Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these micro-environments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases.

Within the hierarchy of the Software Defined Network (SDN) network stack, the control layer operates as the critical middleware facilitator of interactions between the data plane and the network applications, which govern flow routing decisions. In the OpenFlow implementation of the SDN model, the control layer, commonly referred to as a network operating system (NOS), has been realized by a range of competing implementations that offer various performance and functionality advantages: NOX [14], and ONIX [18]. In this paper we focus on the question of control layer resilience, when rapidly developed prototype network applications go awry, or third-party network applications incorporate unexpected vulnerabilities, fatal instabilities, or even malicious logic. We demonstrate how simple and common failures in a network application may lead to loss of the control layer, and in effect, loss of network control.To address these concerns we present the ROSEMARY controller, which implements a network application containment and resilience strategy based around the notion of spawning applications independently within a micro-NOS. ROSEMARY distinguishes itself by its blend of process containment, resource utilization monitoring, and an application permission structure, all designed to prevent common failures of network applications from halting operation of the SDN Stack. We present our design and implementation of ROSE-MARY, along with an extensive evaluation of its performance relative to several of the mostly well-known and widely used controllers. Rather than imposing significant performance costs, we find that with the integration of two optimization features, ROSE-MARY offers a competitive performance advantage over the majority of other controllers.

A 720‐channel LCD source driver with a 12‐bit segmented R‐C DAC has been designed and fabricated by a 16V CMOS process. The proposed DAC consists of a conventional resistor string and a sample‐and‐hold buffer. DNL less than 0.3LSB and output voltage deviations less than 3mV were measured. Die area is 24.9mm2.

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The surface quality control of extruded products is a critical concern in the home appliance manufacturing industry owing to the increasing need for products with a high surface quality, in addition to the essential mechanical properties of the final product. The underlying issue with achieving high-quality extrusion products is that surface defects, especially those resulting in surface gloss differences, called white line defects, are only observed after surface treatment. In this study, we aim to investigate the cause of white line defect generation on the surface of an extruded product. Accordingly, an experimental extrusion program is established using an L-shaped die that has a noticeable change in its bearing length along the inner corner of its cross-sectional profile. Laboratory-scale experiments were performed for the L-shaped extrusion of homogenized Al 6063 alloy at various ram speeds, in order to induce surface defects, considering the production yield rate required for mass production. Subsequently, the microstructural changes near the surface failure region were investigated using an arbitrary Lagrangian–Eulerian (ALE) technique-based thermomechanical finite element (FE) analysis. To scale-up the defect observation method from laboratory-scale to production-scale manufacturing and confirm the reproducibility of the surface defect, scaled-up L-shaped extrusions were performed in an actual industrial production line. Finally, the potential cause of white line defect generation is discussed by comparing the numerical and metallurgical analyses, including the scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) observations.