. This finding offers new insights into the molecular basis of E-selectin-dependent adhesive interactions that mediate breast cancer cell transendothelial metastasis

Antibodies to Placental Immunoregulatory Ferritin with Transfer of Polyclonal Lymphocytes Arrest MCF-7 Human Breast Cancer Growth in a Nude Mouse Model

The recently cloned human gene named “placental immunoregulatory ferritin” (PLIF) is a pregnancy-related immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells), both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, anti-C48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression

FR 26. Feed suplementation with diets based on local resources in postcalving dual purpose cows Guárico state highlands, Venezuela. II. Effect on the reproduction performance

Three different rations were compared during 120 days and treir effects on 125 postcalving dual purpose mature cows, weighting 371 ± 37 kg , grazing native pasture and sorghum crop residues, on highland farms at Guárico State, evaluated throught body condition (BC) and reproductive performance. T1 = grazing sorghum crop residues + sugar cane bagasse + molasses + mineral mixture (Control). T2 = T1 + tomatoes wastes (25 %) + urea + sorghum grain residues and Phithecellobium saman + minerals mixture. T3 = T1 + tomato hulls grinded ad libitum. BC was estimated at beginning on the trial and monthly thereafter. Milk progesterone determination was measured weekly using radioinmunoassay technique (RIA). All time-to-event analysis was accomplished using EGRET program through Product-limit method and Proportional Hazards Model. The supplements represented 4.9; 13.69 and 19.94 (Mj/d) of ME for T1, T2 and T3 respectively. There was no diference between T1 (used as a base category by the model) and T2 (P=0.733). The cows from T1 and T2 had 3.85 times more chances on early cyclicity than the cows from T3 during the period. For each 30 days in the postpartum period the cows had 6.95 more chance on the onset of the ovarian activity (P<.10). For each parity the cows had 1.268 more chances on early ovarian activity (P<.031). Cows with a BC score greater than three at the beninning of the trial had 7.59 more chances to reach cyclicity than cows less than three (P<.03). It is concluded that diets based with local resouses balanced and offered strategically improved reproductive performance

NR 17. Feed supplementation with diets based on local resources in postcalving dual purpose cows on Guarico state highlands. Venezuela. I. Effect on the milk production

Three rations were compared as to their effects on 125 postcalving dual purpose mature cows, weighting 371 +/- 37 kg , grazing native pasture and crop residues, on highland farms at Guárico State. Milk production, body condition (BC) and live weight (LW) was evaluated using a randomized design: T1 = (control), grazing crop residues + Sugar cane bagasse-molasses and mineral mixture; T2 = T1 + tomatoe waste (25 %) + urea mixes of sorghum residues and Pithecelobium saman hulls, urea and minerals mixture; T3 = T1 + tomato waste ad libitum. BC and body weight were estimated at the beginning of the trial and monthly. The milk production was measured weekly. A General Lineal Model was used to analyze: average milk production /month/cow/treatment, and milk production/cow-teat/treatment. The supplements represented 4.9; 13.69 and 19.94 (MJ/d) of Metabolized Energy (EM) for T1, T2 and T3 respectively. The average milk production/cow/week were: 10.92; 11.4; 13.75 kg and the average milk production /teat/cow/week were: 3.51a; 3.26a; 5.57b kg for T1, T2 and T3 respectively. It is concluded that the tomatoes as a local resource could be a strategic in the improvement of the milk production per cow-teat (P<.05)