Design, optimization, and performance analysis of new photodiode structures for CMOS active-pixel-sensor (APS) imager applications

The dark current in the active-pixel-sensor (APS) cell of a CMOS imager is known to be mainly generated in the regions of bird's beak after the local oxidation of silicon process as well as the surface damage caused by the implantation of high doping concentration. Furthermore, shallow and deep pn-junctions can improve the photo-sensitivity for light of short and long wavelengths, respectively. In this paper, two new photodiode structures using p-substrate and lightly-doped sensor implant SN- as pn-junction photodiode with the regions of bird's beak embraced by SN- and p-field implants, respectively, are proposed and analyzed to reduce dark current and enhance the overall spectral response. 5 /spl mu/m/spl times/5 /spl mu/m APS cells fabricated in a 0.35-/spl mu/m single-poly-triple-metal (1P3M) 3.3-V CMOS process are designed by using the proposed photodiode structures. As shown from the experimental results, the two proposed photodiode structures of 5 /spl mu/m/spl times/5 /spl mu/m APS cells have lower dark currents of 30.6 mV/s and 35.2 mV/s at the reverse-biased voltage of 2 V and higher spectral response, as compared to the conventional structure and other photodiode structures. Thus, the two proposed new photodiode structures can be applied to CMOS imager systems with small pixel size, high resolution, and high quality.     

Bibliometric analysis of Patent Ductus Arteriosus treatments

A bibliometric analysis was performed to assess the quantitative trend of Patent Ductus Arteriosus (PDA) treatment research, including intravenous injection of indomethacin and surgery. The documents studied were retrieved from the Science Citation Index (SCI) for the period from 1991 to 2002. The publication pattern concerning authorship, collaboration, original countries, citation frequency, document type, language of publication, distribution of journals, page count and the most frequently cited papers were performed. The results indicated that either treatment was not the recent emphasis of PDA research. The publishing countries of both treatments have also denoted that these researches were mostly done in Europe and North America. Both surgery and drug treatments had few international collaboration papers. English was the dominant language, and collaboration of two to six authors was the most popular level of co-authorship. This revised version was published online in June 2006 with corrections to the Cover Date.     

Seismic Retrofit of Hollow Rectangular Bridge Columns

The seismic performance of rectangular hollow bridge columns is a significant issue of the high-speed rail project in Taiwan. The flexural ductility and shear capacity of such columns with the configuration of lateral reinforcement used in Taiwan have been studied recently. This paper reports that hollow rectangular bridge columns retrofitted with fiber-reinforced polymer (FRP) sheets were tested under a constant axial load and a cyclically reversed horizontal load to investigate their seismic behavior, including flexural ductility, dissipated energy, and shear capacity. An analytical model was also developed to predict the moment-curvature curve of sections and the load-displacement relationship of columns. Based on the test results, the seismic behavior of such columns will be presented. The test results were also compared to the proposed analytical model. It was found that the ductility factors of the tested piers are in the range from 3.4 to 6.3, and the proposed analytical model can predict the load-displacement relationship of such columns with acceptable accuracy. All in all, FRP sheets can effectively improve both the ductility factor and shear capacity of hollow rectangular bridge columns.     

Lithium plasma emitter for collisionless magnetized plasma experiment

This paper presents a newly developed lithium plasma emitter, which can provide quiescent and low-temperature collisionless conditions for magnetized plasma experiments. This plasma emitter generates thermal emissions of lithium ions and electrons to produce a lithium plasma. Lithium type beta-eucryptite and lanthanum-hexaboride (LaB(6)) powders were mixed and directly heated with a tungsten heater to synthesize ion and electron emissions. As a result, a plasma with a diameter of ~15 cm was obtained in a magnetic mirror configuration. The typical range of electron density was 10(12)-10(13) m(-3) and that of electron temperature was 0.1-0.8 eV with the emitter operation temperature of about 1500 K. The amplitude fluctuations for the plasma density were lower than 1%.     

Process quality improvement of a qualitative response with dynamic characteristic

To achieve quality improvement in manufacturing environments, the design of experiment (DOE) and Taguchi methods are two efficiency approaches to address such problems. Applying those methods to resolve quality improvement frequently focuses on the measurable quality response (or quantitative response). However, the complexity of products or processes is gradually increased and due to the limitation of measuring equipment, the quality response could not be directly measured. Visual inspection or measurement is then used to judge the quality for nonmeasurable response (or qualitative response). Basically, for assessing the quality of a qualitative response, it is initially divided into several classes or ordered categories. As for customers’ requirements gradually changing and applications’ flexibility gradually increasing, a dynamic structure for this process will be another important consideration for manufacturers. That is, it causes the work of quality improvement to be dynamically analyzed. Dr. Taguchi had proposed a dynamic method to analyze such issues. However, only several studies focused on quality improvement of a qualitative response during the static characteristic. Parameter optimization approaches were seldom proposed to address quality improvement of a qualitative response with the dynamic characteristic. Therefore, in this study, we proposed an integrated parameter-optimization approach to resolve quality improvement of a qualitative response with dynamic characteristics. An illustrative example, quality improvement of lead twist during the stamping process for lead frame manufacturing at Science-based park in Taiwan, is employed to demonstrate the effectiveness of the proposed approach.     

A simple GPU-based approach for 3D Voronoi diagram construction and visualization

In this paper we propose a simple GPU-based approach for discrete incremental approximation of 3D Voronoi diagram. By constructing region maps via GPU. Nearest sites, space clustering, and shortest distance query can be quickly answered by looking up the region map. In addition, we propose another representation of the 3D Voronoi diagram for visualization.     

Development of an objective mental workload assessment tool based on Rasmussen's skill–rule–knowledge framework

It is important to monitor operators’ mental workload during the operation phase. Physiological measurement approaches could record the operator's mental data continuously, and might be less interruptive on the work activities. However, these methods often require the attachment of physical sensors, which are not unobtrusive in the physical sense. Furthermore, the individual difference makes calibrating to each individual tedious and requires trained persons to use. Often high noise-to-signal ratio data are hard to analyze. Due to these factors, physiological workload measurements are hardly widely applied in practical fields. In this study, an objective, non-intrusive and performance-based mental workload predictive model was proposed with high validity (R² = 0.51), which can be applied during the operation phrase. This model, developed based on the Rasmussen's skill–rule–knowledge framework, is comprised of two novel cognitive indices, the attention required index and uncertainty index. It can be used as the basis for establishing an early online warning system automatically. Furthermore, this model also predicts the types of error-prone tasks. This kind of information is expected to provide managers and supervisors with opportunities to intervene and improve tasks before error occurred. Finally, the predictive model proposed in this paper requires more practical application in fields to be completed.     

Chidamide plus Tyrosine Kinase Inhibitor Remodel the Tumor Immune Microenvironment and Reduce Tumor Progression When Combined with Immune Checkpoint Inhibitor in Naïve and Anti-PD-1 Resistant CT26-Bearing Mice

Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical needs still remain and require improvement in efficacy. Using murine colon carcinoma (CT26) allograft models, we examined the efficacy and elucidated novel tumor microenvironment (TME) remodeling mechanisms underlying the combination of chidamide (a benzamide-based class l histone deacetylase inhibitor; brand name in Taiwan, Kepida^®) with VEGF receptor tyrosine kinase inhibitor (TKIs; cabozantinib/regorafenib, etc.) and immune checkpoint inhibitors (ICIs; anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies). The TME was assessed using flow cytometry and RNA-sequencing to determine the novel mechanisms and their correlation with therapeutic effects in mice with significant treatment response. Compared with ICI alone or cabozantinib/regorafenib + ICI, combination of chidamide + cabozantinib/regorafenib + ICI increased the tumor response and survival benefits. In particular, treatment of CT26-bearing mice with chidamide + regorafenib + anti-PD-1 antibody showed a better objective response rate (ORR) and overall survival (OS). Similar results were observed in anti-PD-1 treatment-resistant mice. After treatment with this optimal combination, in the TME, RNA-sequencing revealed that downregulated mRNAs were correlated with leukocyte migration, cell chemotaxis, and macrophage gene sets, and flow cytometry analysis showed that the cell numbers of myeloid-derived polymorphonuclear suppressor cells and tumor-associated macrophages were decreased. Accordingly, chidamide + regorafenib + anti-PD-1 antibody combination therapy could trigger a novel TME remodeling mechanism by attenuating immunosuppressive cells, and restoring T-cell activation to enhance ORR and OS. Our studies also showed that the addition of Chidamide to the regorafenib + anti-PD-1 Ab combination could induce a durable tumor-specific response by attenuating immune suppression in the TME. In addition, this result suggests that TME remodeling, mediated by epigenetic immunomodulator combined with TKI and ICI, would be more advantageous for achieving a high objective response rate, when compared to TKI plus ICI or ICI alone, and maintaining long-lasting antitumor activity.     

Immune Modulation by Myeloid-Derived Suppressor Cells in Diabetic Kidney Disease

Diabetic kidney disease (DKD) frequently leads to end-stage renal disease and other life-threatening illnesses. The dysregulation of glomerular cell types, including mesangial cells, endothelial cells, and podocytes, appears to play a vital role in the development of DKD. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory and anti-inflammatory properties through the depletion of L-arginine that is required by T cells, through generation of oxidative stress, interference with T-cell recruitment and viability, proliferation of regulatory T cells, and through the promotion of pro-tumorigenic functions. Under hyperglycemic conditions, mouse mesangial cells reportedly produce higher levels of fibronectin and pro-inflammatory cytokines. Moreover, the number of MDSCs is noticeably decreased, weakening inhibitory immune activities, and creating an inflammatory environment. In diabetic mice, immunotherapy with MDSCs that were induced by a combination of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, and IL-6, reduced kidney to body weight ratio, fibronectin expression, and fibronectin accumulation in renal glomeruli, thus ameliorating DKD. In conclusion, MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice. The therapeutic targeting of the proliferative or immunomodulatory pathways of MDSCs may represent an alternative immunotherapeutic strategy for DKD.