Institute of Sociology, Academia Sinica

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.

The function of DNA methylation in higher plants was investigated by expression of a complementary DNA encoding a cytosine methyltransferase (MET1) from Arabidopsis thaliana as an antisense RNA in transgenic plants. This expression resulted in a 34 to 71 percent reduction in total genomic cytosine methylation. Loss of methylation was observed in both repetitive DNA and single-copy gene sequences. Developmental effects included altered heterochrony, changes in meristem identity and organ number, and female sterility. Cytosine demethylation prolonged both vegetative and reproductive phases of development. These findings implicate DNA methylation in establishing or maintaining epigenetic developmental states in the meristem.

BackgroundInformation on the effects of long-term exposure to fine particulate matter with an aerodynamic diameter of 2·5 μm or less (PM2·5) on lung health is scarce. We aimed to investigate the associations between long-term exposure to PM2·5, lung function, and chronic obstructive pulmonary disease (COPD) in a large-scale longitudinal cohort.MethodsWe included 285 046 participants aged 20 years or older from the Taiwan MJ Health Management Institution cohort, who were recruited between 2001 and 2014 and had spirometric tests during the medical examination visit. We used a satellite-based spatiotemporal model to estimate the 2-year average ground concentration of PM2·5 (for the calendar year of each participant's medical examination and for the previous year) at each participant's address. We used the generalised linear mixed model to examine the associations between PM2·5 concentrations and lung function and the Cox proportional hazard regression model with time-dependent covariates to investigate the PM2·5 effects on COPD development.FindingsEvery 5 μg/m3 increment in PM2·5 was associated with a decrease of 1·18% for forced vital capacity (FVC), 1·46% for forced expiratory volume in 1 s (FEV1), 1·65% for maximum mid-expiratory flow (MMEF), and 0·21% for FEV1:FVC ratio. The decrease accelerated over time. Additional annual declines were observed for FVC (0·14%), FEV1 (0·24%), MMEF (0·44%), and FEV1:FVC ratio (0·09%). Compared with the participants exposed to the first quartile of PM2·5, participants exposed to the fourth, third, and second quartiles of PM2·5 had a hazard ratio of 1·23 (95% CI 1·09–1·39), 1·30 (1·16–1·46), and 1·39 (1·24–1·56) for COPD development, respectively.InterpretationLong-term exposure to ambient PM2·5 is associated with reduced, and faster declines in, lung function. Long-term exposure to ambient PM2·5 is also associated with an increased risk of the incidence of COPD. This study reinforces the urgency of global strategies to mitigate air pollution for improvement of pulmonary health and prevention of COPD.FundingEnvironmental Health Research Fund of the Chinese University of Hong Kong and PhD Studentship of the Chinese University of Hong Kong.

AIMS: Compared with other categories of drugs, such as antibiotics and NSAIDs, antiepileptic therapies are associated with a high incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We previously reported that carbamazepine (CBZ)-SJS/TEN is strongly associated with the HLA-B*1502 in Han Chinese, which has been confirmed in other Southeast Asian countries where the allele is prevalent. Here, we extend the study of HLA susceptibility to three different antiepileptic drugs, phenytoin (PHT), lamotrigine (LTG) and oxcarbazepine (OXC), which have structure similarity to CBZ. MATERIALS & METHODS: We carried out a case-control association study. We enrolled 26 PHT-, six LTG- and three OXC-induced SJS/TEN patients, 113 PHT-tolerant and 67 LTG-tolerant subjects who were on the drug, respectively, for more than 3 months without the adverse reactions, and 93 normal subjects from the general population. The HLA-A, B, C and DRB1 genotypes were determined. RESULTS: We found that HLA-B*1502 was present in eight out of 26 (30.8%) PHT-SJS/TEN (OR: 5.1; 95% CI: 1.8-15.1; p = 0.0041), two out of six (33%) LTG-SJS (odds ratio [OR]: 5.1; 95% CI: 0.8-33.8; p = 0.1266) and three out of three (100%) OXC-SJS (OR: 80.7; 95% CI: 3.8-1714.4; p = 8.4 x 10(-4)) patients. In addition, HLA-B*1301, Cw*0801 and DRB1*1602 also showed an association with PHT-SJS/TEN (p = 0.0128-0.0281; OR: 3.0-4.3). CONCLUSION: Our results indicate that OXC, PHT and LTG, which possess an aromatic ring just as CBZ does, when causing SJS/TEN, share a common risk allele. Aromatic antiepileptic drugs causing SJS/TEN in HLA-B*1502 carriers may act on a similar pathogenetic mechanism, although other genetic/nongenetic factor(s) may also contribute to the pathomechanism of the disease. We suggest that aromatic antiepileptic drugs, including CBZ, OXC and PHT, should be avoided in the B*1502 carrier and caution should also be exercised for LTG.

Metal-organic frameworks (MOFs) with low density, high porosity, and easy tunability of functionality and structural properties, represent potential candidates for use as semiconductor materials. The rapid development of the semiconductor industry and the continuous miniaturization of feature sizes of integrated circuits toward the nanometer (nm) scale require novel semiconductor materials instead of traditional materials like silicon, germanium, and gallium arsenide etc. MOFs with advantageous properties of both the inorganic and the organic components promise to serve as the next generation of semiconductor materials for the microelectronics industry with the potential to be extremely stable, cheap, and mechanically flexible. Here, a perspective of recent research is provided, regarding the semiconducting properties of MOFs, bandgap studies, and their potential in microelectronic devices.

ABSTRACT Japonica (Tainung 67 [TNu67]) and waxy (Taichung 70 [TCW70]) rice, normal and waxy corn, and cross‐linked waxy rice and corn starches were used in an investigation of the influence of the granular structure on the pasting behavior of starch, using small amplitude oscillatory rheometry. Both normal corn and normal rice (TNu67) starches had the highest storage moduli ( G ′), followed by their cross‐linked versions; native waxy corn and rice starches had the lowest. Native waxy starches showed paste characteristics ( G ′ &lt; 500 Pa; tan δ &gt; 0.2) at concentrations of up to 35%. However, cross‐linked waxy starches exhibited gel behavior at 10% concentration (cross‐linked TCW70) or higher (cross‐linked waxy corn starch). The degrees of swelling power were in the order: TCW70 &gt; native waxy corn &gt; TNu67 ≅ cross‐linked TCW70 ≅ normal corn ≅ cross‐linked waxy corn starches. Solubilities were in the order: normal corn &gt; TNu67 &gt; native waxy &gt; cross‐linked waxy starches. The addition of 2% purified amylose from indica rice (Kaohsiung Sen 7) did not induce gelation of waxy corn starch. Swelling powers of normal corn, TNu67, and crosslinked waxy starches were similar, but normal corn and TNu67 had much higher G ′ value. Such results implied that the formation of gel structure was governed by the rigidity of swollen granules and that the hot‐water soluble component could strengthen the elasticity of the starch gel or paste.

Highly efficient blue emitters based on the Lewis acid–base carbazole-π-dimesitylborane framework are synthesized and characterized. Among four bipolar blue fluorophores, the nondoped OLED fabricated with CzThB exhibits the best performance blue electroluminescence with CIEx, y (0.13,0.21), maximum electroluminance of 28 300 cd m−2 and external quantum efficiency of 6.9%.

Single-cell proteomics can reveal cellular phenotypic heterogeneity and cell-specific functional networks underlying biological processes. Here, we present a streamlined workflow combining microfluidic chips for all-in-one proteomic sample preparation and data-independent acquisition (DIA) mass spectrometry (MS) for proteomic analysis down to the single-cell level. The proteomics chips enable multiplexed and automated cell isolation/counting/imaging and sample processing in a single device. Combining chip-based sample handling with DIA-MS using project-specific mass spectral libraries, we profile on average ~1,500 protein groups across 20 single mammalian cells. Applying the chip-DIA workflow to profile the proteomes of adherent and non-adherent malignant cells, we cover a dynamic range of 5 orders of magnitude with good reproducibility and <16% missing values between runs. Taken together, the chip-DIA workflow offers all-in-one cell characterization, analytical sensitivity and robustness, and the option to add additional functionalities in the future, thus providing a basis for advanced single-cell proteomics applications.

BACKGROUND: The investigation of protein-protein interactions is important for characterizing protein function. Bimolecular fluorescence complementation (BiFC) has recently gained interest as a relatively easy and inexpensive method to visualize protein-protein interactions in living cells. BiFC uses "split YFP" tags on proteins to detect interactions: If the tagged proteins interact, they may bring the two split fluorophore components together such that they can fold and reconstitute fluorescence. The sites of interaction can be monitored using epifluorescence or confocal microscopy. However, "conventional" BiFC can investigate interactions only between two proteins at a time. There are instances when one may wish to offer a particular "bait" protein to several "prey" proteins simultaneously. Preferential interaction of the bait protein with one of the prey proteins, or different sites of interaction between the bait protein and multiple prey proteins, may thus be observed. RESULTS: We have constructed a series of gene expression vectors, based upon the pSAT series of vectors, to facilitate the practice of multi-color BiFC. The bait protein is tagged with the C-terminal portion of CFP (cCFP), and prey proteins are tagged with the N-terminal portions of either Venus (nVenus) or Cerulean (nCerulean). Interaction of cCFP-tagged proteins with nVenus-tagged proteins generates yellow fluorescence, whereas interaction of cCFP-tagged proteins with nCerulean-tagged proteins generates blue fluorescence. Additional expression of mCherry indicates transfected cells and sub-cellular structures. Using this system, we have determined in both tobacco BY-2 protoplasts and in onion epidermal cells that Agrobacterium VirE2 protein interacts with the Arabidopsis nuclear transport adapter protein importin alpha-1 in the cytoplasm, whereas interaction of VirE2 with a different importin alpha isoform, importin alpha-4, occurs predominantly in the nucleus. CONCLUSION: Multi-color BiFC is a useful technique to determine interactions simultaneously between a given" bait" protein and multiple "prey" proteins in living plant cells. The vectors we have constructed and tested will facilitate the study of protein-protein interactions in many different plant systems.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

High-precision measurements by the ATLAS Collaboration are presented of inclusive W + + , W - - and Z / * ( = e, ) Drell-Yan production cross sections at the LHC. The data were collected in proton-proton collisions at s = 7 TeV with an integrated luminosity of 4.6 fb -1 . Differential W + and W - cross sections are measured in a lepton pseudorapidity range | | < 2.5. Differential Z / * cross sections are measured as a function of the absolute dilepton rapidity, for |y | < 3.6, for three intervals of dilepton mass, m , extending from 46 to 150 GeV. The integrated and differential electron-and muon-channel cross sections are combined and compared to theoretical predictions using recent sets of parton distribution functions. The data, together with the final inclusive e p scattering cross-section data from H1 and ZEUS, are interpreted in a next-to-next-to-leading-order QCD analysis, and a new set of parton distribution functions, ATLAS-epWZ16, is obtained. The ratio of strange-to-light sea-quark densities in the proton is determined more accurately than in previous determinations based on collider data only, and is established to be close to unity in the sensitivity range of the data. A new measurement of the CKM matrix element |V cs | is also provided.

Abstract Designing highly conducting metal–organic frameworks (MOFs) is currently a subject of great interest for their potential applications in diverse areas encompassing energy storage and generation. Herein, a strategic design in which a metal–sulfur plane is integrated within a MOF to achieve high electrical conductivity, is successfully demonstrated. The MOF {[Cu 2 (6-Hmna)(6-mn)]·NH 4 } n ( 1 , 6-Hmna = 6-mercaptonicotinic acid, 6-mn = 6-mercaptonicotinate), consisting of a two dimensional (–Cu–S–) n plane, is synthesized from the reaction of Cu(NO 3 ) 2 , and 6,6′-dithiodinicotinic acid via the in situ cleavage of an S–S bond under hydrothermal conditions. A single crystal of the MOF is found to have a low activation energy (6 meV), small bandgap (1.34 eV) and a highest electrical conductivity (10.96 S cm −1 ) among MOFs for single crystal measurements. This approach provides an ideal roadmap for producing highly conductive MOFs with great potential for applications in batteries, thermoelectric, supercapacitors and related areas.

Cancer is becoming a more important health problem in Taiwan with aging of populations and changes in lifestyles. This indicates that a population-based cancer registration database is essential to providing informative data on cancer prevention and policy setting. The Taiwan Cancer Registry was launched in 1979 and all reporting hospitals were mandated to submit cancer data to the central cancer registry following the enactment of the Cancer Control Act in 2003. The National Health Insurance program in Taiwan has successfully provided quality health care, comprehensive benefits and convenient access to treatment. Most cancers had a rapidly increasing incidence after the initiation of the NHI program. However, cancer incidence rates of nasopharynx of both genders slightly decreased throughout the entire period and incidence of stomach cancer of both genders and cervical cancer of females declined beginning in 1995. For childhood cancers, the major types of leukemia, lymphomas, central nervous system neoplasms and other epithelial neoplasms for males and females accounted for nearly 55% of all types. This study presents for the first time the secular changes and age patterns in the incidence of childhood cancer using national cancer data.

With period fertility having risen in many low‐fertility countries, an important emerging question is whether cohort fertility trends are also reversing. We produce new estimates of cohort fertility for 37 developed countries using a new, simple method that avoids the underestimation typical of previous approaches. Consistent with the idea that timing changes were largely responsible for the last decades' low period fertility, we find that family size has remained considerably higher than the period rates of 1.5 in many “low‐fertility” countries, averaging about 1.8 children. Our forecasts suggest that the long‐term decline in cohort fertility is flattening or reversing in many world regions previously characterized by low fertility. We document the marked increase of cohort fertility in the English‐speaking world and in Scandinavia; signs of an upward reversal in many low‐fertility countries, including Japan and Germany; and continued declines in countries such as Taiwan and Portugal. We include in our forecasts estimates of statistical uncertainty and the possible effects of the recent economic recession.

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Our ability to model the dynamics of signal transduction networks will depend on accurate methods to quantify levels of protein phosphorylation on a global scale. Here we describe a motif-targeting quantitation method for phosphorylation stoichiometry typing. Proteome-wide phosphorylation stoichiometry can be obtained by a simple phosphoproteomic workflow integrating dephosphorylation and isotope tagging with enzymatic kinase reaction. Proof-of-concept experiments using CK2-, MAPK- and EGFR-targeting assays in lung cancer cells demonstrate the advantage of kinase-targeted complexity reduction, resulting in deeper phosphoproteome quantification. We measure the phosphorylation stoichiometry of >1,000 phosphorylation sites including 366 low-abundance tyrosine phosphorylation sites, with high reproducibility and using small sample sizes. Comparing drug-resistant and sensitive lung cancer cells, we reveal that post-translational phosphorylation changes are significantly more dramatic than those at the protein and messenger RNA levels, and suggest potential drug targets within the kinase-substrate network associated with acquired drug resistance.

Political trust reflects people’s evaluative orientation toward the polity and is thus vital to regime stability. Based on data drawn from a cross-national social survey, this article examines the level of political trust in six Asian societies and the possible effects of a series of institutional and cultural factors on political trust. It finds that institutional factors, particularly the economic and political performance of government, are powerful determinants of political trust, whereas the effects of such cultural factors as post-materialism, traditionalism, and authoritarianism are either insignificant or weak. The superiority of the institutional approach over the cultural approach is reconfirmed.

We have demonstrated that an extract of Ganoderma lucidum (Reishi or Ling-Zhi) polysaccharides (EORP) exerts immunomodulating activities by stimulating the expression of inflammatory cytokines from mouse spleen cells. Interestingly, via responding to LPS in genetic variation of murine macrophage HeNC2 and GG2EE cell lines, and using TLR4 Ab blockage in human blood-derived monocytic macrophages, we have found that the TLR4, but not complement receptor type 3, is a putative receptor of EORP, mediating the consequent immunomodulating events associated with IL-1 gene expression. Based on our studies of reactive oxygen species production, polymyxin B inhibition, and protein tyrosine kinase (PTK) activity, we ruled out the possibility of LPS contamination in EORP. We have found that EORP differentially modulates the protein kinase (PK)-mediated signal transduction pathways associated with inflammatory cytokine IL-1. In human macrophages and murine macrophage J774A.1 cells, EORP was found to up-regulate IL-1 secretion and pro-IL-1 (precursor of IL-1) as well as IL-1-converting enzyme expression. Specifically, EORP rapidly stimulates PTK-mediated phosphorylation, followed by induction of PKs and activation of MAPKs: ERK, JNK, and p38. Using PK inhibitors in the kinase activity assays, Western blot analyses and IL-1 ELISA, we have extensively examined and dissected the role of individual PK in the regulation of pro-IL-1/IL-1. Our findings establish that EORP-mediated signaling pathways are involved in the pro-IL-1/IL-1 regulation: PTK/protein kinase C/MEK1/ERK and PTK/Rac1/p21-activated kinase/p38.

Using longitudinal data from five Irish American families in the United States and nine Chinese families in Taiwan, in conjunction with an emerging body of evidence in the cultural psychology literature, we propose universal, culturally variable, and developmental dimensions of young children's pretend play. Possible universal dimensions include the use of objects, and the predominantly social nature of pretend play. Developmental dimensions include increases in the proportion of social pretend play initiated by the child, the proportion of partner initiations elaborated upon by the child, and caregivers' use of pretend play initiations to serve other, nonplay social functions. Culturally variable dimensions include the centrality of objects, the participation of specific play partners, the extent of child initiations of social pretend play with caregivers, the various functions of social pretend play in interaction, and specific themes. These findings raise the theoretical issue of how universal and variable dimensions of pretend play interact in specific communities to create distinctive development pathways.