bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swedish randomized controlled trial of cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram revisited: analysis of data according to standard versus modified intention‐to‐treat principle
Authors: AMER‐WÅHLIN ISIS , KJELLMER INGEMAR , MARŠÁL KAREL , OLOFSSON PER , ROSÉN KARL GUSTAF 
Published: May 2011

AbstractObjective. To undertake a renewed analysis of data from the previously published Swedish randomized controlled trial on intrapartum fetal monitoring with cardiotocography (CTG‐only) vs. CTG plus ST analysis of fetal electrocardiogram (CTG+ST), using current standards of intention‐to‐treat (ITT) analysis and to compare the results with those of the modified ITT (mITT) and per protocol analyses. Methods. Renewed extraction of data from the original database including all cases randomized according to primary case allocation (n=5 049). Main outcome measure. Metabolic acidosis in umbilical artery at birth (pH <7.05, base deficit in extracellular fluid >12.0mmol/l) including samples of umbilical vein blood or neonatal blood if umbilical artery blood was missing. Results. The metabolic acidosis rates were 0.66% (17 of 2 565) and 1.33% (33 of 2 484) in the CTG+ST and CTG‐only groups, respectively [relative risk (RR) 0.50; 95% confidence interval (CI) 0.28–0.88; p=0.019]. The original mITT gave RR 0.47, 95%CI 0.25–0.86 (p=0.015), mITT with correction for 10 previously misclassified cases RR 0.48, 95%CI 0.24–0.96 (p=0.038) and per protocol analysis RR 0.40, 95%CI 0.20–0.80 (p=0.009). The level of significance of the difference in metabolic acidosis rates between the two groups remained unchanged in all analyses. Conclusion. Re‐analysis of data according to the ITT principle showed that regardless of the method of analysis, the Swedish randomized controlled trial maintained its ability to demonstrate a significant reduction in metabolic acidosis rate when using CTG+ST analysis for fetal surveillance in labor.
Photocatalytic Reduction of CO2 over Cu‐TiO2/Molecular Sieve 5A Composite
Authors: Srinivas Basavaraju , Shubhamangala Ballamoole , Lalitha Kannekanti , Anil Kumar Reddy Police , Durga Kumari Valluri , Subrahmanyam Machiraju , De Bhudev Ranjan 
Published: May 2011

AbstractTiO2 and different Cu wt% loaded TiO2 (TC0.5–5.0), 10 wt% TC2.0 supported on molecular sieve 5A (10 wt% TC2.0/MS) were prepared by impregnation and solid‐state dispersion methods. The photocatalysts prepared were characterized using XRD, SEM, and UV–Vis DRS, TEM, XPS spectroscopy techniques. Photocatalytic reduction of CO2 in water and alkaline solution are investigated in a batch reactor. The yield of oxalic acid increased notably when TC was supported on molecular sieve. The Cu‐TiO2 supported on molecular sieve catalyst promotes the charge separation that leads to an increase in the selective formation of oxalic acid in addition to methanol, acetic acid and traces of methane. The product formation is due to the high adsorption of CO2, water and product shape selectivity of the composite photocatalyst. The maximum yield of oxalic acid was found to be 65.6 μg h−1 g−1 per cat using 0.2 N NaOH containing solution over 10 wt% TC2.0/MS photocatalyst. The difference in the photocatalytic activity is related to its physicochemical properties.
First evidence of mineralization of petroleum asphaltenes by a strain of Neosartorya fischeri
Authors: Uribe‐Alvarez Cristina , Ayala Marcela , Perezgasga Lucia , Naranjo Leopoldo , Urbina Héctor , Vazquez‐Duhalt Rafael 
Published: May 2011

SummaryA fungal strain isolated from a microbial consortium growing in a natural asphalt lake is able to grow in purified asphaltenes as the only source of carbon and energy. The asphaltenes were rigorously purified in order to avoid contamination from other petroleum fractions. In addition, most of petroporphyrins were removed. The 18S rRNA and β‐tubulin genomic sequences, as well as some morphologic characteristics, indicate that the isolate is Neosartorya fischeri. After 11 weeks of growth, the fungus is able to metabolize 15.5% of the asphaltenic carbon, including 13.2% transformed to CO2. In a medium containing asphaltenes as the sole source of carbon and energy, the fungal isolate produces extracellular laccase activity, which is not detected when the fungus grow in a rich medium. The results obtained in this work clearly demonstrate that there are microorganisms able to metabolize and mineralize asphaltenes, which is considered the most recalcitrant petroleum fraction.
Sunitinib, a Receptor Tyrosine Kinase Inhibitor, Increases Blood Pressure in Rats without Associated Changes in Cardiac Structure and Function
Authors: Blasi E. , Heyen J. , Patyna S. , Hemkens M. , Ramirez D. , John‐Baptiste A. , Steidl‐Nichols J. , McHarg A. 
Published: June 2011

SUMMARYBackground: Sunitinib, a multi‐tyrosine kinase inhibitor has demonstrated clinical activity in advanced renal cell carcinoma and imatinib‐resistant/intolerant gastrointestinal stromal tumor. It has been associated with manageable hypertension and other unique toxicities. Aims: Two nonclinical studies were conducted to determine if sunitinib has direct/indirect effects on cardiac structure/function that may be related to hypertension at clinically relevant exposures. Materials & Methods: Rats received once‐daily vehicle or sunitinib 1 or 10 mg/kg/day (n = 10/group) orally for 4 weeks, followed by 2 weeks off treatment then a 2‐week rechallenge. Blood pressure (BP) and heart rate (HR) were continuously acquired and echocardiograms were obtained weekly. Effects of sunitinib and its metabolite (0.003–0.3 μM) were also evaluated in guinea pig isolated Langendorff‐perfused hearts (n = 4–6 hearts/group). Results: Sunitinib 10 mg/kg/day produced significant (P < 0.05) hemodynamic changes: 24 h average BP increased during initial dosing/rechallenge, with rebound hypotension during the off‐treatment period; 24 h average HR increased during the off‐treatment period, and decreased during rechallenge; no changes in cardiac structure/function were observed. In guinea pig isolated hearts, neither sunitinib nor its metabolite had direct effects on contractility, HR or left ventricular pressure. Discussion & Conclusion: These studies demonstrate that sunitinib/metabolite had no direct effects on cardiac function ex vivo, and that therapeutically relevant concentrations of sunitinib dosed on a “clinical schedule” increased BP in rats without adverse changes in cardiac structure/function.
Aggregatibacter actinomycetemcomitans leukotoxin is post‐translationally modified by addition of either saturated or hydroxylated fatty acyl chains
Authors: Fong K.P. , Tang H.‐Y. , Brown A.C. , Kieba I.R. , Speicher D.W. , Boesze‐Battaglia K. , Lally E.T. 
Published: June 2011

Summary
Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The LtxA is transcribed as a 114‐kDa inactive protoxin with activation being achieved by attachment of short chain fatty acyl groups to internal lysine residues. Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains JP2 and HK1651 and subjected to gas chromatography/mass spectrometry contained palmitoyl (C16:0, 27–29%) and palmitolyl (C16:1 cis Δ9, 43–44%) fatty acyl groups with smaller quantities of myristic (C14:0, 14%) and stearic (C18:0, 12–14%) fatty acids. Liquid chromatography/mass spectrometry of tryptic peptides from acylated and unacylated recombinant LtxA confirmed that Lys562 and Lys687 are the sites of acyl group attachment. During analysis of recombinant LtxA peptides, we observed peptide spectra that were not observed as part of the RTX acylation schemes of either Escherichia coliα‐hemolysin or Bordetella pertussis cyclolysin. Mass calculations of these spectra suggested that LtxA was also modified by the addition of monohydroxylated forms of C14 and C16 acyl groups. Multiple reaction monitoring mass spectrometry identified hydroxymyristic and hydroxypalmitic acids in wild‐type LtxA methyl esters. Single or tandem replacement of Lys562 and Lys687 with Arg blocks acylation, resulting in a >75% decrease in cytotoxicity when compared with wild‐type toxin, suggesting that these post‐translational modifications are playing a critical role in LtxA‐mediated target cell cytotoxicity.
Pseudoeffective and nef classes on abelian varieties
Authors: Debarre Olivier , Ein Lawrence , Lazarsfeld Robert , Voisin Claire 
Published: June 2011

AbstractWe study the cones of pseudoeffective and nef cycles of higher codimension on the self product of an elliptic curve with complex multiplication, and on the product of a very general abelian surface with itself. In both cases, we find for instance the existence of nef classes that are not pseudoeffective, answering in the negative a question raised by Grothendieck in correspondence with Mumford. We also discuss several problems and questions for further investigation.
Aerothermodynamics of
a High-Pressure Turbine Blade With Very High Loading and Vortex
Generators
Authors: Gomes Reinaldo
A. , Niehuis Reinhard 
Published: May 2011

Abstract
AITEB-2 is a project where aerothermal challenges of modern high pressure turbine designs are analyzed. One of the scopes of the project is to allow for new gas turbine designs with less parts and lighter jet engines by increasing the blade pitch and therefore the aerodynamic blade loading. For transonic profiles, this leads to very high velocities on the suction side and shock induced separation is likely to occur. The total pressure loss increase due to flow separation and strong shocks, as well as the underturning of the flow, limits the increase of the blade pitch. In this paper, experiments using a linear turbine blade cascade with high aerodynamic loading are presented. The blade pitch is increased such that at design conditions, a strong separation occurs on the suction side. The experiments were run at high subsonic exit Mach numbers and at Reynolds numbers of 390,000 and 800,000. In order to reduce the flow separation and the aerodynamic losses, air jet vortex generators are used, which create streamwise vortices prior to the separation start. Since in high pressure turbine blades film cooling is widely used, also the influence of film cooling both with and without using vortex generators is analyzed. Film cooling is provided on the suction side by two rows of cylindrical holes. This paper provides an analysis of the influence of different main flow conditions, film cooling, and vortex generators on total pressure loss, heat transfer and film cooling effectiveness. The experiments show that the vortex generators, as well as the film cooling reduce flow separation and total pressure losses. The effects are also seen in the local heat transfer, especially with enhanced heat transport in the region with flow separation. The cases presented in this paper deal with complex flow phenomena, which are challenging to be predicted with modern numerical tools correctly. Therefore, the experimental data serve as a comprehensive database for validation of simulation tools in the AITEB-2 project.
T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis
Authors: Foo Damian Guang , Tay Hui Chien , Siew Jie Yee , Singhal Amit , Camacho Luis , Bifani Pablo , Dartois Véronique , Hervé Maxime 
Published: June 2011

ABSTRACT

Mycobacterium tuberculosis
is the causative agent of a pulmonary epidemic that is estimated to infect one-third of the world's population and that has an increased incidence of multidrug resistance. The evaluation of new chemical entities against
M. tuberculosis
is hampered by the lack of biological tools to help predict efficacy, from early drug development to clinical trials. As the rat is the animal species of choice in the pharmaceutical industry, we have developed a rat model of acute and chronic phases of
M. tuberculosis
infection for drug efficacy testing. In this model, we have evaluated the impact of tuberculosis drugs on T cell response using the enzyme-linked immunospot assay methodology. Infected rats treated with isoniazid (INH) or rifampin (RIF) responded to therapy, the potency of which was comparable to that seen in the mouse. Peripheral blood mononuclear cells from infected rats produced gamma interferon (IFN-γ) in response to RD-1 antigens, such as the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10). A decrease in IFN-γ spot-forming cells (SFCs) was consistently observed in response to drug treatment. In both the acute- and chronic-phase models, the T cell response was more sensitive to ESAT-6 than to CFP-10. The SFC count in response to ESAT-6 appears to be an indicator of bacterial killing in the rat. Collectively, our data suggest that the ESAT-6 response could be used as a potential surrogate of drug efficacy in the rat and that such a readout could help shorten drug testing during preclinical development.
Novel Method for Simultaneous Quantification of Phenotypic Resistance to Maturation, Protease, Reverse Transcriptase, and Integrase HIV Inhibitors Based on 3′Gag(p2/p7/p1/p6)/PR/RT/INT-Recombinant Viruses: a Useful Tool in the Multitarget Era of Antiretroviral Therapy
Authors: Weber Jan , Vazquez Ana C. , Winner Dane , Rose Justine D. , Wylie Doug , Rhea Ariel M. , Henry Kenneth , Pappas Jennifer , Wright Alison , Mohamed Nizar , Gibson Richard , Rodriguez Benigno , Soriano Vicente , King Kevin , Arts Eric J. , Olivo Paul D. , Quiñones-Mateu Miguel E. 
Published: June 2011

ABSTRACTTwenty-six antiretroviral drugs (ARVs), targeting five different steps in the life cycle of the human immunodeficiency virus type 1 (HIV-1), have been approved for the treatment of HIV-1 infection. Accordingly, HIV-1 phenotypic assays based on common cloning technology currently employ three, or possibly four, different recombinant viruses. Here, we describe a system to assess HIV-1 resistance to all drugs targeting the three viral enzymes as well as viral assembly using a single patient-derived, chimeric virus. Patient-derived p2-INT (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) products were PCR amplified as a single fragment (3,428 bp) or two overlapping fragments (1,657 bp and 2,002 bp) and then recombined into a vector containing a near-full-length HIV-1 genome with theSaccharomyces cerevisiaeuracil biosynthesis gene (URA3) replacing the 3,428 bp p2-INT segment (Dudley et al., Biotechniques 46:458–467, 2009). P2-INT-recombinant viruses were employed in drug susceptibility assays to test the activity of protease (PI), nucleoside/nucleotide reverse transcriptase (NRTI), nonnucleoside reverse transcriptase (NNRTI), and integrase strand-transfer (INSTI) inhibitors. Using a single standardized test (ViralARTS HIV), this new technology permits the rapid and automated quantification of phenotypic resistance for all known and candidate antiretroviral drugs targeting all viral enzymes (PR, RT, including polymerase and RNase H activities, and IN), some of the current and potential assembly inhibitors, and any drug targeting Pol or Gag precursor cleavage sites (relevant for PI and maturation inhibitors) This novel assay may be instrumental (i) in the development and clinical assessment of novel ARV drugs and (ii) to monitor patients failing prior complex treatment regimens.
Tripropeptin C Blocks the Lipid Cycle of Cell Wall Biosynthesis by Complex Formation with Undecaprenyl Pyrophosphate
Authors: Hashizume Hideki , Sawa Ryuichi , Harada Shigeko , Igarashi Masayuki , Adachi Hayamitsu , Nishimura Yoshio , Nomoto Akio 
Published: June 2011

ABSTRACTTripropeptin C (TPPC) is a naturally occurring cyclic lipodepsipeptide antibiotic produced by aLysobactersp. TPPC exhibits potent antibacterial activity against methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistantStreptococcus pneumoniae. This antibiotic also inhibits the incorporation ofN-acetylglucosamine into the peptidoglycan ofS. aureusat a 50% inhibitory concentration (IC50) of 0.7 μM, which is proportional to its MIC (0.87 μM; equivalent to 1.0 μg/ml). Treatment of exponential-phaseS. aureuscells with TPPC resulted in accumulation of UDP-MurNAc-pentapeptide in the cytoplasm. The antimicrobial activity of TPPC was weakened by the addition of prenyl pyrophosphates but not by prenyl phosphates, UDP-linked sugars, or the pentapeptide of peptidoglycan. The direct interaction between TPPC and undecaprenyl pyrophosphate (C55-PP) was observed by mass spectrometry and thin-layer chromatography analysis, indicating that TPPC can potentially inhibit C55-PP phosphatase activity, which plays a crucial role in the lipid cycle of peptidoglycan synthesis. As expected, TPPC inhibits this enzymatic reaction at an IC50of 0.03 to 0.1 μMin vitro, as does bacitracin. From the analysis of accumulation of lipid carrier-related compounds, TPPC was found to cause the accumulation of C55-PPin situ, leading to the accumulation of a glycine-containing lipid intermediate. This suggested that the TPPC/C55-PP complex also inhibits the transglycosylation step or flippase activity, adding to the inhibition of C55-PP dephosphorylation. This mode of action is different from that of currently available drugs such as vancomycin, daptomycin, and bacitracin.
Single Mutations in HIV Integrase Confer High-Level Resistance to Raltegravir in Primary Human Macrophages
Authors: Marsden Matthew D. , Avancena Patricia , Kitchen Christina M. R. , Hubbard Trish , Zack Jerome A. 
Published: June 2011

ABSTRACTCD4+T cells and macrophages are the primary target cells for HIVin vivo, and antiretroviral drugs can vary in their ability to inhibit the infection of these different cell types. Resistance pathways to the HIV integrase inhibitor raltegravir have previously been investigated in T cells. Primary raltegravir resistance mutations, most often at integrase amino acid position 148 or 155, afford some resistance to the drug. The acquisition of pathway-specific secondary mutations then provides higher-level resistance to viruses infecting T cells. We show here that during macrophage infection, the presence of a single primary raltegravir resistance mutation (Q148H, Q148R, N155H, or N155S) is sufficient to provide resistance to raltegravir comparable to that seen in viruses expressing both primary and secondary mutations in costimulated CD4+T cells. These data implicate macrophages as a potentialin vivoreservoir that may facilitate the development of resistance to raltegravir. Notably, the newer integrase inhibitor MK-2048 effectively suppressed the infection of all raltegravir-resistant viruses in both T cells and macrophages, indicating that more recently developed integrase inhibitors are capable of inhibiting infection in both major HIV cellular reservoirs, even in patients harboring raltegravir-resistant viruses.
In Vitro
Efficacy of Antibiotics Commonly Used To Treat Human Plague against Intracellular
Yersinia pestis
Authors: Wendte Jered M. , Ponnusamy Duraisamy , Reiber Deanna , Blair Jeffrey L. , Clinkenbeard Kenneth D. 
Published: June 2011

ABSTRACT

Yersinia pestis
initiates infection as a facultative intracellular parasite in host macrophages; however, little is known about the efficacy of antibiotics commonly used to treat human plague against intracellular
Y. pestis
. Intracellular minimal bactericidal concentrations (MBCs) were determined using a high-throughput broth microdilution assay in which human THP-1 macrophage-like cells were infected with
Y. pestis
strain KIM6-2053.1+ and exposed to 2-fold serial dilutions of antibiotics for 24 h in 96-well plates. The numbers of CFU, upon which minimal bactericidal concentrations were based, were determined by counting “microcolonies” in wells of 96-well plates following lysis of tissue culture cells to release surviving
Y. pestis
, replica dilution, and plating in soft tryptic soy broth agar. For THP-1 cells, streptomycin and ciprofloxacin had comparable efficacies for intra- and extracellular
Y. pestis
, but the MBCs for chloramphenicol, gentamicin, doxycycline, and amoxicillin were two-, three-, four-, and five 2-fold serial dilutions greater, respectively, for intracellular than for extracellular
Y. pestis
. During the initial stage of plague, intracellular
Y. pestis
may be less susceptible to antibiotic killing by particular antibiotics recommended for treatment of plague, such as gentamicin or doxycycline, whereas others, such as streptomycin and ciprofloxacin, may have similar efficacies against extracellular or intracellular
Y. pestis
. This may be of particular importance in the selection of antibiotics for prophylactic treatment in the case of a bioterrorism event.
Expression of Toll-Like Receptor 4 and Downstream Effectors in Selected Cecal Cell Subpopulations of Chicks Resistant or Susceptible to Salmonella Carrier State
Authors: Chaussé Anne-Marie , Grépinet Olivier , Bottreau Elisabeth , Le Vern Yves , Menanteau Pierrette , Trotereau Jérome , Robert Vincent , Wu Zhiguang , Kerboeuf Dominique , Beaumont Catherine , Velge Philippe 
Published: June 2011

ABSTRACT

Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide from Gram-negative bacteria, plays a major role in resistance of mice and humans to
Salmonella
infection. In chickens,
Salmonella
may establish a carrier state whereby bacteria are able to persist in the host organism without triggering clinical signs. Based on cellular morphological parameters, we developed a method, without using antibodies, to separate three cecal cell subpopulations: lymphocytes, enterocytes, and a population encompassing multiple cell types. We analyzed the mRNA expression of TLR4, interleukin-1β (IL-1β), IL-8, IL-12, and lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) in cecal subpopulations of chicks from inbred lines resistant or susceptible to the carrier state infected with
Salmonella enterica
serovar Enteritidis. The results showed that resistance to the carrier state in chicks is associated with a larger percentage of lymphocytes and with higher levels of expression of TLR4 and IL-8 at homeostasis in the three cell subpopulations, as well as with a higher level of expression of LITAF in lymphocytes during the carrier state. In contrast to the early phase of infection, the carrier state is characterized by no major cell recruitment differences between infected and noninfected animals and no significant modification in terms of TLR4, IL-1β, IL-8, IL-12, and LITAF expression in all cell subpopulations measured. However, TLR4 expression increased in the lymphocytes of chicks from the susceptible line, reaching the same level as that in infected chicks from the resistant line. These observations suggest that the carrier state is characterized by a lack of immune activation and highlight the interest of working at the level of the cell population rather than that of the organ.