bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behaviour of a HRSG Steam System During Flying Switch-Over to Fresh Air Operation After Gas Turbine Trip
Authors: Linnemeijer M. J. J. 
Published: January 2015

The reliability and availability of a HRSG steam system can be improved by providing a flying switch over into fresh air operation in case of failure of the gas turbine.
The flying switch over can be designed for a planned switch over in case of no availability of the gas turbine as well for a unplanned switch over in case of gas turbine trip.
Especially during the unplanned switch over the pressure of the steam system will decrease due to a temporarily lack of heat input on the HRSG.
The paper will describe different switch over arrangements and their influences on the pressure of the steam system during the switch over.
Synergistic Suppression of Dengue Virus Replication Using a Combination of Nucleoside Analogs and Nucleoside Synthesis Inhibitors
Authors: Yeo Kim Long , Chen Yen-Liang , Xu Hao Ying , Dong Hongping , Wang Qing-Yin , Yokokawa Fumiaki , Shi Pei-Yong 
Published: January 2015

ABSTRACT
Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen in humans. Currently, there is no clinically approved vaccine or antiviral for DENV. Combination therapy is a common practice in antiviral treatment and a potential approach to search for new treatments for infectious pathogens. In this study, we performed a combination treatment in cell culture by using three distinct classes of inhibitors, including ribavirin (a guanosine analog with several antiviral mechanisms), brequinar (a pyrimidine biosynthesis inhibitor), and INX-08189 (a guanosine analog). The compound pairs were evaluated for antiviral activity by use of a DENV-2 luciferase replicon assay. Our result indicated that the combination of ribavirin and INX-08189 exhibited strong antiviral synergy. This result suggests that synergy can be achieved with compound pairs in which one compound suppresses the synthesis of the nucleoside for which the other compound is a corresponding nucleoside analog. In addition, we found that treatment of cells with brequinar alone could activate interferon-stimulated response elements (ISREs); furthermore, brequinar and NITD-982 (another pyrimidine biosynthesis inhibitor) potentiated interferon-induced ISRE activation. Compared to treatment with brequinar, treatment of cells with ribavirin alone could also induce ISRE activation, but to a lesser extent; however, when cells were cotreated with ribavirin and beta interferon, ribavirin did not augment the interferon-induced ISRE activation.
Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations
Authors: Andréjak Claire , Almeida Deepak V. , Tyagi Sandeep , Converse Paul J. , Ammerman Nicole C. , Grosset Jacques H. 
Published: January 2015

ABSTRACT

The
Mycobacterium avium
complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for
M. avium
complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of
M. avium
lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of
M. avium
infection and to assess the anti-
M. avium
activity of single and combination drug regimens,
in vitro
,
ex vivo
, and in mice.
In vitro
, clarithromycin and moxifloxacin were most active against
M. avium
, and no antagonism was observed between these two drugs. Nude mice were more susceptible to
M. avium
infection than the other mouse strains tested, but the impact of treatment was most clearly seen in
M. avium
-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for
M. avium
infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.
Eravacycline (TP-434) Is Active
In Vitro
against Biofilms Formed by Uropathogenic Escherichia coli
Authors: Grossman Trudy H. , O'Brien William , Kerstein Kathryn O. , Sutcliffe Joyce A. 
Published: January 2015

ABSTRACT

Eravacycline (formerly TP-434) was evaluated
in vitro
against pre-established biofilms formed by a uropathogenic
Escherichia coli
strain. Biofilms were eradicated by 0.5 μg/ml eravacycline, which was within 2-fold of the MIC for planktonic cells. In contrast, colistin and meropenem disrupted biofilms at 32 and 2 μg/ml, respectively, concentrations well above their respective MICs of 0.5 and 0.03 μg/ml. Gentamicin and levofloxacin eradicated biofilms at concentrations within 2-fold of their MICs.
Novel Aggregative Adherence Fimbria Variant of Enteroaggregative Escherichia coli
Authors: Jønsson Rie , Struve Carsten , Boisen Nadia , Mateiu Ramona Valentina , Santiago Araceli E. , Jenssen Håvard , Nataro James P. , Krogfelt Karen A. 
Published: January 2015

ABSTRACT

Enteroaggregative
Escherichia coli
(EAEC) organisms belong to a diarrheagenic pathotype known to cause diarrhea and can be characterized by distinct aggregative adherence (AA) in a stacked-brick pattern to cultured epithelial cells. In this study, we investigated 118 EAEC strains isolated from the stools of Danish adults with traveler's diarrhea. We evaluated the presence of the aggregative adherence fimbriae (AAFs) by a multiplex PCR, targeting the four known major subunit variants as well as their usher-encoding genes. Almost one-half (49/118) of the clinical isolates did not possess any known AAF major fimbrial subunit, despite the presence of other AggR-related loci. Further investigation revealed the presence of an AAF-related gene encoding a yet-uncharacterized adhesin, termed
agg5A
. The sequence of the
agg5DCBA
gene cluster shared fimbrial accessory genes (usher, chaperone, and minor pilin subunit genes) with AAF/III, as well as the signal peptide present in the beginning of the
agg3A
gene. The complete
agg5DCBA
gene cluster from a clinical isolate, EAEC strain C338-14, with the typical stacked-brick binding pattern was cloned, and deletion of the cluster was performed. Transformation to a nonadherent
E. coli
HB101 and complementation of the nonadherent C338-14 mutant with the complete gene cluster restored the AA adhesion. Overall, we found the
agg5A
gene in 12% of the 118 strains isolated from Denmark, suggesting that this novel adhesin represents an important variant.
The Proprotein Convertase Subtilisin/Kexin FurinA Regulates Zebrafish Host Response against Mycobacterium marinum
Authors: Ojanen Markus J. T. , Turpeinen Hannu , Cordova Zuzet M. , Hammarén Milka M. , Harjula Sanna-Kaisa E. , Parikka Mataleena , Rämet Mika , Pesu Marko 
Published: January 2015

ABSTRACT

Tuberculosis is a chronic bacterial disease with a complex pathogenesis. An effective immunity against
Mycobacterium tuberculosis
requires both the innate and adaptive immune responses, including proper T helper (Th) type 1 cell function. FURIN is a proprotein convertase subtilisin/kexin (PCSK) enzyme, which is highly expressed in Th1 type cells.
FURIN
expression in T cells is essential for maintaining peripheral immune tolerance, but its role in the innate immunity and infections has remained elusive. Here, we utilized
Mycobacterium marinum
infection models in zebrafish (
Danio rerio
) to investigate how
furin
regulates host responses against mycobacteria. In steady-state
furinA
td204e/+
fish reduced
furinA
mRNA levels associated with low granulocyte counts and elevated Th cell transcription factor expressions. Silencing
furin
genes reduced the survival of
M. marinum
-infected zebrafish embryos. A mycobacterial infection upregulated
furinA
in adult zebrafish, and infected
furinA
td204e/+
mutants exhibited a proinflammatory phenotype characterized by elevated
tumor necrosis factor a
(
tnfa
),
lymphotoxin alpha
(
lta
) and
interleukin 17a/f3
(
il17a/f3
) expression levels. The enhanced innate immune response in the
furinA
td204e/+
mutants correlated with a significantly decreased bacterial burden in a chronic
M. marinum
infection model. Our data show that upregulated
furinA
expression can serve as a marker for mycobacterial disease, since it inhibits early host responses and consequently promotes bacterial growth in a chronic infection.
Population Distribution of Lifetime Risk of Ovarian Cancer in the United States
Authors: Pearce Celeste Leigh , Stram Daniel O. , Ness Roberta B. , Stram Douglas A. , Roman Lynda D. , Templeman Claire , Lee Alice W. , Menon Usha , Fasching Peter A. , McAlpine Jessica N. , Doherty Jennifer A. , Modugno Francesmary , Schildkraut Joellen M. , Rossing Mary Anne , Huntsman David G. , Wu Anna H. , Berchuck Andrew , Pike Malcolm C. , Pharoah Paul D.P. 
Published: January 2015

Abstract
Background: In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than this average.
Methods: We have characterized the distribution of lifetime risk in the general population. Published data on the relative risks and their variances for five well-accepted risk and protective factors for ovarian cancer, oral contraceptive use, parity, tubal ligation, endometriosis, and first-degree family history of ovarian cancer in conjunction with a genetic risk score using genome-wide significant common, low penetrance variants were used. The joint distribution of these factors (i.e., risk/protective factor profiles) was derived using control data from four U.S. population–based studies, providing a broad representation of women in the United States.
Results: A total of 214 combinations of risk/protective factors were observed, and the lifetime risk estimates ranged from 0.35% [95% confidence interval (CI), 0.29–0.42] to 8.78% (95% CI, 7.10–10.9). Among women with lifetime risk ranging from 4% to 9%, 73% had no family history of ovarian cancer; most of these women had a self-reported history of endometriosis.
Conclusions: Profiles including the known modifiable protective factors of oral contraceptive use and tubal ligation were associated with a lower lifetime risk of ovarian cancer. Oral contraceptive use and tubal ligation were essentially absent among the women at 4% to 9% lifetime risk.
Impact: This work demonstrates that there are women in the general population who have a much higher than average lifetime risk of ovarian cancer. Preventive strategies are available. Should effective screening become available, higher than average risk women can be identified. Cancer Epidemiol Biomarkers Prev; 24(4); 671–6. ©2015 AACR.
Nonviral Oncogenic Antigens and the Inflammatory Signals Driving Early Cancer Development as Targets for Cancer Immunoprevention
Authors: Chu Nina J. , Armstrong Todd D. , Jaffee Elizabeth M. 
Published: January 2015

Abstract
Cancer immunoprevention is an emerging field that holds much promise. Within the past 20 years, prophylactic vaccines have been implemented on the population level for the immunoprevention of carcinomas induced by viruses, specifically hepatitis B virus (HBV) and human papillomavirus (HPV) infection. Armed with the success of prophylactic vaccines that prevent viral-induced tumors, the field must overcome its next hurdle: to develop robust prophylactic vaccines that prevent the remaining &gt;80% of human cancers not induced by viral infection. In this review, we discuss some of the most promising non–virus-associated prophylactic vaccines that target endogenous neoantigens, including the earliest oncogene products, altered mucin 1 (MUC1) and α-enolase (ENO1), all of which produce new targets in the earliest stages of nonviral-induced tumorigenesis. We also highlight a novel attenuated Listeria monocytogenes–based vaccine expressing mutant oncogene KrasG12D (LM-Kras) effective in a pancreatic cancer model. A novel chimeric human/rat HER-2 plasmid vaccine (HuRT-DNA vaccine) effective in a breast cancer model is also discussed. In addition to prophylactic vaccine developments, this review highlights the potential use of classic drugs, such as aspirin and metformin, as chemopreventive agents that can potentially be used as adjuvants to enhance the anticancer immunogenicity and efficacy of noninfectious prophylactic vaccines by modulating the inflammatory pathways within the early tumor microenvironment (TME) that propels tumorigenesis. Finally, timing of prophylactic vaccine administration is critical to its immunopreventive efficacy, providing a necessary role of current and emerging biomarkers for cancer screening and early cancer detection. Clin Cancer Res; 21(7); 1549–57. ©2015 AACR.
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer
Authors: Arena Sabrina , Bellosillo Beatriz , Siravegna Giulia , Martínez Alejandro , Cañadas Israel , Lazzari Luca , Ferruz Noelia , Russo Mariangela , Misale Sandra , González Iria , Iglesias Mar , Gavilan Elena , Corti Giorgio , Hobor Sebastijan , Crisafulli Giovanni , Salido Marta , Sánchez Juan , Dalmases Alba , Bellmunt Joaquim , De Fabritiis Gianni , Rovira Ana , Di Nicolantonio Federica , Albanell Joan , Bardelli Alberto , Montagut Clara 
Published: January 2015

Abstract
Purpose: Patients with colorectal cancer who respond to the anti-EGFR antibody cetuximab often develop resistance within several months of initiating therapy. To design new lines of treatment, the molecular landscape of resistant tumors must be ascertained. We investigated the role of mutations in the EGFR signaling axis on the acquisition of resistance to cetuximab in patients and cellular models.
Experimental Design: Tissue samples were obtained from 37 patients with colorectal cancer who became refractory to cetuximab. Colorectal cancer cells sensitive to cetuximab were treated until resistant derivatives emerged. Mutational profiling of biopsies and cell lines was performed. Structural modeling and functional analyses were performed to causally associate the alleles to resistance.
Results: The genetic profile of tumor specimens obtained after cetuximab treatment revealed the emergence of a complex pattern of mutations in EGFR, KRAS, NRAS, BRAF, and PIK3CA genes, including two novel EGFR ectodomain mutations (R451C and K467T). Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. Structurally, these mutations are located in the cetuximab-binding region, except for the R451C mutant. Functionally, EGFR ectodomain mutations prevent binding to cetuximab but a subset is permissive for interaction with panitumumab.
Conclusions: Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor–antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies. Clin Cancer Res; 21(9); 2157–66. ©2015 AACR.
Gonadal Tumor in Frasier Syndrome: A Review and Classification
Authors: Ezaki Jiro , Hashimoto Kazunori , Asano Tatsuo , Kanda Shoichiro , Akioka Yuko , Hattori Motoshi , Yamamoto Tomoko , Shibata Noriyuki 
Published: January 2015

Abstract
Frasier syndrome is a rare inherited disease characterized by steroid-resistant nephrotic syndrome, gonadal tumor, and male pseudohermaphroditism (female external genitalia with sex chromosomes XY), which is based on a splice site mutation of Wilms tumor-suppressor gene 1 (WT1). Several unusual Frasier syndrome cases have been reported in which male pseudohermaphroditism was absent. We reviewed 88 Frasier syndrome cases in the literature and classified them into three types (type 1–3) according to external genitalia and sex chromosomes, and described their clinical phenotypes. Type 1 Frasier syndrome is characterized by female external genitalia with 46,XY (n = 72); type 2 by male external genitalia with 46,XY (n = 8); and type 3 by female external genitalia with 46,XX (n = 8). Clinical course differs markedly among the types. Although type 1 is noticed at the mean age of 16 due to mainly primary amenorrhea, type 2 and 3 do not present delayed secondary sex characteristics, making diagnosis difficult. The prevalence of gonadal tumor is high in type 1 (67%) and also found in 3 of the 8 type 2 cases, but not in any type 3 cases, which emphasize that preventive gonadectomy is unnecessary in type 3. On the basis of our findings, we propose a new diagnostic algorithm for Frasier syndrome. Cancer Prev Res; 8(4); 271–6. ©2015 AACR.
The Hydrometeorology of the Kariba Catchment Area Based on the Probability Distributions
Authors: Muchuru S. , Botai C. M. , Botai J. O. , Adeola A. M. 
Published: January 2015

Abstract
In this paper, monthly, maximum seasonal, and maximum annual hydrometeorological (i.e., evaporation, lake water levels, and rainfall) data series from the Kariba catchment area of the Zambezi River basin, Zimbabwe, have been analyzed in order to determine appropriate probability distribution models of the underlying climatology from which the data were generated. In total, 16 probability distributions were considered and the Kolmogorov–Sminorv (KS), Anderson–Darling (AD), and chi-square (χ2) goodness-of-fit (GoF) tests were used to evaluate the best-fit probability distribution model for each hydrometeorological data series. A ranking metric that uses the test statistic from the three GoF tests was formulated and used to select the most appropriate probability distribution model capable of reproducing the statistics of the hydrometeorological data series. Results showed that, for each hydrometeorological data series, the best-fit probability distribution models were different for the different time scales, corroborating those reported in the literature. The evaporation data series was best fit by the Pearson system, the Lake Kariba water levels series was best fit by the Weibull family of probability distributions, and the rainfall series was best fit by the Weibull and the generalized Pareto probability distributions. This contribution has potential applications in such areas as simulation of precipitation concentration and distribution and water resources management, particularly in the Kariba catchment area and the larger Zambezi River basin, which is characterized by (i) nonuniform distribution of a network of hydrometeorological stations, (ii) significant data gaps in the existing observations, and (iii) apparent inherent impacts caused by climatic extreme events and their corresponding variability.
Understanding the Influence of Measurement Uncertainty on the Atmospheric Transition in Rainfall and Column Water Vapor
Authors: Gilmore James B. 
Published: January 2015

Abstract
Measurement uncertainty plays a key role in understanding physical relationships. This is particularly the case near phase transitions where order parameters undergo fast changes and display large variability. Here the proposed atmospheric continuous phase transition is examined by analyzing uncertainty in rain-rate and column water vapor measurements from the Tropical Rainfall Measuring Mission and through an idealized error analysis. It is shown through both of these approaches that microwave rain-rate retrievals can mimic a continuous phase transition. This occurs because microwave retrievals of instantaneous rain rates have a suppressed range. This work also suggests that column water vapor noise may provide part of the plateau seen in the observational relationship. Using updated measurements, this work indicates that the atmosphere is unlikely to undergo a continuous phase transition in rain rate but, instead, contains much larger variability in rain rates at extreme column water vapor values than previously thought. This implies that the atmosphere transitions from a low-variance nonraining state to a high-variance raining state at extreme column water vapor values.
A Climatology of the Vertical Structure of Water Vapor Transport to the Sierra Nevada in Cool Season Atmospheric River Precipitation Events
Authors: Backes Tracy M. , Kaplan Michael L. , Schumer Rina , Mejia John F. 
Published: January 2015

AbstractThis study presents the climatology of the vertical structure of water vapor flux above the Sierra Nevada during significant cool season (November–April) precipitation events. Atmospheric river (AR) and non-AR events are analyzed to better understand the effect of this structure on precipitation patterns. Daily measurements of cool season precipitation at seven weather stations around the Tahoe basin from 1974 to 2012 and NCEP/CPC gridded daily precipitation analysis along the Sierra crest for the period 1948–2012 are examined. NCEP–NCAR reanalysis and soundings from Oakland are used to look at upper atmospheric conditions, including the presence of vapor transport by low- and midlevel jets on storm days as well as upstream static stability in relation to significant precipitation events. Key findings are as follows: 1) ARs play a disproportionately large role in generating Tahoe basin precipitation during the cool season; 2) strong midlevel vapor transport needs to occur in tandem with low-level transport to achieve the most extreme 2-day precipitation in the Tahoe basin; 3) when low- to midlevel vapor transport is present on days with a defined AR, the local maximum in 2-day precipitation intensity decreases with distance from the Sierra crest, and on non-AR days, the relative increase in 2-day precipitation intensity due to low- and midlevel vapor transport does not vary based on distance from the Sierra crest; 4) AR and non-AR moisture fluxes are significantly modified by upstream static stability; and 5) understanding the impacts of ARs and their lower- and midlevel moisture flux structure are crucial components of the hydrometeorology in this region.