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Nitrogen-doped TiO2 films exhibit good photocatalytic ability in the visible (VIS) light region. This study reports the fabrication of these films using arc ion plating (AIP) in different ratios of nitrogen partial pressure (PN2) to oxygen partial pressure (PO2) without substrate heating and/or applied bias. This approach allows a significant broadening of the range of possible substrates to be used. X-ray diffraction (XRD) patterns indicate that these films deposited at room temperature are amorphous, and surface electron microscope (SEM) and atomic force microscope (AFM) images show that they have rough surfaces. Their transmittance and optical properties are measured with a spectrometer and ellipsometer, respectively. In addition, the bandgap energies of these amorphous films are derived by the ellipsometer from the Tauc–Lorentz (TL) model. The results indicate that the N-doped TiO2 film with a PN2/PO2 ratio of 1/4 attains the narrowest bandgap and the highest absorbance in the visible region. It can be attributed to the prominent Ti–N peaks observed in the sample’s Ti and N X-ray photoelectron spectroscopy (XPS) spectra. In addition, verified with the methylene blue (MB) test, this sample exhibits the best photocatalytic performance for its narrowest energy gap.

Relative to several other p21-activated kinase (PAK) family members, the role of PAK3 in regulating cancer cell functions remains unclear. Our study obtained evidence that PAK3 regulates the Akt-GSK3β-β-catenin signaling by acting as Ser473-Akt kinase in several pancreatic cancer cell lines. Specifically, knockdown of PAK3 or overexpression of dominant-negative PAK3 inhibited the phosphorylation of Ser473-Akt and GSK3β, resulting in the proteasomal degradation of β-catenin. Conversely, overexpression of PAK3 led to activation of Akt signaling and increased β-catenin expression. These changes, however, were not noted with the silencing and/or overexpression of PAK1, PAK2, or PAK4, which underlies the impetus of PAK3 as a key effector in governing malignant phenotypes in these pancreatic cancer cells, including cancer stem cell (CSC) expansion. Accordingly, PAK3 depletion effectively suppresses tumorsphere formation, ALDH activity, and the expression of CSC surface markers. Moreover, we used a stable knockdown clone of AsPC-1 cells to demonstrate the in vivo efficacy of PAK3 inhibition in suppressing tumorigenesis and xenograft tumor growth. Together, these findings suggest the potential role of PAK3 as a target for pancreatic cancer therapy, which warrants further investigations.

In this study, a new, cost-effective, rapid, and easy method to produce a sunlight-like D65 light source from a typical white light-emitting diode (LED) is discussed. The novelty of this method is that the emission spectrum of a typical white LED is measured first, then the reverse spectrum is used to design and fabricate a double-sided multilayer coating filter to set in front of the typical white LED. This can be verified experimentally to improve the color-rendering index of the white LED to 95.8 at the D65 color temperature. The optical thicknesses of the multilayer film are designed at a quarter wavelength. The layer-thickness errors during the deposition process are reduced due to easy monitoring with the turning-point method. By lowering both the cost and level of technology required to produce D65 light sources, in addition to the most direct consequences of increased D65 availability and affordability, the cost and level of technology required for research that heavily utilizes D65 light sources can also be lowered in turn, especially in the fields of clinical science, medicine, and related industries.

Background African Swine Fever (ASF) is a highly contagious and lethal viral disease of swine, the presence of which in groups of pigs leads to enormous economic losses in the farming industry. However, vaccines and drugs to treat ASF have yet to be developed. To control the spread of the African Swine Fever Virus (ASFV), a diagnostic method that can be applied rapidly and can detect the disease during the early stages of infection is urgently needed. Methods In this study, we demonstrate a rapid and easy-to-use ASFV detection method that combines loop-mediated isothermal amplification (LAMP) and image processing with the hue-saturation-value (HSV) color model. This method was validated through use of synthetic ASFV DNA. Results The method shows high sensitivity, as it detects as few as 10 copies per reaction within 20 min. The speed and sensitivity of this newly developed assay are superior to those reported in previous studies. In addition, through HSV color space transformation, the colorimetric result of this LAMP assay can be used for a semi-quantitative analysis for ASFV (ranging from 108 to 101 copies per reaction) and improve the discern to low concentration samples from a negative control. Conclusion These results show that the combination of ASFV-LAMP assay and HSV color space transformation may accelerate the screening process of pigs for ASFV infection. Overall, this study provides a rapid, sensitive, early-stage, on-site diagnosis of ASFV infection and has potential to be applied to other infectious diseases.

Fused silica surface machined using continuous-wave CO2 laser beams with an energy density of 0.5 J/mm2 presented U-shaped grooves (approximately 47 μm-deep and 250 μm-wide) and asymmetrical craters (2–5 μm high). The fully reacted valley in the groove center exhibited porous microstructures and agglomerated silica nanoparticles in the size of 33–118 nm; whereas, the less reacted peak in the groove edge only presented uneven solidified films from silica ablations. Distinct morphologies in the valley and peak areas were supposed to result from the Gaussian energy distribution of laser beams. The selected area electron diffraction pattern suggested that the laser-reacted silica nanostructures were still amorphous with no obvious composition change. The x-ray photoelectron spectrometric results showed that both Si 2p and O 1s peaks shifted to higher energy sides, implying a more oxidized state of Si4+ and absorbed oxygen or hydroxides on nanostructured silica after CO2 laser machining.

Although the role of insulin-like growth factor-I receptor (IGF-IR) in promoting colorectal liver metastasis is known, the mechanism by which IGF-IR is upregulated in colorectal cancer (CRC) is not defined. In this study, we obtained evidence that mutant KRAS transcriptionally activates IGF-IR gene expression through Y-box-binding protein (YB)-1 upregulation via a novel MEK-Sp1-DNMT1-miR-137 pathway in CRC cells. The mechanistic link between the tumor suppressive miR-137 and the translational regulation of YB-1 is intriguing because epigenetic silencing of miR-137 represents an early event in colorectal carcinogenesis due to promoter hypermethylation. This proposed signaling axis was further verified by the immunohistochemical evaluations of liver metastases from a cohort of 46 KRAS mutant CRC patients, which showed a significant correlation in the expression levels among Sp1, miR-137, YB-1, and IGF-1R. Moreover, suppression of the expression of YB-1 and IGF-IR via genetic knockdown or the pharmacological inhibition of MEK hampers KRAS-driven colorectal liver metastasis in our animal model studies. From a translational perspective, the identification of this KRAS-driven pathway might provide a mechanistic rationale for the use of a MEK inhibitor as an adjuvant, in combination with standard of care, to prevent the recurrence of colorectal liver metastasis in KRAS mutant CRC patients after receiving liver resection, which warrants further investigation.

This paper describes superior candidate substrate material- aluminum nitride (AlN), for the cost-effective and high-performance requirements for aerospace mirrors. In fact, high specific stiffness and thermal stability are not only two major considerations to select ideal material but also machinability, dimensional stability, and cost. Silicon carbide shows the best figure of merits 12627, but it has extremely low remove rate and expensive raw material properties. Extremely low expansion ceramics such as Zerodur may be difficult to obtain in large quantities and its figure of merit is 1151. On the contrary, AlN has outstanding thermal conductivity (~170 W/m°C) and maintain high figure of merit 2222 without compromise. In our fabrication processes, the AlN substrate can be easily polished to 53±1nm Ra surface texture and 66.4±2nm RMS surface form. Its unique thermal stability, specific stiffness, and good figure of merits, associated with its easy machinability and low-cost raw materials, makes AlN an ideal selection for superior mirror substrate in the future space mirror optics.

Mid to high spatial frequency error (MSFR and HSFR) should be strictly controlled in modern optical systems. Pitch tool polishing (PTP) is an effective ultra-smoothing surface manufacturing method to control MSFR and HSFR. But it is difficult to control because it is affected by a lot of factors. The present paper describes the pitch tool polishing study based on eighteen well-planned orthogonal experiments (OA18 matrix). Five main process factors (abrasive particle size, slurry concentration, pad rotation speed, acidity and polishing time) in pitch tool polishing process were investigated. In this study, power spectral density (PSD) based on Fourier analysis of surface topography data obtained by white light interferometer was used as the results of orthogonal experiments instead of material removal rate and surface roughness. A normalization method of PSD was proposed as the range analysis rule. Three parts of spatial frequency bandwidth were selected and discussed. Acidity is the most important factor in part 1 and slurry concentration is the most significant one in part 2; while acidity is the least influenced one in part 3. The result in each part was explained by two-step material removal mechanism. At last, suggestions in low and high spatial frequency are given for pitch tool polishing.

We report on an ambitious project in the field of automation, applied to bound and free abrasive processing of precision and ultra-precision surfaces, with potentially far-reaching consequences. This involves two main aspects:- directly processing surfaces using industrial robots, and combining robots with Zeeko CNC polishing machines to automate operations that are currently manual. These form steps towards our ultimate vision of the Integrated Manufacturing Cell for bespoke optics rather than mass-produced, and manufacture of other precision surfaces including prosthetic joint implants. Projects such as the European Extremely Large Telescope provide a relevant case study, where significant numbers of high-value bespoke optics are required.

This paper addresses computer numerical control (CNC) polishing of aspheric or freeform optics. Prior CNC grinding of the asphere tends to produce mid-spatial frequencies (MSFs) at some level. Precessions polishing can rectify these, but the very ability of the bonnet tooling to adapt to the local asphere enables it to do so, at least in part, to similar spatial frequencies in the MSFs. To accelerate smoothing, hard tools can, in principle, be used, but aspheric misfit is often assumed to preclude this. In this paper, we explore new insight into the role of abrasive particle size in accommodating misfit. First, we report on a glass-bending rig to produce a continuous range of complex surfaces, while withstanding process forces. Then, we describe how this was used to evaluate the triangle of misfit, abrasive size, and MSFs produced for hard rotating tools. This has revealed a regime in which such tools can be used without introducing significant new MSFs, as evidenced by manufacture of prototype off-axis aspheric segments for the European Extremely Large Telescope project.

Aristolochic acid (AA) is a common cause of Chinese herb nephropathy. The mechanisms involved in the pathogenesis of AA nephropathy (AAN) are intricate. One well-documented effect of AA in the kidney is its pro-fibrotic activity. Nitric oxide (NO), a messenger gas generated from l-arginine, is the product of nitric oxide synthase (NOS). NO is involved in renal hemodynamics and exerts cytoprotective effects against renal injury. In the present study, the role of NO in AAN was investigated in MES-13 cells, a glomerular mesangial cell line. NO endogenously generated by the induction of inducible nitric oxide synthase (iNOS) with lipopolysaccharide (LPS)/interferon-γ (IFN-γ) significantly downregulated connective tissue growth factor (CTGF) protein expression in MES-13 cells. AA significantly suppressed LPS/IFN-γ-induced NO production and reversed CTGF expression that was downregulated by LPS/IFN-γ. AA decreased iNOS gene and protein expressions in a concentration-dependent manner. AA caused declines in LPS/IFN-γ-induced signal transducer and activator of transcription-1α (STAT-1α) phosphorylation and interferon response factor-1 (IRF-1) mRNA expression. Furthermore, AA attenuated IκB phosphorylation and reduced NF-κB translocation to the nuclear fraction. Taken together, our data indicate that AA reversed the CTGF expression inhibited by LPS/IFN-γ treatment via suppression of NO and iNOS expressions in MES-13 cells through inhibition of the JAK/STAT-1α and NF-κB signaling pathways. NO potentially exerts antifibrotic activity by down regulation of CTGF in MES-13 cells and inhibition of the iNOS gene by AA might partially account for the fibrotic effects of AA in nephropathy.

In the context of industry 4.0, building data clouds in manufacturing technologies is the fundamental step to approach intelligent automatic process. This new technology has proved to efficiently and effectively monitor five important responses (removal rate, texture, surface accuracy, edge-profiles and mid-spatial frequencies) with more than 95% repeatability in real time. This faster and inexpensive process can serve for the nowadays high-quality segmented telescopes. We illustrate the underlying problem by reference to a case-study - the challenge of an average manufacturing rate of 11.4 segments per month for the 39.3m optical/infrared European Extremely Large Telescope (E-ELT) project.

When a surface experiencing robotic processing to improve its optical performance (such as removing mid-spatial frequencies, localized grinding errors, and regional surface scratches), spindle speed, tool travel speed, pressure, slurry density as well as groove patterns are main factors to influence surface finishes. Based on the desired material removal rate, the Preston equation can provide optimized pressures and velocities between the tool and processed surface. Various groove patterns, however, can hardly predict by the equation because different patterns can cause unique tool deformation and pressure distribution, leading to determine unique smoothing result. In this paper, four typical groove patterns are studied: non-groove, grid grove, annular groove and radial groove with three typical tool types are evaluated by Finite Element Method (FEM) and statistics. Characteristics of these tools and groove patterns are presented in the end of this paper.

We first present a Case Study – the manufacture of 1.4 m prototype mirror-segments for the European Extremely Large Telescope, undertaken by the National Facility for Ultra Precision Surfaces, at the OpTIC facility operated by Glyndwr University. Scale-up to serial-manufacture demands delivery of a 1.4 m off-axis aspheric hexagonal segment with surface precision < 10 nm RMS every four days, compared with a typical year or more for an one-off part. This requires a radically-new approach to large optics fabrication, which will inevitably propagate into wider industrial optics. We report on how these ambitious requirements have stimulated an investigation into the synergy between robots and computer numerically controlled (‘CNC’) polishing machines for optical fabrication. The objective was not to assess which is superior. Rather, it was to understand for the first time their complementary properties, leading us to operate them together as a unit, integrated in hardware and software. Three key areas are reported. First is the novel use of robots to automate currently-manual operations on CNC polishing machines, to improve work-throughput, mitigate risk of damage to parts, and reduce dependence on highly-skilled staff. Second is the use of robots to pre-process surfaces prior to CNC polishing, to reduce total process time. The third draws the threads together, describing our vision of the automated manufacturing cell, where the operator interacts at cell rather than machine level. This promises to deliver a step-change in end-to-end manufacturing times and costs, compared with either platform used on its own or, indeed, the state-of-the-art used elsewhere.

Seven flavonoid glycosides (1–7) and one theasaponin (8) were isolated from the defatted Camellia oleifera seeds using the isopropanol salting-out pretreatment (ISP) technique, followed by column chromatography. Among them, compounds 5, 7, and 8 are new compounds. The comparison of oxygen radical absorbance capacity (ORAC) of crude extracts extracted by the n-butanol partition (BP) with those extracted by the ISP showed that the latter method yields eight times greater scavenging capacities than that of the former approach. Besides, ISP exhibited almost twice the extraction efficiency than that of BP. ORAC and Trolox equivalent antioxidant capacity (TEAC) analysis revealed that the most potent antioxidants are compounds 1 and 2, which exhibited 1.78 and 1.41 times higher antioxidant activity than that of Trolox, respectively. These results indicated that the ISP approach improves the extraction efficiency in the isolation of potent antioxidants, making the defatted C. oleifera seeds valuable in the food additive industry.

p21-activated kinases (PAKs) are important effectors of the Rho family GTPases and has been implicated in cytoskelestal remodeling, cell proliferation, apoptosis, and transformation. Based on the sequence, structure homology, and activation mechanism, six PAKs are classified into two groups, PAK 1-3 (group I) and PAK 4-6 (group II). PAK kinases are frequently overexpressed in various human tumors and represent therapeutically relevant targets for cancer treatments. Previous studies have shown that PAK1 and PAK4 are upregulated and/or hyperactivated in pancreatic cancer, and promotes pancreatic cancer cell motility and invasion. In our study, we showed that knockdown of PAK3, but not that of PAK1 or PAK2, inhibited pancreatic cancer cell proliferation in vitro, and tumor growth in vivo. In addition, our data showed that PAK3 regulated the protein stability of β-catenin via Akt/GSK-3β signaling pathway in pancreatic cancer cells. The role of PAK3 in regulating Akt/GSK-3β phosphorylation was further confirmed by the ectopic expression of wild-type versus kinase-dead (K297L) PAK3. Equally important, the mammosphere formation, aldehyde dehydrogenase (ALDH) activity and cancer stem cell-associated markers, were also down-regulated in PAK3 knockdown cells, suggesting the involvement of PAK3 in regulating cancer stem cell-like properties in pancreatic cancer cells. Together, these findings suggested that PAK3 as a primary regulator of Akt/GSK-3β/β-catenin signaling for maintaining cancer stem cell phenotypes and promoting tumor growth, which underlies the potential of targeting PAK3 in fostering new therapeutic strategies for pancreatic cancer. Citation Format: Hsing-Yu Wu, Ming-Chen Yang, Po-Chen Chu, Samuel K. Kulp, Ching-Shih Chen. Novel function of p21-activated kinase 3 (PAK3) in regulating Akt phosphorylation and pancreatic cancer stem cell phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1360. doi:10.1158/1538-7445.AM2017-1360

Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.

This paper describes the application of loose-abrasive processes to the manufacture of 1.4 meter, off-axis aspheric, hexagonal mirror-segments. These are prototypes for the 39 m European Extremely Large Telescope (E-ELT). The application of active forces to correct the overall form of segments in the telescope, means that the overall form-accuracy achieved in polishing can be less critical than for a non-active mirror. However, it is a requirement that the base-radii and conic constants of mirror-segments are very closely matched, so that the combined image is not degraded. This means that abrasive processes have to operate with respect to anabsoluterather thanrelativedatum. Furthermore, there are stringent requirements on mid-spatial frequency defects on segment surfaces, and on edge-roll. These control stray-light, and ultimately detectability of faint astronomical targets. We describe the CNC abrasive techniques we have developed in response. We then demonstrate the success of the approach, which represents the first time ever that segments have been processed entirely in the hexagonal shape:- a milestone in loose-abrasive processing. Finally, we address up-scale for the unprecedented number of segments required for the E-ELT build-phase.

Diabetes is associated with hyperglycemia and increased thrombin production. However, it is unknown whether a combination of high glucose and thrombin can modulate the expression of NAPDH oxidase (Nox) subtypes in human aortic endothelial cells (HAECs). Moreover, we investigated the role of a diabetes-associated microRNA (miR-146a) in a diabetic atherothrombosis model. We showed that high glucose (HG) exerted a synergistic effect with thrombin to induce a 10.69-fold increase in Nox4 mRNA level in HAECs. Increased Nox4 mRNA expression was associated with increased Nox4 protein expression and ROS production. Inflammatory cytokine kit identified that the treatment increased IL-8 and IL-6 levels. Moreover, HG/thrombin treatment caused an 11.43-fold increase of THP-1 adhesion to HAECs.In silicoanalysis identified the homology between miR-146a and the 3′-untranslated region of the Nox4 mRNA, and a luciferase reporter assay confirmed that the miR-146a mimic bound to this Nox4 regulatory region. Additionally, miR-146a expression was decreased to 58% of that in the control, indicating impaired feedback restraint of HG/thrombin-induced endothelial inflammation. In contrast, miR-146a mimic transfection attenuated HG/thrombin-induced upregulation of Nox4 expression, ROS generation, and inflammatory phenotypes. In conclusion, miR-146a is involved in the regulation of endothelial inflammation via modulation of Nox4 expression in a diabetic atherothrombosis model.

Quercetin, rich in fruits and vegetables, has been used as a nutritional supplement because of its anti-inflammatory and antioxidative properties. Its positive effects on anti-hepatic fibrosis have also been suggested. However the anti-hepatofibrotic mechanisms upon which quercetin acts have yet to be well characterized. In the present study, we investigated the anti-proliferative effect of quercetin on activated hepatic stellate cells (aHSCs), the central role of hepatofibrosis, and evaluated the proteins involved in growth inhibition by a 2D gel electrophoretic analysis. Activated HSCs were isolated from Sprague Dawley rats and were spontaneously activated in vitro. Quercetin restrained the proliferation of aHSCs rather than quiescent HSCs and heptotcytes by inducing a G(1) arrest as examined by cell cycle analysis and evidenced by increased levels of p53, p21(CIP1/WAF1), as well as p27(KIP1), and decreased abundance of cyclins (D(1), D(2), A, E). An apoptosis through extrinsic pathway as demonstrated by elevated expression of Fas/Fas ligand (FasL), annexin V labeling, chromatin condensation, sub-G(1) fraction (7.39%), caspase-3 activity, was also observed. The 2D electrophoresis analysis revealed that quercetin negatively regulated protein molecules associated with metabolism (α-enolase, phosphoglycerate kinase), survival, cytokinesis (tubulin), and protein folding (protein disulfide isomerase A3) leading to cell growth retardation. Furthermore, quercetin might restrain HSC activation through reducing the levels of inflammatory cytokines (CXCL10, Midkine). Taken together, quercetin exerted diverse mechanisms to inhibit the growth of aHSCs. Proper consumption of quercetin could be beneficial to control the progression of heptofibrosis.