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In this study, a process is developed for the fabrication of buried top-gated graphene transistors with Al2O3 as a gate dielectric, yielding devices that can be suitable for not only flexible electronics but also laser-induced graphene (LIG)-based technology implementations. A new processing option is presented with the use of tetraethyl-orthosilicate (TEOS) as an etch stop for contact via etching of Al2O3. Buried locally gated Al/Al2O3 graphene field-effect transistors (GFETs) are fabricated with Dirac points as low as 4 V, with a metal-to-graphene contact resistance as low as ∼1.7 kΩ·µm, and an average hole mobility of 457.97 cm2/V·s with a non-uniformity of 93%. Large device variation and non-uniformity in electrical performance are not uncommon for graphene-based devices, as process-induced defects play a major role in such variation. AFM, SEM, Raman spectroscopy, and model fitting indicated that the rough Al/Al2O3 surface was the main factor for the observed device variation. AFM analysis indicated a graphene surface roughness Ra of 16.19 nm on top of the buried Al/Al2O3 gate in contrast to a Ra of 4.06 nm over Al2O3/SiO2. The results presented indicate the need to reduce device variability and non-uniformity by improving transfer methods, as well as the use of smoother surfaces and compatible materials. The presented analyses provide a framework with which other researchers can analyze and correlate device variation and non-uniformities while methods to reduce variability are investigated.

In this work, we propose a 2TnC ferroelectric random access memory (FeRAM) cell design to realize the quasi- nondestructive readout (QNRO) of ferroelectric polarization (PFE) in a capacitor, which can relax the endurance requirement of the ferroelectric thin film and exploits the benefits of both FeRAM and ferroelectric FET (FeFET). We demonstrate that: i) QNRO sensing of PFE is conducted successfully in experiment with a ON/OFF ratio (ION/IOFF)>103, ION>10 μA, and read endurance>106 cycles, which can relax the FeRAM endurance requirement by 106x; ii) optimization of the cell performance can be realized by tuning the metal-ferroelectric-metal capacitor (MFM) capacitor to read transistor area ratio and read transistor threshold voltage (V TH); iii) the proposed cell structure is 3D-compatible, enabling integration of highly dense memory solution; iv) the proposed cell structure also enables compute-in-memory (CIM) applications of FeRAM, which has not been widely explored. With this technology, storage and memory-centric computing can be enable

The graduate school specializes in introducing novel interdisciplinary courses. Entering students, from a diversity of backgrounds, typically have a low familiarity with current developments in materials science. Hence, interdisciplinary courses invariably erect psychological barriers, thereby reducing willingness to participate and consequently the effectiveness of learning. As a result, it is often a great challenge for students to integrate what they have previously learned with the needs of practical industrial applications. Through this study we aim to address existing questions that reside in the ideology of the “Learning Community” by using the methodology of ‘Teacher’s Action Research’. The interdisciplinary course “Material Science and Simulation” we designed is an attempt to solve problems in traditional teaching methods, such as one-way teaching and examination evaluation, which are replaced with a curriculum that introduces the current situation, describes and analyses basic materials classifications, followed by newly-produced teaching materials consisting of videos and animations offered on online audio-visual platforms, together with the latest recommended readings as references. Furthermore, the course applies the methods of problem-based learning (PBL) to reduce learning barriers, while providing an overall understanding of the latest materials science and current development status of various materials for students with various backgrounds, to facilitate advanced materials science learning. Also, students can amass and assess data through group discussions with peers, put forward their viewpoints, organize their results, and conduct complete in-depth studies. From the students' self-assessment and feedback from the questionnaire, we can see that this method has a positive effect on learning related to current materials science research.

Summary Though platform trials have been touted for their flexibility and streamlined use of trial resources, their statistical efficiency is not well understood. We fill this gap by establishing their greater efficiency for comparing the relative efficacy of multiple interventions over using several separate, 2-arm trials, where the relative efficacy of an arbitrary pair of interventions is evaluated by contrasting their relative risks as compared to control. In theoretical and numerical studies, we demonstrate that the inference of such a contrast using data from a platform trial enjoys identical or better precision than using data from separate trials, even when the former enrolls substantially fewer participants. This benefit is attributed to the sharing of controls among interventions under contemporaneous randomization. We further provide a novel procedure for establishing the noninferiority of a given intervention relative to the most efficacious of the other interventions under evaluation, where this procedure is adaptive in the sense that it need not be a priori known which of these other interventions is most efficacious. Our numerical studies show that this testing procedure can attain substantially better power when the data arise from a platform trial rather than multiple separate trials. Our results are illustrated using data from two monoclonal antibody trials for the prevention of HIV.

In the investigation, we investigate a fiber Bragg grating (FBG) based semicircular sensor architecture with fiber fault monitoring experimentally. Two erbium-doped fiber amplifiers (EDFAs) are used in the monitoring center to generate a broadband light source for sensing the strain and temperature simultaneously. Here, we utilize six FBG based sensors with different reflected wavelength for proof-of-concept demonstration. There is no optical filter used in the FBG sensor system for wavelength-selection. In addition, the proposed sensor system can monitor one to two fiber faults. In the measurement, the temperature- and strain-induced changes are also analyzed and discussed. Therefore, the proposed multiple FBG based semicircular sensor system not only can sense the temperature and strain simultaneously, but also can be used to monitor where is the fiber fault.

The goal of data mining is to discover important associations among items such that the presence of some items in a transaction will imply the presence of some other items. To achieve this purpose, Agrawal and his co-workers proposed several mining algorithms based on the concept of large itemsets to find association rules in transaction data (Agrawal et al., 1993a) (Agrawal et al., 1993b) (Agrawal & Srikant, 1994) (Agrawal & Srikant, 1995). They divided the mining process into two phases. In the first phase, frequent (large) itemsets are found based on the counts by scanning the transaction data. In the second phase, association rules were induced from the large itemsets found in the first phase. After that, several other approaches were also proposed (Fukuda et al., 1996) (Han & Fu, 1995) (Mannila et al., 1994) (Park et al., 1997) (Srikant & Agrawal, 1996) (Han et al., 2000) (Li et al., 2003). Many of the above algorithms for mining association rules from transactions were executed in level-wise processes. That is, itemsets containing single items were processed first, then itemsets with two items were processed, then the process was repeated, continuously adding one more item each time, until some criteria were met. These algorithms usually considered the database size static and focused on batch mining. In real-world applications, however, new records are usually inserted into databases, and designing a mining algorithm that can maintain association rules as a database grows is thus critically important. When new records are added to databases, the original association rules may become invalid, or new implicitly valid rules may appear in the resulting updated databases (Cheung et al., 1996) (Cheung et al., 1997) (Lin & Lee, 1998) (Sarda & Srinivas, 1998) (Zhang, 1999). In these situations, conventional batch-mining algorithms must re-process the entire updated databases to find final association rules. Cheung and his co-workers thus proposed an incremental mining algorithm, called FUP (Fast UPdate algorithm) (Cheung et al., 1996), for incrementally maintaining mined association rules and avoiding the shortcomings mentioned above. The FUP algorithm modified the Apriori mining algorithm (Agrawal & Srikant, 1994) and adopted the pruning techniques used in the DHP (Direct Hashing and Pruning) algorithm (Park et al., 1997). It first calculated large itemsets mainly from newly O pe n A cc es s D at ab as e w w w .in te ch w eb .o rg

Compounds from Lingzhi has been demonstrated the ability for inhibiting tyrosinase (a key enzyme in melanogenesis) activity. In this study, we investigated the anti-melanogenic activity from the submerged mycelial culture of Ganoderma weberianum and elucidated the skin lightening mechanism by B16-F10 murine melanoma cells. From the cellular context, several fractionated mycelium samples exhibited anti-melanogenic activity by reducing more than 40% extracellular melanin content of B16-F10 melanoma cells. In particular, the fractionated chloroform extract (CF-F3) inhibited both secreted and intracellular melanin with the lowest dosage (25 ppm). Further analysis demonstrated that CF-F3 inhibited cellular tyrosinase activity without altering its protein expression. Taken together, our study has demonstrated that the chemical extracts from submerged mycelial culture of G. weberianum have the potential to serve as an alternative anti-melanogenic agent.

In the investigation, we propose and demonstrate a stabilized and wavelength-selectable erbium-doped fiber (EDF) compound-ring laser with single-longitudinal-mode (SLM) oscillation covering both C-band and L-band ranges. Here, the dual-ring-cavity (DRC) scheme with an unpumped EDF-based saturable absorber (SA) is proposed in the EDF laser to guarantee SLM output. The proposed DRC of EDF laser can produce the mode-filter and ultra-narrowband auto-tracking filter effects to suppress the densely multi-longitudinal-mode (MLM) and extend the effective gain of EDF in a wavelength range of 1525.0–1580.0 nm. In addition, the observed output stabilities of power and wavelength in the proposed EDF DRC laser are also experimented and discussed.

In this work, we demonstrate a wavelength-tunable erbium-doped fiber (EDF) ring laser with stable single-longitudinal-mode (SLM) output. Here using the self-injection method and unpumped EDF-based saturable absorber can suppress other densely side-mode to achieve SLM. Hence, the output power and optical signal-to-noise ratio of proposed EDF ring laser are between −7.1 and 2.1 dBm and 30.1 and 36.5 dB in the tuning range of 1525.0 to 1574.0 nm, respectively. According to the proposed EDF laser structure, the wavelength operation range can extend to shorter L-band from C-band. Moreover, the output stability of the proposed EDF ring laser is also executed experimentally.

To achieve a steady single-longitudinal-mode (SLM) erbium-doped fiber (EDF) laser, the wheel-ring architecture is proposed in the laser cavity. According to Vernier effect, the proposed wheel-ring can produce three different free spectrum ranges (FSRs) to serve as the mode-filter for suppressing the densely multi-longitudinal-mode (MLM). Here, to complete wavelength-tunable EDF laser, an optical tunable bandpass filter (OTBF) is utilized inside the cavity for tuning arbitrarily. In addition, the entire output performances of the proposed EDF wheel-ring laser are also discussed and analyzed experimentally.

Compounds from Lingzhi has been demonstrated the ability for inhibiting tyrosinase (a key enzyme in melanogenesis) activity. In this study, we investigated the anti-melanogenic activity from the submerged mycelial culture of Ganoderma weberianum and elucidated the skin lightening mechanism by B16-F10 murine melanoma cells. From the cellular context, several fractionated mycelium samples exhibited anti-melanogenic activity by reducing more than 40% extracellular melanin content of B16-F10 melanoma cells. In particular, the fractionated chloroform extract (CF-F3) inhibited both secreted and intracellular melanin with the lowest dosage (25 ppm). Further analysis demonstrated that CF-F3 inhibited cellular tyrosinase activity without altering its protein expression. Taken together, our study has demonstrated that the chemical extracts from submerged mycelial culture of G. weberianum have the potential to serve as an alternative anti-melanogenic agent.

Poverty, family stability, and social policies influence the ability of adolescents to attend school. Likewise, being enrolled in school may shape an adolescent’s risk for HIV and pregnancy. We identified trends in school enrollment, factors predicting school enrollment (antecedents), and health risks associated with staying in or leaving school (consequences). Data from the Rakai Community Cohort Study (RCCS) were examined for adolescents 15–19 years (n = 21,735 person-rounds) from 1994 to 2013. Trends, antecedents, and consequences were assessed using logistic and linear regression with robust variance estimation. Qualitative data were used to explore school leaving among HIV+ and HIV− youths (15–24 years). School enrollment and socioeconomic status (SES) rose steadily from 1994 to 2013 among adolescents; orphanhood declined after availability of antiretroviral therapy. Antecedent factors associated with school enrollment included age, SES, orphanhood, marriage, family size, and the percent of family members

Numerous breast cancer patients who achieve an initial response to HER-targeted therapy rapidly develop resistance within one year, leading to treatment failure. Observations from clinical samples indicate that such resistance correlates with an increase in Src, EGFR, and PI3K/Akt activities and a decrease in PTEN activity. Furthermore, Akt survival signaling activation is also found in tumors treated by toxic chemotherapeutic agents. Because cotreatment with a PI3K inhibitor is a promising strategy to delay acquired resistance by preventing secondary gene activation, we therefore investigated the effects of a newly identified compound, (-)-Liriopein B (LB), on PI3K/Akt signaling activity in breast cancer cells. Our results showed that nontoxic doses of LB are able to inhibit AKT activation in both luminal-like MCF-7 and basal-like MDA-MB-231 breast cancer cells. Low doses of LB also inhibited cell migration, invasion, and cancer-stem cell sphere formation. Suppression of EGF-induced EGFR and ERK1/2 activation by LB might contribute in part to retardation of cancer progression. Furthermore, LB increases sensitivity of MDA-MB-231 cells to gefitinib in vitro, suggesting that EGFR may not be the only target of LB. Finally, a small scale in vitro kinase assay screen demonstrated that LB has a potent inhibitory effect on multiple kinases, including PI3K, Src, EGFR, Tie2, lck, lyn, RTK5, FGFR1, Abl, and Flt. In conclusion, this study demonstrates for the first time that the compound LB improves tumor therapeutic efficacy and suggests LB as a promising candidate for studying new leads in the development of kinase inhibitors.

The biomedical technology related to prenatal screen/diagnosis has developed rapidly in recent decades. Many prenatal genetic examinations are now available to assist pregnant women to better understand the status and development of their fetus. Moreover, many commercial advertisements for innovative prenatal examinations are now shown in the media. Cell-free DNA Screening (cfDNA screening), a non-invasive prenatal testing (NIPT) procedure, is a safe and high accuracy test that may be done at an earlier gestational age to screen for fetal aneuploidy. The following questions should be considered when applying cfDNA screening in clinical practice: 1. what is cfDNA screening, 2. who are its potential users, and 3. what ethical and policy considerations are associated with this examination? This article provides relevant information, clinical practice guidelines, and ethical / policy considerations related to cfDNA screening. Discussing cases involving different clinical situations helps promote understanding of cfDNA screening and maternal-care quality.新興產前遺傳檢測之臨床運用及倫理考量.藉由生物醫學科技之快速發展，新增許多產前遺傳檢測項目以積極協助孕婦增加對於其懷孕胎兒的了解。而市面亦常見各類針對孕婦產前檢驗的廣告。其中非侵入性胎兒染色體檢測提出可早期、安全又準確的檢測胎兒染色體異常疾病，此新興產前遺傳檢測究竟是指哪個項目？其適用性有何特殊考量？有哪些倫理考量或政策議題是需要去關注的？本文提供新興產前遺傳檢測之相關資訊、臨床指引及其倫理與政策議題，並以案例分析呈現不同情境之執行要點，期能有助於提升對於新時代遺傳檢測於孕產婦照護之多元資訊，以利提升產科照護之品質。.

A modified HPLC method for resveratrol determination for rapid screening of phenotypes of seedling population was developed for the Taiwan native Polygonum cuspidatum. The resveratrol concentration was 3.89 ± 1.03 mg.g−1 of the rhizome dry weight. In in vitro culturing of 11 acclimatized lines of genotype-dependent plants, which were replanted in the original location, only three genotypes showed a distant resemblance to regenerated lines and native plants. The genotype 051111 line in in vitro plants showed high resveratrol expression grown under acclimatized conditions and original locations. Resveratrol and its glucoside-piceid revealed mutual transformation depending on the growth climates.

3α-Hydroxysteroid dehydrogenase/carbonyl reductase reversibly catalyzes the oxidation of androsterone with NAD + to form androstanedione and NADH. In this study, we characterize the role of the conserved residue S114 in cofactor binding and catalysis, using site-directed mutagenesis, steady-state kinetics, fluorescence quenching and anisotropy measurements. The catalytic efficiency of V/K NADH Et for wild-type and S114A is 1.5 × 10 7 and 3.8 × 10 3 M − 1 s − 1 , respectively, suggesting that NADH association to wild-type and S114A mutant enzymes involves two steps, a bimolecular binding step and isomerization. The binding of NADH into a hydrophobic pocket in the active site of wild-type and S114A mutant enzymes restricts its motion and shields the fluorescence quenching from solvent, with an increase in the fluorescence intensity and a blue shift at the maximum wavelength. Furthermore, the binding of NADH leads to the protein fluorescence quenching, mainly due to fluorescence resonance energy transfer to NADH. S114A mutant enzyme decreases 3100-fold in V/Et with no apparent change in K m for substrates. Addition of NADH to S114A mutant enzyme induces a secondary structural change. These results suggest that S114 is important to maintain the correct conformation for the nucleotide binding and facilitate the reaction. Substitution of alanine for S114 eliminates the hydrogen bonding interaction with P185, causing a conformational change in a nonproductive binding of NADH and a significant loss of activity.

In this work, we propose and investigate an intelligent fiber Bragg grating (FBG)-based sensor system in which the proposed stabilized and wavelength-tunable single-longitudinal-mode erbium-doped fiber laser can improve the sensing accuracy of wavelength-division-multiplexing multiple FBG sensors in a longer fiber transmission distance. Moreover, we also demonstrate the proposed sensor architecture to enhance the FBG capacity for sensing strain and temperature, simultaneously.

Importance Polycyclic aromatic hydrocarbons are widespread urban air pollutants from combustion of fossil fuel and other organic material shown previously to be neurotoxic. Objective In a prospective cohort study, we evaluated the relationship between Attention Deficit Hyperactivity Disorder behavior problems and prenatal polycyclic aromatic hydrocarbon exposure, adjusting for postnatal exposure. Materials and Methods Children of nonsmoking African-American and Dominican women in New York City were followed from in utero to 9 years. Prenatal polycyclic aromatic hydrocarbon exposure was estimated by levels of polycyclic aromatic hydrocarbon- DNA adducts in maternal and cord blood collected at delivery. Postnatal exposure was estimated by the concentration of urinary polycyclic aromatic hydrocarbon metabolites at ages 3 or 5. Attention Deficit Hyperactivity Disorder behavior problems were assessed using the Child Behavior Checklist and the Conners Parent Rating Scale- Revised. Results High prenatal adduct exposure, measured by elevated maternal adducts was significantly associated with all Conners Parent Rating Scale-Revised subscales when the raw scores were analyzed continuously (N = 233). After dichotomizing at the threshold for moderately to markedly atypical symptoms, high maternal adducts were significantly associated with the Conners Parent Rating Scale-Revised DSM-IV Inattentive (OR = 5.06, 95% CI [1.43, 17.93]) and DSM-IV Total (OR = 3.37, 95% CI [1.10, 10.34]) subscales. High maternal adducts were positivity associated with the DSM-oriented Attention Deficit/Hyperactivity Problems scale on the Child Behavior Checklist, albeit not significant. In the smaller sample with cord adducts, the associations between outcomes and high cord adduct exposure were not statistically significant (N = 162). Conclusion The results suggest that exposure to polycyclic aromatic hydrocarbons encountered in New York City air may play a role in childhood Attention Deficit Hyperactivity Disorder behavior problems.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may modify the adverse effect of PAH on neurodevelopment. Thus, we examined if micronutrient concentrations modified the association between PAH exposure and neurodevelopmental outcomes.151 children from a birth cohort who had micronutrient concentrations measured in cord blood and completed the Child Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated. Prenatal airborne PAH exposure was measured by personal air monitoring. The betas and 95% CI for the associations of antioxidant concentrations and PAH exposure with each of the outcomes of CBCL raw score and dichotomized standardized T-score (based on clinical cutpoints) were estimated, respectively, by multivariable poisson and logistic models.Children below the median for alpha-tocopherol and gamma-tocopherol concentrations, compared to those above, were more likely to have thought problems, aggressive behavior and externalizing problems (p0.05). Lower carotenoid concentration was associated with more thought problems (MVβ=0.60, p0.001) and externalizing problems (MVβ=0.13, p0.05) for the same contrast. No statistically significant associations were observed between retinol concentrations and neurodevelopmental symptoms. Overall, no consistent patterns were observed when we examined the interaction between antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g., internalizing and externalizing problems, p0.05).Lower alpha-tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure. Future research to confirm these findings are warranted given the importance of identifying modifiable factors for reducing harmful PAH effects.

As NAND flash memory has become a major choice of storage media in diversified computing environments, the performance issue of flash memory has been extensively addressed in many excellent designs. Among them, an effective strategy is to adopt multiple channels and flash-memory chips to improve the performance on data accesses. However, the degree of data access parallelism cannot be increased by simply increasing the number of channels and chips in the storage device, because it is seriously limited by the maximum current constraint of the bus interface and affected by the access patterns of user data. As a consequence, to maximize the degree of access parallelism, it is of paramount significance to have a proper scheduling strategy to determine the order that read/write requests are served. In this paper, a current-aware scheduling strategy for read/write requests is proposed to maximize the read performance without violating the bus current constraint and without missing (the deadline of) written data. The proposed strategy is then evaluated through a series of experiments, in which the results are quite encouraging.

Proper designs of offsets forsignalized intersections in an urban arterial system can help improve the level of service (LoS) significantly. The MAXBAND model has been the most widely used approach for this purpose. In this paper, a MAXBAND model in which the lengt hs of phases in a cycle are variable is proposed. In other words, the lengths of phases in a cycle, as well as the cycle itself, are no longer fixed. Besides, theincorporation oftraffic dispersion module in the proposed model allows that the travel times from upstream intersection to the downstream one are taken into account. Real-world application on an arterial system in Taiwanfor evaluating the performance of the proposed model is conducted to validate the methodology. Actual traffic flow data are collected through on-site experiments. Results suggest that the improvements are around 44%, on average, in terms of total delay of the entire network.

S-Petasin is the main sesquiterpene ofPetasites formosanus, a traditional folk medicine used to treat hypertension, tumors and asthma in Taiwan. The aim of the present study was to investigate its inhibitory effects on phosphodiesterase (PDE) 1–5, and on ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in a murine model of allergic asthma.S-Petasin concentration-dependently inhibited PDE3 and PDE4 activities with 50% inhibitory concentrations (IC50) of 25.5, and 17.5 μM, respectively. According to the Lineweaver-Burk analysis,S-petasin competitively inhibited PDE3 and PDE4 activities with respective dissociation constants for inhibitor binding (Ki) of 25.3 and 18.1 μM, respectively. Both IC50andKivalues for PDE3 were significantly greater than those for PDE4.S-Petasin (10–30 μmol/kg, administered subcutaneously (s.c.)) dose-dependently and significantly attenuated the enhanced pause (Penh) value induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, lymphocytes, neutrophils, eosinophils and levels of cytokines, including interleukin (IL)-2, IL-4 and IL-5, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in bronchoalveolar lavage fluid (BALF) of these mice. In addition,S-petasin (10–30 μmol/kg, s.c.) dose-dependently and significantly attenuated total and OVA-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the IgG2alevel in serum of these mice. The PDE4Hvalue ofS-petasin was >300 μM; therefore, its PDE4H/PDE4Lvalue was calculated to be >17. In conclusion, the present results forS-petasin at least partially explain whyPetasites formosanusis used as a folk medicine to treat asthma in Taiwan.

The dimerization of 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase was studied by interrupting the salt bridge interactions between D249 and R167 in the dimeric interface. Substitution of alanine, lysine and serine for D249 decreased catalytic efficiency 30, 1400 and 1.4-fold, and lowered the melting temperature 6.9, 5.4 and 7.6 degrees C, respectively. The mutated enzymes have the dimeric species but the equilibrium between monomer and dimer for these mutants varies from each other, implying that these residues might contribute differently to the dimer stability. Thermal and urea-induced unfolding profiles for wild-type and mutant enzymes appeared as a two-state transition and three-state transition, respectively. In addition, mutation on D249 breaks the salt bridges and causes different effects on the loss of enzymatic activity for D249A, D249K and D249S mutants in the urea-induced unfolding profiles. Hence, D249 at the dimeric interface in 3alpha-HSD/CR is essential for conformational stability, oligomeric integrity and enzymatic activity.

In the presence of neostigmine (0.1 μM), S-isopetasin competitively antagonized cumulative acetylcholine-induced contractions in guinea pig trachealis, because the slope [1.18±0.15 (n=6)] of Schild's plot did not significantly differ from unity. The pA2 value of S-isopetasin was calculated to be 4.62±0.05 (n=18). The receptor binding assay for muscarinic receptors of cultured human tracheal smooth muscle cells (HTSMCs) was performed using [ 3 H]-N-methylscopolamine ([ 3 H]-NMS). Saturation binding assays were carried out with [ 3 H]-NMS in the presence (non-specific binding) and absence (total binding) of atropine (1 μM). Analysis of the Scatchard plot (y=0.247–1.306x, r 2 =0.95) revealed that the muscarinic receptor binding sites in cultured HTSMCs constituted a single population (nH=1.00). The equilibrium dissociation constant (Kd) and the maximal receptor density (Bmax) for [ 3 H]-NMS binding were 766 pM and 0.189 pmol/mg of protein, respectively. The −logIC50 values of S-isopetasin, methoctramine, and 1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) for displacing 0.4 nM [ 3 H]-NMS-specific binding were 5.05, 6.25, and 8.56, respectively, which suggests that [ 3 H]-NMS binding is predominantly on muscarinic M3 receptors of cultured HTSMCs. The inhibitory effectsofS-isopetasin onenhanced pause (Penh) value were similar to that ofipratropium bromide, areference drug. The duration of action of S-isopetasin (20 μM), also similar to that of ipratropium bromide (20 μM), was 3 h. In contrast to ipratropium bromide, which non-selectively acts on muscarinic receptors, S-isopetasin preferentially acts on muscarinic M3 receptors. In conclusion, S-isopetasin may be beneficial as a bronchodilator in the treatment of chronic obstructive pulmonary disease and asthma exacerbations. © 2008 Elsevier B.V. All rights reserved.

In the past, researchers usually assumed databases were static and items lay on the same level to simplify the mining problem. Modification of records with item taxonomy is, however, commonly seen in real-world applications. In this paper, we thus attempt to extend Han and Fu's approach and our previous concept of pre-large itemsets to maintain discovered multiple-level association rules for record modification. The concept of pre-large itemsets is used to reduce the need for rescanning original databases and to save maintenance costs. A pre-large itemset is not truly large, but promises to be large in the future. An algorithm is proposed based on the concept to achieve this purpose. The proposed algorithm doesn't need to rescan the original database until a number of records have been modified.