Ultrasound-Specific Segmentation via Decorrelation and Statistical Region-Based Active Contours

Segmentation of ultrasound images is often a very challenging task due to speckle noise that contaminates the image. It is well known that speckle noise exhibits an asymmetric distribution as well as significant spatial correlation. Since these attributes can be difficult to model, many previous ultrasound segmentation methods oversimplify the problem by assuming that the noise is white and/or Gaussian, resulting in generic approaches that are actually more suitable to MR and X-ray segmentation than ultrasound. Unlike these methods, in this paper we present an ultrasound-specific segmentation approach that first decorrelates the image, and then performs segmentation on the whitened result using statistical region-based active contours. In particular, we design a gradient ascent flow that evolves the active contours to maximize a log likelihood functional based on the Fisher-Tippett distribution. We present experimental results that demonstrate the effectiveness of our method

Ultrasound-Specific Segmentation via Decorrelation and Statistical Region-Based Active Contours

Segmentation of ultrasound images is often a very challenging task due to speckle noise that contaminates the image. It is well known that speckle noise exhibits an asymmetric distribution as well as significant spatial correlation. Since these attributes can be difficult to model, many previous ultrasound segmentation methods oversimplify the problem by assuming that the noise is white and/or Gaussian, resulting in generic approaches that are actually more suitable to MR and X-ray segmentation than ultrasound. Unlike these methods, in this paper we present an ultrasound-specific segmentation approach that first decorrelates the image, and then performs segmentation on the whitened result using statistical region-based active contours. In particular, we design a gradient ascent flow that evolves the active contours to maximize a log likelihood functional based on the Fisher-Tippett distribution. We present experimental results that demonstrate the effectiveness of our method

Ethnography

Many qualitative studies in journalism and mass communication research draw on ethnographic methods that originated in anthropology and sociology. These methods involve studying people within their own cultural environment through intensive fieldwork; they emphasize the subjects' frames of reference and understandings of the world. This article uses a comparison between journalism and ethnographic research as a framework for highlighting common problems with manuscripts using this method. It offers veteran ethnographers' tips about what they look for in a manuscript and identifies three ethnographies that are examples of successful application of the method to topics of interest to journal readers

Production and characterisation of a recombinant scFv reactive with human gastrointestinal carcinomas

SC142-reactive antigen are highly glycosylated glycoproteins expressed on tissues of gastric and colon cancers but not on normal tissues. Murine SC142 antibody specific for the SC142-reactive antigen has been produced by immunisation with SNU16 stomach cancer cells. However, SC142 antibody has several potential problems such as high immunogenicity and poor tumour penetration owing to their large size. To improve tumour penetration potential in vivo, recombinant single-chain fragments have been produced using the original hybridoma cells as a source of variable heavy- and variable light-chain-encoding antibody genes. The use of the polymerase chain reaction, expression cloning technology and gene expression systems in E. coli has led to the production of SC142 single-chain fragments, which was similar in activity to the SC142 parent antibody confirmed by immunohistochemistry. Analysis by DNA sequencing, SDS–PAGE and Western blotting has demonstrated the integrity of the single-chain fragments. Competitive ELISA showed that SC142 single-chain fragments originated from parent SC142 antibody. BIAcore biosensor binding experiments showed that the SC142 single-chain fragments had an ideal dissociation rate constant as a tumour imaging reagent. These results illustrate the potential application of these novel products as an immunodiagnostic and further immunotherapeutic reagent

Genetically engineered CAR NK cells display selective cytotoxicity against FLT3-positive B-ALL and inhibit in vivo leukemia growth

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a promising effector cell type for adoptive cancer immunotherapy. Both, genetically modified donor-derived NK cells as well as continuously expanding NK-92 cells are currently under clinical development. To enhance their therapeutic utility for the treatment of pre-B-cell acute lymphoblastic leukemia (B-ALL), we engineered NK-92 cells by lentiviral gene transfer to express a FMS-like tyrosine kinase 3 (FLT3)-specific CAR that contains a composite CD28-CD3ζ signaling domain. FLT3 has primarily been described as a therapeutic target for acute myeloid leukemia, but overexpression of FLT3 has also been reported in B-ALL. Exposure of FLT3-positive targets to CAR NK-92 cells resulted in conjugate formation between NK and leukemia cells, NK-cell degranulation and selective cytotoxicity toward established B-ALL cell lines and primary blasts that were resistant to parental NK-92. In a SEM B-ALL xenograft model in NOD-SCID IL2R γnull mice, treatment with CAR NK-92 but not parental NK-92 cells markedly inhibited disease progression, demonstrating high antileukemic activity in vivo. As FLT3 is known to be also expressed on precursor cells, we assessed the feasibility of incorporating an inducible caspase-9 (iCasp9) suicide switch to enhance safety of our approach. Upon addition of the chemical dimerizer AP20187 to NK-92 cells coexpressing the FLT3-specific CAR and iCasp9, rapid iCasp9 activation was observed, precluding further CAR-mediated cytotoxicity. Our data demonstrate that B-ALL can be effectively targeted by FLT3-specific CAR NK cells which may complement CD19-directed immunotherapies, particularly in cases of inherent or acquired resistance to the latter

The cis-regulatory map of Shewanella genomes

While hundreds of microbial genomes are sequenced, the challenge remains to define their cis-regulatory maps. Here, we present a comparative genomic analysis of the cis-regulatory map of Shewanella oneidensis, an important model organism for bioremediation because of its extraordinary abilities to use a wide variety of metals and organic molecules as electron acceptors in respiration. First, from the experimentally verified transcriptional regulatory networks of Escherichia coli, we inferred 24 DNA motifs that are conserved in S. oneidensis. We then applied a new comparative approach on five Shewanella genomes that allowed us to systematically identify 194 nonredundant palindromic DNA motifs and corresponding regulons in S. oneidensis. Sixty-four percent of the predicted motifs are conserved in at least three of the seven newly sequenced and distantly related Shewanella genomes. In total, we obtained 209 unique DNA motifs in S. oneidensis that cover 849 unique transcription units. Besides conservation in other genomes, 77 of these motifs are supported by at least one additional type of evidence, including matching to known transcription factor binding motifs and significant functional enrichment or expression coherence of the corresponding target genes. Using the same approach on a more focused gene set, 990 differentially expressed genes derived from published microarray data of S. oneidensis during exposure to metal ions, we identified 31 putative cis-regulatory motifs (16 with at least one type of additional supporting evidence) that are potentially involved in the process of metal reduction. The majority (18/31) of those motifs had been found in our whole-genome comparative approach, further demonstrating that such an approach is capable of uncovering a large fraction of the regulatory map of a genome even in the absence of experimental data. The integrated computational approach developed in this study provides a useful strategy to identify genome-wide cis-regulatory maps and a novel avenue to explore the regulatory pathways for particular biological processes in bacterial systems

A bispecific chimeric antigen receptor molecule enhances T cell activation through dual immunological synapse formation and offsets antigen escape in glioblastoma

Background Antigen escape tumor cell variants prevail in tumors recurring after treatment with chimeric antigen receptor (CAR) T cells with a single specificity. Recurrent tumors preserve alternative non-targeted tumor associated antigens. Hypothesis A bispecific CAR will mitigate antigen escape enhancing the antitumor activity of T cells. Methods and results HER2 and IL13Rα2 are currently targeted in Phase I glioblastoma (GBM) trials using CAR T cells. We created a bispecific CAR molecule with a HER2-specific scFv joined in tandem to an IL13Rα2-binding moiety in the CAR exodomain (Tandem CAR) and a CD28.ζ signaling endodomain. We used computational modeling to interrogate this design. GBM patients' Tandem CAR T cells showed distinct binding to soluble HER2 and IL13Rα2 and killed primary autologous GBM cells. Three-dimensional reconstitution and quantification of confocal images of the Tandem CAR T cell/tumor interface revealed enhanced bifunctional immunological synapses compared to conventional CARs. Further, Tandem CAR T cells exhibited significantly enhanced inexhaustible activation dynamics when compared to conventional HER2 or IL13Rα2 CAR T cells and better controlled established GBM in an orthotopic murine model by offsetting both HER2 and IL13Rα2 escape. Conclusion Tandem chimeric antigen receptors enhance T cell activation and mitigate antigen escape through bifunctional immunological synapse formation in GBM

Juxtaposing a cultural reading of landscape with institutional boundaries: the case of the Masebe Nature Reserve, South Africa

The article explores theoretically the juxtaposition of local stories about landscape with institutional arrangements and exclusionary practices around a conservation area in South Africa. The Masebe Nature Reserve is used as a case study. The article argues that the institutional arrangements in which the nature reserve is currently positioned are too static, and consequently exclusionary, in their demarcation of boundaries. This stifles local communities’ sense of belonging to these landscapes. Hence, they strongly resent and feel alienated by the nature reserve. Their opposition and alienation often manifests in poaching. The empirical material is based on how local people living adjacent to the Masebe Nature Reserve have historically named and interpreted the area’s impressive sandstone mountains, in the process creating a sense of belonging. Juxtaposing this mostly tranquil cultural reading of the landscape to the institutional practices of boundary demarcation gives the analysis an immediate critical edge regarding issues of social justic