Hypoxia induces a phase transition within a kinase signaling network in cancer cells

Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO_2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO_2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)—a critical component of hypoxic signaling and a compelling cancer drug target—is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO_2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier’s principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles

From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities

Associated production of top quarks at ATLAS and CMS

The latest measurements of the associated production of top quarks are summarised in this contribution, including the production of $t\bar{t}Z$, $t\bar{t}W$, $t\bar{t}\gamma/tq\gamma$ and $t\bar{t}t\bar{t}$. All measurements are in agreement with SM predictions. Sevaral measurements demonstrate tension with the prediction from theory computation or Monte Carlo generators, in particular in the measurement of the inclusive cross section of $t\bar{t}W$ by the CMS experiment

Microring resonator arrays for sensing applications

Integrated optical circuits, including microring resonator elements (MRR), provide a sensitive, specific, and reliable technology platform for the development of compact and smart microsystems for sensing applications, for example, chemical and label-free biochemical analysis as ultra-small MRRs feature extraordinary sensitivity to changes of environmental parameters. Some basic features of MRRs and figure of merits for an appropriate design are given as well as an overview on the most relevant material systems and technologies for the prospective fabrication of MRR devices in high-volume production on wafer level. Application-relevant approaches for an implementation of MRR based on-chip multiparameter analytics by using optical multiplexing techniques are summarized, first experimental results are given, and some architectures of optical circuit approaches for an efficient implementation of MRR-based sensor arrays in entire sensor systems are sketched. Finally, some perspectives extrapolate how well-engineered circuit integration will enable the development of smart, practical, portable, or handheld microsystems