bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Role of the Leukocyte Integrin αMβ2 in Angiogenesis
Authors: Soloviev Dmitry A. , Hazen Stanley L. , Szpak Dorota , Bledzka Kamila M. , Ballantyne Christie M. , Plow Edward F. , Pluskota Elzbieta 
Published: September 2014

Abstract
Polymorphonuclear neutrophils (PMNs) and macrophages are crucial contributors to neovascularization, serving as a source of chemokines, growth factors, and proteases. αMβ2(CD11b/CD18) and αLβ2(CD11a/CD18) are expressed prominently and have been implicated in various responses of these cell types. Thus, we investigated the role of these β2 integrins in angiogenesis. Angiogenesis was analyzed in wild-type (WT), αM-knockout (αM−/−), and αL-deficient (αL−/−) mice using B16F10 melanoma, RM1 prostate cancer, and Matrigel implants. In all models, vascular area was decreased by 50–70% in αM−/− mice, resulting in stunted tumor growth as compared with WT mice. In contrast, αL deficiency did not impair angiogenesis and tumor growth. The neovessels in αM−/− mice were leaky and immature because they lacked smooth muscle cell and pericytes. Defective angiogenesis in the αM−/− mice was associated with attenuated PMN and macrophage recruitment into tumors. In contrast to WT or the αL−/− leukocytes, the αM−/− myeloid cells showed impaired plasmin (Plm)-dependent extracellular matrix invasion, resulting from 50–75% decrease in plasminogen (Plg) binding and pericellular Plm activity. Surface plasmon resonance verified direct interaction of the αMI-domain, the major ligand binding site in the β2 integrins, with Plg. However, the αLI-domain failed to bind Plg. In addition, endothelial cells failed to form tubes in the presence of conditioned medium collected from TNF-α–stimulated PMNs derived from the αM−/− mice because of severely impaired degranulation and secretion of VEGF. Thus, αMβ2 plays a dual role in angiogenesis, supporting not only Plm-dependent recruitment of myeloid cells to angiogenic niches, but also secretion of VEGF by these cells.
IL-22 Fate Reporter Reveals Origin and Control of IL-22 Production in Homeostasis and Infection
Authors: Ahlfors Helena , Morrison Peter J. , Duarte João H. , Li Ying , Biro Judit , Tolaini Mauro , Di Meglio Paola , Potocnik Alexandre J. , Stockinger Brigitta 
Published: September 2014

Abstract
IL-22 is a cytokine that regulates tissue homeostasis at barrier surfaces. A variety of IL-22–producing cell types is known, but identification on the single-cell level remains difficult. Therefore, we generated a fate reporter mouse that would allow the identification of IL-22–producing cells and their fate mapping in vivo. To trace IL-22–expressing cells, a sequence encoding Cre recombinase was cloned into the Il22 locus, and IL22Cre mice were crossed with reporter mice expressing enhanced yellow fluorescence protein (eYFP) under control of the endogenous Rosa26 promoter. In IL22CreR26ReYFP mice, the fluorescent reporter permanently labels cells that have switched on Il22 expression, irrespective of cytokine production. Despite a degree of underreporting, eYFP expression was detectable in nonimmune mice and restricted to group 3 innate lymphoid cells (ILC3) in the gut and γδ T cells in skin or lung. Upon skin challenge with imiquimod, eYFP+ γδ and CD4 T cells expanded in the skin. Infection with Citrobacter rodentium initially was controlled by ILC3, followed by expansion of eYFP+ CD4 T cells, which were induced in innate lymphoid follicles in the colon. No eYFP expression was detected in small intestinal Th17 cells, and they did not expand in the immune response. Colonic eYFP+ CD4 T cells exhibited plasticity during infection with expression of additional cytokines, in contrast to ILC3, which remained largely stable. Single-cell quantitative PCR analysis of eYFP+ CD4 T cells confirmed their heterogeneity, suggesting that IL-22 expression is not confined to particular subsets or a dedicated Th22 subset.
miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection
Authors: Moon Hyung-Geun , Yang Jincheng , Zheng Yijie , Jin Yang 
Published: September 2014

Abstract
Bacterial infection and its associated sepsis are devastating clinical entities that lead to high mortality and morbidity in critically ill patients. Phagocytosis, along with other innate immune responses, exerts crucial impacts on the outcomes of these patients. MicroRNAs (miRNAs) are a novel class of regulatory noncoding RNAs that target specific mRNAs for modulation of translation and expression of a targeted protein. The roles of miRNAs in host defense against bacterial sepsis remain unclear. We found that bacterial infections and/or bacterial-derived LPS enhanced the level of miR-15a/16 in bone marrow–derived macrophages (BMDMs). Deletion of miR-15a/16 (miR-15a/16−/−) in myeloid cells significantly decreased the bacterial infection–associated mortality in sepsis mouse models. Moreover, miR-15a/16 deficiency (miR-15a/16−/−) resulted in augmented phagocytosis and generation of mitochondrial reactive oxygen species in BMDMs. Supportively, overexpression of miR-15a/16 using miRNA mimics led to decreased phagocytosis and decreased generation of mitochondrial reactive oxygen species. Mechanistically, deletion of miR-15a/16 upregulated the expression of TLR4 via targeting the principle transcriptional regulator PU.1 locating on the promoter region of TLR4, and further modulated the downstream signaling molecules of TLR4, including Rho GTPase Cdc 42 and TRAF6. In addition, deficiency of miR-15a/16 also facilitated TLR4-mediated proinflammatory cytokine/chemokine release from BMDMs at the initial phase of infections. Taken together, miR-15a/16 altered phagocytosis and bacterial clearance by targeting, at least partially, on the TLR4-associated pathways, subsequently affecting the survival of septic mice.
mTORC1-Dependent Metabolic Reprogramming Is a Prerequisite for NK Cell Effector Function
Authors: Donnelly Raymond P. , Loftus Róisín M. , Keating Sinéad E. , Liou Kevin T. , Biron Christine A. , Gardiner Clair M. , Finlay David K. 
Published: September 2014

Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cellular metabolism and also has fundamental roles in controlling immune responses. Emerging evidence suggests that these two functions of mTORC1 are integrally linked. However, little is known regarding mTORC1 function in controlling the metabolism and function of NK cells, lymphocytes that play key roles in antiviral and antitumor immunity. This study investigated the hypothesis that mTORC1-controlled metabolism underpins normal NK cell proinflammatory function. We demonstrate that mTORC1 is robustly stimulated in NK cells activated in vivo and in vitro. This mTORC1 activity is required for the production of the key NK cell effector molecules IFN-γ, which is important in delivering antimicrobial and immunoregulatory functions, and granzyme B, a critical component of NK cell cytotoxic granules. The data reveal that NK cells undergo dramatic metabolic reprogramming upon activation, upregulating rates of glucose uptake and glycolysis, and that mTORC1 activity is essential for attaining this elevated glycolytic state. Directly limiting the rate of glycolysis is sufficient to inhibit IFN-γ production and granzyme B expression. This study provides the highly novel insight that mTORC1-mediated metabolic reprogramming of NK cells is a prerequisite for the acquisition of normal effector functions.
Characteristic distribution and possible roles of waves around the lower hybrid frequency in the magnetotail reconnection region
Authors: Zhou Meng , Li Huimin , Deng Xiaohua , Huang Shiyong , Pang Ye , Yuan Zhigang , Xu Xiaojun , Tang Rongxin 
Published: September 2014

AbstractIt has long been suggested that waves around the lower hybrid frequency play a significant role in magnetic reconnection. In this paper we statistically study the distribution and possible roles of waves around lower hybrid frequency based on the wave data recorded by the Cluster spacecraft during 21 magnetotail reconnection events. We find that, as the plasma β increments, magnetic field fluctuations associated with waves increase while electric field fluctuations decrease. As β exceeds 10, both magnetic and electric field fluctuations decrease. Furthermore, a two‐dimensional wave distribution is constructed based on the two‐dimensional reconnection model. The most intense magnetic field fluctuations occur in the outflow region, while they are weaker in the inflow region and separatrix region. The most intense electric field fluctuations occur around the separatrix region, while they are weaker in the inflow and outflow regions. There are positive correlations between wave strength and energetic electron acceleration, as well as between wave strength and reconnection rate. Our results may be important for fully understanding the role of waves around lower hybrid frequency in the dissipation process of magnetic reconnection.
GPS scintillation and irregularities at the front of an ionization tongue in the nightside polar ionosphere
Authors: van der Meeren Christer , Oksavik Kjellmar , Lorentzen Dag , Moen Jøran Idar , Romano Vincenzo 
Published: September 2014

AbstractIn this paper we study a tongue of ionization (TOI) on 31 October 2011 which stretched across the polar cap from the Canadian dayside sector to Svalbard in the nightside ionosphere. The TOI front arrived over Svalbard around 1930 UT. We have investigated GPS scintillation and irregularities in relation to this TOI front. This is the first study presenting such detailed multi‐instrument data of scintillation and irregularities in relation to a TOI front. Combining data from an all‐sky imager, the European Incoherent Scatter Svalbard Radar, the Super Dual Auroral Radar Network Hankasalmi radar, and three GPS scintillation and total electron content (TEC) monitors in Longyearbyen and Ny‐Ålesund, we observe bursts of phase scintillation and no amplitude scintillation in relation to the leading gradient of the TOI. Spectrograms of 50Hz phase measurements show highly localized and variable structuring of the TOI leading gradient, with no structuring or scintillation within the TOI or ahead of the TOI.
Modeling gradual diffusion changes in radiation belt electron phase space density for the March 2013 Van Allen Probes case study
Authors: Li Zhao , Hudson Mary , Jaynes Allison , Boyd Alexander , Malaspina David , Thaller Scott , Wygant John , Henderson Michael 
Published: September 2014

AbstractMarch 2013 provided the first equinoctial period when all of the instruments on the Van Allen Probes spacecraft were fully operational. This interval was characterized by disturbances of outer zone electrons with two time scales of variation, diffusive and rapid dropout and restoration. A radial diffusion model was applied to the monthlong interval to confirm that electron phase space density is well described by radial diffusion for the whole month at low first invariant ≤ 400 MeV/G but peaks in phase space density observed by the Energetic Particle, Composition, and Thermal Plasma (ECT) instrument suite at higher first invariant are not reproduced by radial transport from a source at higher L. The model does well for much of the monthlong interval, capturing three of four enhancements in phase space density which emerge from the outer boundary, while the strong enhancement following dropout on 17–18 March requires local acceleration at higher first invariant (M=1000 MeV/G versus 200 MeV/G) not included in our model. We have incorporated phase space density from ECT measurement at the outer boundary and plasmapause determination from the Electric Field and Waves (EFW) instrument to separate hiss and chorus loss models.
Seismological and geodetic constraints on the 2011Mw5.3 Trinidad, Colorado earthquake and induced deformation in the Raton Basin
Authors: Barnhart W. D. , Benz H. M. , Hayes G. P. , Rubinstein J. L. , Bergman E. 
Published: September 2014

AbstractThe Raton Basin of southern Colorado and northern New Mexico is an actively produced hydrocarbon basin that has experienced increased seismicity since 2001, including the August 2011Mw5.3 Trinidad normal faulting event. Following the 2011 earthquake, regional seismic observations were used to relocate 21 events, including the 2011 main shock, two foreshocks, and 13 aftershocks. Additionally, interferometric synthetic aperture radar (InSAR) observations of both the 2011 event and preevent basin deformation place constraint on the spatial kinematics of the 2011 event and localized basin subsidence due to ground water or gas withdrawal. We find that the 2011 earthquake ruptured an 8–10 km long segment of a normal fault at depths of 1.5–6.0 km within the crystalline Precambrian basement underlying the Raton Basin sedimentary rocks. The earthquake also nucleated within the crystalline basement in the vicinity of an active wastewater disposal site. The ensuing aftershock sequence demonstrated statistical properties expected for intraplate earthquakes, though the length of the 2011 earthquake is unexpectedly long for anMw5.3 event, suggesting that wastewater disposal may have triggered a low stress drop, otherwise natural earthquake. Additionally, preevent and postevent seismicity in the Raton Basin spatially correlates to regions of subsidence observed in InSAR time series analysis. While these observations cannot discern a causal link between hydrocarbon production and seismicity, they constrain spatial relationships between active basin deformation and geological and anthropogenic features. Furthermore, the InSAR observations highlight the utility of space‐based geodetic observations for monitoring and assessing anthropogenically induced and triggered deformation.
Localized fault slip to the trench in the 2010 Maule, Chile Mw = 8.8 earthquake from joint inversion of high‐rate GPS, teleseismic body waves, InSAR, campaign GPS, and tsunami observations
Authors: Yue Han , Lay Thorne , Rivera Luis , An Chao , Vigny Christophe , Tong Xiaopeng , Báez Soto Juan Carlos 
Published: September 2014

AbstractThe 27 February 2010, Mw 8.8 Maule earthquake ruptured ~500 km along the plate boundary offshore central Chile between 34°S and 38.5°S. Establishing whether coseismic fault offset extended to the trench is important for interpreting both shallow frictional behavior and potential for tsunami earthquakes in the region. Joint inversion of high‐rate GPS, teleseismic body waves, interferometric synthetic aperture radar (InSAR), campaign GPS, and tsunami observations yields a kinematic rupture model with improved resolution of slip near the trench. Bilateral rupture expansion is resolved in our model with relatively uniform slip of 5–10 m downdip beneath the coast and two near‐trench high‐slip patches with >12 m displacements. The peak slip is ~17 m at a depth of ~15 km on the central megathrust, located ~200 km north from the hypocenter and overlapping the rupture zone of the 1928 M ~8 event. The updip slip is ~16 m near the trench. Another shallow near‐trench patch is located ~150 km southwest of the hypocenter, with a peak slip of 12 m. Checkerboard resolution tests demonstrate that correctly modeled tsunami data are critical to resolution of slip near the trench, with other data sets allowing, but not requiring slip far offshore. Large interplate aftershocks have a complementary distribution to the coseismic slip pattern, filling in gaps or outlining edges of large‐slip zones. Two clusters of normal faulting events locate seaward along the plate motion direction from the localized regions of large near‐trench slip, suggesting that proximity of slip to the trench enhanced extensional faulting in the underthrusting plate.
The role of river flow and tidal asymmetry on 1‐D estuarine morphodynamics
Authors: Guo L. , van der Wegen M. , Roelvink J. A. , He Q. 
Published: September 2014

AbstractNumerous research efforts have been devoted to understanding estuarine morphodynamics under tidal forcing. However, the impact of river discharge on estuarine morphodynamics is insufficiently examined. Inspired by the Yangtze Estuary, this work explores the morphodynamic impact of river discharge in a 560 km long tidal basin based on a 1‐D model (Delft3D). The model considers total load sediment transport and employs a morphodynamic updating scheme to achieve long‐term morphodynamic evolution. We analyze the role of Stokes drift, tidal asymmetry, and river discharge in generating tidal residual sediment transport. Model results suggest that morphodynamic equilibrium is approached within millennia by vanishing spatial gradients of tidal residual sediment transport. We find that the interaction between ebb‐directed Stokes return flow/river flow with tides is an important mechanism that flushes river‐supplied sediment seaward. Increasing river discharge does not induce continuously eroded or accreted equilibrium bed profiles because of the balance between riverine sediment supply and sediment flushing to the sea. An intermediate threshold river discharge can be defined which leads to a deepest equilibrium bed profile. As a result, the shape (concavity or convexity) of the equilibrium bed profiles will adapt with the magnitude of river discharge. Overall, this study reveals the significant role of river discharge in controlling estuarine morphodynamics by supplying sediment and reinforcing ebb‐directed residual sediment transport.
Risk Classification/Life
Authors: Haberman Steven , Olivieri Annamaria 
Published: September 2014

AbstractThis article gives an overview of the main models used to represent heterogeneity in life insurance. We focus in particular on two classes of models: individual models, which are suitable to represent heterogeneity aspects that are observable at the issue of an insurance; and collective models, which are suitable to assess heterogeneity due to unobservable risk factors.The adoption of (at least some) individual models is common practice in life insurance, in particular for pricing or, more generally, for risk management. On the other hand, collective models are used for certain mortality investigations, in particular for suggesting an appropriate description of the age‐specific mortality shape in some insured portfolios.
Bayesian Analysis andMarkovChainMonteCarlo Simulation
Authors: Medova Elena 
Published: September 2014

AbstractThis chapter describes the use of hierarchical Bayesian analysis using Markov chain Monte Carlo (MCMC) estimation to obtain the parameters of a peaks‐over‐threshold (POT) extreme value theory model of extreme operational losses. Principal MCMC techniques are described and a simple example which illustrates the concepts, including economic capital allocation, is discussed.
Stochastic Deterioration
Authors: Noortwijk Jan M. , Kallen Maarten‐Jan 
Published: September 2014

Abstract
To ensure that a system or structure performs its required functions (including safety), maintenance should be performed on a regular basis. To optimize maintenance, information about the time to failure and/or the deteriorating condition is needed. Unfortunately, there is often a lot of uncertainty involved in the applied deterioration process. Mathematical models can be used to account for the stochastic nature of deterioration over time. This article reviews two approaches in modeling deterioration: the actuarial approach based on the notion of failure rate and the physical approach based on the notion of failure due to the stress exceeding the strength. Candidates for stochastic deterioration models are finite‐state Markov processes and Markov processes with independent increments (e.g., gamma process, compound Poisson process, and Brownian motion with drift).
Least‐Squares Estimation
Authors: Geer Sara A. 
Published: September 2014

Abstract

The method of least‐squares is about estimating parameters by minimizing the squared discrepancies between observed data, on the one hand, and their expected values on the other. It is commonly used in the context of a regression model, where one observes pairs of variables (
X
,
Y
), with
X
, a covariable and
Y
, a response variable. The expectation of the response variable
Y
given the covariable
X
is modeled as a function
f
β
(
X
) depending on parameters β.
Aliasing in Fractional Designs
Authors: McGrath Richard N. , Lin Dennis K.J. 
Published: September 2014

Abstract

In this short exposition, we provide an overview of the aliasing (or confounding) among effects that is caused by studying fewer treatment combinations than required in a full factorial design. We show, by example, how to determine the alias structure of the regular two‐level fractional factorial (2

k
−
p

) designs, nonregular two‐level designs, and the regular three‐level fractional factorial (3

k
−
p

) designs.
Cumulative Damage Models Based on Gamma Processes
Authors: Park Chanseok , Padgett William J. 
Published: September 2014

Abstract
A statistical model for cumulative damage based on gamma processes, incorporating an accelerating variable, is derived. A simpler approximation to the resulting failure distribution is also given which is a Birnbaum–Saunders‐type model. The proposed model is illustrated with a real‐data example which shows that it is a strong competitor to the widely used Weibull accelerated test model.
McNemar Test
Authors: Lachenbruch Peter A. 
Published: September 2014

Abstract

The McNemar test is used for hypothesis testing with paired dichotomous data. The test involves only the off‐diagonal elements and results in a 1 degree of freedom χ
2
test. The dependence on only the discordant means that sample size estimation must rely on assumptions about the proportion of discordant observations. It can be shown that this test is equivalent to a paired t‐test under the assumption of equal means.
Profile Likelihood
Authors: Aitkin M. 
Published: September 2014

AbstractThis is the likelihood for a set of parameters maximized over nuisance parameters. It formalizes the use of likelihood ratio tests to construct confidence regions for a parameter in the presence of nuisance parameters. It may result in overprecision by ignoring uncertainty in the nuisance parameters, and various adjustments have been proposed. The Bayesian viewpoint is discussed.
k

‐means Analysis
Authors: Wishart David 
Published: September 2014

Abstract

Optimization methods for cluster analysis are described, in particular,
k
‐means analysis. It is shown that the original naïve
k
‐means algorithm will not always converge, whereas an exact assignment test for
k
‐means analysis converges to an optimal solution for the Euclidean sum of squares in finite time. A general optimization method is defined for use with any criterion function, for example, an information content statistic or sum of squared distances. The general optimization method also converges provided that the selected criterion function has a theoretical lower bound. The use of random trials to search for the global optimal solution is developed, and the reproducibility of different
k
‐means solutions is discussed. Outlier deletion in
k
‐means analysis helps to tighten a descriptive classification, and a dendrogram for
k
‐means analysis is developed to illustrate the data structure.
Nonparametric correlation (r subscript s)
Authors: Howell David C. 
Published: September 2014

Abstract

Spearman's correlation coefficient (
r

S

) for ranked data, often known as Spearman's rho, actually represents the standard Pearson product‐moment correlation applied to ranked data. Data on
X
and
Y
are replaced by their ranks, and then the correlation between the ranks is computed.
Kruskal‐Wallis Test: Basic
Authors: Sawilowsky Shlomo , Fahoome Gail 
Published: September 2014

AbstractThe nonparametric Kruskal‐Wallis test is an extension of the Wilcoxon‐Mann‐Whitney test. The null hypothesis is that thekpopulations sampled have the same average (median). The alternative hypothesis is that at least one sample is from a distribution with a different average (median). This test is an alternative to the parametric one‐way analysis of variance F test.