MUCKE aims to mine a large volume of images, to structure them conceptually and to use this conceptual structuring in order to improve large-scale image retrieval. The last decade witnessed important progress concerning low-level image representations. However, there are a number problems which need to be solved in order to unleash the full potential of image mining in applications. The central problem with low-level representations is the mismatch between them and the human interpretation of image content. This problem can be instantiated, for instance, by the incapability of existing descriptors to capture spatial relationships between the concepts represented or by their incapability to convey an explanation of why two images are similar in a content-based image retrieval framework. We start by assessing existing local descriptors for image classification and by proposing to use co-occurrence matrices to better capture spatial relationships in images. The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images. Consequently, we introduce methods which tackle these two problems and compare results to state of the art methods. Note: some aspects of this deliverable are withheld at this time as they are pending review. Please contact the authors for a preview.

http://ieeexplore.ieee.org/iel2/4524/12820/00592460.pdf

Image Processing

A surgical stapling device particularly suited for endoscopic procedures is described The device includes a handle assembly and an elongated body extending distally from the handle assembly The distal end of the elongated body is adapted to engage a disposable loading unit A control rod having a proximal end operatively connected to the handle assembly includes a distal end extending through the elongated body A control rod locking member is provided to prevent movement of the control rod until the disposable loading unit is fully secured to the elongated body of the stapling device

Surgical Stapling Apparatus

Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. In order to fit functional demand, materials with desired physical, chemical, biological, biomechanical and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications.

/pdf/biomedical-applications-of-biodegradable-polymers-2db9gcyzxw.pdf

Biomedical Applications of Biodegradable Polymers

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.

/pdf/a-framework-for-advancing-our-understanding-of-cancer-3vf5istnqi.pdf

A framework for advancing our understanding of cancer-associated fibroblasts

Newness and distinctiveness is claimed in the features of ornamentation as shown inside the broken line circle in the accompanying representation.

Display screen or portion thereof with graphical user interface

A main challenge in tissue engineering and regenerative medicine is achieving local and efficient growth factor release to guide cell function. Gelatin is a denatured form of collagen that cells can bind to and degrade through enzymatic action. In this study, gelatin microspheres were used to release bone morphogenetic protein 2 (BMP2). Spherical microparticles with diameters in the range of 2-6 µm were created by an emulsification process and were stabilized by crosslinking with the small molecule genipin. The degree of crosslinking was varied by controlling the incubation time in genipin solution. Loading rate studies, using soy bean trypsin inhibitor as a model protein, showed rapid protein uptake over the first 24 h, followed by a levelling off and then a further increase after approximately 3 days, as the microspheres swelled. Growth factor release studies using microspheres crosslinked to 20%, 50% and 80% of saturation and then loaded with BMP2 showed that higher degrees of crosslinking resulted in higher loading efficiency and slower protein release. After 24 h, the concentration profiles produced by all microsphere formulations were steady and approximately equal. Microspheres incubated with adult human mesenchymal stem cells accumulated preferentially on the cell surface, and degraded over time in culture. BMP2-loaded microspheres caused a three- to eight-fold increase in expression of the bone sialoprotein gene after 14 days in culture, with more crosslinked beads producing a greater effect. These results demonstrate that genipin-crosslinked gelatin microspheres can be used to deliver growth factors locally to cells in order to direct their function.

/pdf/gelatin-microspheres-crosslinked-with-genipin-for-local-3gndr6t3ps.pdf

Gelatin microspheres crosslinked with genipin for local delivery of growth factors.

The advent of microbubble contrast agents has enhanced the capabilities of ultrasound as a medical imaging modality and stimulated innovative strategies for ultrasound-mediated drug and gene delivery. While the utilization of microbubbles as carrier vehicles has shown encouraging results in cancer therapy, their applicability has been limited by a large size which typically confines them to the vasculature. To enhance their multifunctional contrast and delivery capacity, it is critical to reduce bubble size to the nanometer range without reducing echogenicity. In this work, we present a novel strategy for formulation of nanosized, echogenic lipid bubbles by incorporating the surfactant Pluronic, a triblock copolymer of ethylene oxide copropylene oxide coethylene oxide into the formulation. Five Pluronics (L31, L61, L81, L64 and P85) with a range of molecular weights (Mw: 1100 to 4600 Da) were incorporated into the lipid shell either before or after lipid film hydration and before addition of perfluorocarb...

/pdf/formulation-and-characterization-of-echogenic-lipid-pluronic-232vhmpz8p.pdf

Formulation and characterization of echogenic lipid-Pluronic nanobubbles.

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma.

/pdf/acoustic-characterization-and-pharmacokinetic-analyses-of-3dd1lc3j7w.pdf

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

https://www.hormonebalance.org/images/documents/Patel%2010%20Injection%20site%20in%20situ%20implant%20formation%20CR.pdf

Effect of injection site on in situ implant formation and drug release in vivo.

The ability of breast cancer cells to interconvert between epithelial and mesenchymal states contributes to their metastatic potential. As opposed to cell autonomous effects, the impact of epithelial–mesenchymal plasticity (EMP) on primary and metastatic tumor microenvironments remains poorly characterized. Herein we utilize global gene expression analyses to characterize a metastatic model of EMP as compared to their non-metastatic counterparts. Using this approach, we demonstrate that upregulation of the extracellular matrix crosslinking enzyme tissue transglutaminase-2 (TG2) is part of a novel gene signature that only emerges in metastatic cells that have undergone induction and reversion of epithelial–mesenchymal transition (EMT). Consistent with our model system, patient survival is diminished when primary tumors demonstrate enhanced levels of TG2 in conjunction with its substrate, fibronectin. Targeted depletion of TG2 inhibits metastasis, while overexpression of TG2 is sufficient to enhance this process. In addition to being present within cells, we demonstrate a robust increase in the amount of TG2 and crosslinked fibronectin present within extracellular vesicle (EV) fractions derived from metastatic breast cancer cells. Confocal microscopy of these EVs suggests that FN undergoes fibrillogenesis on their surface via a TG2 and Tensin1-dependent process. Upon in vivo administration, the ability of tumor-derived EVs to induce metastatic niche formation and enhance subsequent pulmonary tumor growth requires the presence and activity of TG2. Finally, we develop a novel 3D model of the metastatic niche to demonstrate that conditioning of pulmonary fibroblasts via pretreatment with tumor-derived EVs promotes subsequent growth of breast cancer cells in a TG2-dependent fashion. Overall, our studies illustrate a novel mechanism through which EMP contributes to metastatic niche development and distant metastasis via tumor-derived EVs containing aberrant levels of TG2 and fibrillar FN.

Luis Solorio

Papers

Gelatin microspheres crosslinked with genipin for local delivery of growth factors.

Formulation and characterization of echogenic lipid-Pluronic nanobubbles.

Acoustic Characterization and Pharmacokinetic Analyses of New Nanobubble Ultrasound Contrast Agents

Effect of injection site on in situ implant formation and drug release in vivo.

Transglutaminase-2 facilitates extracellular vesicle-mediated establishment of the metastatic niche.