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Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL)., Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models., Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types., Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis., Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer., (©2023 American Association for Cancer Research.)

Background: Epstein-Barr virus (EBV) infection contributes to cancers in a fraction of seropositive individuals, but much remains to be learned about variation in EBV-directed humoral immunity in cancer-free adults., Methods: A protein microarray was used to probe serum from 175 Taiwanese and 141 Northern European adults for immunoglobulin G (IgG) antibody responses to 115 different peptide sequences, representing protein segments or protein variants, from 45 EBV proteins. It was posited that this antibody-based approach could identify EBV peptide sequences representing immunodominant regions relevant for B-cell immunity., Results: Analyses of 45 EBV proteins with multiple protein segments or variants printed on the array identified eight EBV peptide sequences that appear to play a role in immunogenicity. This included: (1) three proteins with segments/regions associated with IgG reactivity (BALF5, LMP1, LMP2A); and (2) five proteins with sequence variants/amino acid changes associated with IgG reactivity (BDLF4, EBNA3A, EBNA3B, EBNA-LP, LF1)., Conclusion: This examination of IgG antibody responses against 115 EBV peptide sequences in 316 cancer-free adults represents an important step toward identifying specific EBV protein sequences that play a role in generating B-cell immunity in humans., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

The synthesis, structural characteristics, and photophysical properties of luminescent Cu-rich bimetallic superatomic clusters [Au@Cu 12 (S 2 CN n Pr 2 ) 6 (C≡CPh) 4 ] + ( 1a + ), [Au@Cu 12 {S 2 P(OR) 2 } 6 (C≡CPh) 4 ] + ( 2 + ), ( 2a + = i Pr; 2b + = n Pr), [Au@Cu 12 {S 2 P(C 2 H 4 Ph) 2 } 6 (C≡CPh) 4 ] + ( 2c + ), and [Ag@Cu 12 {S 2 P(O n Pr) 2 } 6 (C≡CPh) 4 ] + ( 3 + ) were studied. Compositionally uniform clusters 1 + - 3 + were isolated from the reaction of dithiolato-stabilized, polyhydrido copper clusters with phenylacetylene in the presence of heterometal salts. By using X-ray diffraction, the structures of 1a + , 2a + , 2b + , and 3 + were able to be determined. ESI-mass spectrometry and elemental analysis confirmed their compositions and purity. The structural characteristics of these clusters are similar with respect to displaying gold (or silver)-centered Cu 12 cuboctahedra surrounded by six dithiocarbamate/dithiophosph(in)ate and four alkynyl ligands. The doping of Au and Ag atoms into the polyhydrido copper nanoclusters significantly enhances their PL quantum yields from Ag@Cu 12 (0.58%) to Au@Cu 12 (55%) at ambient temperature in solution. In addition, the electrochemical properties of the new alloys were investigated by cyclic voltammetry.

The family Eolepadidae is the only stalked barnacle in hydrothermal vent regions. Here, we determined the mitogenome of the eolepadid Vulcanolepas fijiensis . The mitogenome was 17,374 bp long, with 76.6% AT content. Its protein-coding gene organization was identical to that of the deep-sea scalpellid Arcoscalpellum epeeum . On the mitogenomic tree, two scalpellomorphan families (Eolepadidae and Scalpellidae) were monophyletic while the other scalpellomorphan family Pollicipedidae did not form the monophyletic group with them. Further mitogenomic analysis of undetermined taxa in hydrothermal vents is required to deepen our understanding of their phylogenetic relationships., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Scalpellids are one of the largest families of Scalpelliformes and reproduce either androdioeciously or dioeciously. Here, we characterized the first mitogenome of a scalpellid barnacle ( Arcoscalpellum epeeum ), which was 15,593 bp in length with a 71.5% AT content. In comparison with the pollicipedids Capitulum mitella and Pollicipes polymerus , the tRNA genes of A . epeeum were rearranged between ND3 and ND5, between CYTB and ND1, and between 12S rRNA and ND2. On the mitogenomic tree, the Scalpelliformes families Pollicipedidae and Scalpellidae were not monophyletic, which concurs with previous studies., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The family Catophragmidae is one of the lower balanomorphs from traditional and recent multiple mitochondrial and nuclear markers molecular analysis. Here, we characterized the first mitogenome of the catophragmid barnacle Catomerus polymerus , which was 15,446 bp in length with a 68.3% AT content. The mitogenome had the typical pancrustacean gene arrangement, which was identical to the mitogenome configurations of the chthamalid Octomeris sp. and pachylasmatoid Eochionelasmus ohtai . On the mitogenomic tree, the catophragmid Catomerus polymerus formed an independent branch that was basal to the members of the superfamilies Tetraclitoidea and Balanoidea, which was inconsistent with previous findings., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The extreme rarity of asexual vertebrates in nature is generally explained by genomic decay due to absence of meiotic recombination, thus leading to extinction of such lineages. We explore features of a vertebrate asexual genome, the Amazon molly, Poecilia formosa, and find few signs of genetic degeneration but unique genetic variability and ongoing evolution. We uncovered a substantial clonal polymorphism and, as a conserved feature from its interspecific hybrid origin, a 10-fold higher heterozygosity than in the sexual parental species. These characteristics seem to be a principal reason for the unpredicted fitness of this asexual vertebrate. Our data suggest that asexual vertebrate lineages are scarce not because they are at a disadvantage, but because the genomic combinations required to bypass meiosis and to make up a functioning hybrid genome are rarely met in nature.

Background Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. Methods We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts. Findings Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls ( P < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status-BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%-98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%-90%, P ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%-96%) compared with current biomarkers (78%; 95% CI, 66%-90%, P ≤ 0.03). Interpretation We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. Clin Cancer Res; 24(6); 1305-14. ©2017 AACR ., (©2018 American Association for Cancer Research.)

The hitherto suborder Verrucomorpha contains asymmetrical barnacles of two groups: the true Verrucomorpha ( Eoverruca  + Verrucidae) and the Neoverrucidae. Here, we determined the mitochondrial genome (mitogenome) of Altiverruca navicula , a true Verrucomorpha species. The mitogenome was 15,976 base pairs in length and had the typical pancrustacean gene arrangement. Its protein-coding genes were very similar to those of other thoracican species in terms of length, AT content, and start and stop codons. In phylogenetic trees constructed with 13 protein-coding genes, A . navicula was positioned at an ancestral node of sessile barnacles, consistent with the findings of previous studies., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The first atomically and structurally precise silver-nanoclusters stabilized by Se-donor ligands, [Ag 20 {Se 2 P(O i Pr) 2 } 12 ] (3) and [Ag 21 {Se 2 P(OEt) 2 } 12 ] + (4), were isolated by ligand replacement reaction of [Ag 20 {S 2 P(O i Pr) 2 } 12 ] (1) and [Ag 21 {S 2 P(O i Pr) 2 } 12 ] + (2), respectively. Furthermore, doping reactions of 4 with Au(PPh 3 )Cl resulted in the formation of [AuAg 20 {Se 2 P(OEt) 2 } 12 ] + (5). Structures of 3, 4, and 5 were determined by single-crystal X-ray diffraction. The anatomy of cluster 3 with an Ag 20 core having C 3 symmetry is very similar to that of its dithiophosphate analogue 1. Clusters 4 and 5 exhibit an Ag 21 and Au@Ag 20 core of O h symmetry composed of eight silver capping atoms in a cubic arrangement and encapsulating an Ag 13 and Au@Ag 12 centered icosahedron, respectively. Both ligand exchange and heteroatom doping result in significant changes in optical and emissive properties for chalcogen-passivated silver nanoparticles, which have been theoretically confirmed as 8-electron superatoms., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The origin of domesticated Asian rice (Oryza sativa) has been a contentious topic, with conflicting evidence for either single or multiple domestication of this key crop species. We examined the evolutionary history of domesticated rice by analyzing de novo assembled genomes from domesticated rice and its wild progenitors. Our results indicate multiple origins, where each domesticated rice subpopulation (japonica, indica, and aus) arose separately from progenitor O. rufipogon and/or O. nivara. Coalescence-based modeling of demographic parameters estimate that the first domesticated rice population to split off from O. rufipogon was O. sativa ssp. japonica, occurring at ∼13.1-24.1 ka, which is an order of magnitude older then the earliest archeological date of domestication. This date is consistent, however, with the expansion of O. rufipogon populations after the Last Glacial Maximum ∼18 ka and archeological evidence for early wild rice management in China. We also show that there is significant gene flow from japonica to both indica (∼17%) and aus (∼15%), which led to the transfer of domestication alleles from early-domesticated japonica to proto-indica and proto-aus populations. Our results provide support for a model in which different rice subspecies had separate origins, but that de novo domestication occurred only once, in O. sativa ssp. japonica, and introgressive hybridization from early japonica to proto-indica and proto-aus led to domesticated indica and aus rice., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The first structurally characterized copper cluster with a Cu 13 centered cuboctahedral arrangement, a model of the bulk copper fcc structure, was observed in [Cu 13 (S 2 CN n Bu 2 ) 6 (C≡CR) 4 ](PF 6 ) (R=C(O)OMe, C 6 H 4 F) nanoclusters. Four of the eight triangular faces of the cuboctahedron are capped by acetylide groups in μ 3  fashion, and each of the six square faces is bridged by a dithiolate ligand in μ 2 ,μ 2 fashion, which leads to a truncated tetrahedron of twelve sulfur atoms. DFT calculations are fully consistent with the description of these Cu 13 clusters as two-electron superatoms, that is, a [Cu 13 ] 11+ core passivated by ten monoanionic ligands, with an a 1 HOMO containing two 1S jellium electrons., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background & Aims: Taiwan began a universal hepatitis B virus (HBV) vaccination program for infants in July 1984. The seroprevalence of hepatitis B surface antigen (HBsAg) decreased from 9.8% before the vaccination program to less than 1% by 25 years afterward. We continued to monitor HBV infections in this population., Methods: We conducted a series of serologic and epidemiologic surveys in the Taipei metropolitan area every 5 years from 1984 through 2014. From January 1 through December 31 of 2014, we collected serum samples from 4605 apparently healthy individuals (ages: 287 were <3 y, 405 were 3-6 y, 675 were 7-12 y, 686 were 13-18 y, 468 were 18-22 y, and 2084 were 22-50 y). All subjects were tested for HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). We performed genotype and viral load analyses for patients who tested positive for anti-HBc., Results: Of vaccinated participants (age, <30 y; n = 3299), 0.5% tested positive for HBsAg, 47.4% tested positive for anti-HBs, and 4.5% tested positive for anti-HBc. Of unvaccinated participants (age, 30-50 y, n = 1306), 6.7% tested positive for HBsAg (P < .0001), 69.4% tested positive for anti-HBs, and 44.1% tested positive for anti-HBc. One occult HBV infection was found in each age group. Among subjects positive for HBsAg younger than age 30, 77% were born to mothers positive for HBsAg., Conclusions: Based on a series of serologic and epidemiologic surveys performed in the Taipei metropolitan area, 6.7% of persons born before the universal HBV vaccination program were positive for HBsAg, compared with 0.5% of those born afterward. Most subjects positive for HBsAg younger than age 30 were born to mothers positive for HBsAg., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The synthesis and structural determination of a silver nanocluster [Ag20 {S2 P(OiPr)2 }12 ] (2), which contains an intrinsic chiral metallic core, is produced by reduction of one silver ion from the eight-electron superatom complex [Ag21 {S2 P(OiPr)2 }12 ](PF6 ) (1) by borohydrides. Single-crystal X-ray analysis displays an Ag20 core of pseudo C3 symmetry comprising a silver-centered Ag13 icosahedron capped by seven silver atoms. Its n-propyl derivative, [Ag20 {S2 P(OnPr)2 }12 ] (3), can also be prepared by the treatment of silver(I) salts and dithiophosphates in a stoichiometric ratio in the presence of excess amount of [BH4 ](-) . Crystal structure analyses reveal that the capping silver-atom positions relative to their icosahedral core are distinctly different in 2 and 3 and generate isomeric, chiral Ag20 cores. Both Ag20 clusters display an emission maximum in the near IR region. DFT calculations are consistent with a description within the superatom model of an 8-electron [Ag13 ](5+) core protected by a [Ag7 {S2 P(OR)2 }12 ](5-) external shell. Two additional structural variations are predicted by DFT, showing the potential for isomerism in such [Ag20 {S2 P(OR)2 }12 ] species., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A polyhydrido copper nanocluster, [Cu20H11{Se2P(OiPr)2}9] (2H), which exhibits an intrinsically chiral inorganic core of C3 symmetry, was synthesized from achiral [Cu20H11{S2P(OiPr)2}9] (1H) of C(3h) symmetry by a ligand-exchange method. The structure has a distorted cuboctahedral Cu13 core, two triangular faces of which are capped along the C3 axis, one by a Cu6 cupola and the other by a single Cu atom. The Cu20 framework is further stabilized by 9 diselenophosphate and 11 hydride ligands. The number of hydride, phosphorus, and selenium resonances and their splitting patterns in multinuclear NMR spectra of 2H indicate that the chiral Cu20H11 core retains its C3 symmetry in solution. The 11 hydride ligands were located by neutron diffraction experiments and shown to be capping μ3-H and interstitial μ5-H ligands (in square-pyramidal and trigonal-bipyramidal cavities), as supported by DFT calculations on [Cu20H11(Se2PH2)9] (2H') as a simplified model., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Endosomal entrapment is known to be a major bottleneck to successful cytoplasmic delivery of nucleic acids (NAs) using cationic liposome-NA nanoparticles (NPs). Quantitative measurements of distributions of NPs within early endosomes (EEs) have proven difficult due to the sub-resolution size and short lifetime of wildtype EEs. In this study we used Rab5-GFP, a member of the large family of GTPases which cycles between the plasma membrane and early endosomes, to fluorescently label early endosomes. Using fluorescence microscopy and quantitative image analysis of cells expressing Rab5-GFP, we found that at early time points (t<1h), only a fraction (≈35%) of RGD-tagged NPs (which target cell surface integrins) colocalize with wildtype EEs, independent of the NP's membrane charge density. In comparison, a GTP-hydrolysis deficient mutant, Rab5-Q79L, which extends the size and lifetime of EEs yielding giant early endosomes (GEEs), enabled us to resolve and localize individual NPs found within the GEE lumen. Remarkably, nearly all intracellular NPs are found to be trapped within GEEs implying little or no escape at early time points. The observed small degree of colocalization of NPs and wildtype Rab5 is consistent with recycling of Rab5-GDP to the plasma membrane and not indicative of NP escape from EEs. Taken together, our results show that endosomal escape of PEGylated nanoparticles occurs downstream of EEs i.e., from late endosomes/lysosomes. Our studies also suggest that Rab5-Q79L could be used in a robust imaging assay which allows for direct visualization of NP interactions with the luminal membrane of early endosomes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

RNA granules have been likened to liquid droplets whose dynamics depend on the controlled dissolution and condensation of internal components. The molecules and reactions that drive these dynamics in vivo are not well understood. In this study, we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos. The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility. We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A(PPTR-½). Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. Using lattice light sheet microscopy on live embryos, we show that GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule. We conclude that, despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation.

We herein describe the first synthesis of iminosugar C-glycosides of α-D-GlcNAc-1-phosphate in 10 steps starting from unprotected D-GlcNAc. A diastereoselective intramolecular iodoamination-cyclization as the key step was employed to construct the central piperidine ring of the iminosugar and the C-glycosidic structure of α-D-GlcNAc. Finally, the iminosugar phosphonate and its elongated phosphate analogue were accessed. These phosphorus-containing iminosugars were coupled efficiently with lipophilic monophosphates to give lipid-linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent inhibitory properties toward bacterial transglycosylases (TGase).

Steric stabilization of cationic liposome-DNA (CL-DNA) complexes is required for in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene glycol)) of CL-DNA complexes by addition of PEG2000-lipids yields sterically stabilized nanoparticles but strongly reduces their gene delivery efficacy. PEGylation-induced weakening of the electrostatic binding of CL-DNA nanoparticles to cells (leading to reduced uptake) has been considered as a possible cause, but experimental results have been ambiguous. Using quantitative live-cell imaging in vitro, we have investigated cell attachment and uptake of PEGylated CL-DNA nanoparticles with and without a custom synthesized RGD-peptide grafted to the distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly increased cellular attachment as well as uptake compared to nanoparticles without grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL-DNA NPs increases by about an order of magnitude between NPs with low and high membrane charge density (σM; the average charge per unit area of the membrane; controlled by the molar ratio of cationic to neutral lipid), even though imaging data show that uptake of RGD-tagged particles is only slightly enhanced by high σM. This suggests that endosomal escape and, as a result, transfection efficiency of RGD-tagged NPs is facilitated by high σM. We present a model describing the interactions between PEGylated CL-DNA nanoparticles and the anionic cell membrane which shows how the PEG grafting density and membrane charge density affect adhesion of nanoparticles to the cell surface., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Purpose: In Asian populations, few studies investigated the association between stroke and common carotid artery intima-media thickness (IMT). Our previous case-control studies showed that low end-diastolic velocity (EDV) in common carotid artery, a potential hemodynamic marker of intracranial resistance, was associated with ischemic stroke. Therefore, we investigated the relationship between both EDV and IMT and incident ischemic stroke in an Asian population., Methods: Baseline data from 3175 adults (30 years or older) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental ischemic stroke status derived from insurance claims and death certificate records. Hazard ratios for risk of ischemic stroke for high IMT and low EDV values measured in common carotid artery were calculated using Cox proportional hazard models., Results: With 9.85 years (median) of follow-up, 184 persons had ischemic stroke develop. Compared with the first tertile of IMT, hazard ratios were 2.03 (95% confidence intervals, 1.27-3.25) for the second tertile and 3.87 (95% confidence intervals, 2.36-5.69) for the third tertile. Hazard ratios of EDV were 5.31 (95% confidence intervals, 3.52-7.99; first tertile) and 1.94 (95% confidence intervals, 1.21-3.09; second tertile) compared with the third tertile. The individuals with high IMT and low EDV had >2-fold ischemic stroke risk compared to those with low IMT and high EDV (2.10; 95% confidence intervals, 1.35-3.26) after adjusting for age, sex, and traditional cardiovascular risk., Conclusions: Common carotid IMT and EDV jointly and independently predicted future ischemic stroke in this Taiwanese population. More prospective studies are required in various ethnic groups to understand the significance and implication of the current findings, particularly with respect to EDV.

Hepatocytes maintained in culture provide an attractive model system for the study of liver function. Furthermore, hepatocyte transplantation offers an alternative cellular therapy to orthotopic liver transplantation for the treatment of hepatic failure and hereditary liver disease. To overcome the problem of organ shortage, additional source of hepatocytes must be found. Here, we present a strategy and protocol to transdifferentiate (or convert) developmentally related pancreatic cells into hepatocytes based on the addition of the synthetic glucocorticoid dexamethasone.

The first reports on a slow earthquake were for an event in the Izu peninsula, Japan, on an intraplate, seismically active fault. Since then, many slow earthquakes have been detected. It has been suggested that the slow events may trigger ordinary earthquakes (in a context supported by numerical modelling), but their broader significance in terms of earthquake occurrence remains unclear. Triggering of earthquakes has received much attention: strain diffusion from large regional earthquakes has been shown to influence large earthquake activity, and earthquakes may be triggered during the passage of teleseismic waves, a phenomenon now recognized as being common. Here we show that, in eastern Taiwan, slow earthquakes can be triggered by typhoons. We model the largest of these earthquakes as repeated episodes of slow slip on a reverse fault just under land and dipping to the west; the characteristics of all events are sufficiently similar that they can be modelled with minor variations of the model parameters. Lower pressure results in a very small unclamping of the fault that must be close to the failure condition for the typhoon to act as a trigger. This area experiences very high compressional deformation but has a paucity of large earthquakes; repeating slow events may be segmenting the stressed area and thus inhibiting large earthquakes, which require a long, continuous seismic rupture.

Background and Purpose: Of few prospective studies that have focused on the relationship between fibrinogen and ischemic stroke (IS) in Asian populations, the findings were inconsistent with those conducted in Western countries. Therefore, we aimed to investigate the temporal relationship between fibrinogen levels (plus several related parameters) and IS in a community-based study in Taiwan., Methods: Baseline data from 3281 adults (>or=20 years of age) in the Cardiovascular Diseases Risk Factor Two-Township Study were linked to incidental IS status derived from insurance claims and death certificate records. Hazard ratios and 95% CIs of clotting factors (fibrinogen, factor VII, factor VIII, and antithrombin-III) for IS events were estimated using Cox proportional hazard models., Results: With 10.4 years (average) follow-up, 128 persons developed IS (3.75 per 1000 person-years). As expected, elevated blood pressure and diabetes were independent predictors of IS events. A dose-response relationship was found in univariate analysis between IS risk and tertiles of fibrinogen (hazard ratio, 3.73; 2.19 to 1.00), factor VII (hazard ratio, 1.86; 1.35 to 1.00), and factor VIII (2.97; 1.70 to 1.00), respectively, but not for antithrombin-III. After adjusting for confounding and known risk factors, fibrinogen independently predicted IS events. A 72% increase (hazard ratio, 1.72; 1.02 to 2.90) in IS risk was observed for individuals with fibrinogen >or=8.79 mumol/L compared with those <7.03 micromol/L., Conclusions: In addition to hypertension and diabetes, fibrinogen independently predicted future IS risk. We suggest that fibrinogen may be considered in the risk assessment model for IS in the Taiwanese population.

The stilbene synthase (STS) from Scots pine (Pinus sylvestris), which is a type III polyketide synthase, produces the well known tetraketide resveratrol from coumaroyl-CoA and three molecules of malonyl-CoA. The same stilbene synthase, however, also generates the previously unknown pentaketide 2-malonylresveratrol from coumaroyl-CoA and four molecules of malonyl-CoA; this indicates that the enzyme does not precisely control the number of condensations leading to diverse products. Tetraketide- and pentaketide-CoA intermediates of the STS were identified by LC-MS/MS; this suggests that CoA-bound polyketide intermediates are involved in the product formation of type III polyketide synthases.

Background: To determine whether separate anthropometric screening tools are needed for obesity and the metabolic syndrome in children, we compared the predictability of several anthropometric indices, including waist circumference (WC) and body mass index (BMI), with regard to metabolic disorders., Study Design: The Nutrition and Health Survey in Taiwan Elementary School Children (2000-2001) collected data from 2,215 children. Logistic regression analysis was used to study the association between anthropometric indices and metabolic abnormalities, which was defined as two or more of the following conditions: high fasting triglycerides, high fasting glucose levels, high blood pressure and low high-density lipoprotein-cholesterol. The receiver operating characteristic curve was used to study the sensitivity and specificity of these anthropometric indices., Results: predictability was the ranked highest for WC (R2=10.69%), followed by BMI (R2=9.80%), arm girth (R2=9.75%), hip circumference (R2=9.43%), scapular skinfold thickness (R2=9.28%) and waist-to-height ratio (R2=9.25%). Waist circumference or BMI cut-offs for maximal balanced sensitivity and specificity were close to the 60th percentile for each age and gender group. Values were greater in boys than in girls and increased with age., Conclusion: It is justifiable to use the WC criteria to define the metabolic syndrome in children. Due to its practicality, BMI remains the most suitable index for defining overweight/obesity. Only moderate levels of sensitivity and specificity were achieved with these two popular obesity indices with regard to metabolic abnormalities.

We consider a Brownian particle acted on by a linear conservative force, a nonlinear frictional force, and multiplicative colored and additive white noises; the frictional force can be negative when the external energy supply is large enough. We numerically calculate the mean first passage time (MFPT) for the particle to escape from an unstable limit cycle and find resonant activation, i.e., the MFPT first decreases, followed by a rise after passing through a minimum with increasing noise correlation time tau for a fixed noise variance. For fixed noise strength of the multiplicative noise the MFPT increases linearly with tau. This is in sharp contrast to the case of fluctuations of nonlinear potentials, in which the MFPT first increases nonlinearly before reaching a limiting value. Our model could be useful for understanding some biological processes.

The crystal structure of human muscle creatine kinase has been determined by the molecular-replacement method and refined at 3.5A resolution. The structures of both the monomer and the dimer closely resemble those of the other known structures in the creatine kinase family. Two types of dimers, one with a non-crystallographic twofold symmetry axis and the other with a crystallographic twofold symmetry axis, were found to exist simultaneously in the crystal. These dimers form an infinite "double-helix"-like structure along an unusual long crystallographic 3(1) axis.

The evolutionary origin of feathers has long been obscured because no morphological antecedents were known to the earliest, structurally modern feathers of Archaeopteryx. It has been proposed that the filamentous integumental appendages on several theropod dinosaurs are primitive feathers; but the homology between these filamentous structures and feathers has been disputed, and two taxa with true feathers (Caudipteryx and Protarchaeopteryx) have been proposed to be flightless birds. Confirmation of the theropod origin of feathers requires documentation of unambiguously feather-like structures in a clearly non-avian theropod. Here we describe our observations of the filamentous integumental appendages of the basal dromaeosaurid dinosaur Sinornithosaurus millenii, which indicate that they are compound structures composed of multiple filaments. Furthermore, these appendages exhibit two types of branching structure that are unique to avian feathers: filaments joined in a basal tuft, and filaments joined at their bases in series along a central filament. Combined with the independent phylogenetic evidence supporting the theropod ancestry of birds, these observations strongly corroborate the hypothesis that the integumental appendages of Sinornithosaurus are homologous with avian feathers. The plesiomorphic feathers of Sinornithosaurus also conform to the predictions of an independent, developmental model of the evolutionary origin of feathers.

A novel, to our knowledge, two-step digit-set-restricted modified signed-digit (MSD) addition-subtraction algorithm is proposed. With the introduction of the reference digits, the operand words are mapped into an intermediate carry word with all digits restricted to the set {1, 0} and an intermediate sum word with all digits restricted to the set {0, 1}, which can be summed to form the final result without carry generation. The operation can be performed in parallel by use of binary logic. An optical system that utilizes an electron-trapping device is suggested for accomplishing the required binary logic operations. By programming of the illumination of data arrays, any complex logic operations of multiple variables can be realized without additional temporal latency of the intermediate results. This technique has a high space-bandwidth product and signal-to-noise ratio. The main structure can be stacked to construct a compact optoelectronic MSD adder-subtracter.

A general method for detecting protease activities on acrylamide or agarose gels after sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) using specific aminoacyl p-nitroanilide (NA) or peptidyl NA as substrate is described. This method is extended from the spectrophotometric assay of p-nitroaniline, which is a chromogenic product liberated by protease action on aminoacyl NA or peptidyl NA. The acrylamide gel containing protein bands was dipped directly into a solution which contained specific synthetic aminoacyl NA or peptidyl NA as a substrate or had been overlaid with an agarose gel containing the same substrate. The p-nitroaniline released on the acrylamide or agarose gel by the specific protease was diazotized with sodium nitrite and then coupled to N-(1-naphthyl)-ethylenediamine to produce distinct activity band(s). The substrates used for protease activity staining on gels were identical to those used for spectrophotometric assays. Some applications are described.

The conformation of 24p3 protein purified from mouse uterine luminal fluid was studied by circular dichroism spectroscopy in 200-300 nm. At pH 7.4, the spectrum in the UV region appears as one negative band with a minimum mean residue ellipticity of -3,600 deg.cm2.dmole(-1) at 217 nm, suggesting a very low or no helical content, but a considerable amount of beta-form, beta-turn, and unordered form in the protein molecule. This agrees with the predicted secondary structures consisting of only one a-helical segment of residues 150-163 and nine segments of residues 28-35, 50-60, 67-72, 78-86, 94-97, 106-114, 119-125, 136-140 and 166-172 in beta-forms, which would construct two orthonormal beta-sheets to form a less polar beta-barrel. The environments around Trp-31 and Trp-81 of this protein were studied by intrinsic fluorescence and solute quenching. They give an emission peak at 332 nm, and only about 21% of them are accessible to quenching by acrylamide. This together with their low accessibility to either CsCI or KI suggests that they are located in the less polar beta-barrel. Hydrophobic compounds such as fatty acids, retinoids, and cholesteryl oleate in the protein solution diminish the protein fluorescence. Analysis of the fluorescence data suggests that the protein has a binding site for hydrophobic ligand. The association constants for the complex formation are 1.03 x 10(6) MM(-1), 1.92 x 10(5) M(-1), 2.38 x 10(5) M(-1) or 1.25 x 10(5) M(-1) for cholesteryl oleate, oleic acid, retinol, or retinoic acid at pH 7.4. Analysis of the equilibrium binding data from binding assay using [H3]-retinol and [H3]-retinoic acid reveals a singular type of retinoid-binding site in the protein with the association constant of 4.92 x 10(5) M(-1) and 1.17 x 10(5) M(-1) for retinol and retinoic acid, respectively. Trp-31 or/ and Trp-81 is in or very near the binding site and the gross conformation of protein changes considerably as the formation of protein-ligand complex.

Zhoukoudian is widely regarded as having the oldest reliable evidence for the controlled use of fire by humans. A reexamination of the evidence in Layer 10, the earliest archaeological horizon in the site, shows that burned and unburned bones are present in the same layer with stone tools. However, no ash or charcoal remnants could be detected. Hence, although indirect evidence for burning is present, there is no direct evidence for in situ burning.

Pectinesterase (PE), from commercial orange peels or ammonium sulfate fractionation (50-80% saturation) of pea pods, was detected on polyacrylamide gels after native acidic polyacrylamide gel electrophoresis (PAGE) or sodium dodecyl sulfate (SDS)-PAGE by using the synthetic substrate beta-naphthyl acetate (beta-NA). The release of beta-naphthol (at 322 nm) from beta-NA was proportional to PE activity. The PE activity bands on polyacrylamide gels after native acidic PAGE or SDS-PAGE were stained with a combination of tetrazotized o-dianisidine and beta-NA. This fast and sensitive method can be used for enzyme purification and characterization.

A rapid method for the production of a glass-insulated microwire electrode is described. A microwire was threaded into a glass capillary which was then pulled on a vertical pipette puller. A conical tip of the microwire was formed when the strongly heated glass capillary broke together with the wire in it. A tight seal of the glass-insulated microwire electrode between the glass and the metal was accomplished with silicone glue. The manufactured electrode performed consistently at different immersion depths, and yielded stable recordings of single units in the cerebral cortex and the medulla of rats. The strength and low impedance characteristics of the glass-insulated microwire electrode may make it useful for the recording of single units in deep brain structures. Furthermore, the electrode can be easily combined with another glass micropipette to form a dual recording-injection microelectrode unit.

Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of their dependent cytokine. In this report, we have isolated and characterized some spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of several signaling molecules known to be activated by the GM-CSF pathway revealed that two non-autocrine variants were still responsive to GM-CSF stimulation. However, both variants, without ligand stimulation, already had some activated forms of Raf and MAP kinases. Given current knowledge, the activated Raf/MAP kinase pathway was likely to be responsible for the survival of both variants in the cytokine-free medium. However, the growth of hybrids between wild type and either variant was unexpectedly dependent on GM-CSF. Both variants like the wild type cells were still susceptible to apoptosis induced by other stimuli. These results suggest that either the activated Raf/MAP kinase pathway in both variants is not sufficient to repress the 'two-fold' death signals generated from the hybrids or that there is another mechanism that is responsible for the factor-independent growth of both variants.

Hydrolysis of the crude saponin isolated from the leaves of PANAX NOTOGINSENG (Burk.) F. H. Chen yields five sapogenins which are separated by column chromatography. The structures of four of those were elucidated earlier to be panaxadiol, panaxatriol, dammar-20(22)en-3beta, 12beta,26-triol and 20(R)-dammaran-3beta, 12beta,20,25-tetrol. The fifth sapogenin is identified as an oxepane derivative probably arising from acid catalyzed dehydration and rearrangement of panaxadiol. The structure as proposed from NMR data was confirmed by single-crystal X-ray diffractometry.

From the aerial parts of KADSURA INTERIOR A. C. Sm. (Schizan-draceae) a neolignan, interiorin ( 1), with a new skeleton was isolated. Its structure was elucidated by spectroscopic methods and by single X-ray diffraction analysis.

A new sesquiterpene ether, nardonoxide ( 1), with the nardosinane skeleton, was isolated from the underground parts of NARDOSTACHYS CHINENSIS Batalin (Valerianaceae), growing in the province Sichuan (China). The structure of 1 was elucidated by spectroscopic methods, including 2D-NMR-spectroscopy.

Oxygen consumption during the respiratory burst of human polymorphonuclear leukocytes (PMN) stimulated with phorbol myristate acetate (PMA) was studied with spin probe oxymetry and using the transition metal ion CrOX (potassium trioxalatochromate) as a widening agent. The experimental results demonstrated that during the respiratory burst of PMN stimulated with PMA, oxygen consumption was found mainly in the intercellular medium but no change of oxygen concentration was found in the intracellular medium.

The mechanism and process of production of active oxygen radicals in the respiratory burst of polymorphonuclear leukocytes (PMN) stimulated with PMA (phorbol myristate acetate) was studied in this paper. The experimental results indicate that when the PMA was dilute enough or at the beginning of stimulation even when the PMA concentration was high, the spectrum of hydroxyl radical spin adducts, DMPO-OH, was dominant in the ESR spectra. However, at the maximum level of the respiratory burst, the spectrum of superoxide anion spin adducts, DMPO-OOH, was dominant.