bluuebunny/crossref_metadata_2025_split huggingface dataset:
RTX Toxin Plays a Key Role in Kingella kingae Virulence in an Infant Rat Model
Authors: Chang Dennis W. , Nudell Yoav A. , Lau Jenny , Zakharian Eleonora , Balashova Nataliya V. 
Published: March 2014

ABSTRACT

Kingella kingae
is a human oral bacterium that can cause diseases of the skeletal system in children and infective endocarditis in children and adults.
K. kingae
produces a toxin of the RTX group, RtxA. To investigate the role of RtxA in disease pathogenesis
in vivo
,
K. kingae
strain PYKK081 and its isogenic RtxA-deficient strain KKNB100 were tested for their virulence and pathological consequences upon intraperitoneal injections in 7-day-postnatal (PN 7) rats. At the doses above 8.0 × 10
6
cells/animal, PYKK081 was able to cause a fatal illness, resulting in rapid weight loss, bacteremia, and abdominal necrotic lesion formation. Significant histopathology was observed in thymus, spleen, and bone marrow. Strain KKNB100 was less toxic to animals. Neither weight loss, bacteremia, nor histopathological changes were evident. Animals injected with KKNB100 exhibited a significantly elevated circulating white blood cell (WBC) count, whereas animals injected with PYKK081 had a WBC count that resembled that of the uninfected control. This observation parallels the subtleties associated with clinical presentation of
K. kingae
disease in humans and suggests that the toxin contributes to WBC depletion. Thus, our results demonstrate that RtxA is a key
K. kingae
virulence factor. Furthermore, our findings suggest that the PN 7 rat can serve as a useful model for understanding disease caused by
K. kingae
and for elucidating diagnostic parameters in human patients.
Aerobactin Mediates Virulence and Accounts for Increased Siderophore Production under Iron-Limiting Conditions by Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae
Authors: Russo Thomas A. , Olson Ruth , MacDonald Ulrike , Metzger Daniel , Maltese Lauren M. , Drake Eric J. , Gulick Andrew M. 
Published: March 2014

ABSTRACT

Hypervirulent (hypermucoviscous)
Klebsiella pneumoniae
(hvKP) strains are an emerging variant of “classical”
K. pneumoniae
(cKP) that cause organ and life-threatening infection in healthy individuals. An understanding of hvKP-specific virulence mechanisms that enabled evolution from cKP is limited. Observations by our group and previously published molecular epidemiologic data led us to hypothesize that hvKP strains produced more siderophores than cKP strains and that this trait enhanced hvKP virulence. Quantitative analysis of 12 hvKP strains in iron-poor minimal medium or human ascites fluid showed a significant and distinguishing 6- to 10-fold increase in siderophore production compared to that for 14 cKP strains. Surprisingly, high-pressure liquid chromatography (HPLC)-mass spectrometry and characterization of the hvKP strains hvKP1, A1142, and A1365 and their isogenic aerobactin-deficient (Δ
iucA
) derivatives established that aerobactin accounted for the overwhelming majority of increased siderophore production and that this was not due to gene copy number. Further, aerobactin was the primary factor in conditioned medium that enhanced the growth/survival of hvKP1 in human ascites fluid. Importantly the
ex vivo
growth/survival of hvKP1 Δ
iucA
was significantly less than that of hvKP1 in human ascites fluid, and the survival of outbred CD1 mice challenged subcutaneously or intraperitoneally with hvKP1 was significantly less than that of mice challenged with hvKP1 Δ
iucA
. The lowest subcutaneous and intraperitoneal challenge inocula of 3 × 10
2
and 3.2 × 10
1
CFU, respectively, resulted in 100% mortality, demonstrating the virulence of hvKP1 and its ability to cause infection at a low dose. These data strongly support that aerobactin accounts for increased siderophore production in hvKP compared to cKP (a potential defining trait) and is an important virulence factor.
Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke
Authors: Liggins John T P , Mlynash Michael , Jovin Tudor G , Straka Matus , Kemp Stephanie , Bammer Roland , Marks Michael P , Albers Gregory W , Lansberg Maarten G 
Published: March 2014

BackgroundPatients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion.MethodsNine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0–2) or good (3–4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion.Results36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ2p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05).ConclusionsReperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.
ATR Pathway Inhibition Is Synthetically Lethal in Cancer Cells with ERCC1 Deficiency
Authors: Mohni Kareem N. , Kavanaugh Gina M. , Cortez David 
Published: March 2014

Abstract
The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions, with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase cyclin E. Here, we report a systematic screen to identify synthetic lethal interactions with ATR pathway–targeted drugs, rationalized by their predicted therapeutic utility in the oncology clinic. We found that reduced function in the ATR pathway itself provided the strongest synthetic lethal interaction. In addition, we found that loss of the structure-specific endonuclease ERCC1-XPF (ERCC4) is synthetic lethal with ATR pathway inhibitors. ERCC1-deficient cells exhibited elevated levels of DNA damage, which was increased further by ATR inhibition. When treated with ATR or CHEK1 inhibitors, ERCC1-deficient cells were arrested in S-phase and failed to complete cell-cycle transit even after drug removal. Notably, triple-negative breast cancer cells and non–small cell lung cancer cells depleted of ERCC1 exhibited increased sensitivity to ATR pathway–targeted drugs. Overall, we concluded that ATR pathway–targeted drugs may offer particular utility in cancers with reduced ATR pathway function or reduced levels of ERCC4 activity. Cancer Res; 74(10); 2835–45. ©2014 AACR.
The Dose-Dependent Tumor Targeting of Antibody–IFNγ Fusion Proteins Reveals an Unexpected Receptor-Trapping Mechanism In Vivo
Authors: Hemmerle Teresa , Neri Dario 
Published: March 2014

Abstract
Cytokines often display substantial toxicities at low concentrations, preventing their escalation for therapeutic treatment of cancer. Fusion proteins comprising cytokines and recombinant antibodies may improve the anticancer activity of proinflammatory cytokines. Murine IFNγ was appended in the diabody format at the C-terminus of the F8 antibody, generating the F8–IFNγ fusion protein. The F8 antibody is specific for the extra-domain A (EDA) of fibronectin, a tumor-associated antigen that is expressed in the vasculature and stroma of almost all tumor types. Tumor-targeting properties were measured in vivo using a radioiodinated preparation of the fusion protein. Therapy experiments were performed in three syngeneic murine models of cancer [F9 teratocarcinoma, WEHI-164 fibrosarcoma, and Lewis lung carcinoma (LLC)]. F8–IFNγ retained the biologic activity of both the antibody and the cytokine moiety in vitro, but, unlike the parental F8 antibody, it did not preferentially localize to the tumors in vivo. However, when unlabeled F8–IFNγ was administered before radioiodinated F8–IFNγ, a selective accumulation at the tumor site was observed. F8–IFNγ showed dose-dependent anticancer activity with a clear superiority over untargeted recombinant IFNγ. The anticancer activity was potentiated by combining with F8–IL4 without additional toxicities, whereas combination of F8–IFNγ with F8–TNF was lethal in all mice. Unlike other antibody–cytokine fusions, the use of IFNγ as payload for anticancer therapy is associated with a receptor-trapping mechanism, which can be overcome by the administration of a sufficiently large amount of the fusion protein without any detectable toxicity at the doses used. Cancer Immunol Res; 2(6); 559–67. ©2014 AACR.
Cardiopulmonary Fitness and Heart Rate Recovery as Predictors of Mortality in a Referral Population
Authors: Dhoble Abhijeet , Lahr Brian D. , Allison Thomas G. , Kopecky Stephen L. 
Published: March 2014

Background

Exercise testing provides valuable information in addition to
ST
‐segment changes. The present study evaluated the associations among exercise test parameters and all‐cause mortality in a referral population.

Methods and Results

We examined conventional cardiovascular risk factors and exercise test parameters in 6546 individuals (mean age 49 years, 58% men) with no known cardiovascular disease who were referred to our clinic for exercise stress testing between 1993 and 2003. The association of exercise parameters with mortality was assessed during a follow‐up of 8.1±3.7 years. A total of 285 patients died during the follow‐up period. Adjusting for age and sex, the variables associated with mortality were: smoking, diabetes, functional aerobic capacity (
FAC
), heart rate recovery (
HRR
), chronotropic incompetence, and angina during the exercise. Adjusting for cardiovascular risk factors (diabetes, smoking, body mass index, blood pressure, serum total,
HDL
,
LDL
cholesterol, and triglycerides) and other exercise variables in a multivariable model, the only exercise parameters independently associated with mortality were lower
FAC
(adjusted hazard ratio [
HR
] per 10% decrease in
FAC
, 1.21; 95% confidence interval [
CI
], 1.13 to 1.29;
P
<0.001), and abnormal
HRR
, defined as failure to decrease heart rate by 12 beats at 1 minute recovery (adjusted
HR
per 1‐beat decrease, 1.05; 95%
CI
, 1.03 to 1.07;
P
<0.001). The additive effects of
FAC
and
HRR
on mortality were also highly significant when considered as categorical variables.

Conclusion

In this cohort of patients with no known cardiovascular disease who were referred for exercise electrocardiography,
FAC
and
HRR
were independently associated with all‐cause mortality.
Set-relevance Determines the Impact of Distractors on Episodic Memory Retrieval
Authors: Kwok Sze Chai , Shallice Tim , Macaluso Emiliano 
Published: March 2014

AbstractWe investigated the interplay between stimulus-driven attention and memory retrieval with a novel interference paradigm that engaged both systems concurrently on each trial. Participants encoded a 45-min movie on Day 1 and, on Day 2, performed a temporal order judgment task during fMRI. Each retrieval trial comprised three images presented sequentially, and the task required participants to judge the temporal order of the first and the last images (“memory probes”) while ignoring the second image, which was task irrelevant (“attention distractor”). We manipulated the content relatedness and the temporal proximity between the distractor and the memory probes, as well as the temporal distance between two probes. Behaviorally, short temporal distances between the probes led to reduced retrieval performance. Distractors that at encoding were temporally close to the first probe image reduced these costs, specifically when the distractor was content unrelated to the memory probes. The imaging results associated the distractor probe temporal proximity with activation of the right ventral attention network. By contrast, the precuneus was activated for high-content relatedness between distractors and probes and in trials including a short distance between the two memory probes. The engagement of the right ventral attention network by specific types of distractors suggests a link between stimulus-driven attention control and episodic memory retrieval, whereas the activation pattern of the precuneus implicates this region in memory search within knowledge/content-based hierarchies.
Disposed to Distraction: Genetic Variation in the Cholinergic System Influences Distractibility But Not Time-on-Task Effects
Authors: Berry Anne S. , Demeter Elise , Sabhapathy Surya , English Brett A. , Blakely Randy D. , Sarter Martin , Lustig Cindy 
Published: March 2014

Abstract
Both the passage of time and external distraction make it difficult to keep attention on the task at hand. We tested the hypothesis that time-on-task and external distraction pose independent challenges to attention and that the brain's cholinergic system selectively modulates our ability to resist distraction. Participants with a polymorphism limiting cholinergic capacity (Ile89Val variant [rs1013940] of the choline transporter gene SLC5A7) and matched controls completed self-report measures of attention and a laboratory task that measured decrements in sustained attention with and without distraction. We found evidence that distraction and time-on-task effects are independent and that the cholinergic system is strongly linked to greater vulnerability to distraction. Ile89Val participants reported more distraction during everyday life than controls, and their task performance was more severely impacted by the presence of an ecologically valid video distractor (similar to a television playing in the background). These results are the first to demonstrate a specific impairment in cognitive control associated with the Ile89Val polymorphism and add to behavioral and cognitive neuroscience studies indicating the cholinergic system's critical role in overcoming distraction.
The Thinking behind the Creation of a Basic Law for Social Organizations
Authors: Peifeng Liu , Bing Shui , Guosheng Deng , Ming Wang , Jianyin Ma 
Published: March 2014

Abstract
This paper is the second from the “Salon Series on the Creation of Legislation on the Right of Association and Social Organizations”. This was a series of salons jointly hosted by Tsinghua University’s ngo Research Center, the Philanthropy and ngo Support Center, and the editorial office of the China Nonprofit Review. The formulation of a basic law on social organizations is an important issue for China’s social sector, and particularly for the social organization sector. It is also one of the conditions necessary for a transformation in the way social organizations are managed, from the current form of governance, which is achieved through administrative regulations, to management by ‘rule of law’ in the truest sense. Recently, in academic circles, many different lines of thought have developed about the formulation of a basic law for social organizations, including the argument for ‘governance through administrative law’, which adopts a public law perspective; the argument for ‘special civil laws’, which approaches the question from the perspective of private law; and the argument for a ‘combination of legal forms’. This paper explores the content of a basic law, as well as the objectives, nature of and skills involved in formulating such a law. It examines the necessity and feasibility of creating such legislation, and the key ideas that need to be transformed during the legislative process. At the same time, the paper considers the differences between this and the thinking behind other legislation such as the charity law.
Genesis of Hurricane Julia (2010) within an African Easterly Wave: Developing and Nondeveloping Members from WRF–LETKF Ensemble Forecasts
Authors: Cecelski Stefan F. , Zhang Da-Lin , Miyoshi Takemasa 
Published: March 2014

Abstract
In this study, the predictability of and parametric differences in the genesis of Hurricane Julia (2010) are investigated using 20 mesoscale ensemble forecasts with the finest resolution of 1 km. Results show that the genesis of Julia is highly predictable, with all but two members undergoing genesis. Despite the high predictability, substantial parametric differences exist between the stronger and weaker members. Notably, the strongest-developing member exhibits large upper-tropospheric warming within a storm-scale outflow during genesis. In contrast, the nondeveloping member has weak and more localized warming due to inhibited convective development and a lack of a storm-scale outflow. A reduction in the Rossby radius of deformation in the strongest member aids in the accumulation of the warmth, while little contraction takes place in the nondeveloping member. The warming in the upper troposphere is responsible for the development of meso-α-scale surface pressure falls and a meso-β surface low in the strongest-developing member. Such features fail to form in the nondeveloping member as weak upper-tropospheric warming is unable to induce meaningful surface pressure falls. Cloud ice content is nearly doubled in the strongest member as compared to its nondeveloping counterparts, suggesting the importance of depositional heating of the upper troposphere. It is found that the stronger member undergoes genesis faster due to the lack of convective inhibition near the African easterly wave (AEW) pouch center prior to genesis. This allows for the faster development of a mesoscale convective system and storm-scale outflow, given the already favorable larger-scale conditions.
Some Aspects of Western Hemisphere Circulation and the Madden–Julian Oscillation
Authors: Roundy Paul E. 
Published: March 2014

Abstract
Although the greatest variance in convection associated with the Madden–Julian oscillation (MJO) occurs over the Indo-Pacific warm pool, the MJO is associated with substantial circulation patterns in the tropics and the extratropics of the Western Hemisphere. Reanalysis data suggest that upper-tropospheric easterly wind anomalies on the equator between 40° and 140°W precede 86% of active convective phases of MJO events greater than one standard deviation in amplitude over the Indian Ocean basin during the Northern Hemisphere winter. Composites of those MJO events that are preceded by westerly wind anomalies and those events preceded by easterly wind anomalies are compared. Results show that those events that are preceded by westerly wind anomalies fail to thrive and do not yield the amplitude in convection or the canonical atmospheric circulation response that is associated with those preceded by easterly wind. The composite of events preceded by easterly winds reveals that these winds amplify coincident with arrival of an anticyclone into the tropics from a wave train that extends across the middle latitudes of the Pacific Ocean and North America. The resultant easterlies then radiate eastward across Africa to the Indian Ocean basin at the phase speed of convectively coupled Kelvin waves, where they are joined by other anticyclones propagating into the tropics, apparently facilitating westward outflow from the amplifying Indian Ocean basin convection.
Observation Operator for Visible and Near-Infrared Satellite Reflectances
Authors: Kostka Philipp M. , Weissmann Martin , Buras Robert , Mayer Bernhard , Stiller Olaf 
Published: March 2014

Abstract
Operational numerical weather prediction systems currently only assimilate infrared and microwave satellite observations, whereas visible and near-infrared reflectances that comprise information on atmospheric clouds are not exploited. One of the reasons for that is the absence of computationally efficient observation operators. To remedy this issue in anticipation of the future regional Kilometer-Scale Ensemble Data Assimilation (KENDA) system of Deutscher Wetterdienst, we have developed a version that is fast enough for investigating the assimilation of cloudy reflectances in a case study approach. The operator solves the radiative transfer equation to simulate visible and near-infrared channels of satellite instruments based on the one-dimensional (1D) discrete ordinate method. As input, model output of the operational limited-area Consortium for Small-Scale Modeling (COSMO) model of Deutscher Wetterdienst is used. Assumptions concerning subgrid-scale processes, calculation of in-cloud values of liquid water content, ice water content, and cloud microphysics are summarized, and the accuracy of the 1D simulation is estimated through comparison with three-dimensional (3D) Monte Carlo solver results. In addition, the effects of a parallax correction and horizontal smoothing are quantified. The relative difference between the 1D simulation in “independent column approximation” and the 3D calculation is typically less than 9% between 0600 and 1500 UTC, computed from four scenes during one day (with local noon at 1115 UTC). The parallax-corrected version reduces the deviation to less than 6% for reflectance observations with a central wavelength of 810 nm. Horizontal averaging can further reduce the error of the 1D simulation. In all cases, the bias is less than 1% for the model domain.
A Comparison of Vessel-Mounted Acoustic Doppler Current Profiler and Satellite Altimeter Estimates of Sea Surface Height and Transports between New Jersey and Bermuda along the CMV Oleander Route
Authors: Worst Jessica S. , Donohue Kathleen A. , Rossby T. 
Published: March 2014

Abstract
In recent years the acoustic Doppler current profiler (ADCP) has found increasing use on commercial vessels to measure currents and their variability along selected routes in the ocean. One such dataset, in operation since late 1992, is the ADCP record from the Container Motor Vessel (CMV) Oleander, which operates between New Jersey and Bermuda. Because the Oleander ADCP system measures upper-ocean currents of O(10−2) m s−1 accuracy every 2.5 km, it provides excellent coverage of the mesoscale and submesoscale velocity field, and also of transport. The question addressed here is how well do estimates of fluxes between the continental shelf break and Bermuda compare with corresponding geostrophic estimates derived from satellite altimeter measurements of sea level extracted from weekly mapped fields along the same route. The Oleander route spans three distinct deep-sea regions: the Slope Sea, the Gulf Stream, and the Sargasso Sea. Agreement in sea surface height variability depends principally upon the length of the section being compared, and not upon eddy kinetic energy levels. Thus, yearly averages for short subsections such as across the quiet Slope Sea and energetic Gulf Stream both have correlation coefficients in excess of 0.9, whereas across the longer Sargasso Sea the correlation coefficient drops to 0.64 and to 0.58 for the 950-km-long Slope–Bermuda section. The principal cause of decrease in correlation with increasing distance appears to be due to ageostrophic flow, principally the Ekman layer and inertial motion, measured by the ADCP but not represented in the altimeter-derived geostrophic fluxes.