bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel Optimization Procedures for Gas Turbine Design: Part I — Mathematical Formulation
Authors: Ghiglino Fabio , Massardo Aristide 
Published: February 2015

Two procedures for splitting a large optimization energy systems problem into a hierarchy of separated but coupled subproblems are introduced.
The mathematical formulations of the two multilevel optimization procedures are presented and discussed. Both the methods are based on a linear decomposition principle. In the first, the concept of optimal sensitivity is utilized, while in the second this concept is relaxed and the mathematical formulation is more simple.
The applicability of the analyzed procedures will be illustrated by formulation of realistic analysis and design problems in the field of gas turbine systems, in the second part of the present work (Ghiglino and Massardo, 1994).
Conversion of T-100 MPSPU Technology
Authors: Thompson R. G. , Napier J. , Rodgers C. 
Published: February 2015

Conversion of small tutbomachinery advanced technology from USA Department of Defense to commercial markets of opportunity is discussed in the light of recent development of the T-100 Multipurpose Small Power Unit (MPSPU) for the U.S. Army.
For the power class from 50 SHP to 75 SHP (37 KW to 56 KW), the small T-100 MPSPU Gas Turbine represents a milestone in achieved simple-cycle non-heat-exchanged thermal efficiency. Application of this turbomachinery technology, and in combination with heat recovery to compact turboalternator systems, is a prime candidate for conversion from airborne/defense use only to defense/commercial and airborne/ground implementation.
The T-100 MPSPU Test Program achievements are summarized in this paper. Also, preliminary design/off-design studies are presented for a turboalternator based on T-100 MPSPU components, and a scaled derivative that would achieve 60 KWe at modest turbine inlet temperature is presented. The turboalternator design objective is to provide a reliable compact source of electric power for military and commercial use in stationary, vehicular and aircraft applications that will run on most fuels, with low initial and operating costs, runs quietly, has low emissions and provides good to excellent specific fuel consumption.
GT Prime: Improvements to General Electric MS7001B Gas Turbines
Authors: Fuselier Edward M. , Prugger David K. 
Published: February 2015

The eight General Electric MS7001B gas turbines in combined cycle service at the T.H. Wharton Station of Houston Lighting and Power currently have 85000 hours of operation with 2000 starts. The units are ready for their second major overhaul. A number of hot gas path components will require replacement at that time. Rather than replacing components one by one the user devised a Program for Reliability, Improved Maintenance and Efficiency (GT Prime) with an objective of achieving twenty additional years of trouble free service. Fortunately, the supplier had developed many improved parts for his newer units which could be applied to older machines with an attendant increase in component life, inspection intervals, system reliability, availability and performance. The significant impact on customer operating costs resulted in a very attractive payback period.
A contract for modification of all eight units was signed in December, 1991. Teardown of the first unit for modification started in November, 1992 with the rebuild and test completed in July, 1993.
This paper will discuss turbine condition, differences between the old and new parts, improved performance and reduced emissions attained as a result of implementing the program.
Assessment of SYBR Green I Dye-Based Fluorescence Assay for Screening Antimalarial Activity of Cationic Peptides and DNA Intercalating Agents
Authors: Bhatia Rakesh , Gautam Ankur , Gautam Shailendra K. , Mehta Divya , Kumar Vinod , Raghava Gajendra P. S. , Varshney Grish C. 
Published: February 2015

ABSTRACT

The SYBR green I (SG) dye-based fluorescence assay for screening antimalarial compounds is based on direct quantitation of parasite DNA. We show that DNA-interacting cationic cell-penetrating peptides (CPPs) and intercalating agents compete with SG dye to bind to DNA. Therefore, readouts of this assay, unlike those of the [
3
H]hypoxanthine incorporation assay, for the antimalarial activity of the above DNA binding agents may be erroneous. In the case of CPPs, false readouts can be improved by the removal of excess peptides.
Comparison of Antimicrobial Susceptibilities of Pharyngeal, Rectal, and Urethral Neisseria gonorrhoeae Isolates among Men Who Have Sex with Men
Authors: Kidd Sarah , Zaidi Akbar , Asbel Lenore , Baldwin Tamara , Gratzer Beau , Guerry Sarah , Kerani Roxanne P. , Pathela Preeti , Pettus Kevin , Soge Olusegun O. , Stirland Ali , Weinstock Hillard S. 
Published: February 2015

ABSTRACT

U.S. surveillance for
Neisseria gonorrhoeae
antimicrobial susceptibilities is based exclusively on male urethral isolates. These data inform gonorrhea treatment guidelines, including recommendations for the treatment of extragenital infections, but data on the susceptibilities of extragenital isolates are limited. We compared the antimicrobial susceptibilities of pharyngeal, rectal, and urethral gonococcal isolates collected from men who have sex with men (MSM), at five sentinel sites throughout the United States. MICs were determined by the agar dilution method. Generalized linear models were used to compare (i) the proportions of isolates with elevated MICs and (ii) geometric mean MICs according to anatomic site, adjusted for city. In December 2011 to September 2013, totals of 205 pharyngeal, 261 rectal, and 976 urethral isolates were obtained. The proportions of isolates with elevated ceftriaxone MICs (≥0.125 μg/ml) did not differ according to anatomic site (0.5% of pharyngeal isolates, 1.5% of rectal isolates, and 1.7% of urethral isolates, with a city-adjusted odds ratio [aOR] of 0.4 [95% confidence interval {CI}, 0.0 to 3.9] for pharyngeal versus urethral isolates and an aOR of 0.9 [95% CI, 0.2 to 4.2] for rectal versus urethral isolates). The city-adjusted geometric mean ceftriaxone MICs of pharyngeal (0.0153 μg/ml) and rectal (0.0157 μg/ml) isolates did not differ from that of urethral isolates (0.0150 μg/ml) (ratios of geometric mean MICs of 1.02 [95% CI, 0.90 to 1.17] and 1.05 [95% CI, 0.93 to 1.19], respectively). Similar results were observed for other antimicrobials, including cefixime and azithromycin. These findings suggest that, at the population level, gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSM adequately reflects the susceptibilities of
N. gonorrhoeae
strains circulating among MSM.
Raltegravir Permeability across Blood-Tissue Barriers and the Potential Role of Drug Efflux Transporters
Authors: Hoque M. Tozammel , Kis Olena , De Rosa María F. , Bendayan Reina 
Published: February 2015

ABSTRACT

The objectives of this study were to investigate raltegravir transport across several blood-tissue barrier models and the potential interactions with drug efflux transporters. Raltegravir uptake, accumulation, and permeability were evaluated
in vitro
in (i) P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1), or MRP4-overexpressing MDA-MDR1 (P-gp), HEK-ABCG2, HeLa-MRP1, or HEK-MRP4 cells, respectively; (ii) cell culture systems of the human blood-brain (hCMEC/D3), mouse blood-testicular (TM4), and human blood-intestinal (Caco-2) barriers; and (iii) rat jejunum and ileum segments using an
in situ
single-pass intestinal perfusion model. [
3
H]Raltegravir accumulation by MDA-MDR1 (P-gp) and HEK-ABCG2-overexpressing cells was significantly enhanced in the presence of PSC833 {6-[(2
S
,4
R
,6
E
)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-
l
-valine-cyclosporine}, a P-gp inhibitor, or Ko143 [(3
S
,6
S
,12
aS
)-1,2,3,4,6,7,12,12
a
-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1′,2′:1,6]pyrido[3,4-
b
]indole-3-propanoic acid 1,1-dimethylethyl ester], a BCRP inhibitor, suggesting the inhibition of a P-gp- or BCRP-mediated efflux process, respectively. Furthermore, [
3
H]raltegravir accumulation by human cerebral microvessel endothelial hCMEC/D3 and mouse Sertoli TM4 cells was significantly increased by PSC833 and Ko143. In human intestinal Caco-2 cells grown on Transwell filters, PSC833, but not Ko143, significantly decreased the [
3
H]raltegravir efflux ratios. In rat intestinal segments, [
3
H]raltegravir
in situ
permeability was significantly enhanced by the concurrent administration of PSC833 and Ko143. In contrast, in the transporter inhibition assays, raltegravir (10 to 500 μM) did not increase the accumulation of substrate for P-gp (rhodamine-6G), BCRP ([
3
H]mitoxantrone), or MRP1 [2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)] by MDA-MDR1 (P-gp)-, HEK-ABCG2-, or HeLa-MRP1-overexpressing cells, respectively. Our data suggest that raltegravir is a substrate but not an inhibitor of the drug efflux transporters P-gp and BCRP. These transporters might play a role in the restriction of raltegravir permeability across the blood-brain, blood-testicular, and blood-intestinal barriers, potentially contributing to its low tissue concentrations and/or low oral bioavailability observed in the clinic setting.
Emergence of KPC-2-Producing Pseudomonas aeruginosa Sequence Type 463 Isolates in Hangzhou, China
Authors: Hu Yan-yan , Gu Dan-xia , Cai Jia-chang , Zhou Hong-wei , Zhang Rong 
Published: February 2015

ABSTRACT

Thirty-nine
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Pseudomonas aeruginosa
isolates, all exhibiting high-level resistance to carbapenems and other β-lactam antibiotics, were isolated in Hangzhou, China. Molecular epidemiology analysis indicated the presence of two dominant clones, namely, clones A and B, both of which belong to sequence type 463 (ST463). A genetic environment analysis demonstrated that both clones harbor an IS
Kpn8
transposase,
bla
KPC-2
, and an IS
Kpn6
-like transposase. These findings depict the features of clonal expansion and transmission of KPC-2-producing
P. aeruginosa
strains in Hangzhou, China.
Polymyxin Resistance Caused by
mgrB
Inactivation Is Not Associated with Significant Biological Cost in Klebsiella pneumoniae
Authors: Cannatelli Antonio , Santos-Lopez Alfonso , Giani Tommaso , Gonzalez-Zorn Bruno , Rossolini Gian Maria 
Published: February 2015

ABSTRACT

The inactivation of the
mgrB
gene, which encodes a negative-feedback regulator of the PhoPQ signaling system, was recently shown to be a common mutational mechanism responsible for acquired polymyxin resistance among carbapenemase-producing
Klebsiella pneumoniae
strains from clinical sources. In this work, we show that
mgrB
mutants can easily be selected
in vitro
from different
K. pneumoniae
lineages, and
mgrB
inactivation is not associated with a significant biological cost.
Pharmacological Activation of Rap1 Antagonizes the Endothelial Barrier Disruption Induced by Exotoxins ExoS and ExoT of Pseudomonas aeruginosa
Authors: Bouillot Stéphanie , Attrée Ina , Huber Philippe 
Published: February 2015

ABSTRACT

Most clinical strains of
Pseudomonas aeruginosa
, a leading agent of nosocomial infections, are multiresistant to antibiotherapy. Because of the paucity of new available antibiotics, the investigation of strategies aimed at limiting the action of its major virulence factors has gained much interest. The type 3 secretion system of
P. aeruginosa
and its effectors are known to be major determinants of toxicity and are required for bacterial dissemination in the host. Bacterial transmigration across the vascular wall is considered to be an important step in the infectious process. Using human endothelial primary cells, we demonstrate that forskolin (FSK), a drug inducing cyclic AMP (cAMP) elevation in eukaryotic cells, strikingly reduced the cell retraction provoked by two type 3 toxins, ExoS and ExoT, found in the majority of clinical strains. Conversely, cytotoxicity of a strain carrying the type 3 effector ExoU was unaffected by FSK. In addition, FSK altered the capacity of two ExoS/ExoT strains to transmigrate across cell monolayers. In agreement with these findings, other drugs and a cytokine inducing the increase of cAMP intracellular levels have also protected cells from retraction. cAMP is an activator of both protein kinase A and EPAC, a GTPase exchange factor of Rap1. Using activators or inhibitors of either pathway, we show that the beneficial effect of FSK is exerted by the activation of the EPAC/Rap1 axis, suggesting that its protective effect is mediated by reinforcing cell-cell and cell-substrate adhesion.
Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts
Authors: Weerdenburg Eveline M. , Abdallah Abdallah M. , Rangkuti Farania , Abd El Ghany Moataz , Otto Thomas D. , Adroub Sabir A. , Molenaar Douwe , Ummels Roy , ter Veen Kars , van Stempvoort Gunny , van der Sar Astrid M. , Ali Shahjahan , Langridge Gemma C. , Thomson Nicholas R. , Pain Arnab , Bitter Wilbert 
Published: February 2015

ABSTRACT

The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen
Mycobacterium marinum
whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that
M. marinum
contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore,
M. marinum
contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.
The Quorum Sensing Regulator CinR Hierarchically Regulates Two Other Quorum Sensing Pathways in Ligand-Dependent and -Independent Fashions in Rhizobium etli
Authors: Zheng Huiming , Mao Yiling , Zhu Qingcheng , Ling Jun , Zhang Na , Naseer Nawar , Zhong Zengtao , Zhu Jun 
Published: February 2015

ABSTRACTMany rhizobial species use complexN-acyl-homoserine lactone (AHL)-based quorum sensing (QS) systems to monitor their population density and regulate their symbiotic interactions with their plant hosts. There are at least three LuxRI-type regulatory systems inRhizobium etliCFN42: CinRI, RaiRI, and TraRI. In this study, we show that CinI, RaiI, and TraI are responsible for synthesizing all AHLs under the tested conditions. The activation of these AHL synthase genes requires their corresponding LuxR-type counterparts. We further demonstrate that CinRI is at the top of the regulatory cascade that activates RaiRI and TraRI QS systems. Moreover, we discovered that CinR possesses a specific affinity to bindcinIpromoter in the absence of its cognate AHL ligand, thereby activatingcinItranscription. Addition of AHLs leads to improved binding to thecinIpromoter and enhancedcinIexpression. Furthermore, we found that compared to the wild type, thecinRmutation displayed reduced nodule formation, andcinR,raiR, andtraImutants show significantly lower levels of nitrogen fixation activity than the wild type. These results suggest that the complex QS regulatory systems inR. etliplay an important role in its symbiosis with legume hosts.IMPORTANCEMany bacteria use quorum sensing (QS) to monitor their cell densities and coordinately regulate a number of physiological functions. Rhizobia often have diverse and complex LuxR/LuxI-type quorum sensing systems that may be involved in symbiosis and N2fixation. In this study, we identified three LuxR/LuxI-type QS systems inRhizobium etliCFN42: CinRI, RaiRI, and TraRI. We established a complex network of regulation between these QS components and found that these QS systems played important roles in symbiosis processes.
An Escherichia coli Mutant That Makes Exceptionally Long Cells
Authors: El-Hajj Ziad W. , Newman Elaine B. 
Published: February 2015

ABSTRACT

Although
Escherichia coli
is a very small (1- to 2-μm) rod-shaped cell, here we describe an
E. coli
mutant that forms enormously long cells in rich media such as Luria broth, as long indeed as 750 μm. These
e
xtremely
el
ongated (eel) cells are as long as the longest bacteria known and have no internal subdivisions. They are metabolically competent, elongate rapidly, synthesize DNA, and distribute cell contents along this length. They lack only the ability to divide. The concentration of the essential cell division protein FtsZ is reduced in these eel cells, and increasing this concentration restores division.

IMPORTANCE
Escherichia coli
is usually a very small bacterium, 1 to 2 μm long. We have isolated a mutant that forms enormously long cells, 700 times longer than the usual
E. coli
cell.
E. coli
filaments that form under other conditions usually die within a few hours, whereas our mutant is fully viable even when it reaches such lengths. This mutant provides a useful tool for the study of aspects of
E. coli
physiology that are difficult to investigate with small cells.
A Single Serine Residue Determines Selectivity to Monovalent Metal Ions in Metalloregulators of the MerR Family
Authors: Ibáñez María M. , Checa Susana K. , Soncini Fernando C. 
Published: February 2015

ABSTRACTMerR metalloregulators alleviate toxicity caused by an excess of metal ions, such as copper, zinc, mercury, lead, cadmium, silver, or gold, by triggering the expression of specific efflux or detoxification systems upon metal detection. The sensor protein binds the inducer metal ion by using two conserved cysteine residues at the C-terminal metal-binding loop (MBL). Divalent metal ion sensors, such as MerR and ZntR, require a third cysteine residue, located at the beginning of the dimerization (α5) helix, for metal coordination, while monovalent metal ion sensors, such as CueR and GolS, have a serine residue at this position. This serine residue was proposed to provide hydrophobic and steric restrictions to privilege the binding of monovalent metal ions. Here we show that the presence of alanine at this position does not modify the activation pattern of monovalent metal sensors. In contrast, GolS or CueR mutant sensors with a substitution of cysteine for the serine residue respond to monovalent metal ions or Hg(II) with high sensitivities. Furthermore, in a mutant deleted of the Zn(II) exporter ZntA, they also trigger the expression of their target genes in response to either Zn(II), Cd(II), Pb(II), or Co(II).IMPORTANCESpecificity in a stressor's recognition is essential for mounting an appropriate response. MerR metalloregulators trigger the expression of specific resistance systems upon detection of heavy metal ions. Two groups of these metalloregulators can be distinguished, recognizing either +1 or +2 metal ions, depending on the presence of a conserved serine in the former or a cysteine in the latter. Here we demonstrate that the serine residue in monovalent metal ion sensors excludes divalent metal ion detection, as its replacement by cysteine renders a pan-metal ion sensor. Our results indicate that the spectrum of signals detected by these sensors is determined not only by the metal-binding ligand availability but also by the metal-binding cavity flexibility.
Genetic Basis for Metabolism of Methylated Sulfur Compounds in Methanosarcina Species
Authors: Fu He , Metcalf William W. 
Published: February 2015

ABSTRACT

Methanosarcina acetivorans
uses a variety of methylated sulfur compounds as carbon and energy sources. Previous studies implicated the
mtsD
,
mtsF
, and
mtsH
genes in catabolism of dimethylsulfide, but the genes required for use of other methylsulfides have yet to be established. Here, we show that a four-gene locus, designated
mtpCAP-msrH
, is specifically required for growth on methylmercaptopropionate (MMPA). The
mtpC
,
mtpA
, and
mtpP
genes encode a putative corrinoid protein, a coenzyme M (CoM) methyltransferase, and a
m
ajor
f
acilitator
s
uperfamily (MFS) transporter, respectively, while
msrH
encodes a putative transcriptional regulator. Mutants lacking
mtpC
or
mtpA
display a severe growth defect in MMPA medium but are unimpaired during growth on other substrates. The
mtpCAP
genes comprise a transcriptional unit that is highly and specifically upregulated during growth on MMPA, whereas
msrH
is monocistronic and constitutively expressed. Mutants lacking
msrH
fail to transcribe
mtpCAP
and grow poorly in MMPA medium, consistent with the assignment of its product as a transcriptional activator. The
mtpCAP-msrH
locus is conserved in numerous marine methanogens, including eight
Methanosarcina
species that we showed are capable of growth on MMPA. Mutants lacking the
mtsD
,
mtsF
, and
mtsH
genes display a 30% reduction in growth yield when grown on MMPA, suggesting that these genes play an auxiliary role in MMPA catabolism. A quadruple Δ
mtpCAP
Δ
mtsD
Δ
mtsF
Δ
mtsH
mutant strain was incapable of growth on MMPA. Reanalysis of
mtsD
,
mtsF
, and
mtsH
mutants suggests that the preferred substrate for MtsD is dimethylsulfide, while the preferred substrate for MtsF is methanethiol.

IMPORTANCE
Methylated sulfur compounds play pivotal roles in the global sulfur and carbon cycles and contribute to global temperature homeostasis. Although the degradation of these molecules by aerobic bacteria has been well studied, relatively little is known regarding their fate in anaerobic ecosystems. In this study, we identify the genetic basis for metabolism of methylmercaptopropionate, dimethylsulfide, and methanethiol by strictly anaerobic methanogens of the genus
Methanosarcina
. These data will aid the development of predictive sulfur cycle models and enable molecular ecological approaches for the study of methylated sulfur metabolism in anaerobic ecosystems.