St. Jude Children's Research Hospital

About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.

TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection

Abstract: Respiratory infection with highly pathogenic influenza A viruses is characterized by the exuberant production of cytokines and chemokines and the enhanced recruitment of innate inflammatory cells. Here, we show that challenging mice with virulent influenza A viruses, including currently circulating H5N1 strains, causes the increased selective accumulation of a particular dendritic cell subset, the tipDCs, in the pneumonic airways. These tipDCs are required for the further proliferation of influenza-specific CD8(+) T cells in the infected lung, because blocking their recruitment in CCR2(-/-) mice decreases the numbers of CD8(+) effectors and ultimately compromises virus clearance. However, diminution rather than total elimination of tipDC trafficking by treatment with the peroxisome proliferator-activated receptor-gamma agonist pioglitazone moderates the potentially lethal consequences of excessive tipDC recruitment without abrogating CD8(+) T cell expansion or compromising virus control. Targeting the tipDCs in this way thus offers possibilities for therapeutic intervention in the face of a catastrophic pandemic.

The confounding effect of class size on the validity of object-oriented metrics

Abstract: Much effort has been devoted to the development and empirical validation of object-oriented metrics. The empirical validations performed thus far would suggest that a core set of validated metrics is close to being identified. However, none of these studies allow for the potentially confounding effect of class size. We demonstrate a strong size confounding effect and question the results of previous object-oriented metrics validation studies. We first investigated whether there is a confounding effect of class size in validation studies of object-oriented metrics and show that, based on previous work, there is reason to believe that such an effect exists. We then describe a detailed empirical methodology for identifying those effects. Finally, we perform a study on a large C++ telecommunications framework to examine if size is really a confounder. This study considered the Chidamber and Kemerer metrics and a subset of the Lorenz and Kidd metrics. The dependent variable was the incidence of a fault attributable to a field failure (fault-proneness of a class). Our findings indicate that, before controlling for size, the results are very similar to previous studies. The metrics that are expected to be validated are indeed associated with fault-proneness.

A note on Gauss—Hermite quadrature

Abstract: SUMMARY For Gauss-Hermite quadrature, we consider a systematic method for transforming the variable of integration so that the integrand is sampled in an appropriate region. The effectiveness of the quadrature then depends on the ratio of the integrand to some Gaussian density being a smooth function, well approximated by a low-order polynomial. It is pointed out that, in this approach, order one Gauss-Hermite quadrature becomes the Laplace approximation. Thus the quadrature as implemented here can be thought of as a higher-order Laplace approximation.

Programmed necrosis in inflammation: Toward identification of the effector molecules

Abstract: Until recently, programmed cell death was conceived of as a single set of molecular pathways. We now know of several distinct sets of death-inducing mechanisms that lead to differing cell-death processes. In one of them--apoptosis--the dying cell affects others minimally. In contrast, programmed necrotic cell death causes release of immunostimulatory intracellular components after cell-membrane rupture. Defining the in vivo relevance of necrotic death is hampered because the molecules initiating it [such as receptor-interacting protein kinase-1 (RIPK1), RIPK3, or caspase-1] also serve other functions. Proteins that participate in late events in two forms of programmed necrosis [mixed lineage kinase domain-like protein (MLKL) in necroptosis and gasdermin-D in pyroptosis] were recently discovered, bringing us closer to identifying molecules that strictly serve in death mediation, thereby providing probes for better assessing its role in inflammation.