bluuebunny/crossref_metadata_2025_split huggingface dataset:
LuxS Promotes Biofilm Maturation and Persistence of Nontypeable
Haemophilus influenzae
In Vivo via Modulation of Lipooligosaccharides on the Bacterial Surface
Authors: Armbruster Chelsie E. , Hong Wenzhou , Pang Bing , Dew Kristin E. , Juneau Richard A. , Byrd Matthew S. , Love Cheraton F. , Kock Nancy D. , Swords W. Edward 
Published: June 2009

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHI) is an extremely common airway commensal which can cause opportunistic infections that are usually localized to airway mucosal surfaces. During many of these infections, NTHI forms biofilm communities that promote persistence in vivo. For many bacterial species, density-dependent quorum-signaling networks can affect biofilm formation and/or maturation. Mutation of
luxS
, a determinant of the autoinducer 2 (AI-2) quorum signal pathway, increases NTHI virulence in the chinchilla model for otitis media infections. For example, bacterial counts in middle-ear fluids and the severity of the host inflammatory response were increased in
luxS
mutants compared with parental strains. As these phenotypes are consistent with those that we have observed for biofilm-defective NTHI mutants, we hypothesized that
luxS
may affect NTHI biofilms. A
luxS
mutant was generated using the well-characterized NTHI 86-028NP strain and tested to determine the effects of the mutation on biofilm phenotypes in vitro and bacterial persistence and disease severity during experimental otitis media. Quantitation of the biofilm structure by confocal microscopy and COMSTAT analysis revealed significantly reduced biomass for NTHI 86-028NP
luxS
biofilms, which was restored by a soluble mediator in NTHI 86-028NP supernatants. Analysis of lipooligosaccharide moieties using an enzyme-linked immunosorbent assay and immunoblotting showed decreased levels of biofilm-associated glycoforms in the NTHI 86-028NP
luxS
strain. Infection studies showed that NTHI 86-028NP
luxS
had a significant persistence defect in vivo during chronic otitis media infection. Based on these data, we concluded that a
luxS
-dependent soluble mediator modulates the composition of the NTHI lipooligosaccharides, resulting in effects on biofilm maturation and bacterial persistence in vivo.
A Regulator of
Aspergillus fumigatus
Extracellular Proteolytic Activity Is Dispensable for Virulence
Authors: Bergmann Anna , Hartmann Thomas , Cairns Timothy , Bignell Elaine M. , Krappmann Sven 
Published: June 2009

ABSTRACT

Virulence of the fungal pathogen
Aspergillus fumigatus
is in part based on the saprophytic lifestyle that this mold has evolved. A crucial function for saprophytism resides in secreted proteases that allow assimilation of proteinaceous substrates. The impact of extracellular proteolytic activities on the pathogenesis of aspergillosis, however, remains controversial. In order to address this issue, characterization of a conserved regulatory factor, PrtT, that acts on expression of secreted proteases was pursued. Expression of PrtT appears to be regulated posttranscriptionally, and the existence of an mRNA leader sequence implies translational control via eIF2α kinase signaling. Phenotypic classification of a
prtT
Δ deletion mutant revealed that expression of several major extracellular proteases is PrtT dependent, resulting in the inability to utilize protein as a nutritional source. Certain genes encoding secreted proteases are not regulated by PrtT. Most strikingly, the deletant strain is not attenuated in virulence when tested in a leukopenic mouse model, which makes a strong case for reconsidering any impact of secreted proteases in pulmonary aspergillosis.
Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection withCryptococcus neoformans
Authors: Osterholzer John J. , Milam Jami E. , Chen Gwo-Hsiao , Toews Galen B. , Huffnagle Gary B. , Olszewski Michal A. 
Published: June 2009

ABSTRACTSuccessful pulmonary clearance of the encapsulated yeastCryptococcus neoformansrequires a T1 adaptive immune response. This response takes up to 3 weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. The results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days postinfection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B-cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection withC. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.
Infection withAnaplasma phagocytophilumInduces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells
Authors: Johns J. L. , MacNamara K. C. , Walker N. J. , Winslow G. M. , Borjesson D. L. 
Published: June 2009

ABSTRACTInfection withAnaplasma phagocytophilum, a gram-negative, lipopolysaccharide (LPS)-negative, obligate intracellular bacterium, results in multiple peripheral blood cytopenias. We hypothesized that infection with this organism would result in decreased bone marrow (BM) function and shifts in hematopoietic progenitor cells (HPCs) and lineage-committed cells in a well-established murine model of infection. HPCs and lineage-committed progenitors were enumerated in the BM and spleen during acute infection. BM cytokine production and BM CXCL12 expression were determined. Infection resulted in peripheral blood bicytopenia, marked decreases in the number of lineage-committed HPCs in the BM along with concurrent increases in the number of lineage-committed HPCs in the spleen, and a mixed, predominantly myelosuppressive BM cytokine environment. There was significant downregulation of CXCL12 in BM cells that may have been partially responsible for changes in HPC trafficking observed. Changes occurred in the absence of direct pathogen infection of BM cells. Hematopoietic lineage assessment demonstrated that there was loss of erythrocytes and B lymphocytes from the BM along with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on the BM and spleen; however, the numbers of peripheral blood neutrophils appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Our findings highlight a well-conserved series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.
Transmembrane Tumor Necrosis Factor Alpha Is Required for Enteropathy and Is Sufficient To Promote Parasite Expulsion in Gastrointestinal Helminth Infection
Authors: Ierna M. X. , Scales H. E. , Mueller C. , Lawrence C. E. 
Published: June 2009

ABSTRACTTo study the specific role of transmembrane tumor necrosis factor (tmTNF) in protective and pathological responses against the gastrointestinal helminthTrichinella spiralis, we compared the immune responses of TNF-α/lymphotoxin alpha (LTα)−/−mice expressing noncleavable transgenic tmTNF to those of TNF-α/LTα−/−and wild-type mice. The susceptibility of TNF-α/LTα−/−mice toT. spiralisinfection was associated with impaired induction of a protective Th2 response and the lack of mucosal mastocytosis. Although tmTNF-expressing transgenic (tmTNF-tg) mice also had a reduced Th2 response, the mast cell response was greater than that observed in TNF-α/LTα−/−mice and was sufficient to induce the expulsion of the parasite.T. spiralisinfection of tmTNF-tg mice resulted in significant intestinal pathology characterized by villus atrophy and crypt hyperplasia comparable to that induced following the infection of wild-type mice, while pathology in TNF-α/LTα−/−mice was significantly reduced. Our data thus indicate a role for tmTNF in host defense against gastrointestinal helminths and in the accompanying enteropathy. Furthermore, they also demonstrate that TNF-α is required for the induction of Th2 immune responses related to infection with gastrointestinal helminth parasites.
Staphylococcal Alpha-Toxin Is Not Sufficient To Mediate Escape from Phagolysosomes in Upper-Airway Epithelial Cells
Authors: Giese Bernd , Dittmann Silvia , Paprotka Kerstin , Levin Katja , Weltrowski Annett , Biehler Diana , Lâm Thiên-Trí , Sinha Bhanu , Fraunholz Martin J. 
Published: June 2009

ABSTRACT

Intracellular
Staphylococcus aureus
has been implicated in the establishment of chronic infections. It is therefore imperative to understand by what means
S. aureus
is able to survive within cells. Here we use two expression systems with a fluorescent readout to assay alpha-toxin expression and function within phagolysosomes of infected upper-airway epithelial cells: avirulent
Staphylococcus carnosus
TM300 and phenotypically alpha-toxin-negative
S. aureus
laboratory strains. Data from CFU recovery assays suggest that the presence of alpha-toxin is not beneficial for the intracellular survival of recombinant
Staphylococcus
strains. This finding was corroborated by immunofluorescence studies: whereas
S. carnosus
and
S. aureus
are able to deliver
S. aureus
alpha-toxin to lumina of host cell phagolysosomes, the membrane integrity of these organelles was not affected. Alpha-toxin-expressing strains were detected exclusively within lysosome-associated membrane protein 1 (LAMP1)-yellow fluorescent protein (YFP)-positive vesicles. Measurements of intraphagosomal pH illustrated that all infected phagolysosomes acidified regardless of alpha-toxin expression. In contrast,
S. aureus
expressing
Listeria monocytogenes
listeriolysin O leads to the breakdown of the phagolysosomal membrane, as indicated by staphylococci that are not associated with LAMP1-YFP-decorated vesicles and that do not reside within an acidic cellular environment. Thus, our results suggest that staphylococcal alpha-toxin is not sufficient to mediate phagolysosomal escape in upper-airway epithelial cells.
Elevation errors in a LIDAR digital elevation model of West Seattle and their effects on slope-stability calculations
Authors: Haneberg William C. 
Published: June 2009

Abstract
A comparison of 1719 differential global positioning system (GPS) measurements with a 1 m LIDAR (light detection and ranging) digital elevation model (DEM) covering West Seattle shows that DEM elevation errors range from −4.88 m to +3.32 m. The errors are spatially correlated with a semivariogram range of 40 m, an unclustered mean of −0.11 m, and an unclustered standard deviation of ±0.75 m. Although there are statistically significant correlations between elevation error and elevation, slope angle, and topographic roughness, the relationships are weak and have little explanatory power. Monte Carlo simulations of slope angle, static factor of safety, Newmark yield acceleration, and log Newmark displacement show that elevation errors of the magnitude reported here can have significant effects on derivative calculations. The standard deviation of simulated slope angles increases from ~±2° to ±3° as the true slope angle approaches zero. Errors in slope angles calculated from the LIDAR DEM are smaller than those previously reported for a conventional 10 m DEM covering the same area, but the decrease is not proportional to the decrease in DEM grid spacing. The influence of elevation errors on static factor of safety errors is strongly dependent upon the slope angle and decreases significantly as the slope angle increases. Effects on Newmark yield acceleration and log Newmark displacement are not as profound but are still large enough to impart significant uncertainty into calculated results. Therefore, slope angle errors should be considered to be as significant as geotechnical parameter and pore-water pressure uncertainties when performing slope-stability calculations based on high-resolution LIDAR DEMs.
Shallow landslide hazard map of Seattle, Washington
Authors: Harp Edwin L. , Michael John A. , Laprade William T. 
Published: June 2009

Abstract
Landslides, particularly debris flows, have long been a significant cause of damage and destruction to people and property in the Puget Sound region. Following the years of 1996 and 1997, the Federal Emergency Management Agency designated Seattle as a “Project Impact” city with the goal of encouraging the city to become more disaster resistant to landslides and other natural hazards. A major recommendation of the Project Impact council was that the city and the U.S. Geological Survey collaborate to produce a landslide hazard map. An exceptional data set archived by the city containing more than 100 yr of landslide data from severe storm events allowed comparison of actual landslide locations with those predicted by slope-stability modeling. We used an infinite-slope analysis, which models slope segments as rigid friction blocks, to estimate the susceptibility of slopes to debris flows, which are water-laden slurries that can form from shallow failures of soil and weathered bedrock and can travel at high velocities down steep slopes. Data used for the analysis consisted of a digital slope map derived from recent light detection and ranging (LiDAR) imagery of Seattle, recent digital geologic mapping of the city, and shear-strength test data for the geologic units found in the surrounding area. The combination of these data layers within a geographic information system (GIS) platform allowed us to create a shallow landslide hazard map for Seattle.
Assessing deep-seated landslide susceptibility using 3-D groundwater and slope-stability analyses, southwestern Seattle, Washington
Authors: Brien Dianne L. , Reid Mark E. 
Published: June 2009

Abstract
In Seattle, Washington, deep-seated landslides on bluffs along Puget Sound have historically caused extensive damage to land and structures. These large failures are controlled by three-dimensional (3-D) variations in strength and pore-water pressures. We assess the slope stability of part of southwestern Seattle using a 3-D limit-equilibrium analysis coupled with a 3-D groundwater flow model. Our analyses use a high-resolution digital elevation model (DEM) combined with assignment of strength and hydraulic properties based on geologic units. The hydrogeology of the Seattle area consists of a layer of permeable glacial outwash sand that overlies less permeable glacial lacustrine silty clay. Using a 3-D groundwater model, MODFLOW-2000, we simulate a water table above the less permeable units and calibrate the model to observed conditions. The simulated pore-pressure distribution is then used in a 3-D slope-stability analysis, SCOOPS, to quantify the stability of the coastal bluffs. For wet winter conditions, our analyses predict that the least stable areas are steep hillslopes above Puget Sound, where pore pressures are elevated in the outwash sand. Groundwater flow converges in coastal reentrants, resulting in elevated pore pressures and destabilization of slopes. Regions predicted to be least stable include the areas in or adjacent to three mapped historically active deep-seated landslides. The results of our 3-D analyses differ significantly from a slope map or results from one-dimensional (1-D) analyses.
A prototype system for forecasting landslides in the Seattle, Washington, area
Authors: Chleborad Alan F. , Baum Rex L. , Godt Jonathan W. , Powers Phillip S. 
Published: June 2009

Abstract
Empirical rainfall thresholds and related information form the basis of a prototype system for forecasting landslides in the Seattle area. The forecasts are tied to four alert levels, and a decision tree guides the use of thresholds to determine the appropriate level. From analysis of historical landslide data, we developed a formula for a cumulative rainfall threshold (CT), P3  =  88.9 − 0.67P15, defined by rainfall amounts in millimeters during consecutive 3 d (72 h) periods, P3, and the 15 d (360 h) period before P3, P15. The variable CT captures more than 90% of historical events of three or more landslides in 1 d and 3 d periods recorded from 1978 to 2003. However, the low probability of landslide occurrence on a day when the CT is exceeded at one or more rain gauges (8.4%) justifies a low-level of alert for possible landslide occurrence, but it does trigger more vigilant monitoring of rainfall and soil wetness. Exceedance of a rainfall intensity-duration threshold I  =  82.73D−1.13, for intensity, I (mm/hr), and duration, D (hr), corresponds to a higher probability of landslide occurrence (30%) and forms the basis for issuing warnings of impending, widespread occurrence of landslides. Information about the area of exceedance and soil wetness can be used to increase the certainty of landslide forecasts (probabilities as great as 71%). Automated analysis of real-time rainfall and subsurface water data and digital quantitative precipitation forecasts are needed to fully implement a warning system based on the two thresholds.
Metformin: safety in cardiac patients
Authors: Khurana R , Malik I S 
Published: June 2009

Abstract
Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels. There are concerns about the risk of lactic acidosis in patients receiving metformin who have procedures requiring iodinated contrast, and in those with renal impairment or heart failure. The data on which these concerns are based are reviewed, with the conclusion that metformin treatment is rarely to blame for lactic acidosis. A generic policy of stopping metformin 48 h before and 48 h after the procedure in all patients is counterintuitive, lacks any evidence base and does not conform to the principles of best practice. In patients with heart failure, although the underlying condition can predispose to lactic acidosis, existing evidence suggests that metformin use is associated with improved outcome rather than increased risk.
Work status, work hours and health in women with and without children
Authors: Floderus B , Hagman M , Aronsson G , Marklund S , Wikman A 
Published: June 2009

Objectives:The authors studied self-reported health in women with and without children in relation to their work status (employed, student, job seeker or homemaker), work hours and having an employed partner.Methods:The study group comprised of 6515 women born in 1960–1979 who were interviewed in one of the Swedish Surveys of Living Conditions in 1994–2003. Self-rated health, fatigue and symptoms of anxiety were analysed.Results:Having children increased the odds of poor self-rated health and fatigue in employed women, female students and job seekers. The presence of a working partner marginally buffered the effects. In dual-earner couples, mothers reported anxiety symptoms less often than women without children. Few women were homemakers (5.8%). The odds of poor self-rated health and fatigue increased with increasing number of children in employed women, and in women working 40 h or more. Poor self-rated health was also associated with the number of children in students. Many mothers wished to reduce their working hours, suggesting time stress was a factor in their impaired health. The associations between having children and health symptoms were not exclusively attributed to having young children.Conclusions:Having children may contribute to fatigue and poor self-rated health particularly in women working 40 h or more per week. Student mothers and job seeking mothers were also at increased risk of poor self-rated health. The results should be noted by Swedish policy-makers. Also countries aiming for economic and gender equality should consider factors that may facilitate successful merging of work and family life.
ON THE USE OF INTELLIGENT AGENTS TO GUIDE TEST SEQUENCE SELECTION AND OPTIMIZATION
Authors: MALA D. JEYA , MOHAN V. 
Published: June 2009

Many of the automated testing tools concentrate on the automatic generation of test cases but do not worry about their optimization. In our paper, we analyzed the system model, which is represented as a state diagram and selected a very limited set of test sequences to be executed from the extreme large number (usually infinitely many) of potential ones. This paper demonstrates a way to generate optimal test sequences that are guaranteed to take the least possible time to execute and also satisfies both state and branch coverage criteria using Intelligent Agents. In the proposed approach, the Intelligent Search Agent (ISA) takes the decision of optimized test sequences by searching through the SUT, which is represented as a graph in which each node is associated with a heuristic value and each edge is associated with an edge weight. The Intelligent Agent finds the best sequence by following the nodes that satisfy the fitness criteria and generates the optimized test sequences for the SUT. Finally we compared our approach with existing Ant Colony Optimization (ACO)-based test sequence optimization approach and proved that our approach produces better results.
Apprenticeship learning for helicopter control
Authors: Coates Adam , Abbeel Pieter , Ng Andrew Y. 
Published: June 2009

Autonomous helicopter flight is widely regarded to be a highly challenging control problem. As helicopters are highly unstable and exhibit complicated dynamical behavior, it is particularly difficult to design controllers that achieve high performance over a broad flight regime.
While these aircraft are notoriously difficult to control, there are expert human pilots who are nonetheless capable of demonstrating a wide variety of maneuvers, including aerobatic maneuvers at the edge of the helicopter's performance envelope. In this paper, we present algorithms for modeling and control that leverage these demonstrations to build high-performance control systems for autonomous helicopters. More specifically, we detail our experiences with the Stanford Autonomous Helicopter, which is now capable of extreme aerobatic flight meeting or exceeding the performance of our own expert pilot.
On the bias of traceroute sampling
Authors: Achlioptas Dimitris , Clauset Aaron , Kempe David , Moore Cristopher 
Published: June 2009

Understanding the graph structure of the Internet is a crucial step for building accurate network models and designing efficient algorithms for Internet applications. Yet, obtaining this graph structure can be a surprisingly difficult task, as edges cannot be explicitly queried. For instance, empirical studies of the network of Internet Protocol (IP) addresses typically rely on indirect methods liketracerouteto build what are approximately single-source, all-destinations, shortest-path trees. These trees only sample a fraction of the network's edges, and a paper by Lakhina et al. [2003] found empirically that the resulting sample is intrinsically biased. Further, in simulations, they observed that the degree distribution under traceroute sampling exhibits a power law even when the underlying degree distribution is Poisson.In this article, we study the bias of traceroute sampling mathematically and, for a very general class of underlying degree distributions, explicitly calculate the distribution that will be observed. As example applications of our machinery, we prove that traceroute sampling finds power-law degree distributions in both δ-regular and Poisson-distributed random graphs. Thus, our work puts the observations of Lakhina et al. on a rigorous footing, and extends them to nearly arbitrary degree distributions.