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Recently, sapphire has been used in a wide range of applications including optics, consumer electronics, and especially the rapidly growing LED wafer manufacturing. This paper investigates effects of a novel compound slurry composed of micron scaled diamond abrasives and various nano-platelets of graphene oxide (GO) for improving lapping performance of c-plane single-crystal aluminum oxide (Al2O3) sapphire wafers. Four kinds of graphenes including GO, reduced graphene oxide (RGO), ML-RGO (laminate), and MF-RGO (few-layer) are added into the diamond slurry to achieve compound slurries. Those compound slurries have been prepared with various graphene weight fractions in the range of 0.3 to 2.0 wt%, by LP (low power) or HP (high power) ultrasonication with different time spans in the range of 10 min to 48 h to adjust size of GOs. For the lapping process conducted by 10-min HP ultrasonicated GO (2.0 wt%)/diamond slurry, combination of medium down force pressure and the highest platen rotation speed of 45 kPa/80 rpm results in highest material removal rate (MRR) of 926.73 nm/min, which is 324% higher than MRR by pure diamond slurry. It is caused by high reactivity of GOs with sapphire wafer. As lapped at pressure/speed of 45 kPa/70 rpm by ultrasonicated GO (0.5 wt%)/diamond compound slurry, the average surface roughness Ra of wafer can reach 7.19 nm, which is 0.7% lower than 7.24 nm by pure diamond slurry. Experimental results demonstrate that the optimized planarization of sapphire wafer with high MRR and low surface roughness can be achieved using the GO compound slurry when the mechanical removal effect and the chemical reaction mechanism are in synergistic equilibrium. The XPS and EDS analyses clearly support the material removal model that a reactant aluminum carbonate layer and a residual carbon layer exist and both are efficiently removed by diamond abrasives. Results of this study can be applied to further explore high volume production of CMP of sapphire wafers.

Simple Summary Conventional serum markers such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and tissue polypeptide antigen (TPA) have a low sensitivity in predicting the prognosis of locoregional esophageal squamous cell carcinoma cell (ESCC). In our clinical study, we found high serum elafin to be an independent outcome predictor for stage I-IIIA ESCC, considering T, N, overall stage, and treatment. In vitro experiments showed that adding recombinant elafin drove ESCC cell proliferation, migration and invasion, while shRNA attenuated elafin levels, abrogating those effects. Our results suggested serum elafin might be a noninvasive biomarker to predict the outcome of locoregional ESCC and could potentially be used as a therapeutic target. Abstract Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor known to have locally advanced and metastatic features which cause a dismal prognosis. We sought to determine whether elafin, a non-invasive and secretory small-molecule marker, could be used to predict prognosis in locoregional ESCC patients in human and in vitro studies. In our human study, 119 subjects were identified as having incident and pathologically-proved ESCC with stage I-IIIA tumors from southern Taiwan between 2000 and 2016. We measured their serum elafin levels at baseline and followed them until the date of cancer death or until January 2020, the end of this study. Those with high serum elafin levels were found to have a 1.99-fold risk (95% confidence interval: 1.17–3.38) shorter survival than those who did not. In our in vitro experiments, elevated elafin levels were found to drive ESCC cell proliferation, migration and invasion, while attenuation of elafin level by shRNA abrogated those effects. We concluded that elafin promotes ESCC motility and invasion and leads to a worse clinical prognosis in ESCC patients without distant metastasis.

A quantitative analytical method to discriminate among the various types of cancerous esophagus tissue is essential for accurate cancer staging. This paper reports on the use of ratiometric nonlinear optical microscopy to reveal the ratio of two-photon excited fluorescence (TPEF) to second harmonic generation (SHG) and forward to backward (F/B) SHG from single collagen fibers only in submucosa of esophageal squamous cell carcinoma. This makes it possible to accurately differentiate among the four stages of esophageal cancer, providing results that are in good agreement with histopathology. Furthermore, it is confirmed by polarization-dependent SHG that the varied SHG response in esophageal cancer tissues is mainly from the shrinkage in diameter of collagen fibers instead of the collagen triple helixes altered by cancer cells. Based on the results of TPEF/SHG and F/B SHG ratio, they can cooperatively improve the precision of diagnostics on esophageal cancer and could be transferred to other types of cancer diseases with changed collagen fibers. Impact statement The issue of classifying esophageal cancer at various developmental stages is crucial for determining the optimized treatment protocol for the patients, as well as the prognosis. Precision improvement in staging esophageal cancer keeps seeking quantitative and analytical imaging methods that could augment histopathological techniques. In this work, we used nonlinear optical microscopy for ratiometric analysis on the intrinsic signal of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) from single collagen fibers only in submucosa of esophageal squamous cell carcinoma (ESCC). The blind tests of TPEF/SHG and forward (F)/backward (B) SHG were demonstrated to compare with the histology conclusion. The discussion of sensitivity and specificity was provided via statistical comparison between the four stages of esophageal cancer. To the best of our knowledge, this is the first study of using these two ratios in combination for staging ESCC.

ObjectiveIt is unclear whether endoscopic assessment of scars after colorectal endoscopic mucosal resection (EMR) has to include biopsies, even if endoscopy is negative. Vice versa, endoscopic diagnosis of recurrent adenoma may not require biopsy before endoscopic reinterventions. We prospectively analysed various endoscopic modalities in the diagnosis of recurrence following EMR.DesignWe conducted a prospective study of patients undergoing colonoscopy after EMR of large (≥20 mm) colorectal neoplasia. Endoscopists predicted recurrence and confidence level with four imaging modes: high-definition white light (WL) and narrow-band imaging (NBI) with and without near focus (NF). Separately, 26 experienced endoscopists assessed offline images.ResultsTwo hundred and thirty patients with 255 EMR scars were included. The prevalence of recurrent adenoma was 24%. Diagnostic values were high for all modes (negative predictive value (NPV) ≥97%, positive predictive value (PPV) ≥81%, sensitivity ≥90%, specificity ≥93% and accuracy ≥93%). In high-confidence cases, NBI with NF had NPV of 100% (95% CI 98% to 100%) and sensitivity of 100% (95% CI 93% to 100%). Use of clips at initial EMR increased diagnostic inaccuracy (adjusted OR=1.68(95% CI 1.01 to 2.75)). In offline assessment, specificity was high for all imaging modes (mean: ≥93% (range: 55%–100%)), while sensitivity was significantly higher for NBI-NF (82%(72%–93%)%)) compared with WL (69%(38%–86%); pConclusionOur study demonstrates very high sensitivity and accuracy for all four imaging modalities, especially NBI with NF, for diagnosis of recurrent neoplasia after EMR. Our data strongly suggest that in cases of high confidence negative optical diagnosis based on NBI-NF, no biopsy is needed to confirm absence of recurrence during colorectal EMR follow-up. A high confidence positive optical diagnosis can lead to immediate resection of any suspicious area. In all cases of low confidence, biopsy is still required.Trial registration numberNCT02668198.

To investigate the determinants related to the ability to drive a motorized mobility scooter after a stroke.The study was a cross-sectional study. The ability to drive a motorized mobility scooter was measured with the Power Mobility Clinical Driving Assessment. The independent variables included cognitive functions measured by the Color Trails Test and reaction time test, visual functions measured by a visual acuity test and visual field test, and motor functions measured with a dynamometer, the Box and Block Test, and the Functional Independence Measure.The correlation analyses revealed that the Power Mobility Clinical Driving Assessment scores had significant correlations with reaction time (The reaction time, binocular visual field, and grip strength of the unaffected hand were the most significant determinants related to the ability to drive a motorized mobility scooter after a stroke. IMPLICATIONS FOR REHABILITATIONMotorized mobility scooter driving ability for stroke patients is correlated with demographics (age, mobility scooter driving experience, time since last drive) and cognitive, visual and motor functions (reaction time, binocular visual field, visual acuity, and the grip strength of unaffected hand).Primary determinants of motorized mobility scooter driving ability for stroke patients include reaction time, binocular visual field, and grip strength of the unaffected hand.Comprehensive assessments incorporating cognitive, visual and motor functions are needed to evaluate the ability to drive a motorized mobility scooter after a stroke.

Sporadic nonampullary duodenal neoplasms (SNADN) can have malignant potential for which endoscopic and surgical resections are offered. We report combined gastroenterologic and surgical experience for treatment of SNADN, including endoscopic mucosal resection (EMR) and pancreas-preserving partial duodenectomy (PPPD).We retrospectively reviewed 121 consecutive patients, who underwent 30 PPPDs and 91 EMRs for mucosal and submucosal SNADN. Decision to undergo EMR or surgical resection was based on expert endoscopist and surgeon discretion including multidisciplinary tumor board review. Main outcomes were recurrence rate of neoplasia and adverse events requiring hospital admission or prolonged care. EMRs were performed with submucosal lifting followed by snare resection. PPPD included total duodenectomy, supra-ampullary PPPD for neoplasms proximal to the ampulla, and infra-ampullary PPPD for lesions distal to the ampulla. Follow-up data were available for 65% of EMR and 73% of surgical patients.Surgically resected neoplasia was larger with more advanced neoplasia and submucosal lesions. En bloc resection was achieved in all surgical resections and in 53% of EMRs. Post-EMR, mucosal and submucosal neoplasia recurred in 32 and 0%, respectively, including five neoplasms (26%) after an initial negative esophagogastroduodenoscopy. All recurrences were treated endoscopically. Complications occurred in 14 endoscopically and eight surgically treated patients, none requiring surgical intervention.Post-EMR patients had higher recurrence of mucosal neoplasia, whereas submucosal neoplasms, mainly carcinoid, did not recur. Polyp size and positive resection margin were not associated with neoplasia recurrence. Patients with SNADN could benefit from a multidisciplinary approach to stratify the optimal treatment based on local expertise.

In this paper, a novel method with addition of graphene in diamond slurry is proposed to conduct CMP lapping of sapphire wafer. Two kinds of graphenes are added including graphene oxide (GO), reduced graphene oxide (RGO). Effect of three important processing parameters on material removal rate (MRR) and surface roughness is investigated, including graphene type, graphene weight fraction, and ultrasonication time. Weight fractions of various graphenes versus diamond slurry are controlled in the range from 0.5 to 2.0 wt%. Results indicate that addition of graphene in diamond slurry can significantly increase MRR of sapphire wafer. MRR of sapphire wafer is proportional to graphene weight fraction. At higher weight fraction, GO/diamond slurry leads to higher MRR than RGO/diamond slurry does. MRR by the pure diamond is 285.80 nm/min, while MRR by the diamond/GO(2.0wt%) with 48-hour ultrasonication is 832.1 nm/min. Surface roughness is inversely proportional to graphene weight fraction and proportional to graphene particle size. Ultrasonication is able to efficiently reduce graphene particle size. RGO/diamond slurry can result in lower surface roughness than GO/diamond slurry.

Compact size wearable devices require multiple supplies with relative large loading difference, which causes serious cross regulation, large ripple, and oscillation in single-inductor multiple-output (SIMO) DC–DC converter. Thus, a continuous conduction mode/green mode (CCM/GM) relative skip energy control (RSEC) in SIMO is proposed for wearable device power solution. Different from the conventional absolute skip method, the RSEC eliminates unnecessary skip-induced voltage ripple and cross regulation with well regulation performance over wide load and voltage ranges. Optimization between efficiency and voltage ripple achieves low noise supply and reduced switching loss. In addition, smooth transition between CCM and GM provides high power and longer usage time in wearable devices. Furthermore, bidirectional dynamic slope compensation conquers subharmonic oscillation and avoids invalid pulses in the energy delivery operation of current-mode SIMO DC–DC converters. The test chip fabricated in the 0.18 μm CMOS process occupies $2.24\, {\rm mm}^{2}$ active area. Maximum output ripple, overshoot/undershoot, and cross regulation are kept below 40 mV, 27 mV, and 0.0432 mV/mA, respectively.

The organic light-emitting transistors (OLETs) with a novel tri-layer organic semiconducting heterostructure architecture and good performance, including record high EQE, is presented. In addition, an active-matrix display based on OLETs, without driving TFTs, will be demonstrated on a plastic substrate. The potential advantages of such technologies will be discussed.

The predicting correction technique (PCT) is proposed to achieve an adaptive on-time control for ripple-based buck converters. The switching frequency $f_{{\rm SW}}$ variation is suppressed when the PCT technique considers complete parasitic resistances of the components and devices. Even without extra clock-controlled circuits and current sensing circuits, the buck converter operates with a nearly constant $f_{{\rm SW}}$ over a wide load range. Parasitic resistances almost cause no influence and restriction on $f_{{\rm SW}}$ . Only input voltage is used to predict the adaptive on-time. Measurement results show only 0.32% in $\Delta f_{{\rm SW}}/f_{{\rm SW}}$ and 5.7 kHz/A in $\Delta f_{{\rm SW}}/\Delta I_{{\rm LOAD}}$ in case of 1.4 A load current change and $f_{{\rm SW}}$ is 2.5 MHz. Consequently, a pseudo-constant $f_{{\rm SW}}$ with well-defined noise spectrum strongly benefits the solution of electromagnetic interference (EMI) for system-on-a-chip (SoC) applications.

The dynamic bootstrap voltage (DBV) technique is proposed to keep high efficiency over wide ranges of load currents for high-power universal serial bus devices. The silicon area of the embedded power management with the DBV technique in the system-on-a-chip can be effectively reduced to 50% of the conventional design with a P-type high-side power MOSFET. Test chips fabricated in 0.25-μm CMOS process showed a 92% peak efficiency from 1 mA to 1 A. The maximum driving current was higher than 5 A, and the efficiency was 88%. Compared with the efficiency of the converter without the DBV technique, the efficiency of the converter with DBV technique was improved by about 28%.

Development of 2.1D package with organic interposer in panel size based on the high resolution dry film photo resist and the ultra-thin electro-less copper seed layer will be reported in this paper. The aim of 2.1D technology is to focus on the reducing of production cost and increase I/O counts simultaneously. Compare to the wafer level lithography process, substrate-based process leads to the benefit in cost reduction and risk elusion form chip first process. Dry film photo resist and electro-less copper seed layer processes can significantly save the equipment and material cost compared to the wafer patterning process. High density interconnection routings are integrated on an organic film in 25 µm thickness. Micro-bump is designed as 25 µm size with 40 µm pitch. Embedded trace substrate (ETS) also reported here by using plated nickel seed layer as etching resistance, copper trace with 3 µm width and spacing embedded in the organic film can be achieved. This designed 2.1D organic interposer substrate has passed MSL3 (Moisture Soaking Level 3) standard and TCT (Thermal Cycling Test) reliability test with 1000 cycles. In terms of electrical property study, the electrical measurement including DC resistance and S-parameter is performed to tell apart the different performance of dielectric and photo resist materials, and the result show agreement with the formed appearance of copper traces.

The thickness of thin liquid films is of great interest to industrial processes and life science. Here we propose a holographic system for the evaluation of the 3D topography and thickness of evolving thin liquid film.

Development of 2.1D package with organic interposer in panel size based on the high resolution dry film photoresist and the ultra-thin electro-less copper seed layer will be reported in this paper. The aim of 2.1D technology is focus on the reducing of production cost and increase I/O counts simultaneously. Compare to the wafer level lithography process, substrate-based process leads to the benefit in cost reduction and risk elusion form chip first process. The high resolution photolithography semi-additive processes (SAP) can achieve 3 µm copper line width and 25 µm laser drilled vias in panel size (510*408mm). On the other hand, the sputtered metal seed layer can be replaced by electro-less copper plating seed layer (approximately 0.1 µm). When it comes to cost, dry film photoresist and electro-less copper seed layer processes can significantly save the equipment and material cost compared to the wafer patterning process. These high density interconnection lines, micro-bump pads and vias are integrated and demonstrated on an organic film in the thickness of 25 µm. Micro-bump pads designed for the copper pillar bond are with a 25 µm diameter and a 40 µm pitch. Flip chip bond alignment is verified by the x-ray examination. The embedded trace substrate (ETS) by using plating nickel thin layer for etching resistance, copper trace with 3 µm width and spacing embedded in the organic film can be formed with very good flatness performance. Moreover, this designed 2.1D organic interposer substrate has passed the MSL3 (Moisture Soaking Level 3) standard and the TCT (Thermal Cycling Test) reliability test with 1000 cycles. In terms of electrical property study, kinds of dielectric materials and high resolution photoresists are employed in this study. The electrical measurement including DC resistance and S-parameter is performed to tell apart the different performance of dielectric and photoresist materials, and the result show agreement with the formed appearance of copper traces.

In this paper, we propose a driving system consisting of an autonomous and manual system for a four-wheel independent steering and four-wheel independent driving (4WIS4WID) vehicle. The autonomous driving system consists of three applications, lane following, reverse parking, and parallel parking, and is based on machine vision and fuzzy control theory. The vehicle implements these functions by using four webcams to detect lines on the ground and by using related control technologies to command all the server motors. The webcams are installed on all sides of the 4WIS4WID vehicle for all around viewing, but the vehicle still has many blind spots and the view is not wide enough. In additon, a parking space cannot be viewed completely in one image. Therefore, the integrating judgements of vision with the fuzzy control methods is necessary to make sure that the 4WIS4WID vehicle can perform the correct motions. By using the proposed fuzzy rules, the 4WIS4WID vehicle can change its velocity in a timely way under any condition and can successfully move in a narrow and curved lane. Moreover, the manual driving system is designed based on the traditional driving system, so that people can easily adapt to it. In order to verify the feasibility of these applications for the 4WIS4WID vehicle, an indoor real-time experiment is conducted.

Can a robot think like a human being? Scientists in recent years have been trying to achieve this dream, and we are also committed to this same goal. In this paper, we use an example of throwing the ball into the basket to make the robots process with human-like thinking behavior. Such thinking behavior adopted in this paper is divided into two modes: fast and slow. The fast mode belongs to the intuitional reaction, and the slow mode represents the complicated cogitation in human brain. This fascinating human thinking concept is inspired by the book, Thinking, Fast and Slow , which explains the process of the human brain. In addition, the psychology theories proposed in this book are also adopted to realize the thinking algorithms, and our experiments verify that the thinking mode of human beings is reasonable and effective in robots.

With the increasing role of endoscopy in patient evaluation, more mucosal lesions, including gastric, duodenal and colonic polyps, are encountered during routine examinations. It is imperative for gastroenterologists to become familiar with the endoscopic management of these various gastrointestinal lesions. In this article, various resection techniques will be discussed, including hot/cold forceps polypectomy, hot/cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. The article will also discuss the evidence regarding the efficacy and safety of these techniques and the future direction of endoscopic management of mucosal lesions in the gastrointestinal tract.

The excited-state relaxation dynamics of trans -4-( N , N -dimethylamino)-4′-nitrostilbene excited to the first absorption band in nonpolar solvents (cyclohexane and n -hexadecane) has been studied with ultrafast time-resolved broadband fluorescence spectroscopy. The temporal evolution of the time-resolved fluorescence spectra and bandwidth narrowing reveal a multiple-stage vibrational relaxation within ∼15 ps followed by slower excited-state deactivation steps (80 and 950 ps in cyclohexane). In addition, an oscillatory fluorescence with a period of about 1.1 ps was observed and attributed to the coherent vibrational motion of the nitrophenyl/aminophenyl torsion that modulates the early-time fluorescence spectra. The decay of the total fluorescence intensity with cubic frequency correction was found to be consistent with a competitive triplet–single deactivation mechanism.