bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclopropavir Susceptibility of Cytomegalovirus DNA Polymerase Mutants Selected after Antiviral Drug Exposure
Authors: Chou Sunwen , Marousek Gail , Bowlin Terry L. 
Published: October 2011

ABSTRACT

Human cytomegalovirus (CMV) UL54 DNA polymerase (
pol
) mutants with known patterns of resistance to current antivirals ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV) were tested for cyclopropavir (CPV) susceptibility by a standardized reporter-based yield reduction assay. Exonuclease and A987G (region V) mutations at codons commonly associated with dual GCV-CDV resistance in clinical isolates paradoxically conferred increased CPV susceptibility. Various polymerase catalytic region mutations conferring FOS resistance with variable low-grade GCV and CDV cross-resistance also conferred CPV resistance, with 50% effective concentration (EC
50
) increases of 3- to 13-fold. CPV EC
50
values against several
pol
mutants were increased about 2-fold by adding UL97 mutation C592G. Propagation of a CMV exonuclease mutant under CPV selected for
pol
mutations less often than UL97 mutations. In 21 experiments, one instance each of mutations E756D and M844V, which were shown individually to confer 3- to 4-fold increases in CPV EC
50
, was detected. Unlike GCV and CDV, exonuclease mutations are not a preferred mechanism of CPV resistance, but mutations in and near
pol
region III may confer CPV resistance by affecting its recognition as an incoming base for DNA polymerization.
Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans
Authors: Cordero Radames J. B. , Pontes Bruno , Guimarães Allan J. , Martinez Luis R. , Rivera Johanna , Fries Bettina C. , Nimrichter Leonardo , Rodrigues Marcio L. , Viana Nathan B. , Casadevall Arturo 
Published: October 2011

ABSTRACTDoes the age of a microbial cell affect its virulence factors? To our knowledge, this question has not been addressed previously, but the answer is of great relevance for chronic infections where microbial cells persist and age in hosts.Cryptococcus neoformansis an encapsulated human-pathogenic fungus notorious for causing chronic infections where cells of variable age persist in tissue. The major virulence factor forC. neoformansis a polysaccharide (PS) capsule. To understand how chronological age could impact the cryptococcal capsule properties, we compared the elastic properties, permeabilities, zeta potentials, and glycosidic compositions of capsules from young and old cells and found significant differences in all parameters measured. Changes in capsular properties were paralleled by changes in PS molecular mass and density, as well as modified antigenic density and antiphagocytic properties. Remarkably, chronological aging under stationary-phase growth conditions was associated with the expression of α-1,3-glucans in the capsule, indicating a new structural capsular component. Our results establish that cryptococcal capsules are highly dynamic structures that change dramatically with chronological aging under prolonged stationary-phase growth conditions. Changes associated with cellular aging in chronic infections could contribute to the remarkable capacity of this fungus to persist in tissues by generating phenotypically and antigenically different capsules.
Genetic mating system and population history of the endangered Western Yellow-breasted Chat (Icteria virens auricollis) in British Columbia, Canada
Authors: Miño Carolina I. , Pollet Ingrid L. , Bishop Christine A. , Russello Michael A. 
Published: October 2011

The Western Yellow-breasted Chat ( Icteria virens auricollis (Deppe, 1830)) is a Neotropical migrant, with a Canadian distribution restricted to breeding populations in southern British Columbia. Given its small population size and diminishing breeding habitat, Yellow-breasted Chats are federally endangered in Canada. We used genotypic data at eight microsatellite loci to assess genetic diversity, reconstruct population structure and demographic history, and characterize genetic mating system of Yellow-breasted Chats sampled across 60 nesting sites at five locations in the Okanagan Valley (n = 148). Microsatellite-based analyses indicated lack of significant genetic differentiation among breeding sites and no genetic evidence of population decline. Parentage assignments indicated moderate levels of extra-pair paternity, with 30.7% offspring not sired by attending males. Patterns of sibship among nestlings revealed 49.1% of the clutches were composed entirely of full-siblings, with half-siblings and unrelated nestlings present in some broods. These findings suggest that extra-pair paternity is common in Yellow-breasted Chats, similar to other avian species, and present the first evidence of conspecific brood parasitism in warblers. Our findings add to a growing body of research informing the need to establish a national park in the south Okanagan to preserve critical habitat and connect populations of species at risk.
Contender pressure versus resource dispersion as predictors of territory size of coyotes (Canis latrans)
Authors: Wilson R.R. , Shivik J.A. 
Published: October 2011

Many studies have proposed resource dispersion as the main determinant of territory size in coyotes ( Canis latrans Say, 1823), but few have considered contender pressure as an alternative hypothesis. We tested for differences in rates of intra-territorial visitation, movement, and extra-territorial excursions between two populations of coyotes with large differences in territory sizes. We collected fine-scale (15 min) movement data of coyotes in southeastern Texas and south-central Idaho. Both populations were active for similar lengths of each day, but coyotes in Idaho had territories 10× larger, moved 2× faster, traveled 2× farther daily, and made extra-territorial excursions 3× less. Even with increased movement rates, coyotes in Idaho traversed territories slower than coyotes in Texas as predicted by the contender pressure hypothesis. We propose that in regions with high resource abundance, territory size of coyotes is determined by contender pressure and an inability to defend larger areas. Conversely, in low-resource areas, territory sizes are determined more by prey abundance and dispersion because intrusion rates are reduced given the lower density of conspecifics.
Enzymatic flux capacities in hummingbird flight muscles: a “one size fits all” hypothesis
Authors: Fernández M.J. , Bozinovic F. , Suarez R.K. 
Published: October 2011

Hummingbirds (family Trochilidae) are among the smallest endothermic vertebrates representing an extreme, among birds, in their physiological design. They are unique in their ability to sustain hovering flight, one of the most energetically demanding forms of locomotion. Given that hovering metabolic rate (HMR) in hummingbirds scales allometrically as M0.78(M is mass), we tested the hypothesis that variation in HMR may be correlated with variation in maximal enzyme activities (Vmaxvalues) of key enzymes in glucose and fatty acid oxidation pathways in the flight muscles of four species of hummingbirds ranging in body mass from 4 to 20 g. We also estimated metabolic flux rates from respirometric data obtained during hovering flight. The data are striking in the lack of correlation between Vmaxvalues and flux rates at most steps in energy metabolism, particularly at the hexokinase and carnitine palmitoyltransferase reactions. In the context of hierarchical regulation analysis, this finding suggests that metabolic regulation (resulting from variation in substrate, product, or allosteric regulator concentrations) dominates as the proximate explanation for the interspecific variation in flux. On the other hand, we found no evidence of hierarchical regulation of flux, which results from variation in Vmaxand is based on variation in enzyme concentration [E]. The evolutionary conservation of pathways of energy metabolism suggests that “one size fits all” among hummingbirds.
Empowering End Users to Confine Their Own Applications
Authors: Schreuders Z. Cliffe , McGill Tanya , Payne Christian 
Published: October 2011

Protecting end users from security threats is an extremely difficult, but increasingly critical, problem. Traditional security models that focused on separating users from each other have proven ineffective in an environment of widespread software vulnerabilities and rampant malware. However, alternative approaches that provide more finely grained security generally require greater expertise than typical end users can reasonably be expected to have, and consequently have had limited success.
The functionality-based application confinement (FBAC) model is designed to allow end users with limited expertise to assign applications hierarchical and parameterised policy abstractions based upon the functionalities each program is intended to perform. To validate the feasibility of this approach and assess the usability of existing mechanisms, a usability study was conducted comparing an implementation of the FBAC model with the widely used Linux-based SELinux and AppArmor security schemes. The results showed that the functionality-based mechanism enabled end users to effectively control the privileges of their applications with far greater success than widely used alternatives. In particular, policies created using FBAC were more likely to be enforced and exhibited significantly lower risk exposure, while not interfering with the ability of the application to perform its intended task. In addition to the success of the functionality-based approach, the usability study also highlighted a number of limitations and problems with existing mechanisms. These results indicate that a functionality-based approach has significant potential in terms of enabling end users with limited expertise to defend themselves against insecure and malicious software.
CANTINA+
Authors: Xiang Guang , Hong Jason , Rose Carolyn P. , Cranor Lorrie 
Published: October 2011

Phishing is a plague in cyberspace. Typically, phish detection methods either use human-verified URL blacklists or exploit Web page features via machine learning techniques. However, the former is frail in terms of new phish, and the latter suffers from the scarcity of effective features and the high false positive rate (FP). To alleviate those problems, we propose a layered anti-phishing solution that aims at (1) exploiting the expressiveness of a rich set of features with machine learning to achieve a high true positive rate (TP) on novel phish, and (2) limiting the FP to a low level via filtering algorithms.
Specifically, we proposed CANTINA+, the most comprehensive feature-based approach in the literature including eight novel features, which exploits the HTML Document Object Model (DOM), search engines and third party services with machine learning techniques to detect phish. Moreover, we designed two filters to help reduce FP and achieve runtime speedup. The first is a near-duplicate phish detector that uses hashing to catch highly similar phish. The second is a login form filter, which directly classifies Web pages with no identified login form as legitimate.
We extensively evaluated CANTINA+ with two methods on a diverse spectrum of corpora with 8118 phish and 4883 legitimate Web pages. In the randomized evaluation, CANTINA+ achieved over 92% TP on unique testing phish and over 99% TP on near-duplicate testing phish, and about 0.4% FP with 10% training phish. In the time-based evaluation, CANTINA+ also achieved over 92% TP on unique testing phish, over 99% TP on near-duplicate testing phish, and about 1.4% FP under 20% training phish with a two-week sliding window. Capable of achieving 0.4% FP and over 92% TP, our CANTINA+ has been demonstrated to be a competitive anti-phishing solution.
Enhanced speculative parallelization via incremental recovery
Authors: Tian Chen , Lin Changhui , Feng Min , Gupta Rajiv 
Published: October 2011

The widespread availability of multicore systems has led to an increased interest in speculative parallelization of sequential programs using software-based thread level speculation. Many of the proposed techniques are implemented via state separation where non-speculative computation state is maintained separately from the speculative state of threads performing speculative computations. If speculation is successful, the results from speculative state are committed to non-speculative state. However, upon misspeculation, discard-all scheme is employed in which speculatively computed results of a thread are discarded and the computation is performed again. While this scheme is simple to implement, one disadvantage of discard-all is its inability to tolerate high misspeculation rates due to its high runtime overhead. Thus, it is not suitable for use in applications where misspeculation rates are input dependent and therefore may reach high levels.
In this paper we develop an approach for incremental recovery in which, instead of discarding all of the results and reexecuting the speculative computation in its entirety, the computation is restarted from the earliest point at which a misspeculation causing value is read. This approach has two advantages. First, the cost of recovery is reduced as only part of the computation is reexecuted. Second, since recovery takes less time, the likelihood of future misspeculations is reduced. We design and implement a strategy for implementing incremental recovery that allows results of partial computations to be efficiently saved and reused. For a set of programs where misspeculation rate is input dependent, our experiments show that with inputs that result in misspeculation rates of around 40% and 80%, applying incremental recovery technique results in 1.2x-3.3x and 2.0x-6.6x speedups respectively over the discard-all recovery scheme. Furthermore, misspeculations observed during discard-all scheme are reduced when incremental recovery is employed -- reductions range from 10% to 85%.
Long-Term Follow-Up of Participants With Heart Failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Authors: Piller Linda B. , Baraniuk Sarah , Simpson Lara M. , Cushman William C. , Massie Barry M. , Einhorn Paula T. , Oparil Suzanne , Ford Charles E. , Graumlich James F. , Dart Richard A. , Parish David C. , Retta Tamrat M. , Cuyjet Aloysius B. , Jafri Syed Z. , Furberg Curt D. , Saklayen Mohammad G. , Thadani Udho , Probstfield Jeffrey L. , Davis Barry R. ,   for the ALLHAT Collaborative Research Group
Published: October 2011

Background—
In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5–10 mg/d) and lisinopril (10–40 mg/d) arms compared with the chlorthalidone (12.5–25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases.

Methods and Results—
With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81–1.12) and 1.05 (0.89–1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm.

Conclusions—
Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00000542.
Maternal and Fetal Factors Associated With Mortality and Morbidity in a Multi–Racial/Ethnic Registry of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus
Authors: Izmirly Peter M. , Saxena Amit , Kim Mimi Y. , Wang Dan , Sahl Sara K. , Llanos Carolina , Friedman Deborah , Buyon Jill P. 
Published: October 2011

Background—
Cardiac manifestations of neonatal lupus include conduction disease and, rarely, an isolated cardiomyopathy. This study was initiated to determine the mortality and morbidity of cardiac neonatal lupus and associated risk factors in a multi–racial/ethnic US-based registry to provide insights into the pathogenesis of antibody-mediated injury and data for counseling.

Methods and Results—
Three hundred twenty-five offspring exposed to maternal anti-SSA/Ro antibodies with cardiac neonatal lupus met entry criteria. Maternal, fetal echocardiographic, and neonatal risk factors were assessed for association with mortality. Fifty-seven (17.5%) died, 30% in utero. The probability of in utero death was 6%. The cumulative probability of survival at 10 years for a child born alive was 86%. Fetal echocardiographic risk factors associated with increased mortality in a multivariable analysis of all cases included hydrops and endocardial fibroelastosis. Significant predictors of in utero death were hydrops and earlier diagnosis, and of postnatal death were hydrops, endocardial fibroelastosis, and lower ventricular rate. Isolated heart block was associated with a 7.8% case fatality rate, whereas the concomitant presence of dilated cardiomyopathy or endocardial fibroelastosis quadrupled the case fatality rate. There was a significantly higher case fatality rate in minorities compared with whites, who were at a lower risk of hydrops and endocardial fibroelastosis. Pacing was required in 70%; cardiac transplantation was required in 4 children.

Conclusion—
Nearly one fifth of fetuses who develop cardiac neonatal lupus die of complications predicted by echocardiographic abnormalities consistent with antibody-associated disease beyond the atrioventricular node. The disparity in outcomes observed between minorities and whites warrants further investigation.
Transcoronary Concentration Gradients of Circulating MicroRNAs
Authors: De Rosa Salvatore , Fichtlscherer Stephan , Lehmann Ralf , Assmus Birgit , Dimmeler Stefanie , Zeiher Andreas M. 
Published: October 2011

Background—
Circulating levels of microRNA (miR) have been proposed as biomarkers for cardiovascular disease. To identify the heart as a potential source for miRs released into the circulation, we measured concentration gradients across the coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular (miR-126, miR-92a), leukocyte-related (miR-155), and platelet-enriched (miR-223) miRs.

Methods and Results—

Circulating miRs were measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the aorta and the coronary venous sinus in patients without coronary artery disease (n=7), with stable coronary artery disease (n=31), and with troponin-positive acute coronary syndromes (n=19). Circulating levels of the muscle-enriched miR-499 (>20-fold;
P
<0.01), miR-133a (11-fold;
P
<0.01), and miR-208a (5-fold;
P
<0.01) were significantly elevated in the aorta of troponin-positive acute coronary syndrome patients compared with patients with coronary artery disease. Importantly, there was a significant increase in circulating levels of miR-499 and miR-133a across the coronary circulation in troponin-positive acute coronary syndrome patients, suggestive of a release into the coronary circulation during myocardial injury. Indeed, miR-499 concentration gradients were significantly correlated with the extent of myocardial damage as measured by high-sensitivity troponin T (
r
=0.70,
P
<0.01). In contrast, circulating levels of miR-126 (
P
=0.16) decreased during transcoronary passage in patients with evidence of myocardial injury, suggesting consumption during transcoronary passage.

Conclusions—
Muscle-enriched miR-499 and miR-133a are released from the heart into the coronary circulation on myocardial injury, whereas the vascular miR-126 is consumed during transcoronary passage. The differential regulation of circulating miRs during the transcoronary passage might provide important insights to exploit their role as cardiac biomarkers.

Clinical Trial Registration—

URL:
http://www.germanctr.de
. Unique identifier: DRKS00000207; in German Clinical Trials Registry.
Effect of Lead Use on Back and Shoulder Postural Muscle Activity in Healthy Young Adults
Authors: Johnson Daniel D. , Kirkpatrick Anne E. , Ashton-Miller James A. , Shih Albert J. 
Published: October 2011

Objective: The primary goal of this study was to test the hypothesis that wearing the 3.7 kg vest portion of a radiological shielding garment (a “lead”) significantly increases lower back and shoulder muscle activity in quasistatic erect and forward-flexed postures. Secondarily, the authors examined the effects of gender and forward-flexed posture as well as their interactions with lead use. Background: The use of a lead is mandatory for interventionalists during surgical procedures. Because the vest portion of a lead weighs considerably more than normal clothing, there is concern that its use increases the risk of developing back and shoulder pain. Method: In a repeated-measures study design, 19 young healthy male and female adults assumed standardized erect or forward-flexed postures, both with and without wearing the vest portion of a lead. Shoulder and lower back muscle activity was measured via surface electromyography, normalized by maximum voluntary contraction values. Data were analyzed using general linear models and repeated-measures ANOVA (significant for p < .05). Results: Use of the lead did not result in a significant increase in muscle activity in the lower back or shoulders, despite perceived increases in effort and discomfort. Posture proved to be the most significant secondary factor affecting activity in the lower back, and participant gender proved insignificant. Conclusion: Short-term use of the lead does not appear to contribute to the incidence of back pain or injury in interventionalists. Avoiding flexed postures could more directly reduce the likelihood of pain or injury. Application: Potential applications include assessing and improving operating room ergonomics for physicians.