bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Physicochemical, Antifungal, and Toxic Properties of Two Liposomal Amphotericin B Products
Authors: Olson Jon A. , Adler-Moore Jill P. , Jensen Gerard M. , Schwartz Julie , Dignani M. Cecilia , Proffitt Richard T. 
Published: October 2007

ABSTRACTSmall unilamellar amphotericin B liposomes can reduce the toxicity of amphotericin B. In this study, we compared the physical, antifungal, pharmocokinetic, and toxic properties of two liposomal amphotericin B products, AmBisome and Anfogen, that have the same chemical composition but are manufactured differently. In vitro tests included determinations of the MICs and the concentrations causing the release of 50% of the intracellular potassium from red blood cells (K50values) to assess toxicity. The 50% lethal dose (LD50) was evaluated by using uninfected C57BL/6 mice and single intravenous (i.v.) doses of 1 to 100 mg/kg of body weight. Multiple i.v. dosing over 18 days was performed with 0.5, 1.0, or 5.0 mg of Anfogen/kg or 1.0, 5.0, or 25 mg of AmBisome/kg to evaluate chronic toxicity. DBA/2 mice were infected intranasally with 2.5 × 106Aspergillus fumigatusconidia, treated for 3 or 4 days with 3.0, 5.0, or 7.5 mg of Anfogen/kg or 3, 5, 7.5, or 15 mg of AmBisome/kg, and evaluated to assess the toxicity of the drugs to the kidneys (by measurement of blood urea nitrogen and creatinine levels and histopathology) and the drug efficacy. The median particle size was 77.8 nm for AmBisome and 111.5 nm for Anfogen. In vitro K50values were significantly lower for Anfogen (0.9 μg/ml) than for AmBisome (20 μg/ml), and the LD50of AmBisome was >100 mg/kg, versus 10 mg of Anfogen/kg. There was significant renal tubular necrosis in uninfected and infected mice given Anfogen but no tubular necrosis in AmBisome-treated mice. AmBisome at 7.5 or 15 mg/kg was also more efficacious than 7.5 mg of Anfogen/kg for the treatment of pulmonary aspergillosis, based on survival and weight loss data and numbers of CFU per gram of lung. In conclusion, the efficacy and toxicity of these two liposomal amphotericin B products were significantly different, and thus, the products were not comparable.
Madurahydroxylactone Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and RNase H
Authors: Marchand Christophe , Beutler John A. , Wamiru Antony , Budihas Scott , Möllmann Ute , Heinisch Lothar , Mellors John W. , Le Grice Stuart F. , Pommier Yves 
Published: October 2007

ABSTRACT
A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors.
Toluidine Blue-Mediated Photodynamic Effects on Staphylococcal Biofilms
Authors: Sharma Mrinalini , Visai Livia , Bragheri Francesca , Cristiani Ilaria , Gupta Pradeep Kumar , Speziale Pietro 
Published: October 2007

ABSTRACT

Staphylococci are important causes of nosocomial and medical-device-related infections. Their virulence is attributed to the elaboration of biofilms that protect the organisms from immune system clearance and to increased resistance to phagocytosis and antibiotics. Photodynamic treatment (PDT) has been proposed as an alternative approach for the inactivation of bacteria in biofilms. In this study, we have investigated the effect of the photodynamic action of toluidine blue O (TBO) on the viability and structure of biofilms of
Staphylococcus epidermidis
and of a methicillin-resistant
Staphylococcus aureus
strain. Significant inactivation of cells was observed when staphylococcal biofilms were exposed to TBO and laser simultaneously. The effect was found to be light dose dependent. Confocal laser scanning microscopic study suggested damage to bacterial cell membranes in photodynamically treated biofilms. In addition, scanning electron microscopy provided direct evidence for the disruption of biofilm structure and a decrease in cell numbers in photodynamically treated biofilms. Furthermore, the treatment of biofilms with tetrasodium EDTA followed by PDT enhanced the photodynamic efficacy of TBO in
S. epidermidis
, but not in
S. aureus
, biofilms. The results suggest that photodynamic treatment may be a useful approach for the inactivation of staphylococcal biofilms adhering to solid surfaces of medical implants.
Recombinant Holotoxoid Vaccine against Botulism
Authors: Pier Christina L. , Tepp William H. , Bradshaw Marite , Johnson Eric A. , Barbieri Joseph T. , Baldwin Michael R. 
Published: October 2007

ABSTRACTThe botulinum neurotoxins (BoNT) are the most toxic proteins for humans and designated “Category A Select Agents.” The current vaccine against botulism is in limited supply, and there is a need to develop new vaccine strategies. A recombinant BoNT/A toxoid was produced inClostridium botulinumthat contained a double amino acid substitution, R363A Y365F (termed BoNT/ARYM). BoNT/ARYMwas noncatalytic for SNAP25 and nontoxic for mice. Immunization with BoNT/ARYMprotected mice from challenge at levels that were similar to chemically inactivated BoNT/A toxoid. BoNT/ARYMelicited an immune response against the light-chain and heavy-chain components of the toxin. Neutralizing anti-BoNT/ARYMsera blocked BoNT toxicity in primary cortical neurons and blocked ganglioside binding by the heavy chain. BoNT/ARYMrepresents a viable vaccine candidate for a holotoxoid against botulism.
Host Transmission of
Salmonella enterica
Serovar Typhimurium Is Controlled by Virulence Factors and Indigenous Intestinal Microbiota
Authors: Lawley Trevor D. , Bouley Donna M. , Hoy Yana E. , Gerke Christine , Relman David A. , Monack Denise M. 
Published: October 2007

ABSTRACT

Transmission is an essential stage of a pathogen's life cycle and remains poorly understood. We describe here a model in which persistently infected 129X1/SvJ mice provide a natural model of
Salmonella enterica
serovar Typhimurium transmission. In this model only a subset of the infected mice, termed supershedders, shed high levels (>10
8
CFU/g) of
Salmonella
serovar Typhimurium in their feces and, as a result, rapidly transmit infection. While most
Salmonella
serovar Typhimurium-infected mice show signs of intestinal inflammation, only supershedder mice develop colitis. Development of the supershedder phenotype depends on the virulence determinants
Salmonella
pathogenicity islands 1 and 2, and it is characterized by mucosal invasion and, importantly, high luminal abundance of
Salmonella
serovar Typhimurium within the colon. Immunosuppression of infected mice does not induce the supershedder phenotype, demonstrating that the immune response is not the main determinant of
Salmonella
serovar Typhimurium levels within the colon. In contrast, treatment of mice with antibiotics that alter the health-associated indigenous intestinal microbiota rapidly induces the supershedder phenotype in infected mice and predisposes uninfected mice to the supershedder phenotype for several days. These results demonstrate that the intestinal microbiota plays a critical role in controlling
Salmonella
serovar Typhimurium infection, disease, and transmissibility. This novel model should facilitate the study of host, pathogen, and intestinal microbiota factors that contribute to infectious disease transmission.
Outer Membrane Protein Sequence Variation in Lambs Experimentally Infected with
Anaplasma phagocytophilum
Authors: Granquist Erik G. , Stuen Snorre , Lundgren Anna M. , Bråten Margrethe , Barbet Anthony F. 
Published: October 2007

ABSTRACT

Anaplasma phagocytophilum
has long been known to cause tick-borne fever in ruminants and has been identified more recently as the causative agent of the emerging disease human granulocytic anaplasmosis. The related organism
Anaplasma marginale
uses gene conversion of the expression site for two major outer membrane proteins (OMPs) to generate extensive sequence and antigenic variation in these OMPs. This is thought to present a continuously varying repertoire of epitopes to the mammalian host and allow disease persistence. Recent genomic and structural data on human strains of
A
.
phagocytophilum
, together with animal studies in model systems, have implicated an orthologous OMP of
A
.
phagocytophilum
in a similar mechanism of variation. However, to date there has been little investigation of the mechanisms of antigenic variation or disease persistence in hosts naturally infected with field strains of
A
.
phagocytophilum
. Approximately 300,000 lambs in Norway suffer severe disease caused by
A
.
phagocytophilum
annually. We show here the persistent and cyclic nature of infection in these animals that is accompanied by loosely programmed sequence variation of the major OMP expression site in each rickettsemic peak. These data will allow analysis of interactions between
A
.
phagocytophilum
and the host immune system in naturally occurring persistent infections and provide an important comparison with enduring infections of cattle caused by
A
.
marginale
.
A Comparison of DNA Copy Number Profiling Platforms
Authors: Greshock Joel , Feng Bin , Nogueira Cristina , Ivanova Elena , Perna Ilana , Nathanson Katherine , Protopopov Alexei , Weber Barbara L. , Chin Lynda 
Published: October 2007

Abstract
The accurate mapping of recurring DNA copy number aberrations (CNAs), a hallmark feature of the cancer genome, has facilitated the discovery of tumor suppressor genes and oncogenes. Microarray-based assays designed to detect these chromosomal copy number alterations on a genome-wide and high-resolution scale have emerged as a cornerstone technology in the genomic era. The diversity of commercially available platforms prompted a systematic comparison of five copy number profiling assays for their ability to detect 2-fold copy number gain and loss (4n or 1n, respectively) as well as focal high-amplitude CNAs. Here, using a collection of established human melanoma cell lines, we defined the reproducibility, absolute signals, signal to noise, and false-positive and false-negative rates for each of the five assays against ground truth defined by spectral karyotyping, in addition to comparing the concordance of CNA detection by two high-resolution Agilent and Affymetrix microarray platforms. Our analyses concluded that the Agilent's 60-mer oligonucleotide microarray with probe design optimized for genomic hybridization offers the highest sensitivity and specificity (area under receiver operator characteristic curve &gt;0.99), whereas Affymetrix's single nucleotide polymorphism microarray seems to offer better detection of CNAs in gene-poor regions. Availability of these comparison results should guide study design decisions and facilitate further computational development. [Cancer Res 2007;67(21):10173–80]
Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study
Authors: Yang Xiaohong R. , Pfeiffer Ruth M. , Garcia-Closas Montserrat , Rimm David L. , Lissowska Jolanta , Brinton Louise A. , Peplonska Beata , Hewitt Stephen M. , Cartun Richard W. , Mandich Daniza , Sasano Hironobu , Evans Dean B. , Sutter Thomas R. , Sherman Mark E. 
Published: October 2007

AbstractThe objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns (factors): “nuclear receptor factor” [estrogen receptor (ER)-α, progesterone receptor, androgen receptor, cyclin D1, and aromatase], “estrogen metabolism/ER-β factor” (ER-β, peroxisome proliferator-activated receptor-γ, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), “HER2 factor” (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and “proliferation factor” (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-β factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity = 0.01), and older age at menopause (P heterogeneity = 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity &lt; 0.0001), and in contrast to the estrogen metabolism/ER-β factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-β and enzymes involved in hormone metabolism. [Cancer Res 2007;67(21):10608–17]
Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction
Authors: Nicholls Stephen J. , Wang Zeneng , Koeth Robert , Levison Bruce , DelFraino Brian , Dzavik Vladimir , Griffith Owen W. , Hathaway David , Panza Julio A. , Nissen Steven E. , Hochman Judith S. , Hazen Stanley L. 
Published: October 2007

Background—It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction.Methods and Results—Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (n=79) and age- and gender-matched patients with coronary artery disease and normal left ventricular function (n=79). CS patients had higher levels of asymmetric dimethylarginine (ADMA;P<0.0001), symmetric dimethylarginine (P<0.0001), monomethylarginine (P=0.0003), nitrotyrosine (P<0.0001), and bromotyrosine (P<0.0001) and lower levels of arginine (P<0.0001), ratio of arginine to ornithine (P=0.03), and ratio of arginine to ornithine plus citrulline) (P=0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3;P=0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients.Conclusions—CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality.
Humans, Nature and God: Exploring Images of Their Interrelationships in Victoria, Canada
Authors: de Groot Mirjam , van den Born Riyan 
Published: October 2007

AbstractThis study explores visions of nature among five populations in Victoria, a small city in British Columbia, Canada: Christians, Muslims, Native Americans, Buddhists, and secularists. Each group was asked to express their view of the human relationships with nature based upon four approaches: mastery over nature, stewardship in regard to the creation, a partner, or a participant in the processes of nature. The first model, in which humans wield hierarchical power and mastery over nature, was rejected by all groups. Christians and Muslims adhered to the stewardship image of the human/nature relationship, while Buddhists and Native Americans considered themselves to be participants in nature. The secularists made combinations of the approaches to exemplify their view. Twenty-seven individuals participated in extensive interviews as part of this study, which also included a small scale written survey of fifty-three persons.
The Soft Power Differential: Network Communication and Mass Communication in Public Diplomacy
Authors:   Zaharna
Published: October 2007

AbstractThis study posits that advocacy NGOs are successfully creating soft power using relational, network-centric public diplomacy. The United States, on the other hand, struggles to wield its soft power and continues to apply the outdated information, media-driven approach to its public diplomacy efforts. This article suggests that a public diplomacy strategy that tailors itself to the dynamics of the international context will prove most effective in achieving its tactical goals. The first section highlights changes in the international arena since the end of the Cold War and their corresponding impact on communication dynamics. The second section delineates the critical features that define mass communication and the network communication approach. The third examines specific applications of both communication approaches, drawing on examples from the US's post-'9/11' public diplomacy in the Arab world and those from advocacy NGOs. The paper concludes with implications of the differences between wielding versus creating soft power for state actors.
Evaluating Public Diplomacy Programmes
Authors: Pahlavi Pierre 
Published: October 2007

AbstractThe new operational environment generated by the mass media revolution and the advent of the global information society lays the ground for a generalized re-emergence of public diplomacy (PD). After having been dismantled during the 1990s, this branch of foreign policy is undergoing a redevelopment phase within the chancelleries of many states around the globe. The growing salience of public opinion and the exponential development of the new information and communication technologies predispose this diplomacy of persuasion to play an increasing role at the forefront of twenty-first century international relations.Inspite of the increased importance that public diplomacy is acquiring, the question of its real effectiveness nevertheless remains unanswered. For the moment, governments are still unable to determine to what extent their PD initiatives are able to influence foreign audiences or contribute to the achievement of their foreign policy goals. Without a valid evaluation tool, PD will remain condemned to play a secondary role within states' foreign policy systems. This article addresses the main aspects of this issue by analysing the many technical and methodological problems that are attached to PD evaluation, exploring research avenues that could remedy these gaps, and thus helping to resolve a problem that is still underestimated yet bound to become increasingly important in the 'hyper-media' age of international relations.
The Ties that Bind: Dutch-American Relations, US Public Diplomacy and the Promotion of American Studies since the Second World War
Authors: Scott-Smith Giles 
Published: October 2007

AbstractThis article examines the linkages between diplomacy and public diplomacy activities by tracing the promotion of American Studies in the Netherlands against the backdrop of US-Dutch diplomatic relations. The development of American Studies within the university systems of other nations has been a central part of US public diplomacy strategy since the Second World War. The belief has always been that this will contribute towards foreign publics being well-informed about the United States, its people and policies. By providing opportunities for research and teaching in the United States, and ultimately by establishing permanent positions, an academic community could be nurtured whose members would function as interpreters of all things American within their national environment. In this way a cross-border cultural affinity can be cultivated to provide a positive context for the practice of diplomatic relations. The case of the Netherlands demonstrates the interlinkage of short-term and long-term interests in pursuing this approach.
Geo-Social Mapping of the International Communications Environment or Why Abdul Isn't Listening
Authors: Fulton Barry 
Published: October 2007

AbstractThe paper suggests a radical redefinition of public diplomacy, asserting its primary role should be to stimulate the imagination of those who make a difference within their own cultures — to give them the means and motivation to address the global requirements of the 21st century, therein enhancing security for the sponsoring nations. Public diplomats also have an ancillary role in supporting other elements of international engagement, including promoting foreign investment, new energy resources, developmental assistance, education, medicine, and law.A three-point agenda for reforming the conduct of public diplomacy is proposed: reach beyond short-term parochial interests by providing knowledge to the curious, the innovative, and the restless. Hold public diplomats responsible for enabling connectivity and serving as cultural interpreters. Recruit and train artists, scholars, and scientists as public diplomats to engage actively in indigenous social networks.The article concludes by citing famed American journalist and former distinguished director of USIA, Edward R. Murrow: "There is a great and perhaps decisive battle to be fought against ignorance, intolerance and indifference." To join this battle, public diplomacy can best honor its past by rethinking its future.
Bursting and Grab Tests for Knit Fabrics Compared
Authors: Foster B.H. 
Published: October 2007

Publication of important textile research work previously unpublished is one of the functions of this magazine. The accompanying paper was presented by the author before Committee D-13 of the American Society for Testing Materials, February, 1925, but only excerpts therefrom have been published heretofore. In 1925 Committee D-13 of the A. S. T. M. adopted tentatively the 1 × 1 × 1" Grab Test,2 and at that time the Burcau of Standards recommended,3 and the Associated Knit Underwear Manufacturers of America generally adopted this test method. In 1928, however, the A. S. T. M. revised the tentative specifications in favor of a bursting test.5
X-Ray Analysis of Fibers
Authors: Sisson Wayne A. 
Published: October 2007

The March number of TEXTILE RESEARCH carried Mr. Sisson's literature surve y and references up to the year 1929 and it is here concluded. Following publication of the first instalment of the survey, The Textile Foundation decided to make available complete mimeographed copies of Mr. Sisson's literature survey. Those desiring copies should address E. T. Pickard, Secretary, The Textlie Foundation, Commerce Building, Washington, D. C.