RF-thermal-structural-RF coupled analysis on the travelling wave disk-loaded accelerating structure

Travelling wave (TW) disk-loaded accelerating structure is one of the key components in normal conducting (NC) linear accelerators, and has been studied for many years. In the design process, usually after the dimensions of each cell and the two couplers are finalized, the structure is fabricated and tuned, and then the whole structure characteristics can be measured by the vector network analyzer. Before the structure fabrication, the whole structure characteristics are less simulated limited by the available computer capability. In this paper, we described the method to do the RF-thermal-structural-RF coupled analysis on the TW disk-loaded structure with one single PC. In order to validate our method, we first analyzed and compared our RF simulation results on the 3m long BEPCII structure with the corresponding experimental results, which shows very good consistency. Finally, the RF-thermal-structure-RF coupled analysis results on the 1.35m long NSC KIPT linac accelerating structure are presented.Comment: 5 pages, 16 figures, Submitted to the Chinese Physics C (Formerly High Energy Physics and Nuclear Physics

QED and relativistic nuclear recoil corrections to the 413 nm tune-out wavelength for the 2\,^3S_1 state of helium

Comparison of high accuracy calculations with precision measurement of the 413 nm tune-out wavelength of the He(2\,^3S_1) state provides a unique test of quantum electro-dynamic (QED). We perform large-scale relativistic-configuration-interaction (RCI) calculations of the tune-out wavelength, that include the mass-shift operator, and fully account for leading relativistic nuclear recoil terms in the Dirac-Coulomb-Breit (DCB) Hamiltonian. We obtain the QED correction to the tune-out wavelength using perturbation theory, and the effect of finite nuclear size is also evaluated. The resulting tune-out wavelengths for the 2\,^3S_1(M_J=0) and 2\,^3S_1(M_J=\pm 1) states are 413.084 26(4) nm and 413.090 15(4) nm, respectively. Compared with the only current experimental value of 413.0938(9stat)(20syst) nm for the 2\,^3S_1(M_J=\pm 1) state, there is 1.8$\sigma$ discrepancy between present theoretical work and experiment, which stimulates further theoretical and higher-precision experimental investigations on the 413 nm tune-out wavelength. In addition, we also determine the QED correction for the static dipole polarizability of the He(2\,^3S_1) state to be 22.5 ppm, which may enable a new test of QED in the future.Comment: 6 pages; 2 figure

Cis-regulatory control of the nodal gene, initiator of the sea urchin oral ectoderm gene network

Expression of the nodal gene initiates the gene regulatory network which establishes the transcriptional specification of the oral ectoderm in the sea urchin embryo. This gene encodes a TGFβ ligand, and in Strongylocentrotus purpuratus its transcription is activated in the presumptive oral ectoderm at about the 30-cell stage. Thereafter Nodal signaling occurs among all cells of the oral ectoderm territory, and nodal expression is required for expression of oral ectoderm regulatory genes. The cis-regulatory system of the nodal gene transduces anisotropically distributed cytoplasmic cues that distinguish the future oral and aboral domains of the early embryo. Here we establish the genomic basis for the initiation and maintenance of nodal gene expression in the oral ectoderm. Functional cis-regulatory control modules of the nodal gene were identified by interspecific sequence conservation. A 5′ cis-regulatory module functions both to initiate expression of the nodal gene and to maintain its expression by means of feedback input from the Nodal signal transduction system. These functions are mediated respectively by target sites for bZIP transcription factors, and by SMAD target sites. At least one SMAD site is also needed for the initiation of expression. An intron module also contains SMAD sites which respond to Nodal feedback, and in addition acts to repress vegetal expression. These observations explain the main features of nodal expression in the oral ectoderm: since the activity of bZIP factors is redox sensitive, and the initial polarization of oral vs. aboral fate is manifested in a redox differential, the bZIP sites account for the activation of nodal on the oral side; and since the immediate early signal transduction response factors for Nodal are SMAD factors, the SMAD sites account for the feedback maintenance of nodal gene expression

Tracing star formation in galaxies with molecular line and continuum observations

We report our recent progress on extragalactic spectroscopic and continuum observations, including HCN(J=1-0), HCO$^+$(J=1-0), and CN(N=1-0) imaging surveys of local Seyfert and starburst galaxies using the Nobeyama Millimeter Array, high-J CO observations (J=3-2 observations using the Atacama Submillimeter Telescope Experiment (ASTE) and J=2-1 observations with the Submillimeter Array) of galaxies, and $\lambda$ 1.1 mm continuum observations of high-z violent starburst galaxies using the bolometer camera AzTEC mounted on ASTE.Comment: 6 pages, 5 figures, To appear in proceedings of "Far-Infrared and Submillimeter Emission of the Interstellar Medium", EAS Publication Series, Bad Honnef, November 2007, Eds. C. Kramer, S. Aalto, R. Simon. See http://www.nro.nao.ac.jp/~f0212kk/FIR07/kk-ver20.pdf for a version with high resolution figure

Associations Between Hepatitis B Virus Genotype and Mutants and the Risk of Hepatocellular Carcinoma

Background The risk of hepatocellular carcinoma (HCC) increases with increasing level of hepatitis B virus (HBV) in serum (viral load). However , it is unclear whether genetic characteristics of HBV, including HBV genotype and specific genetic mutations, contribute to the risk of HCC. We examined the HCC risk associated with HBV genotypes and common variants in the precore and basal core promoter (BCP) regions. Methods From January 5, 1991, to December 21, 1992 , baseline blood samples were collected from 2762 Taiwanese men and women who were seropositive for HBV surface antigen but had not been diagnosed with HCC; the samples were tested for HBV viral load by real-time polymerase chain reaction and genotyped by melting curve analysis. Participants who had a baseline serum HBV DNA level greater than 101 copies/ mL (n = 1526) were tested for the precore G 1896A and BCP A 1762T/G1764A mutants by direct sequencing. Incident cases of HCC were ascertained through follow-up examinations and computerized linkage to the National Cancer Registry and death certification profiles. A Cox proportional hazards model was used to estimate the risk of HCC associated with HBV genotype and precore and BCP mutants after adjustment for other risk factors. All statistical tests were two-sided . Results A total of 153 HCC cases occurred during 33847 person-years of follow-up. The HCC incidence rates per 100000 person-years for participants infected with HBV genotype B or C were 305.6 (95% confidence interval [CI] = 236.9 to 388.1) and 785.8 (95% CI = 626.8 to 972.9), respectively. Among participants with a baseline HBV DNA level of at least 10(4) copies/mL, HCC incidence per 100000 person-years was higher for those with the precore G1896 ( wild-type) variant than for those with the G1896A variant ( 955.5 [95% CI = 749.0 to 1201.4] vs 269.4 [95% CI = 172.6 to 400.9]) and for those with the BCP A1762T/G1764A double mutant than for those with BCP A1762/G1764 (wild-type) variant (1149.2 [95% CI = 872.6 to 1485.6] vs 358.7 [95% Cl = 255.1 to 490.4]). The multivariable-adjusted hazard ratio of developing HCC was 1.76 (95% CI = 1.19 to 2.61) for genotype C vs genotype B, 0.34 (95% CI = 0.21 to 0.57) for precore G1896A vs wild type, and 1.73 (95% CI = 1.13 to 2.67 ) for BCP A1762T/G1764A vs wild type. Risk was highest among participants infected with genotype C HBV and wild type for the precore 1896 variant and mutant for the BCP 1762/1764 variant ( adjusted hazard ratio = 2.99, 95% CI = 1.57 to 5.70 , P<.001). Conclusions HBV genotype C and specific alleles of BCP and precore were associated with risk of HCC. These associations were independent of serum HBV DNA level

Obscured and powerful AGN and starburst activities at z~3.5

We report the discovery of two sources at z=3.867 and z=3.427 that exhibit powerful starburst and AGN activities. They benefit from data from radio to X rays from the CFHTLS-D1/SWIRE/XMDS surveys. Follow-up optical and near-infrared spectroscopy, and millimeter IRAM/MAMBO observations are also available. We performed an analysis of their spectral energy distributions to understand the origin of their emission and constrain their luminosities. A comparison with other composite systems at similar redshifts from the literature is also presented. The AGN and starburst bolometric luminosities are ~10^13 Lsun. The AGN emission dominates at X ray, optical, mid-infrared wavelengths, and probably in the radio. The starburst emission dominates in the far-infrared. The estimated star formation rates range from 500 to 3000Msun/yr. The AGN near-infrared and X ray emissions are heavily obscured in both sources with an estimated dust extinction Av>4, and Compton-thick gas column densities. The two sources are the most obscured and most luminous AGNs detected at millimeter wavelengths currently known. The sources presented in this work are heavily obscured QSOs, but their properties are not fully explained by the standard AGN unification model. In one source, the ultraviolet and optical spectra suggest the presence of outflowing gas and shocks, and both sources show emission from hot dust, most likely in the vicinity of the nucleus. Evidence of moderate AGN-driven radio activity is found in both sources. The two sources lie on the local M_BH-M_bulge relation. To remain on this relation, their star formation rate has to decrease. Our results support evolutionary models that invoke radio feedback as star formation quenching mechanism, and suggest that such a mechanism might play a major role also in powerful AGNs.Comment: Accepted for publication in Astronomy & Astrophysics (12 pages; 6 figures); replaced version includes minor language editing and revised reference

Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in South-East Asia

Bloodstream infections (BSIs) are a leading cause of sepsis, a life-threatening condition that contributes significantly to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside- and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections. Here, we collected a panel of 470 MDR GNB isolates from health care facilities in Cambodia, Laos, Singapore, Thailand, and Vietnam for a multi-centre assessment of their antimicrobial susceptibility to apramycin in comparison to other aminoglycosides and colistin by broth microdilution assays. Apramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem- and third-generation cephalosporin (3GC) resistant Enterobacterales, all Acinetobacter baumannii, and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, only four (6.2%) had an apramycin MIC > 16 µg/mL. Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, 3GC, and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of multidrug-resistant BSIs. Keywords: Bloodstream infection; Gram negative; aminoglycoside; antimicrobial resistance; apramycin; blood culture isolates

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

GWAS of epigenetic aging rates in blood reveals a critical role for TERT.

DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P < 2.7 × 10-11). Causal modeling indicates TERT-specific and independent effects on LTL and IEAA. Experimental hTERT-expression in primary human fibroblasts engenders a linear increase in DNA methylation age with cell population doubling number. Together, these findings indicate a critical role for hTERT in regulating the epigenetic clock, in addition to its established role of compensating for cell replication-dependent telomere shortening