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Institution

Vanderbilt University

EducationNashville, Tennessee, United States
About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.


Papers
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Journal ArticleDOI
TL;DR: This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen–host interface and investigates both the essentiality and toxicity of transition metals in biological systems.
Abstract: Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface.

1,206 citations

Journal ArticleDOI
TL;DR: Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b5, divalent cations, and acidic phospholipid systems for optimal activity.
Abstract: Cytochrome P-450 (P-450) 3A4 is the most abundant P-450 expressed in human liver and small intestine. P-450 3A4 contributes to the metabolism of approximately half the drugs in use today, and variations in its catalytic activity are important in issues of bioavailability and drug-drug interactions. The gene is known to be inducible by barbiturates, glucocorticoids, and rifampicin in humans and in isolated hepatocytes, although the mechanism remains unclear. The 5'-untranslated region includes putative basal transcription element, hepatocyte nuclear factor, p53, AP-3, glucocorticoid regulatory element, pregnane X receptor, and estrogen receptor element sequences. Recently, the GRE element has been shown to act in a classic glucocorticoid response. Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b5, divalent cations, and acidic phospholipid systems for optimal activity. Another issue involves the basis of the homotropic and heterotropic cooperativity seen with the enzyme. The in vivo significance of these findings remains to be further established. In addition to more basic studies on P-450 3A4, several areas of practical interest to the pharmaceutical industry require development.

1,202 citations

Journal ArticleDOI
TL;DR: A novel region-based method for image segmentation, which is able to simultaneously segment the image and estimate the bias field, and the estimated bias field can be used for intensity inhomogeneity correction (or bias correction).
Abstract: Intensity inhomogeneity often occurs in real-world images, which presents a considerable challenge in image segmentation. The most widely used image segmentation algorithms are region-based and typically rely on the homogeneity of the image intensities in the regions of interest, which often fail to provide accurate segmentation results due to the intensity inhomogeneity. This paper proposes a novel region-based method for image segmentation, which is able to deal with intensity inhomogeneities in the segmentation. First, based on the model of images with intensity inhomogeneities, we derive a local intensity clustering property of the image intensities, and define a local clustering criterion function for the image intensities in a neighborhood of each point. This local clustering criterion function is then integrated with respect to the neighborhood center to give a global criterion of image segmentation. In a level set formulation, this criterion defines an energy in terms of the level set functions that represent a partition of the image domain and a bias field that accounts for the intensity inhomogeneity of the image. Therefore, by minimizing this energy, our method is able to simultaneously segment the image and estimate the bias field, and the estimated bias field can be used for intensity inhomogeneity correction (or bias correction). Our method has been validated on synthetic images and real images of various modalities, with desirable performance in the presence of intensity inhomogeneities. Experiments show that our method is more robust to initialization, faster and more accurate than the well-known piecewise smooth model. As an application, our method has been used for segmentation and bias correction of magnetic resonance (MR) images with promising results.

1,201 citations

Journal ArticleDOI
TL;DR: Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation, which may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.
Abstract: Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.

1,201 citations


Authors

Showing all 45403 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Meir J. Stampfer2771414283776
John Q. Trojanowski2261467213948
Robert M. Califf1961561167961
Matthew Meyerson194553243726
Scott M. Grundy187841231821
Tony Hunter175593124726
David R. Jacobs1651262113892
Donald E. Ingber164610100682
L. Joseph Melton16153197861
Ralph A. DeFronzo160759132993
David W. Bates1591239116698
Charles N. Serhan15872884810
David Cella1561258106402
Jay Hauser1552145132683
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023141
2022540
20215,134
20205,232
20194,883
20184,649