A novel breast-cancer model of early stage invasion

The majority of breast cancer deaths are not caused by the primary tumor, but by metastasis to other organs. However, the mechanisms that underlie the first stage of metastasis, the invasion of cancer cells into surrounding tissue remain elusive, due to the complexity of the cellular, biochemical, and biophysical interactions in cancer tissue. In this work, we propose a novel in vitro breast cancer model that focuses on dissecting the influence of the biophysical properties of the extracellular matrix (ECM) on the onset of cancer invasion. Based on microfluidic technology, it will provide us with the necessary tools to independently vary different material and cell properties, while it provides the cells with a physiologically relevant environment.<br/

Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting

Spatial regulation of angiogenesis is important for the generation of functionalengineered vasculature in regenerative medicine. The Notch ligands Jag1 andDll4 show distinct expression patterns in endothelial cells and, respectively, pro-mote and inhibit endothelial sprouting. Therefore, patterns of Notch ligands maybe utilized to spatially control sprouting, but their potential and the underlyingmechanisms of action are unclear. Here, we coupled in vitro and in silico modelsto analyze the ability of micropatterned Jag1 and Dll4 ligands to spatially controlendothelial sprouting. Dll4 patterns, but not Jag1 patterns, elicited spatial con-trol. Computational simulations of the underlying signaling dynamics suggestthat different timing of Notch activation by Jag1 and Dll4 underlie their distinctability to spatially control sprouting. Hence, Dll4 patterns efficiently direct thesprouts, whereas longer exposure to Jag1 patterns is required to achieve spatialcontrol. These insights in sprouting regulation offer therapeutic handles forspatial regulation of angiogenesis.</p

MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device

Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration

Mesoporous silica nanoparticles in tissue engineering : a perspective

In this review, we summarize the latest developments and give a perspective on future applications of mesoporous silica nanoparticles (MSNs) in regenerative medicine. MSNs constitute a flexible platform for controlled delivery of drugs and imaging agents in tissue engineering and stem cell therapy. We highlight the recent advances in applying MSNs for controlled drug delivery and stem cell tracking. We touch upon novel functions of MSNs in real time imaging of drug release and biological function, and as tools to control the chemical and mechanical environment of stem cells. We discuss the need for novel model systems for studying biofunctionality and biocompatibility of MSNs, and how the interdisciplinary activities within the field will advance biotechnology research

Parallel streaming signature EM-tree: A clustering algorithm for web scale applications

The proliferation of the web presents an unsolved problem of automatically analyzing billions of pages of natural language. We introduce a scalable algorithm that clusters hundreds of millions of web pages into hundreds of thousands of clusters. It does this on a single mid-range machine using efficient algorithms and compressed document representations. It is applied to two web-scale crawls covering tens of terabytes. ClueWeb09 and ClueWeb12 contain 500 and 733 million web pages and were clustered into 500,000 to 700,000 clusters. To the best of our knowledge, such fine grained clustering has not been previously demonstrated. Previous approaches clustered a sample that limits the maximum number of discoverable clusters. The proposed EM-tree algorithm uses the entire collection in clustering and produces several orders of magnitude more clusters than the existing algorithms. Fine grained clustering is necessary for meaningful clustering in massive collections where the number of distinct topics grows linearly with collection size. These fine-grained clusters show an improved cluster quality when assessed with two novel evaluations using ad hoc search relevance judgments and spam classifications for external validation. These evaluations solve the problem of assessing the quality of clusters where categorical labeling is unavailable and unfeasible