bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sildenafil Citrate Improves Self-Esteem, Confidence, and Relationships in Men with Erectile Dysfunction: Results from an International, Multi-Center, Double-Blind, Placebo-Controlled Trial
Authors: Althof Stanley E. , O'Leary Michael P. , Cappelleri Joseph C. , Hvidsten Kyle , Stecher Vera J. , Glina Sidney , King Rosie , Siegel Richard L. 
Published: February 2006

ABSTRACT

Introduction
Erectile dysfunction (ED) can significantly impact a man's relationships and well-being.

Aim
We assessed changes in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction in men with ED using the validated Self-Esteem And Relationship questionnaire (SEAR).

Methods
This was a 12-week, double-blind, placebo-controlled, flexible-dose (25, 50, 100 mg, as needed) international study of sildenafil in men ≥18 years of age in Mexico, Brazil, Australia, and Japan.

Main Outcome Measures
The primary study outcome was change in self-esteem from baseline to the end of treatment. Secondary study measures were changes in other SEAR components, International Index of Erectile Function (IIEF) domains, percentage of intercourse attempts that were successful, and the response to a global efficacy question at the end of treatment.

Results
Patients were well balanced for age and duration of ED (placebo = 149 and sildenafil = 151). Compared with placebo, sildenafil significantly improved self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction (P &lt; 0.0001). The psychosocial measures of well-being assessed with the SEAR were positively correlated (range 0.60–0.86, P &lt; 0.0001) with erectile function, the frequency of achieving erections that allowed satisfactory sexual intercourse, the percentage of successful sexual intercourse attempts, and global treatment efficacy.

Conclusions
Significant improvements in self-esteem, confidence, sexual relationship satisfaction, and overall relationship satisfaction after treatment of ED with sildenafil were consistent among countries. These data suggest a substantial cross-cultural improvement in well-being after successful treatment of ED with sildenafil.
The synergistic effects of the IL‐9 gene and environmental exposures on asthmatic Taiwanese families as determined by the transmission/disequilibrium test
Authors: Wang T‐N. , Chen W‐Y. , Huang Y‐F. , Shih N‐H. , Feng W‐W. , Tseng H‐I. , Lee C‐H. , Ko Y‐C. 
Published: February 2006

SummaryAsthma occurs in genetically susceptible individuals in the presence of environmental factors. The interleukin‐9 (IL‐9) gene, one of the cytokine genes located on chromosome 5q31, plays an important role in the development of asthmatic syndrome by enhancing both T‐cell and mast‐cell function. This study investigated GT repeat polymorphism of the IL‐9 gene and the gene–environment interactions, which may predispose individuals to asthma and atopy pathogenesis. In this study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IL‐9 gene by studying 123 parent–offspring trios and 91 siblings. For allele‐specific TDT chi‐squared test, allele 122 of the IL‐9 gene showed significant association with asthmatics with specific IgE against house dust (HD) (P = 0.038). The additions of covariates to TDT to conduct the synergistic effects between the IL‐9 gene and environmental factors into account were estimated by conditional logistic regression models. The odds ratio for transmission of allele 122 of the IL‐9 gene was 1.23 (P = 0.28) for all asthmatic probands. There was slight increased interaction effect on asthma between transmission of allele 122 of IL‐9 gene to offspring and who were exposed to the fur of pets (OR = 3.33, P = 0.047). We also detected elevated odds of transmission of allele 122 to atopic asthmatic probands (OR = 2.08, P = 0.03) and offspring with very high levels of serum IgE (≥ 800 IU mL−1). In conclusion, this study has found that the IL‐9 gene was slightly associated with asthmatics who have positive specific IgE against Der p (or Der f) and house dust, when information on environmental factors was incorporated as effect modifiers.
Reduced coronary reserve in response to short‐term ischaemia and vasoactive drugs in ex vivo hearts from diabetic mice
Authors: Bratkovsky S. V. , Aasum E. , Riemersma R. A. , Myhre E. S. P. , Larsen T. S. 
Published: February 2006

AbstractAim:  The aim of the present study was to compare the coronary flow (CF) reserve of ex vivo perfused hearts from type 2 diabetic (db/db) and non‐diabetic (db/+) mice.Methods:  The hearts were perfused in the Langendorff mode with Krebs–Henseleit bicarbonate buffer (37 °C, pH 7.4) containing 11 mmol L−1 glucose as energy substrate. The coronary reserve was measured in response to three different interventions: (1) administration of nitroprusside (a nitric oxide donor), (2) administration of adenosine and (3) production of reactive hyperaemia by short‐term ischaemia.Results:  Basal CF was approximately 15% lower in diabetic when compared with non‐diabetic hearts (2.1 ± 0.1 vs. 2.6 ± 0.2 mL min−1). The maximum increase in CF rate in response to sodium nitroprusside and adenosine was significantly lower in diabetic (0.6 ± 0.1 and 0.9 ± 0.1 mL min−1 respectively) than in non‐diabetic hearts (1.2 ± 0.1 and 1.4 ± 0.1 mL min−1 respectively). Also, there was a clear difference in the rate of return to basal CF following short‐term ischaemia between diabetic and non‐diabetic hearts. Thus, basal tone was restored 1–2 min after the peak hyperaemic response in non‐diabetic hearts, whereas it took approximately 5 min in diabetic hearts.Conclusion:  These results show that basal CF, as well as the CF reserve, is impaired in hearts from type 2 diabetic mice. As diabetic and non‐diabetic hearts were exposed to the same (maximum) concentrations of NO or adenosine, it is suggested that the lower coronary reserve in type 2 diabetic hearts is, in part, because of a defect in the intracellular pathways mediating smooth muscle relaxation.
Abundance and co‐occurrence patterns of core and satellite species of ground beetles on small lake islands
Authors: Ulrich Werner , Zalewski Marcin 
Published: February 2006

15 lake islands and two mainland sites of Mamry lake in Poland were sampled to investigate community structures and patterns of co‐occurrences of ground beetles (Carabidae). The total ground beetle metacommunity of 71 species was divided into a group of core species occupying at least half of all study sites and of satellite species, which occurred at two sites or less. This division is mirrored by reduced dispersal abilities and non‐random patterns of site occupancy. Core and satellite species also differed in patterns of relative abundance. The core group followed a lognormal distribution, the satellite group a power function as predicted by the self‐similarity model of occurrence. We conclude that the division into core and satellite species is not a sample artefact but reflects different life history strategies. We also conclude that current models of niche division and co‐occurrence might miss important aspects of community structure if they do not refer to patterns of dispersal.From these findings we infer that the regional distribution of core species might be shaped by species interactions and processes of niche divisions whereas the spatial distribution of satellite species are best interpreted as stemming from random dispersal.
On Generating a Class of Foldable Six-Bar Spatial Linkages
Authors: Baker J. Eddie 
Published: February 2006

AbstractRecently isolated through fortuity and subsequent inference, a family of six-revolute spatial linkages is distinguished by dimensional properties which allow the individual loops to be folded, hence making them of possible interest in the field of deployable structures. The purpose of this paper is to demonstrate a novel method for generating each of the linkages from planar and Bennett chains. Alternative compositions are discussed, along with the family's potential for being fashioned into nests of linkages.
Topological Representations and Characteristics of Variable Kinematic Joints
Authors: Yan Hong-Sen , Kuo Chin-Hsing 
Published: February 2006

AbstractThere exist some mechanisms with variable topologies that have interesting applications, for examples, legged walking machines, mechanical push-button stopper locks, and various toys. A variable kinematic joint is a kinematic joint that is capable of topological variation in a mechanism with variable topology. This work aims at the topological representations and characteristic analysis of variable kinematic joints. During the operation process of a mechanism, the topology states of a variable kinematic joint can be expressed symbolically as the joint sequences, graphically the digraphs, and mathematically the matrices. With the applications of graph theory, it proves that the topological characteristics of variable kinematic joints appeared with the abilities of reversibility, continuity, variability of degrees of freedom, joint homomorphism, contractibility, and expansibility. Two examples are provided for illustrating how the proposed concepts can be used to analyze and synthesize the variable joints. The results of this work provide a logical foundation for the systematic structural synthesis regarding the kinematic joints and mechanisms with variable topologies.
Symmetrical Coupler Curve and Singular Point Classification in Planar and Spherical Swinging-Block Linkages
Authors: Shirazi Kourosh H. 
Published: February 2006

Abstract
The purpose of the present paper is coupler curve synthesis and classification in planar and spherical swinging block linkages for path generation problem. It is shown that the swinging block mechanism, which is an inversion of the slider crank mechanism, can be classified into two types. The first type generates Lemniscate coupler curves consisting one or two loops. In this case, two double points, namely cusp and crunode, occur depending on the mechanism's dimension. The second type generates Cardioid and Limaçon type coupler-curves consisting of one, two, three, and four loops. In this case, three kinds of double points, namely cusp, crunode, and tacnode, occur. For the spherical swinging-block linkages, a parametric coupler curve equation is derived. Using a trigonometric similitude between the planar and spherical linkages, a symmetrical coupler curve and singular point classification is accomplished.
MyD88 Deficiency Results in Tissue-Specific Changes in Cytokine Induction and Inflammation in Interleukin-18-Independent Mice Infected withBorrelia burgdorferi
Authors: Behera Aruna K. , Hildebrand Ethan , Bronson Roderick T. , Perides George , Uematsu Satoshi , Akira Shizuo , Hu Linden T. 
Published: February 2006

ABSTRACTToll-like receptors (TLRs) play an important role in the control of infection withBorrelia burgdorferi. Deficiencies in TLR-2 or the shared TLR adapter molecule MyD88 have been shown to result in greatly increased bacterial burdens in mice. However, although in vitro studies have shown that the activation of TLR pathways byB. burgdorferiresults in the release of inflammatory cytokines, studies in deficient mice have shown either no change or increased rather than decreased inflammation in infected animals. In this study, we looked at mechanisms to explain the increase in inflammation in the absence of MyD88. We found that MyD88-deficient mice infected withB. burgdorferidid not show increased inflammation at sites typically associated with Lyme disease (joints and heart). However, there was markedly increased inflammation in the muscles, kidneys, pancreas, and lungs of deficient animals. Muscle inflammation was typically seen perivascularly and perineuronally similar to that seen in infected humans. Chemotactic chemokines and cytokines were greatly increased in the muscle and kidneys of MyD88-deficient animals but not in the joints or heart tissue, suggesting that MyD88-independent pathways for recognizingB. burgdorferiand inducing these chemokines are present in the muscle and kidneys. Interleukin-18 signaling through MyD88 does not appear to play a role in either control of infection or inflammation.
Profiling of Human Antibody Responses toChlamydia trachomatisUrogenital Tract Infection Using Microplates Arrayed with 156 Chlamydial Fusion Proteins
Authors: Sharma Jyotika , Zhong Youmin , Dong Feng , Piper Jeanna M. , Wang Guqi , Zhong Guangming 
Published: February 2006

ABSTRACTThe available chlamydial genome sequences have made it possible to comprehensively analyze host responses to all chlamydial proteins, which is essential for further understanding of chlamydial pathogenesis and development of effective chlamydial vaccines. Microplates arrayed with 156Chlamydia trachomatisfusion proteins were used to evaluate antibody responses in women urogenitally infected withC. trachomatis. Based on both the antibody recognition frequency and titer, seven chlamydial antigens encoded by open reading frames (ORFs) CT089, CT147, CT226, CT681, CT694, CT795, and CT858, respectively, were identified as relatively immunodominant; six of these are encoded by hypothetical ORFs. Antibody binding to these chlamydial fusion proteins was blocked byC. trachomatis-infected but not by normal HeLa cell lysates or irrelevant bacterial lysates. These results have revealed novel immune-reactive chlamydial antigens, not only indicating that the hypothetical ORF-encoded proteins are expressed during chlamydial infection in humans but also providing the proof of principle that the fusion protein-based approach can be used to profile human immune responses to chlamydial infection at the whole-genome scale.
Estimating the Relative Contributions of Virulence Factors for Pathogenic Microbes
Authors: McClelland Erin E. , Bernhardt Paul , Casadevall Arturo 
Published: February 2006

ABSTRACT

Many pathogenic microbes have multiple virulence factors that can cause damage to the host and thus contribute to an overall virulence phenotype for that organism. Although current techniques are suitable for demonstrating that a particular microbial characteristic contributes to virulence, no formal approach for defining the relative contributions of multiple virulence factors to overall virulence has been proposed. This paper describes the use of multivariate linear regression to estimate the relative contributions of virulence factors to the overall phenomenon of virulence. The approach is illustrated here with sample calculations of the relative contributions of individual
Cryptococcus neoformans
and
Bacillus anthracis
virulence factors to the overall virulence phenotype. These calculations were derived from a small underpowered experimental data set for the fungus and two larger sets of randomly generated data for both microbes. The major limitation of this method is a requirement for large data sets of microbial strains that differ in virulence and virulence factor expression. Multivariate linear regression can be used to identify the relative levels of importance of virulence factors in virulence studies, and this information can be used to prioritize antigen identification for vaccine development and the design of antimicrobial strategies that target virulence mechanisms.
The Proinflammatory Response Induced by Wild-TypeYersinia pseudotuberculosisInfection Inhibits Survival ofyopMutants in the Gastrointestinal Tract and Peyer's Patches
Authors: Logsdon Lauren K. , Mecsas Joan 
Published: February 2006

ABSTRACTSingle-strain infections and coinfections are frequently used to assess roles of virulence factors in infected tissues. After oral inoculation of mice,Yersinia pseudotuberculosis yopEandyopHmutants colonize the intestines and Peyer's patches in single-strain infections but fail to persist in competition with wild-typeY. pseudotuberculosis, indicating that these two infection models provide different insights into the roles of Yops. To determine how wild-typeY. pseudotuberculosishindersyopmutant survival,yopmutant colonization and host responses were investigated in several different infection models that isolated specific features of wild-typeY. pseudotuberculosisinfection. Infection with wild-typeY. pseudotuberculosiscaused significantly more inflammation thanyopmutants. Results from coinfections of gamma interferon (IFN-γ)−/−mice revealed that IFN-γ-regulated defenses target these mutants, suggesting that YopE and YopH protectY. pseudotuberculosisfrom these defenses in BALB/c mice. We developed an oral-intraperitoneal infection model to evaluate the effects of spleen and liver colonization byY. pseudotuberculosisonyopmutants in the intestines. Spleen and liver infection increased inflammation and decreasedyopmutant survival in the intestines, indicating that infection of these organs has consequences in intestinal tissues. Finally, competition infections withY. pseudotuberculosismutants with various abilities to induce inflammation demonstrated that survival of theyopE, but not theyopH, mutant was consistently decreased in inflamed tissues. In summary, infection withY. pseudotuberculosisin intestinal and systemic sites induces intestinal inflammation, which decreasesyopmutant survival. Thus, competition studies with wild-type yersiniae reveal critical roles of Yops in combating host responses to a normal virulent infection.
The Onset of CD8+-T-Cell Contraction Is Influenced by the Peak ofListeria monocytogenesInfection and Antigen Display
Authors: Porter Brandon B. , Harty John T. 
Published: February 2006

ABSTRACTThe CD8+-T-cell response to infection withListeria monocytogenesconsists of expansion, contraction, and memory phases. The transition between expansion and contraction is reported to occur on different days postinfection with virulent (8 to 9 days) and attenuated (ΔactA) (7 days)L. monocytogenesstrains. We hypothesized that differences in the infectious courses, and therefore antigen (Ag) display, determine the precise time of the expansion/contraction transition in response to these infections. To test this, we infected BALB/c mice with 0.1 50% lethal dose of ΔactAor virulentL. monocytogenesand measured bacterial numbers, Ag display, and Ag-specific CD8+-T-cell responses on various days after infection. We found that bacterial numbers and Ag display peaked between 12 and 36 h and between 36 and 60 h after infection with ΔactAand virulentL. monocytogenesstrains, respectively. Infection with ΔactA L. monocytogenesresulted in a sharp peak in the Ag-specific CD8+-T-cell response on day 7, while infection with virulentL. monocytogenesyielded a prolonged peak with equivalent numbers of Ag-specific CD8+T cells on days 6, 7, and 8 after infection. Truncating virulent infection with antibiotics on day 1 or 2 after infection resulted in a shift in the expansion/contraction transition from day 8 to day 7 after infection. However, antibiotic treatment beginning on day 3, after the peak of virulentL. monocytogenesinfection and Ag display, had no effect upon the magnitude or timing of the CD8+-T-cell response. These results demonstrate a direct relationship between the course of infection and Ag display and that the timing of these events is important in shaping the T-cell response to infection.
The Outer Core Lipopolysaccharide of
Salmonella enterica
Serovar Typhi Is Required for Bacterial Entry into Epithelial Cells
Authors: Hoare Anilei , Bittner Mauricio , Carter Javier , Alvarez Sergio , Zaldívar Mercedes , Bravo Denisse , Valvano Miguel A. , Contreras Inés 
Published: February 2006

ABSTRACT

Salmonella enterica
serovar Typhi causes typhoid fever in humans. Central to the pathogenicity of serovar Typhi is its capacity to invade intestinal epithelial cells. The role of lipopolysaccharide (LPS) in the invasion process of serovar Typhi is unclear. In this work, we constructed a series of mutants with defined deletions in genes for the synthesis and polymerization of the O antigen (
wbaP
,
wzy
, and
wzz
) and the assembly of the outer core (
waaK
,
waaJ
,
waaI
,
waaB
, and
waaG
). The abilities of each mutant to associate with and enter HEp-2 cells and the importance of the O antigen in serum resistance of serovar Typhi were investigated. We demonstrate here that the presence and proper chain length distribution of the O-antigen polysaccharide are essential for serum resistance but not for invasion of epithelial cells. In contrast, the outer core oligosaccharide structure is required for serovar Typhi internalization in HEp-2 cells. We also show that the outer core terminal glucose residue (Glc II) is necessary for efficient entry of serovar Typhi into epithelial cells. The Glc I residue, when it becomes terminal due to a polar insertion in the
waaB
gene affecting the assembly of the remaining outer core residues, can partially substitute for Glc II to mediate bacterial entry into epithelial cells. Therefore, we conclude that a terminal glucose in the LPS core is a critical residue for bacterial recognition and internalization by epithelial cells.
Trypanosoma cruziInfection and Nuclear Factor Kappa B Activation Prevent Apoptosis in Cardiac Cells
Authors: Petersen Christine A. , Krumholz Katherine A. , Carmen John , Sinai Anthony P. , Burleigh Barbara A. 
Published: February 2006

ABSTRACTStudies of cardiac pathology and heart failure have implicated cardiomyocyte apoptosis as a critical determinant of disease. Recent evidence indicates that the intracellular protozoan parasiteTrypanosoma cruzi, which causes heart disease in chronically infected individuals, impinges on host apoptotic pathways in a cell type-dependent manner.T. cruziinfection of isolated neuronal cells and cardiomyocytes protects against apoptotic cell death, whereas apoptosis is triggered in T cells inT. cruzi-infected animals. In this study, we demonstrate that the ability ofT. cruzito protect cardiac cells in vitro from apoptosis triggered by a combination of tumor necrosis factor alpha and serum reduction correlates with the presence of intracellular parasites and involves activation of host cell NF-κB. We further demonstrate that the apoptotic block diminishes activation of caspase 3. The ability ofT. cruzito prevent apoptosis of infected cardiomyocytes is likely to play an important role in establishment of persistent infection in the heart while minimizing potential damage and remodeling that is associated with cardiomyocyte apoptosis in cardiovascular disease.
Vaccination of Mice with Gonococcal TbpB Expressed In Vivo from Venezuelan Equine Encephalitis Viral Replicon Particles
Authors: Thomas Christopher E. , Zhu Weiyan , Van Dam Cornelius N. , Davis Nancy L. , Johnston Robert E. , Sparling P. Frederick 
Published: February 2006

ABSTRACTWe investigated the immunogenicity of gonococcal transferrin binding protein B (TbpB) expressed with and without a eukaryotic secretion signal from a nonpropagating Venezuelan equine encephalitis virus replicon particle (VRP) delivery system. TbpB was successfully expressed in baby hamster kidney (BHK) cells, and the presence of the eukaryotic secretion signal not only apparently increased the protein's expression but also allowed for extracellular localization and glycosylation. Mice immunized with VRPs produced significant amounts of serum antibody although less than the amounts produced by mice immunized with recombinant protein. The response of mice immunized with VRPs encoding TbpB was consistently more Th1 biased than the response of mice immunized with recombinant protein alone. Boosting with recombinant protein following immunization with TbpB VRPs resulted in higher specific-antibody levels without altering the Th1/Th2 bias. Most of the immunization groups produced significant specific antibody binding to the intact surface of the homologousNeisseria gonorrhoeaestrain. Immunization with TbpB VRPs without a eukaryotic secretion signal generated no measurable specific antibodies on the genital mucosal surface, but inclusion of a eukaryotic secretion signal or boosting with recombinant protein resulted in specific immunoglobulin G (IgG) and IgA in mucosal secretions after TbpB VRP immunization. The TbpB VRP system has potential for anN. gonorrhoeaevaccine.