PolySi-SiO 2 -ZrO 2 -SiO 2 -Si Flash Memory Incorporating a Sol-Gel-Derived ZrO 2 Charge Trapping Layer

In this paper, we propose a method for depositing the charge trapping layer of a high-k polySi-SiO 2 -ZrO 2 -SiO 2 -Si ͑SOZOS͒ memory device. In this approach, the trapping layer was formed through simple two steps: ͑i͒ spin-coating of the ZrCl 4 precursor and ͑ii͒ rapid thermal annealing for 1 min at 900°C under an oxygen atmosphere. The morphology of the ZrO 2 charge trapping layer was confirmed through X-ray photoemission spectroscopy analysis. The sol-gel-derived layer exhibited improved charge trapping in the SOZOS memory device, resulting in a threshold voltage shift of 2.7 V in the I d -V g curve, P/E ͑program/erase͒ speeds as fast as 0.1 ms, good data retention up to 10 4 s ͑only a 5% charge loss due to deep trapping in the ZrO 2 layer͒, and good endurance ͑no memory window narrowing after 10 5 P/E cycles͒. © 2006 The Electrochemical Society. ͓DOI: 10.1149/1.2337846͔ All rights reserved. The first floating-gate ͑FG͒ nonvolatile semiconductor memory was invented by Sze and Kahng in 1967. 1 Conventional FG memory uses polysilicon as a charge-storage layer surrounded by the dielectric. 2 Although floating-gate structures can achieve high densities and good program/erase ͑P/E͒ speeds and exhibit good reliability in portable flash memory devices, there are concerns regarding the ability to scale up their production. 3 When the tunneling oxide thickness is below 10 nm, the storage charge in the FG leaks readily because defects form in the tunneling oxide after repeated write-erase cycles or through direct tunneling of the current. PolySi-oxide-nitride-oxide-silicon ͑SONOS͒ memory devices have been studied recently as an approach to solving the issue of scaling FG memory. 3 Because of their spatially isolated deep-level traps, SONOS memories exhibit better charge retention than do FG memories that have a bitcell tunneling oxide layer thinner than 10 nm. As a result, a single defect in the tunneling oxide will not cause the discharge of the memory cell. 3 SONOS memory devices use silicon nitride as a charge trapping layer; the conduction band offset between the tunneling oxide and nitride is 1.05 eV. When a positive voltage is applied on the gate, the band bends downward so that the electrons in the Si subconduction band will tunnel through the tunneling oxide and a portion of the nitride will become trapped in the charge trapping layer. Before they become trapped in the nitride, the electrons must tunnel through a portion of the nitride, which degrades the program speed. In addition, because the conduction band offset of the nitride is only 1.05 eV, back tunneling of the trapped electron may also occur. To solve these problems, high-k materials are potential candidates to replace the traditional silicon nitride as the charge trapping layer. The advantages of using high-k materials are the larger band offset with the tunneling oxide and the greater number of trapping sites than those found in silicon nitride. For an HfO 2 high-k material, the conduction band offset between the tunneling oxide and HfO 2 is 1.6 eV. When programming, the electron will tunnel through a shorter distance in HfO 2 than in the nitride to become trapped. This feature can be exploited to achieve high P/E speeds. Thus, it will be beneficial to use a high-k material as the charge trapping layer in a SONOS-type memory device, provided that there are many deep-level trapping sites in the high-k material. Many technologies have been developed recently for the deposition of high-k layers onto tunneling oxides, 7-10 including atomic layer deposition ͑ALD͒, metallorganic chemical vapor deposition ͑MOCVD͒, and physical vapor deposition ͑PVD͒. In the ALD method, ZrCl 4 and H 2 O are used to prepare the ZrO 2 films. For the PVD process, a zirconium metal target is used for sputtering under ambient oxygen to deposit the ZrO 2 films. In the CVD method, ZrCl 4 is used as a precursor to deposit ZrO 2 films. Recently, we proposed the first so-called sol-gel spin-coating method for the deposition of the thin film. 11 Sol-gel spin-coating methods use metal halides hydrolyzed in organic or colloidal solvents to form precursor compounds that undergo hydrolysis, condensation, and polymerization to form metal-oxide networks. The advantages of using sol-gel methods to fabricate high-k films are that they are cheaper than ALD, PVD, and MOCVD approaches, and that various types of thin films can be synthesized. To the best of our knowledge, sol-gel spin-coating of a high-k film has yet to be reported for the preparation of charge trapping layers for flash memory devices. In this paper, we describe the fabrication of a polySi-SiO 2 -ZrO 2 -SiO 2 -Si ͑SOZOS͒ flash memory device prepared through the deposition of ZrCl 4 using the sol-gel spin-coating method and subsequent rapid thermal annealing ͑RTA͒. We performed physical and electrical analyses, including X-ray photoemission spectroscopy ͑XPS͒, I d -V g , retention, and P/E speed measurements, to evaluate the performance of the sol-gel ZrO 2 films for their potential use as charge trapping layers in SOZOS memory devices. Experimental ZrCl 4 ͑99.5%, Aldrich, USA͒ was used as the synthetic precursor of the zirconia. A mother sol solution was first prepared by dissolving ZrCl 4 in isopropanol ͑IPA; Fluka; water content Ͻ0.1%͒ under vigorous stirring in an ice bath. The sol solution was obtained by fully hydrolyzing ZrCl 4 with a stoichiometric quantity of water in IPA to yield a Zr:IPA molar ratio of 1:1000. The fabrication of the sol-gel spin-coated SOZOS memory began with LOCOS isolation process on p-type 150 mm silicon ͑100͒ substrate. At first, a 4 nm tunneling oxide layer was grown thermally at 925°C through furnace oxidation. The Zr:IPA solution ͑molar ratio: 1:1000͒ was coated using a spin-coater at 3000 rpm for 60 s at 25°C. A TEL Clean Track model-MK8 ͑Japan͒ spin-coater was used. The as-deposited thin film was initially baked at 200°C for 10 min to perform densification, followed by high-k RTA for 1 min in an O 2 atmosphere to form the ZrO 2 charge trapping layer. The film thickness, measured using an ellipsometer, was 10 nm. A 30 nm thick blocking oxide was deposited using high-density-plasmaenhanced chemical vapor deposition ͑HDPCVD͒, followed by deposition of a poly-Si gate ͑200 nm͒. After gate deposition, the following processes were applied to fabricate the SOZOS memory: * Electrochemical Society Active Member.

Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA), and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc), five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group), 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second of 10, but different electric field strengths of 0 (ie, no voltage, control group), 74, 148, 296, and 592 V/cm. Before and after each extraction experiment, skin impedance was measured at 20 Hz.Results: It was found that urea could be extracted transdermally using reverse iontophoresis alone, and further enhancement of extraction could be achieved by combined use of electroporation and reverse iontophoresis. Conversely, PSA and osteopontin were found to be extracted transdermally only by use of reverse iontophoresis and electroporation with a high electrical field strength (>296 V/cm). After application of reverse iontophoresis, electroporation, or a combination of the two techniques, a reduction in skin impedance was observed.Conclusion: Simultaneous transdermal extraction of urea, PSA, and osteopontin is possible only for the condition of applying reverse iontophoresis in conjunction with high electroporation.Keywords: electroporation, reverse iontophoresis, nanochannels, noninvasive, urea, prostate-specific antigen, osteoponti

Strong association of lumbar disk herniation with diabetes mellitus: a 12-year nationwide retrospective cohort study

BackgroundDespite reports on the association between diabetes mellitus (DM) and lumbar disk herniation (LDH), large-scale, nationwide studies exploring this relationship are lacking. We aimed to examine the profiles of DM in individuals with LDH and explore the potential mechanisms underlying the development of these disorders.MethodsThis retrospective, population-based study was conducted between 2008 and 2019 using data from the National Health Insurance (NHI) research database in Taiwan. The primary outcome was the date of initial LDH diagnosis, death, withdrawal from the NHI program, or end of the study period.ResultsIn total, 2,662,930 individuals with and 16,922,546 individuals without DM were included in this study; 719,068 matched pairs were established following propensity score matching (1:1 ratio) for sex, age, comorbidities, smoking, alcohol consumption, antihyperglycemic medications, and index year. The adjusted risk for developing LDH was 2.33-fold (95% confidence interval: 2.29−2.37; P<0.001), age-stratified analysis revealed a significantly greater risk of LDH in every age group, and both males and females were approximately twice as likely to develop LDH in the DM compared with non-DM cohort. Individuals with DM and comorbidities had a significantly higher risk of developing LDH than those without, and the serial models yielded consistent results. Treatment with metformin, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or alpha-glucosidase inhibitors was associated with a more than 4-fold increased risk of LDH in the DM cohort. DM was strongly associated with the long-term development of LDH; over the 12-year follow-up period, the cumulative risk of LDH was significantly higher in patients with than without DM (log-rank P<0.001).ConclusionDM is associated with an increased risk of LDH, and advanced DM may indicate a higher risk of LDH

Genetic and Functional Analysis of the DLG4 Gene Encoding the Post-Synaptic Density Protein 95 in Schizophrenia

Hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated signal transduction has been implicated in the pathophysiology of schizophrenia. Post-synaptic density protein 95 (PSD95) plays a critical role in regulating the trafficking and activity of the NMDA receptor and altered expression of the PSD95 has been detected in the post-mortem brain of patients with schizophrenia. The study aimed to examine whether the DLG4 gene that encodes the PSD95 may confer genetic susceptibility to schizophrenia. We re-sequenced the core promoter, all the exons, and 3′ untranslated regions (UTR) of the DLG4 gene in 588 Taiwanese schizophrenic patients and conducted an association study with 539 non-psychotic subjects. We did not detect any rare mutations at the protein-coding sequences of the DLG4 gene associated with schizophrenia. Nevertheless, we identified four polymorphic markers at the core promoter and 5′ UTR and one single nucleotide polymorphism (SNP) at the 3′UTR of the DLG4 gene in this sample. Genetic analysis showed an association of a haplotype (C–D) derived from 2 polymorphic markers at the core promoter (odds ratio = 1.26, 95% confidence interval = 1.06–1.51, p = 0.01), and a borderline association of the T allele of the rs13331 at 3′UTR with schizophrenia (odds ratio = 1.19, 95% confidence interval = 0.99–1.43, p = 0.06). Further reporter gene assay showed that the C-D-C-C and the T allele of the rs13331 had significant lower activity than their counter parts. Our data indicate that the expression of the DLG4 gene is subject to regulation by the polymorphic markers at the core promoter region, 5′ and 3′UTR of the gene, and is associated with the susceptibility of schizophrenia

Evaluation of Antioxidant and Free Radical Scavenging Capacities of Polyphenolics from Pods of Caesalpinia pulcherrima

Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-d-glucoside (3), methyl 6-O-galloyl-β-d-glucoside (4), methyl 3,6-di-O-galloyl-α-d-glucopyranoside (5), gentisic acid 5-O-α-d-(6′-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-β-d-(6′-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-β-d-(6′-O-galloyl) glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases

Production of Active Nonglycosylated Recombinant B-Chain of Type-2 Ribosome-Inactivating Protein from Viscum articulatum and Its Biological Effects on Peripheral Blood Mononuclear Cells

Type-2 ribosome-inactivating proteins, composed of a toxic A-chain and lectin-like B-chain, display various biological functions, including cytotoxicity and immunomodulation. We here cloned the lectin-like B-chain encoding fragment of a newly identified type-2 RIP gene, articulatin gene, from Viscum articulatum, into a bacterial expression vector to obtain nonglycosylated recombinant protein expressed in inclusion bodies. After purification and protein refolding, soluble refolded recombinant articulatin B-chain (rATB) showed lectin activity specific toward galactoside moiety and was stably maintained while stored in low ionic strength solution. Despite lacking glycosylation, rATB actively bound leukocytes with preferential binding to monocytes and in vitro stimulated PBMCs to release cytokines without obvious cytotoxicity. These results implicated such a B-chain fragment as a potential immunomodulator

Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

[[abstract]]Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.[[notice]]補正完畢[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]電子

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted