bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emphysema Mediated by Lung Overexpression of ADAM10
Authors: Saitoh Hiroki , Leopold Philip L. , Harvey Ben‐Gary , O'Connor Timothy P. , Worgall Stefan , Hackett Neil R. , Crystal Ronald G. 
Published: February 2009

AbstractCigarette smoking is the major risk factor for emphysema, a disorder of the lung parenchyma characterized by destruction of the alveolar walls. Current concepts of the pathogenesis of emphysema hold that the destruction of the lung parenchyma results, in part, from a local imbalance of proteases and antiproteases. Based on the knowledge that human alveolar macrophages express ADAM 10, a protease capable of destroying basement membrane collagen but not previously implicated in emphysema, we used adenovirus‐mediated lung expression of ADAM 10 in a mouse model to assess whether an increased burden of ADAM 10 was capable of inducing emphysema. To assess this, the human ADAM 10 cDNA under control of a constitutive promoter was inserted into an adenovirus gene transfer vector (AdhADAMlO), and the vector (1011 particle units) administered to the respiratory tract of wild type C57BI/6 mice. Lung levels of ADAM 10 mRNAand protein were upregulated following AdhADAMlO administration. After 8 weeks, quantitative morphometry of the lung parenchyma demonstrated that AdhADAMlO administration induced emphysema (mean linear intercept of 60.6 + 1.3 μm compared with 55.6 + 0.8 in mice treated with a control vector, p < 0.003). These results suggest a role of ADAM 10 in the pathogenesis of emphysema, adding to the list of proteases expressed in the lung that are capable of contributing to the development of lung destruction.
c‐Kit+ Bone Marrow Stem Cells Differentiate into Functional Cardiac Myocytes
Authors: Kubo Hajime , Berretta Remus M. , Jaleel Naser , Angert David , Houser Steven R. 
Published: February 2009

AbstractThe utility of bone marrow cells (BMCs) to regenerate cardiac myocytes is controversial. The present study examined the capacity of different types of BMCs to generate functional cardiac myocytes. Isolated c‐kit+ BMCs (BMSCs), c‐kit+ and crude BMCs from the adult feline femur were membrane stained with PKH26 dye or infected with a control enhanced green fluorescence protein transcript (EGFP)‐adenovirus prior to co‐culture upon neonatal rat ventricular myocytes (NRVM). Co‐cultured cells were immuno‐stained for c‐kit, α‐tropomyosin, α‐actinin, connexin 43 (C×43) and Ki67 and analyzed with confocal microscopy. Electrophysiology of BMSC derived myocytes were compared to NRVMs within the same culture dish. Gap junction function was analyzed by fluorescence recovery after photo‐bleaching (FRAP). BMCs proliferated and differentiated into cardiac myocytes during the first 48 hours of co‐culturing. These newly formed cardiac myocytes were able to contract spontaneously or synchronously with neighboring NRVMs. The myogenic rate of c‐kit+ BMSCs was significantly greater than c‐kit+ and crude BMCs (41.2 ± 2.1, 6.1 ± 1.2, and 17.1 ± 1.5%, respectively). The newly formed cardiac myocytes exhibited an immature electrophysiological phenotype until they became electrically coupled to NRVMs through functional gap junctions. BMSCs did not become functional myocytes in the absence of NRVMs. In conclusion, c‐kit+ BMSCs have the ability to transdifferentiate into functional cardiac myocytes.
A Paradise Within? Mary Astell, Sarah Scott and the Limits of Utopia
Authors: DEVEREAUX JOHANNA 
Published: February 2009

AbstractMary Astell and Sarah Scott's feminist texts A Serious Proposal and Milennium Hall, written sixty years apart from each other, both espouse theories of feminine retreat and education. However, the changing philosophical context in which these texts were written, from the 1690s Cambridge Platonists to the mid‐century theorists of sociable benevolence, makes them very different in their intellectual perspectives. The feminist possibilities identified by Astell and Scott arise from their responses to contemporary male philosophers. Their texts, far from straightforwardly utopian, identify how through the correct kind of philosophical education, women might learn to be of social and spiritual worth.
‘At This Period Peculiarly Necessary’: The Republication of Milton's Political Tracts in the 1790s
Authors: CRAWFORD JOSEPH 
Published: February 2009

AbstractThis article investigates the republication of Milton's political pamphlets in the 1790s, locating them in their context as part of the ‘pamphlet wars’ that followed the outbreak of the French Revolution. It discusses the reception history of Milton's political works between his death and the French Revolution, demonstrating their extreme rarity and low cultural profile before 1790. It then gives a detailed account of each of the reprinted Milton pamphlets of which any copies have survived, analysing their paratexts to explore how and why these 150‐year‐old pamphlets were deployed as contributions to the political and ideological debates of the 1790s.
Modified quantum dimensions and re-normalized link invariants
Authors: Geer Nathan , Patureau-Mirand Bertrand , Turaev Vladimir 
Published: February 2009

AbstractIn this paper we give a re-normalization of the Reshetikhin–Turaev quantum invariants of links, using modified quantum dimensions. In the case of simple Lie algebras these modified quantum dimensions are proportional to the usual quantum dimensions. More interestingly, we give two examples where the usual quantum dimensions vanish but the modified quantum dimensions are non-zero and lead to non-trivial link invariants. The first of these examples is a class of invariants arising from Lie superalgebras previously defined by the first two authors. These link invariants are multivariable and generalize the multivariable Alexander polynomial. The second example is a hierarchy of link invariants arising from nilpotent representations of quantized$\mathfrak {sl}(2)$at a root of unity. These invariants contain Kashaev’s quantum dilogarithm invariants of knots.
The exceptional zero conjecture for Hilbert modular forms
Authors: Mok Chung Pang 
Published: February 2009

AbstractUsing ap-adic analogue of the convolution method of Rankin–Selberg and Shimura, we construct the two-variablep-adicL-function of a Hida family of Hilbert modular eigenforms of parallel weight. It is shown that the conditions of Greenberg–Stevens [R. Greenberg and G. Stevens,p-adic L-functions and p-adic periods of modular forms, Invent. Math.111(1993), 407–447] are satisfied, from which we deduce special cases of the Mazur–Tate–Teitelbaum conjecture in the Hilbert modular setting.
Tropical fans and the moduli spaces of tropical curves
Authors: Gathmann Andreas , Kerber Michael , Markwig Hannah 
Published: February 2009

AbstractWe give a rigorous definition of tropical fans (the ‘local building blocks for tropical varieties’) and their morphisms. For a morphism of tropical fans of the same dimension we show that the number of inverse images (counted with suitable tropical multiplicities) of a point in the target does not depend on the chosen point; a statement that can be viewed as one of the important first steps of tropical intersection theory. As an application we consider the moduli spaces of rational tropical curves (both abstract and in some ℝr) together with the evaluation and forgetful morphisms. Using our results this gives new, easy and unified proofs of various tropical independence statements, e.g. of the fact that the numbers of rational tropical curves (in any ℝr) through given points are independent of the points.
Metabolism of an Alkyl Polyamine Analog by a Polyamine Oxidase from the Microsporidian
Encephalitozoon cuniculi
Authors: Bacchi Cyrus J. , Yarlett Nigel , Faciane Evangeline , Bi Xiangdong , Rattendi Donna , Weiss Louis M. , Woster Patrick M. 
Published: February 2009

ABSTRACT

Encephalitozoon cuniculi
is a microsporidium responsible for systemic illness in mammals. In the course of developing leads to new therapy for microsporidiosis, we found that a bis(phenylbenzyl)3-7-3 analog of spermine, 1,15-bis{
N
-[
o
-(phenyl)benzylamino}-4,12-diazapentadecane (BW-1), was a substrate for an
E. cuniculi
amine oxidase activity. The primary natural substrate for this oxidase activity was
N
′-acetylspermine, but BW-1 had activity comparable to that of the substrate. As the sole substrate, BW-1 gave linear reaction rates over 15 min and
K

m

of 2 μM. In the presence of
N
′-acetylspermine, BW-1 acted as a competitive inhibitor of oxidase activity and may be a subversive substrate, resulting in increased peroxide production. By use of
13
C-labeled BW-1 as a substrate and nuclear magnetic resonance analysis, two products were determined to be oxidative metabolites, a hydrated aldehyde or dicarboxylate and 2(phenyl)benzylamine. These products were detected after exposure of
13
C-labeled BW-1 to
E. cuniculi
preemergent spore preparations and to uninfected host cells. In previous studies, BW-1 was curative in a rodent model of infection with
E. cuniculi
. The results in this study demonstrate competitive inhibition of oxidase activity by BW-1 and support further studies of this oxidase activity by the parasite and host.
A Small-Molecule Dengue Virus Entry Inhibitor
Authors: Wang Qing-Yin , Patel Sejal J. , Vangrevelinghe Eric , Xu Hao Ying , Rao Ranga , Jaber Deana , Schul Wouter , Gu Feng , Heudi Olivier , Ma Ngai Ling , Poh Mee Kian , Phong Wai Yee , Keller Thomas H. , Jacoby Edgar , Vasudevan Subhash G. 
Published: February 2009

ABSTRACT
The incidence of dengue fever epidemics has increased dramatically over the last few decades. However, no vaccine or antiviral therapies are available. Therefore, the need for safe and effective antiviral drugs has become imperative. The entry of dengue virus into a host cell is mediated by its major envelope (E) protein. The crystal structure of the E protein reveals a hydrophobic pocket that is presumably important for low-pH-mediated membrane fusion. High-throughput docking with this hydrophobic pocket was performed, and hits were evaluated in cell-based assays. Compound 6 was identified as one of the inhibitors and had an average 50% effective concentration of 119 nM against dengue virus serotype 2 in a human cell line. Mechanism-of-action studies demonstrated that compound 6 acts at an early stage during dengue virus infection. It arrests dengue virus in vesicles that colocalize with endocytosed dextran and inhibits NS3 expression. The inhibitors described in this report can serve as molecular probes for the study of the entry of flavivirus into host cells.
Prospectively Validated Dosing Nomograms for Maximizing the Pharmacodynamics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients
Authors: Pea Federico , Furlanut Mario , Negri Camilla , Pavan Federica , Crapis Massimo , Cristini Francesco , Viale Pierluigi 
Published: February 2009

ABSTRACT

The efficacy of vancomycin against methicillin-resistant
Staphylococcus aureus
(MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL
Cr
) estimates for use in daily clinical practice to target the steady-state concentrations (
C
ss
s) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CL
v
) and CL
Cr
was retrospectively assessed in a cohort of critically ill patients (group 1,
n
= 70) to create a formula for dosage calculation to target
C
ss
at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2,
n
= 63) by comparison of the observed and the predicted
C
ss
s. A significant relationship between CL
v
and CL
Cr
was observed in group 1 (
P
< 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 × CL
Cr
(ml/min) + 0.94] × target C
ss
× (24/1,000)} led to a significant correlation between the observed and the predicted
C
ss
s (
r
= 0.80,
P
< 0.001). Two dosing nomograms based on CL
Cr
were created to target the vancomycin
C
ss
at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin.
Functional Characterization of the σ
B
-Dependent
yabJ
-
spoVG
Operon in
Staphylococcus aureus
: Role in Methicillin and Glycopeptide Resistance
Authors: Schulthess Bettina , Meier Stefan , Homerova Dagmar , Goerke Christiane , Wolz Christiane , Kormanec Jan , Berger-Bächi Brigitte , Bischoff Markus 
Published: February 2009

ABSTRACT

The alternative sigma factor σ
B
of
Staphylococcus aureus
controls the expression of multiple genes, including virulence determinants and global regulators; promotes capsule production; and increases the resistance levels of methicillin-resistant
S. aureus
(MRSA) and glycopeptide-intermediate-resistant
S. aureus
(GISA) strains. We show here that deletion of the σ
B
-controlled
yabJ-spoVG
operon, which codes for potential downstream regulators of σ
B
, abolished capsule synthesis and reduced resistance in MRSA and GISA to the same extent that σ
B
inactivation did. Introduction of the
yabJ-spoVG
operon in
trans
restored the original phenotype. By genetic manipulations, we show that SpoVG but not YabJ is required for complementation. We therefore postulate that SpoVG is the major factor of the
yabJ-spoVG
operon required in
S. aureus
for capsule formation and antibiotic resistance.
Pharmacokinetics of EDP-420 after Ascending Single Oral Doses in Healthy Adult Volunteers
Authors: Jiang Li-Juan , Wang Michelle , Or Yat Sun 
Published: February 2009

ABSTRACT

EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including
Haemophilus influenzae
, atypical organisms (e.g.,
Chlamydia pneumoniae, Mycoplasma pneumoniae
, and
Legionella pneumophila
), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 μg·h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections.
Emergence of Plasmid-Mediated Quinolone Resistance among Non-Typhi
Salmonella enterica
Isolates from Humans in the United States
Authors: Sjölund-Karlsson Maria , Folster Jason P. , Pecic Gary , Joyce Kevin , Medalla Felicita , Rickert Regan , Whichard Jean M. 
Published: February 2009

ABSTRACT

Plasmid-mediated quinolone resistance determinants are emerging among gram-negative pathogens. Here we report results of a retrospective study investigating the prevalence of
aac(6′)-Ib-cr
,
qepA
, and
qnr
genes among 19,010 human isolates of non-Typhi
Salmonella enterica
collected in the United States from 1996 to 2006.
Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress
Staphylococcus aureus
Production of Toxic Shock Syndrome Toxin 1
Authors: McNamara Peter J. , Syverson Rae Ellen , Milligan-Myhre Kathy , Frolova Olga , Schroeder Sarah , Kidder Joshua , Hoang Thanh , Proctor Richard A. 
Published: February 2009

ABSTRACT

Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of
Staphylococcus aureus
toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of
S. aureus
and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (
e.g
. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced
S. aureus
TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.
Serial Plasma Voriconazole Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Trifilio Steven M. , Yarnold Paul R. , Scheetz Marc H. , Pi Judy , Pennick Gennethel , Mehta Jayesh 
Published: February 2009

ABSTRACT

Plasma voriconazole concentrations vary considerably between patients receiving standard dosing, and trough voriconazole concentrations are known to affect efficacy and toxicity. Temporal variations in serial plasma voriconazole concentrations through the course of therapy in hematopoietic stem cell transplantation patients has not been carefully described. Paired voriconazole concentrations in 64 patients were studied to determine the predictability of the second concentration based on the first. The difference between the two values was ≤5% in six patients. In 25 patients, the second concentration was higher by a median of 40%. In 33 patients, the subsequent concentration was lower by a median of 59%. For patients with an initial concentration of <2 μg/ml, the correlation between the two values was poor (
r
= 0.24;
P
< 0.17). For those with an initial concentration of ≥2 μg/ml, the correlation was good (
r
= 0.72;
P
< 0.0001). There was no relationship between the magnitude of the change and the time elapsing between the two measurements. Among the 43 patients who had an initial concentration of ≥1 μg/ml, the two voriconazole measurements were strongly correlated (
r
= 0.66,
P
< 0.0001), but only 67% had a voriconazole serum concentration of ≥1 μg/ml on the second measurement. No studied variables were reliable predictors in identifying concentrations above or below 1 or 2 μg/ml. Our data suggest that variations in voriconazole concentrations are unpredictable despite standard dosing, and the acceptability of a concentration on one occasion cannot be extrapolated to future concentrations in the same patient. This suggests that ongoing therapeutic drug monitoring and dose adjustment may be beneficial in patients requiring prolonged voriconazole therapy.
Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of
Leishmania major
Infection in Susceptible BALB/c Mice
Authors: Jaafari Mahmoud R. , Bavarsad Neda , Fazly Bazzaz Bibi Sedigheh , Samiei Afshin , Soroush Dina , Ghorbani Serajodin , Lotfi Heravi Mohammad M. , Khamesipour Ali 
Published: February 2009

ABSTRACT

The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in
Leishmania major
-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against
L. major
promastigotes in culture were 65.32 and 59.73 μg/ml, respectively, and those against
L. major
amastigotes in macrophages were 24.64 and 26.44 μg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat
L. major
lesions on BALB/c mice, and the results showed a significantly (
P
< 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (
P
< 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.
Fenticonazole Activity Measured by the Methods of the European Committee on Antimicrobial Susceptibility Testing and CLSI against 260
Candida
Vulvovaginitis Isolates from Two European Regions and Annotations on the Prevalent Genotypes
Authors: Antonopoulou Stavroula , Aoun Michel , Alexopoulos Evangelos C. , Baka Stavroula , Logothetis Emanuel , Kalambokas Theodoros , Zannos Andreas , Papadias Konstantine , Grigoriou Odysseas , Kouskouni Evangelia , Velegraki Aristea 
Published: February 2009

ABSTRACT

The activity of fenticonazole was studied against 260 West and Southeast European vulvovaginal candidiasis isolates, and low MICs were displayed. Fenticonazole was assessed by European Committee on Antimicrobial Susceptibility Testing and CLSI microdilution methods for the first time, and the results showed excellent agreement (97%) and significant interclass correlation coefficient (
P
< 0.0001). Also, the levels of agreement for the results for itraconazole, fluconazole, and ketoconazole were 84%, 90%, and 98% (
P
< 0.0001), respectively. Multilocus typing by PCR fingerprinting and subsequent cluster analysis delineated geographically associated alignments for
Candida albicans
and fluconazole resistance-related clusters for
Candida glabrata
.