bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of CFD to Partial Admission Stages of Steam Turbine
Authors: Sakai Naoto , Harada Tetsuya , Imai Yoshinobu
Published: October 2008

This paper deals with an application of Computational Fluid Dynamics, CFD, to partial admission stages in a steam turbine. Calculation of partial admission stages requires unsteady analysis and full circle modeling. Therefore quasi-3 dimensional analysis on the mean radius is conducted to reduce computational load. First, an experiment of air turbine which has one stage is carried out. This result shows a good agreement with the result of CFD analysis which has the same condition as the experiment, and applying the Q-3D method to partial admission stage analysis is validated. Using this method, 2 stage analysis of partial admission are conducted. The influence of circumferential position of admitted arc on stage efficiency is discussed. The efficiency difference is related to the windage loss which is caused by pressure distribution in the circumferential direction. It was found that there is an optimum circumferential position of admitted arc from the point of view of turbine efficiency.
Development of Low-NOx DME Multi-Ports Burner
Authors: Matsumoto Ryosuke , Ozawa Mamoru , Ishihara Isao , Sasaki Shingo , Takaichi Masahiro
Published: October 2008

This study focuses on fundamental characteristics of DME combustion, aiming at the development of low-NOx multi-ports burner. Multi-ports burner consists of a fuel-port and surrounding multi-air-ports. The strong re-circulation flow is formed by the small air jets, thus the short flames form a cluster on every burner unit so that the thermal NOx generation is significantly suppressed to a very low level. The NOx emission of the DME from the co-axial diffusion burner was over 130ppm beyond the level of the other fuels. On the other hand; NOx emission of DME from the newly advanced multi-ports burner was reduced to 60ppm at 0% O2. With the help of the low-NOx combustion system, referred to as the tube-nested combustion, NOx emission of DME was further reduced to 20ppm at 0% O2.
Characterization of Coal Ash Emissivity in High-Temperature Atmospheres
Authors: Shimogori Miki , Yoshizako Hidehisa , Shimogori Yoshio , Richardson Mark
Published: October 2008

This paper presents a method for determining coal ash emissivity in high temperature atmospheres. We applied a tube-dropping mechanism to suppress reflection from the sample, and tried other new approaches for measurements at high temperatures. One approach was a shielding time reduction using tube motorization, which reduces measurement errors to a negligible level. Another approach was determining emissivity by fitting a calculation curve to transient experimental data. In these calculations, emissivity was an adjustable parameter. An ash sample was heated in an electric furnace in the range from 500 to 1300°C and the radiation intensity from the sample was measured with a digital pyrometer. Each measurement was carried out within 0.3 seconds, including the time required for shielding the sample (0.1 seconds). Once the tube had been dropped into the furnace, radiation intensities from the sample began decreasing. Emissivity characteristics were compared between Powder River Basin (PRB) coal ash and bituminous coal ash. It was found that coal-ash emissivity depends on coal types and changes significantly as a function of ash surface temperature.
Performance Evaluation of the Micro Cogeneration System Composed of Microturbine, Solid Oxide Fuel Cell, and H2O/LIBR Absorption Refrigerator
Authors: Yoshida Hideo , Iwamoto Yuhei , Ueda Akio , Saito Motohiro
Published: October 2008

A micro cogeneration system composed of a microturbine (MGT), a solid oxide fuel cell (SOFC) and an absorption refrigerator is analyzed thermodynamically. The performance analysis is conducted on the basis of the macroscopic mass and energy balances with additional empirical correlations and operating data. First, the basic characteristics of the power generation (MGT+SOFC) section and the absorption refrigerator section are clarified. Second, under the conditions of the cell temperature of 900 °C and the turbine inlet temperature of 900 °C, the optimum design points are determined. Furthermore, the energy saving obtained by the present system through the annual operation is also evaluated in the light of the measured data in Japan. As a result, the annual fuel consumptions are reduced by 32%, 36% and 42%, for apartments, offices and hotels, respectively.
Performance Improvement of an Ammonia-Water Mixture Turbine Cycle With Ejector
Authors: Amano Yoshiharu , Takeshita Keisuke , Hashizume Takumi
Published: October 2008

This paper presents the results of a preliminary investigation into the effect of installing an ejector in an ammonia-water mixture turbine cycle, also called a Kalina cycle. To enhance the availability of the cycle, we focus on the pressure difference in the cycle. The temperature difference between the heat source and sink enhances the efficiency of the thermodynamic cycle, as does the pressure difference in the cycle. To improve the heat recovery in the cycle, other heat exchangers are required, and to utilize the pressure difference in the cycle, an ejector is a reasonable choice. From the viewpoint of the impact on the initial cost of the plant, the heat exchanger option is more costly than the ejector option. The authors investigated a simple AWM turbine cycle with an ejector driven by the high-pressure solution stream to vacuum the turbine exhaust. Simulations of several AWM turbine cycle configurations, with or without heat recovery exchangers and ejectors were performed. The specific power, which is the output power per unit mass flow rate of the heat source, of the proposed cycle EJT34 was 103% that of the WMTS. The thermal conductance is only about 24% of that of the WMTS, which is almost the same as the value of the KCS34. The results shows that the EJT34 produced as much power as that from the WMTS with 24% of the heat transfer area.
Development of a Dual-Fuel Gas Turbine Engine of Liquid and Low-Calorific Gas
Authors: Koyama Masamichi , Fujiwara Hiroshi
Published: October 2008

We developed a dual-fuel single can combustor for the Niigata Gas Turbine (NGT2BC), which was developed as a continuous-duty gas turbine capable of burning both kerosene and digester gas. The output of the NGT2BC is 920 kW for continuous use with digester gas and 1375 kW for emergency use with liquid fuel. Digester gas, obtained from sludge processing at sewage treatment plants, is a biomass energy resource whose use reduces CO2 emissions and take advantage of an otherwise wasted energy source. Design features for good combustion with digester gas include optimized the good matching of gas injection and swirl air and reduced reference velocity. The optimal combination of these parameters was determined through CFD analysis and atmospheric rig testing.
Diagnosis of Thermal Efficiency of Advanced Combined Cycle Power Plants Using Optical Torque Sensor
Authors: Umezawa Shuichi
Published: October 2008

A new optical torque measurement method was applied to diagnosis of thermal efficiency of advanced combined cycle, i.e. ACC, plants. Since the ACC power plant comprises a steam turbine and a gas turbine and both of them are connected to the same generator, it is difficult to identify which turbine in the plant deteriorates the performance when the plant efficiency is reduced. The sensor measures axial distortion caused by power transmission by use of He-Ne laser beams, small stainless steel reflectors having bar-code patterns, and a technique of signal processing featuring high frequency. The sensor was applied to the ACC plants of TOKYO ELECTRIC POWER COMPANY, TEPCO, following the success in the application to the early combined cycle plants of TEPCO. The sensor performance was inspected over a year. After an improvement related to the signal process, it is considered that the sensor performance has reached a practical use level.
Development of Gas Mixture System of Biogas and Natural Gas for Gas Engine Cogeneration
Authors: Kokubu Kunihiro , Hishinuma Masakazu , Isshiki Daisuke
Published: October 2008

Tokyo Gas has developed a compact and high-efficiency cogeneration system which can run with the mixture of biogas and natural gas, based on a new concept. To utilize the biogas whose amount of production varies from time to time, we have developed a gas mixture system that utilizes as much biogas as possible under simple and reliable control. Also, we have developed an air dilution system of natural gas to maintain stable combustion at the engine. Due to this system, the mixture ratio of biogas and natural gas can be anything from 0% to 100%. Further more, since this system is equipped with multiple safety measures, cogeneration system can continue its operation even after any thinkable malfunctions of the system. This gas mixture system and cogeneration plant has been installed at a beer brewery near Tokyo, and operating without any major troubles.
Study of the In Vitro Activities of Rifaximin and Comparator Agents against 536 Anaerobic Intestinal Bacteria from the Perspective of Potential Utility in Pathology Involving Bowel Flora
Authors: Finegold S. M. , Molitoris D. , Väisänen M.-L.
Published: October 2008

Rifaximin, ampicillin-sulbactam, neomycin, nitazoxanide, teicoplanin, and vancomycin were tested against 536 strains of anaerobic bacteria. The overall MIC of rifaximin at which 50% of strains were inhibited was 0.25 μg/ml. Ninety percent of the strains tested were inhibited by 256 μg/ml of rifaximin or less, an activity equivalent to those of teicoplanin and vancomycin but less than those of nitazoxanide and ampicillin-sulbactam.
In Vitro Model of Mycobacterial Growth Arrest Using Nitric Oxide with Limited Air
Authors: Hussain Syed , Malik Muhammad , Shi Lanbo , Gennaro Maria Laura , Drlica Karl
Published: October 2008

An in vitro model of mycobacterial growth arrest was developed using
Mycobacterium bovis
BCG. When an exponentially growing culture was transferred to an evacuated tube, growth continued; treatment with a source of nitric oxide (diethylenetriamine-nitric oxide adduct [DETA-NO] at 50 μM) halted growth immediately, and aeration restored growth. When the period of growth arrest exceeded 4 h, a time lag occurred before aeration could restore growth. The lag time was maximal (24 h) after 16 h of growth arrest. These time lags indicated that one transition period was required for cells to achieve full arrest of growth and another for them to recover fully from growth arrest. DETA-NO-induced growth arrest failed to protect from the lethal effects of anaerobic shock, which caused rapid lysis of both growing and growth-arrested cells. While growth arrest had little effect on the lethal action of rifampin, it eliminated isoniazid lethality. Growth arrest reduced but did not eliminate fluoroquinolone lethality. Two fluoroquinolones, moxifloxacin and gatifloxacin, were equally lethal to exponentially growing cells, but moxifloxacin was more active during growth arrest. This difference is attributed to the fluoroquinolone C-7 ring structure, the only difference between the compounds. Collectively these data characterize a new system for halting mycobacterial growth that may be useful for evaluating new antituberculosis agents.
In Vitro Activity of Tomopenem (CS-023/RO4908463) against Anaerobic Bacteria
Authors: Tanaka Kaori , Mikamo Hiroshige , Nakao Kenichi , Ichiishi Taku , Goto Takatsugu , Yamagishi Yuka , Watanabe Kunitomo
Published: October 2008

The antianaerobic activity of tomopenem, a new longer-half-life parenteral carbapenem, was compared with other carbapenems. Tomopenem showed broad activity against 63 reference species. The activity of tomopenem against 293 clinical isolates was potent (MIC
90
, 0.06 to 4 μg/ml) and comparable to those of meropenem and doripenem and more potent than that of panipenem.
Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates
Authors: Ahsman Maurice J. , Wildschut Enno D. , Tibboel Dick , Mathot Ron A.
Published: October 2008

Rational dosing of antibiotics in neonates should be based on pharmacokinetic (PK) parameters assessed in specific populations. PK studies of neonates are hampered by the limited total plasma volume, which restricts the sample volume and sampling frequency. Available drug assay methods require large sample volumes and are labor-intensive or time-consuming. The objective of this study was to develop a rapid ultra-performance liquid chromatographic method with tandem mass spectrometry detection for simultaneous quantification of amoxicillin, meropenem, cefazolin, cefotaxime, deacetylcefotaxime, ceftriaxone, and vancomycin in 50 μl of plasma. Cleanup consisted of protein precipitation with cold acetonitrile (1:4) and solvent evaporation before reversed-phase chromatographic separation and detection using electrospray ionization tandem mass spectrometry. Standard curves were prepared over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 100% ± 15% and 15%, respectively, with acceptable matrix effects. Coefficients of variation for matrix effects and recovery were <10% over six batches of plasma. Stability in plasma and aqueous stocks was generally sufficient, but stability of meropenem and ceftriaxone in extracts could limit autosampler capacity. The instrument run time was approximately 3.50 min per sample. Method applicability was demonstrated with plasma samples from an extracorporeal membrane oxygenation-treated neonate. Different β-lactam antibiotics can be added to this method with additional ion transitions. Using ultra-performance liquid chromatography mass spectrometry, this method allows simple and reliable quantification of multiple antibiotics in 50 μl of plasma for PK studies of neonates.
In Vitro Activities of a Novel Nanoemulsion against
Burkholderia
and Other Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
Authors: LiPuma John J. , Rathinavelu Sivaprakash , Foster Bridget K. , Keoleian Jordan C. , Makidon Paul E. , Kalikin Linda M. , Baker James R.
Published: October 2008

Respiratory tract infection, most often involving opportunistic bacterial species with broad-spectrum antibiotic resistance, is the primary cause of death in persons with cystic fibrosis (CF). Species within the
Burkholderia cepacia
complex are especially problematic in this patient population. We investigated a novel surfactant-stabilized oil-in-water nanoemulsion (NB-401) for activity against 150 bacterial isolates recovered primarily from CF respiratory tract specimens. These specimens included 75
Burkholderia
isolates and 75 isolates belonging to other CF-relevant species including
Pseudomonas
,
Achromobacter
,
Pandoraea
,
Ralstonia
,
Stenotrophomonas
, and
Acinetobacter
. Nearly one-third of the isolates were multidrug resistant, and 20 (13%) were panresistant based on standard antibiotic testing. All isolates belonging to the same species were genotyped to ensure that each isolate was a distinct strain. The MIC
90
of NB-401 was 125 μg/ml. We found no decrease in activity against multidrug-resistant or panresistant strains. MBC testing showed no evidence of tolerance to NB-401. We investigated the activity of NB-401 against a subset of strains grown as a biofilm and against planktonic strains in the presence of CF sputum. Although the activity of NB-401 was decreased under both conditions, the nanoemulsion remained bactericidal for all strains tested. These results support NB-401's potential role as a novel antimicrobial agent for the treatment of infection due to CF-related opportunistic pathogens.
Plasmid-Mediated 16S rRNA Methylases in Aminoglycoside-Resistant
Enterobacteriaceae
Isolates in Shanghai, China
Authors: Wu Qiong , Zhang Yibo , Han Lizhong , Sun Jingyong , Ni Yuxing
Published: October 2008

High-level resistance to aminoglycosides produced by 16S rRNA methylases in
Enterobacteriaceae
isolates was investigated. The prevalences of
armA
in
Escherichia coli
,
Klebsiella pneumoniae
, and
Enterobacter cloacae
were 0.6%, 3.0%, and 10%, respectively.
rmtB
was more prevalent than
armA
. Pulsed-field gel electrophoresis patterns indicated that
armA
and
rmtB
have spread horizontally and clonally.
Characterization of
tet
(32) Genes from the Oral Metagenome
Authors: Warburton Philip , Roberts Adam P. , Allan Elaine , Seville Lorna , Lancaster Holli , Mullany Peter
Published: October 2008

tet
(32) was identified in three bacterial isolates and in metagenomic DNA from the human oral cavity. The regions immediately flanking the gene were found to have similarities to the mobile elements Tn
B1230
from
Butyrivibrio fibrisolvens
, ATE-3 from
Arcanobacterium pyogenes
, and CTn
5
from
Clostridium difficile
.
Correlating Echinocandin MIC and Kinetic Inhibition of
fks1
Mutant Glucan Synthases for
Candida albicans
: Implications for Interpretive Breakpoints
Authors: Garcia-Effron Guillermo , Park Steven , Perlin David S.
Published: October 2008

A detailed kinetic characterization of echinocandin inhibition was performed for mutant 1,3-β-
d
-glucan synthase enzymes from clinical isolates of
Candida albicans
with nine different
FKS1
mutations resulting in high MICs. Among 14 mutant Fks1p enzymes studied, the kinetic parameters 50% inhibitory concentration and
K

i

increased 50-fold to several thousandfold relative to those for the wild type. Enzymes with mutations at Ser645 (S645P, S645Y, and S645F) within hot spot 1 showed the most prominent decrease in sensitivity, while those with mutations at the N- and C-terminal ends of hot spot 1 generally retained greater sensitivity to all three drugs. Kinetic inhibitions by caspofungin, micafungin, and anidulafungin were comparable among the
fks1
mutant enzymes, although absolute values did vary with specific mutations. Amino acid substitutions in Fks1p did not alter
K

m

values, although some mutations decreased the
V
max
. Given the association of
FKS1
mutations with clinical resistance, an evaluation of the kinetic parameters for the inhibition of mutant 1,3-β-
d
-glucan synthase as a function of the MIC enabled an independent evaluation of the recently adopted susceptibility breakpoint for echinocandin drugs. Overall, a breakpoint MIC of ≥2 μg/ml for caspofungin captured nearly 100% of
fks1 C. albicans
strains when a kinetic inhibition rise threshold of ≤50-fold for the
K

i

was used as a measure of susceptibility. A similar MIC breakpoint for micafungin and anidulafungin was less inclusive, and a projected MIC of ≥0.5 μg/ml was required for >95% coverage of clinical isolates. However, when MIC determinations were performed in the presence of 50% serum, all
fks1
mutants showed MIC values of ≥2 μg/ml for the three echinocandin drugs. The 1,3-β-
d
-glucan synthase kinetic inhibition data support the proposed susceptibility breakpoint for caspofungin in
C. albicans
, but a lower susceptibility breakpoint (≤0.5 μg/ml) may be more appropriate for anidulafungin and micafungin. Overall, the data indicate that MIC testing with caspofungin may serve as a surrogate marker for resistance among the class of echinocandin drugs.
Clinical Outcomes, Safety, and Pharmacokinetics of OPT-80 in a Phase 2 Trial with Patients withClostridium difficileInfection
Authors: Louie T. , Miller M. , Donskey C. , Mullane K. , Goldstein E. J. C.
Published: October 2008

OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option forClostridium difficileinfection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity againstC. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically ≤20 ng/ml across the dose range; the mean fecal concentrations exceeded the MIC at which 90% of the isolates tested are inhibited by 2,000- to 10,000-fold with increasing dosages. Resolution of diarrhea within 10 days was achieved in 10/14 patients (71%), 12/15 patients (80%), and 15/16 patients (94%), and the median time to resolution of diarrhea was reduced from 5.5 to 3.0 days with increasing dosages. Across all groups, the clinical cure rate, which was defined as resolution of diarrheal disease without the need for further treatment, was 41/45 patients (91%). Recurrence of CDI at ∼1 month after treatment was observed in two (5%) patients, one each in the 100-mg and 400-mg groups. The apparent high clinical response, good tolerance, low recurrence rate, and more-complete and rapid symptom control with the highest dosage support the selection of the 200-mg twice-daily dose for further clinical development of OPT-80 for treatment of CDI.
Four Superoxide Dismutases Contribute to
Bacillus anthracis
Virulence and Provide Spores with Redundant Protection from Oxidative Stress
Authors: Cybulski Robert J. , Sanz Patrick , Alem Farhang , Stibitz Scott , Bull Robert L. , O'Brien Alison D.
Published: October 2008

The
Bacillus anthracis
genome encodes four superoxide dismutases (SODs), enzymes capable of detoxifying oxygen radicals. That two of these SODs, SOD15 and SODA1, are present in the outermost layers of the
B. anthracis
spore is indicated by previous proteomic analyses of the exosporium. Given the requirement that spores must survive interactions with reactive oxygen species generated by cells such as macrophages during infection, we hypothesized that SOD15 and SODA1 protect the spore from oxidative stress and contribute to the pathogenicity of
B. anthracis
. To test these theories, we constructed a double-knockout (Δ
sod15
Δ
sodA1
) mutant of
B. anthracis
Sterne strain 34F2 and assessed its lethality in an A/J mouse intranasal infection model. The 50% lethal dose of the Δ
sod15
Δ
sodA1
strain was similar to that of the wild type (34F2), but surprisingly, measurable whole-spore SOD activity was greater than that in 34F2. A quadruple-knockout strain (Δ
sod15
Δ
sodA1
Δ
sodC
Δ
sodA2
) was then generated, and as anticipated, spore-associated SOD activity was diminished. Moreover, the quadruple-knockout strain, compared to the wild type, was attenuated more than 40-fold upon intranasal challenge of mice. Spore resistance to exogenously generated oxidative stress and to macrophage-mediated killing correlated with virulence in A/J mice. Allelic exchange that restored
sod15
and
sodA1
to their wild-type state restored wild-type characteristics. We conclude that SOD molecules within the spore afford
B. anthracis
protection against oxidative stress and enhance the pathogenicity of
B. anthracis
in the lung. We also surmise that the presence of four SOD alleles within the genome provides functional redundancy for this key enzyme.
SarZ Promotes the Expression of Virulence Factors and Represses Biofilm Formation by Modulating SarA and
agr
in
Staphylococcus aureus
Authors: Tamber Sandeep , Cheung Ambrose L.
Published: October 2008

Staphylococcus aureus
is a remarkably adaptable organism capable of multiple modes of growth in the human host, as a part of the normal flora, as a pathogen, or as a biofilm. Many of the regulatory pathways governing these modes of growth are centered on the activities of two regulatory molecules, the DNA binding protein SarA and the regulatory RNAIII effector molecule of the
agr
system. Here, we describe the modulation of these regulators and their downstream target genes by SarZ, a member of the SarA/MarR family of transcriptional regulators. Transcriptional and phenotypic analyses of a
sarZ
mutant demonstrated that the decreased transcription of
mgrA
and the
agr
RNAIII molecule was accompanied by increased transcription of
spa
(protein A) and downregulation of
hla
(alpha-hemolysin) and
sspA
(V8 protease) transcripts when compared to its isogenic parent. The decrease in protease activity was also associated with an increase in SarA expression. Consistent with an increase in SarA levels, the
sarZ
mutant displayed an enhanced ability to form biofilms. Together, our results indicate that SarZ may be an important regulator governing the dissemination phase of
S. aureus
infections, as it promotes toxin expression while repressing factors required for biofilm formation.
Interleukin-23 Orchestrates Mucosal Responses to
Salmonella enterica
Serotype Typhimurium in the Intestine
Authors: Godinez Ivan , Raffatellu Manuela , Chu Hiutung , Paixão Tatiane A. , Haneda Takeshi , Santos Renato L. , Bevins Charles L. , Tsolis Renée M. , Bäumler Andreas J.
Published: October 2008

Salmonella enterica
serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice that involves T-cell-dependent induction of gamma interferon (IFN-γ), interleukin-22 (IL-22), and IL-17 expression (genes
Ifn-γ
,
Il-22
, and
Il-17
, respectively). We investigated here the role of IL-23 in initiating these inflammatory responses using the streptomycin-pretreated mouse model. Compared to wild-type mice, the expression of IL-17 was abrogated, IL-22 expression was markedly reduced, but IFN-γ expression was normal in the ceca of IL-23p19-deficient mice during serotype Typhimurium infection. IL-23p19-deficient mice also exhibited a markedly reduced expression of regenerating islet-derived 3 gamma, keratinocyte-derived cytokine, and reduced neutrophil recruitment into the cecal mucosa during infection. Analysis of CD3
+
lymphocytes in the intestinal mucosa by flow cytometry revealed that αβ T cells were the predominant cell type expressing the IL-23 receptor in naive mice. However, a marked increase in the number of IL-23 receptor-expressing γδ T cells was observed in the lamina propria during serotype Typhimurium infection. Compared to wild-type mice, γδ T-cell-receptor-deficient mice exhibited blunted expression of IL-17 during serotype Typhimurium infection, while IFN-γ expression was normal. These data suggested that γδ T cells are a significant source, but not the sole source, of IL-17 in the acutely inflamed cecal mucosa of mice. Collectively, our results point to IL-23 as an important player in initiating a T-cell-dependent amplification of inflammatory responses in the intestinal mucosa during serotype Typhimurium infection.
Cytotoxic Necrotizing Factor Type 1-Neutralizing Monoclonal Antibody NG8 Recognizes Three Amino Acids in a C-Terminal Region of the Toxin and Reduces Toxin Binding to HEp-2 Cells
Authors: Grande Kerian K. , Meysick Karen C. , Rasmussen Susan B. , O'Brien Alison D.
Published: October 2008

Cytotoxic necrotizing factor type 1 (CNF1) and CNF2 are toxins of pathogenic
Escherichia coli
that share 85% identity over 1,014 amino acids. Although both of these toxins modify GTPases, CNF1 is a more potent inducer of multinucleation in HEp-2 cells, binds more efficiently to HEp-2 cells, and, despite the conservation of amino acids (C866 and H881) required for enzymatic activity of the toxins, deamidates RhoA and Cdc42 better than CNF2. Here we exploited the differences between CNF1 and CNF2 to define the epitope on CNF1 to which the CNF1-specific neutralizing monoclonal antibody (MAb) (MAb NG8) binds and to determine the mechanism by which MAb NG8 neutralizes CNF1 activity on HEp-2 cells. For these purposes, we generated a panel of 21 site-directed mutants in which amino acids in CNF1 were exchanged for the amino acids in CNF2 between amino acids 546 and 869 and vice versa. This region of CNF1 not only is recognized by MAb NG8 but also is involved in binding of this toxin to HEp-2 cells. All the mutants retained the capacity to induce multinucleation of HEp-2 cells. However, the CNF1 double mutant with D591E and F593L mutations (CNF1
D591E F593L
) and the CNF1
H661Q
single mutant displayed drastically reduced reactivity with MAb NG8. A reverse chimeric triple mutant, CNF1
E591D L593F Q661H
, imparted MAb NG8 reactivity to CNF2. MAb NG8 neutralized CNF2
E591D L593F Q661H
activity in a dose-dependent manner and reduced the binding of this chimeric toxin to HEp-2 cells. Taken together, these results pinpoint three amino acids in CNF1 that are key amino acids for recognition by neutralizing MAb NG8 and further help define a region in CNF1 that is critical for full toxin binding to HEp-2 cells.
Loss of Allergen 1 Confers a Hypervirulent Phenotype That Resembles Mucoid Switch Variants of
Cryptococcus neoformans
Authors: Jain Neena , Li Li , Hsueh Ye-Ping , Guerrero Abraham , Heitman Joseph , Goldman David L. , Fries Bettina C.
Published: October 2008

Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus
Cryptococcus neoformans
undergoes phenotypic switching in vivo that promotes persistence in tissue. By microarray and real-time PCR analyses, the allergen 1 gene (
ALL1
) was found to be downregulated in the hypervirulent mucoid switch variant, both during logarithmic growth and during intracellular growth in macrophages. The
ALL1
gene encodes a small cytoplasmic protein that is involved in capsule formation. Growth of an
all1
Δ gene deletion mutant was normal. Similar to cells of the mucoid switch variant,
all1
Δ cells produced a larger polysaccharide capsule than cells of the smooth parent and the complemented strain produced, and the enlarged capsule inhibited macrophage phagocytosis. The mutant exhibited a modest defect in capsule induction compared to all of the other variants. In animal models the phenotype of the
all1
Δ mutant mimicked the hypervirulent phenotype of the mucoid switch variant, which is characterized by decreased host survival and elevated intracranial pressure. Decreased survival is likely the result of both an ineffective cell-mediated immune response and impaired phagocytosis by macrophages. Consequently, we concluded that, unlike loss of most virulence-associated genes, where loss of gene function results in attenuated virulence, loss of the
ALL1
gene enhances virulence by altering the host-pathogen interaction and thereby impairing clearance. Our data identified the first cryptococcal gene associated with elevated intracranial pressure and support the hypothesis that an environmental opportunistic pathogen has modified its virulence in vivo by epigenetic downregulation of gene function.
Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency ofAnaplasma marginale
Authors: Ueti Massaro W. , Knowles Donald P. , Davitt Christine M. , Scoles Glen A. , Baszler Timothy V. , Palmer Guy H.
Published: October 2008

The relative fitness of arthropod-borne pathogens within the vector can be a major determinant of pathogen prevalence within the mammalian host population. Strains of the tick-borne rickettsiaAnaplasma marginalediffer markedly in transmission efficiency, with a consequent impact on pathogen strain structure. We have identified twoA. marginalestrains with significant differences in the transmission phenotype that is effected following infection of the salivary gland. We have proposed competing hypotheses to explain the phenotypes: (i) both strains are secreted equally, but there is an intrinsic difference in infectivity for the mammalian host, or (ii) one strain is secreted at a significantly higher level and thus represents delivery of a greater pathogen dose. Quantitative analysis of pathogen replication and secretion revealed that the high-efficiency St. Maries strain replicated to a 10-fold-higher titer and that a significantly greater percentage of infected ticks secretedA. marginaleinto the saliva and did so at a significantly higher level than for the low-efficiency Israel vaccine strain. Furthermore, the transmission phenotype of the vaccine strain could be restored to that of the St. Maries strain simply by increasing the delivered pathogen dose, either by direct inoculation of salivary gland organisms or by increasing the number of ticks during transmission feeding. We identified morphological differences in the colonization of each strain within the salivary glands and propose that these reflect strain-specific differences in replication and secretion pathways linked to the vector-pathogen interaction.
Early diagenetic processes in deep Labrador Sea sediments: reactive and nonreactive iron and phosphorus
Authors: Lucotte Marc , Mucci Alfonso , Hillaire-Marcel Claude , Tran Sophie
Published: October 2008

A sequential extraction procedure was applied to separate the oxides and lithogenous phases of iron and manganese and the organic and inorganic phosphorus phases in four box cores and one piston core from the slopes and rises of the Labrador Sea. Sedimentation rate, rather than the location in the basin, appears as a master variable of the diagenetic transformations of Fe, Mn, and P. High sedimentation rate, characteristic of two of the box cores, led to the creation of zones near the redox boundary of partial reprecipitation of dissolved Fe, Mn, and P released in the deeper reducing portions of the sediments. In contrast, surficial sediments from box cores with 10 times lower sedimentation rate only have sufficient reductive capacity to remobilize Mn hydroxides while leaving the Fe oxyhydroxides intact. Under these conditions, there is evidence for a redistribution of reactive inorganic P leading to the crystallization of carbonate fluorapatite in the top 30 cm of the cores. Gradual transformation of buried orthophosphate to authigenic apatite under suboxic conditions is also observed in the top 400 cm of the high sedimentation rate piston core. As in the box cores, the reaction is complete after several thousand years of burial and occurs in sediments characterized by low CaCO3 content. Depending upon the sedimentation rates, the carbonate fluor-apatite crystallization may be superimposed on the changes in detrital sedimentary fluxes accompanying the onset of deglaciation. A proxy indicator of paleo-redox conditions, and thus of biodegradable organic matter accumulation at the sediment–water interface, is given by the ratio of iron oxides to the reactive inorganic P (solid orthophosphate plus authigenic apatite).
Accelerator mass spectrometry radiocarbon stratigraphies in deep Labrador Sea cores: paleoceanographic implications
Authors: Wu Guoping , Hillaire-Marcel Claude
Published: October 2008

Foraminiferal accelerator mass spectrometry (AMS) 14C ages and benthic–planktonic age differences in surface-layer sediments of Labrador Sea are influenced by bioturbation and by changes in the relative abundance of foraminiferal species carrying the 14C signal. Using benthic-mixing models we demonstrate that inverse benthic–planktonic age differences can be generated when the effect of benthic mixing and abundance change exceeds apparent age differences between surface water and deep water. AMS 14C ages obtained put constraints on the timing of major paleoceanographic changes in the basin, notably on the history of the Western Boundary Undercurrent, which was clearly reinitiated during the mid-deglaciation and intensified during the last 2–3 ka.
Dinoflagellate cyst distribution in high-latitude marine environments and quantitative reconstruction of sea-surface salinity, temperature, and seasonality
Authors: Vernal Anne de , Turon Jean-Louis , Guiot Joel
Published: October 2008

A data base of 179 reference sites documents the relations between the assemblages of organic-walled dinoflagellate cysts and sea-surface temperature, salinity, and seasonality throughout the North Atlantic, adjacent subpolar basins (Labrador Sea, Baffin Bay, Irminger and Iceland basins) and epicontinental environments off eastern Canada (estuary and Gulf of St. Lawrence, Hudson Bay). Principal-component analyses show close relationships between dinoflagellate cyst data and sea-surface conditions: the first component (71.1% of the variance) correlates with the winter temperature, salinity, and seasonal duration of sea-ice cover, whereas the second component (11.3% of the variance) appears mainly related to summer temperature. Transfer functions using the best analogue method were tested by reconstructing modern sea-surface conditions on the basis of the reference dinoflagellate cyst assemblages. The correlation coefficient between instrumental averages and reconstructed values ranges from 0.87 (August temperature) to 0.97 (annual duration of sea-ice cover). These transfer functions appear most accurate for the reconstruction of sea-surface conditions in marginal marine environments of high-latitude basins. The only reservation concerns the validity of reconstruction in offshore regions characterized by low productivity where sparse cyst fluxes may result from long-distance transport through currents. The transfer functions that were applied in, as an example, a late Quaternary sequence of the Davis Strait in the northern Labrador Sea, notably suggest seasonal sea-ice cover extent of 6–10 months/year and August temperature and salinity of 1–4 °C and 31–33‰, respectively, during the last glacial optimum (isotopic stage 2).
Isotope stratigraphy, sedimentation rates, deep circulation, and carbonate events in the Labrador Sea during the last ~ 200 ka
Authors: Hillaire-Marcel C. , Vernal A. de , Bilodeau G. , Wu G.
Published: October 2008

High-resolution stable-isotope and accelerator mass spectrometry 14C measurements in 25 box and piston cores from the Labrador Sea allow the reconstruction of major paleoceanographical changes during the last ~ 200 ka in this basin and also document the links between the interior of the Laurentide Ice Sheet and the North Atlantic Ocean during this interval. Two deep circulation regimes are indicated by contrasting sedimentation rates on the slopes: (i) the modern situation is characterized by a gyre of the North Atlantic Deep Water (NADW) components into the basin, which is responsible for the high-energy Western Boundary Undercurrent; this regime also prevailed during the former "true" interglacials and possibly during shorter "warm" intervals (e.g., Bølling-Allerød); (ii) a more frequent NADW-free situation during glacial and interstadial intervals is marked by the presence of a vertically homogeneous water mass in the basin. Sedimentological records also indicate that carbonate events (i.e., pulses of detrital Paleozoic carbonates from Hudson Strait) and Heinrich events (sharp increases in ice-rafted lithic fragments), which are observed during the last two glaciations, are due to two distinct mechanisms. We hypothesize that detrital-carbonate events are linked to the triggering of turbidity currents in the western Labrador Sea by surges of the ice margin off Hudson Strait, and that the North Atlantic Mid-Ocean Channel, and possibly the Charlie Gibbs Fracture Zone, played a role in the spreading of these carbonates into the North Atlantic. Rapid calving would have been responsible for the intense ice rafting responsible for the Heinrich events stricto sensu. During such intervals, low productivity in surface waters is inferred from light carbon events and low concentrations in primary productivity indicators.
Palynomorph distribution in Recent sediments from the Labrador Sea
Authors: Rochon André , Vernal Anne de
Published: October 2008

Surface sediments from the Labrador Sea and Baffin Bay have been examined for their palynomorph content. Pollen and spore assemblages reflect the vegetation zones of eastern Canada, although long-distance atmospheric transport results in over-representation of Pinus and spores. A linear decrease of pollen input is observed with distance from the source vegetation; the abyssal domain receives less than 2% of the initial input. The abundance of dinoflagellate cysts reflects a relatively high primary productivity in surface water masses which seems proportional to the benthic productivity, as shown by the concentrations of organic linings of foraminifers. The relative abundance of dinoflagellate cyst taxa and principal component analysis led to the definition of three assemblages that can be related to sea-surface conditions and current pattern. The modern distribution of dinoflagellate cysts was used to interpret assemblages recovered in five box cores from the deep Labrador Sea. Results reveal important changes in sea-surface conditions during the Holocene. At the end of the last glacial period, the productivity in surface waters was sparse, notably on the continental slope off southwest Greenland. Shortly after the deglaciation, the primary productivity increased, probably due to the improvement of sea-surface conditions. At about 5000 BP, the dinoflagellate cyst concentrations and fluxes reach maximum values, and the assemblages are marked by the augmentation of Nematosphaeropsis labyrinthus relative to Operculodinium centrocarpum. This trend is associated with a cooling and the increased influence of the inner component of the Greenland Current in surface water masses of the Labrador Sea. It marks the establishment of modern conditions in the basin.
Benthic foraminiferal assemblages in Labrador Sea sediments: relations with deep-water mass changes since deglaciation
Authors: Bilodeau Guy , Vernal Anne de , Hillaire-Marcel Claude
Published: October 2008

Surface sediment samples from the Labrador Sea and the Irminger and Iceland basins have been analysed for their benthic foraminiferal content to define the relationship between benthic foraminiferal assemblages and bottom-water characteristics. On the shelf (301–530 m) and the upper slope (1364 and 1980 m) the distribution of assemblages is complex and appears related to diversified microhabitats. In the deep-sea domain (> 2600 m) three main assemblages have been identified: the first, dominated by Epistominella exigua, is related to the North East Atlantic Deep Water (NEADW); the second, characterized by the co-dominance of Cibicides wuellerstorfi and E. exigua, seems to characterize the North West Atlantic Bottom Water (NWABW); the third, marked by the occurrence of Nuttalides umbonifera, is recorded at depths greater than 3500 m and is associated with the northern extent of the Antarctic Bottom Water (AABW).Microfaunal and isotopic analyses of two cores from the Greenland slope (90-013-011, 2800 m) and rise (90-013-013, 3300 m) provide insight into the changes in the deep-water mass characteristics of the Labrador Sea over the past 15 000 years. Prior to 8500 BP, sparse assemblages dominated by either Pullenia quinqueloba, Uvigerina peregrina, or Melonis pompiloides suggest changing environmental conditions. In particular, a peak of U. peregrina recorded just before the Younger Dryas event in the deepest core is associated with the northward advance of a relatively warm, oxygen-poor bottom-water mass from the Atlantic. After 8500 BP, the increasing proportion of E. exigua suggests the formation of a bottom-water mass similar to the modern NEADW. Finally, higher percentages of C. wuellerstorfi in late Holocene sediments (after 5500 BP) are associated with increased NWABW and indicate the development of modern bottom water.
Controls on the regional distribution of iron – nickel – copper – platinum-group element sulfide mineralization in the eastern Cape Smith Belt, Quebec
Authors: St-Onge M. R. , Lucas S. B.
Published: October 2008

Fe – Ni – Cu – platinum-group element (PGE) mineralization in the eastern Cape Smith Belt (Quebec) is hosted by ultra-mafic and differentiated mafic–ultramafic bodies (high-level sills and dykes, lava lakes, or channelized lava flows). These units of Early Proterozoic age are associated with both volcanic and sedimentary rocks (Povungnituk Group) that accumulated during continental rifting and a transitional continental to oceanic basalt sequence (Chukotat Group). Mineralization is found in two principal horizons. Important deposits occur in the Raglan horizon located near the tectonic boundary between the Povungnituk and Chukotat groups. A second mineralized zone, termed the Delta horizon, occurs within the Povungnituk Group and contains smaller sulfide showings. The distribution of proximal–distal sedimentary facies in the Povungnituk Group represents an important control on the localization, grade, and size of the sulfide deposits and showings. Deposits in the Raglan horizon are associated with relatively distal sedimentary units of the Povungnituk Group. In contrast, the Delta horizon occurs in a more proximal (quartz-rich) facies of the Povungnituk Group which is interlayered with volcanic rocks and marked by a profound decrease in the proportion of fine-grained, sulfuric beds relative to the Raglan horizon. Regional mapping has shown that the Cape Smith Belt is a thin-skinned thrust belt containing imbricates of Povungnituk Group and Chukotat Group rocks and thus controlling the regional extent of the mineralized horizons. Critically, the along-strike continuity of the Raglan horizon (85 km) is determined by the three-dimensional structural geometry of a late thrust fault.
Economic and business dimensionsSearch engine advertising
Authors: Goldfarb Avi , Tucker Catherine
Published: October 2008

Examining a profitable side of the long tail of advertising that is not possible under the traditional broadcast advertising model.
EducationReprogramming college preparatory computer science
Authors: Goode Joanna
Published: October 2008

The college preparatory computer science education curriculum must be improved, beginning with the earliest phases of the process.
Real-world concurrency
Authors: Cantrill Bryan , Bonwick Jeff
Published: October 2008

What does the proliferation of concurrency mean for the software you develop?
Software transactional memory
Authors: Cascaval Calin , Blundell Colin , Michael Maged , Cain Harold W. , Wu Peng , Chiras Stefanie , Chatterjee Siddhartha
Published: October 2008

The promise of STM may likely be undermined by its overheads and workload applicabilities.
The convergence of social and technological networks
Authors: Kleinberg Jon
Published: October 2008

Internet-based data on human interaction connects scientific inquiry like never before.
Technical perspectiveThe Polaris Tableau system
Authors: Gray Jim
Published: October 2008

Jim Gray nominated the Polaris paper for the Research Highlights section and wrote the first draft of this Technical Perspective in November 2006. David Patterson revised the essay in August 2008.
A survey of query log privacy-enhancing techniques from a policy perspective
Authors: Cooper Alissa
Published: October 2008

As popular search engines face the sometimes conflicting interests of protecting privacy while retaining query logs for a variety of uses, numerous technical measures have been suggested to both enhance privacy and preserve at least a portion of the utility of query logs. This article seeks to assess seven of these techniques against three sets of criteria: (1) how well the technique protects privacy, (2) how well the technique preserves the utility of the query logs, and (3) how well the technique might be implemented as a user control. A user control is defined as a mechanism that allows individual Internet users to choose to have the technique applied to their own query logs.