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NKX3.1’s downregulation is strongly associated with prostate cancer (PCa) initiation, progression, and CRPC development. Nevertheless, a clear disagreement exists between NKX3.1 protein and mRNA levels in PCa tissues, indicating that its regulation at a post-translational level plays a vital role. This study identified a strong negative relationship between NKX3.1 and LIMK2, which is critical in CRPC pathogenesis. We identified that NKX3.1 degradation by direct phosphorylation by LIMK2 is crucial for promoting oncogenicity in CRPC cells and in vivo. LIMK2 also downregulates NKX3.1 mRNA levels. In return, NKX3.1 promotes LIMK2’s ubiquitylation. Thus, the negative crosstalk between LIMK2-NKX3.1 regulates AR, ARv7, and AKT signaling, promoting aggressive phenotypes. We also provide a new link between NKX3.1 and PTEN, both of which are downregulated by LIMK2. PTEN loss is strongly linked with NKX3.1 downregulation. As NKX3.1 is a prostate-specific tumor suppressor, preserving its levels by LIMK2 inhibition provides a tremendous opportunity for developing targeted therapy in CRPC. Further, as NKX3.1 downregulates AR transcription and inhibits AKT signaling, restoring its levels by inhibiting LIMK2 is expected to be especially beneficial by co-targeting two driver pathways in tandem, a highly desirable requisite for developing effective PCa therapeutics.

In recent years, the need to exploit digitized document data has been increasing. In this paper, we address the problem of parsing digitized Vietnamese paper documents. The digitized Vietnamese documents are mainly in the form of scanned images with diverse layouts and special characters introducing many challenges. To this end, we first collect the UIT-DODV dataset, a novel Vietnamese document image dataset that includes scientific papers in Vietnamese derived from different scientific conferences. We compile both images that were converted from PDF and scanned by a smartphone in addition a physical scanner that poses many new challenges. Additionally, we further leverage the state-of-the-art object detector along with the fused loss function to efficiently parse the Vietnamese paper documents. Extensive experiments conducted on the UIT-DODV dataset provide a comprehensive evaluation and insightful analysis.

This paper evaluates the performances of dry, minimum quantity lubrication (MQL), and MQL with nanofluid conditions in turning of the most common titanium (Ti) alloy, Ti-6Al-4 V, in a solution treated and aged (STA) microstructure. In particular, the nanofluid evaluated here is vegetable (rapeseed) oil mixed with small concentrations of exfoliated graphite nanoplatelets (xGnPs). This paper focuses on turning process that imposes a challenging condition to apply the oil or nanofluid droplets directly onto the tribological surfaces of a cutting tool due to the uninterrupted engagement between tool and work material during cutting. A series of turning experiments was conducted with uncoated carbide inserts, while measuring the cutting forces with a dynamometer under the dry, MQL and MQL with nanofluid conditions supplying oil droplets externally from our MQL device. The inserts are retrieved intermittently to measure the progress of flank and crater wear using a confocal microscopy. This preliminary experimental result shows that MQL and in particular MQL with the nanofluid significantly improve the machinability of Ti alloys even in turning process. However, to attain the best performance, the MQL conditions such as nozzle orientation and the concentration of xGnP must be optimized.

Introduction: Spheroids show great promise in being a better model for testing treatments for cancer in vitro when compared to monolayer cells. Single photon imaging of spheroids is limited by depth. Due to this reason, two photon imaging is necessary to obtain a full image of the spheroid. We developed a software that can evaluate the cellular metabolism of a spheroid by calculating the Redox Index (NADH divided by FAD). We tried to validate this software by treating the spheroids with an ATP antagonist.

Titanium alloys typically do not contain hard inclusion phases typically observed in other metallic alloys. However, the characteristic scoring marks and more distinctive micro- and/or macro-chippings are ubiquitously observed on the flank faces of cutting tools in machining titanium alloys, which is the direct evidence of abrasive wear (hard phase(s) in the microstructure abrading and damaging the flank surface). Thus, an important question lies with the nature of the hard phases present in the titanium microstructure. In this work, we present a comprehensive study that examines the microstructural impact on flank wear attained by turning various Ti-6Al-4V bars having distinct microstructures with uncoated carbide inserts. In particular, four samples with elongated, mill-annealed, solution treated & annealed and fully-lamellar microstructures were selected for our turning experiments. After turning each sample, the flank surface of each insert was observed with confocal laser scanning microscopy (CLSM) and analyzed to determine the flank wear behavior in relation to each sample' distinct microstructures. To characterize the microstructure, scanning electron microscopy (SEM) together with Orientation imaging microstructure (OIM) was used to identify and distinguish the phases present in each sample and the content and topography of each phase was correlated to the behavior of flank wear.more »The flank wear is also affected by the interface conditions such as temperature and pressure, which were estimated using finite element analysis (FEA) models. The temperature dependent abrasion models enable us to estimate the flank wear rate for each microstructure, and are compared with the experimentally measured wear data.« less