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Institution

Yale University

EducationNew Haven, Connecticut, United States
About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.


Papers
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Journal ArticleDOI
07 Jul 2005-Nature
TL;DR: It is suggested that MITF represents a distinct class of ‘ lineage survival’ or ‘lineage addiction’ oncogenes required for both tissue-specific cancer development and tumour progression, and Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm.
Abstract: Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification. We found that MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. BRAF mutation and p16 inactivation accompanied MITF amplification in melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression.

1,455 citations

Journal ArticleDOI
01 Jan 1994-Nature
TL;DR: Skin appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells, and if this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p 53-mutated cell into the AK.
Abstract: Squamous cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratinocytes; actinic keratosis (AK), spontaneously regressing keratinized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in > 90% of human SCCs were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.

1,455 citations

Journal ArticleDOI
TL;DR: Internal Organization of the Plant Body, from embryo to the Adult Plant, and some Factors in Development of Secondary Xylem: Common Types of Secondary Growth.
Abstract: INTRODUCTION. Internal Organization of the Plant Body. Summary of Types of Cells and Tissues. General References. DEVELOPMENT OF THE SEED PLANT. The Embryo. From embryo to the Adult Plant. Apical Meristems and Their Derivatives. Differentiation, Specialization, and Morphogenesis. References. THE CELL. Cytoplasm. Nucleus. Plastids. Mitochondria. Microbodies. Vacuoles. Paramural Bodies. Ribosomes. Dictyosomes. Endoplasmic Reticulum. Lipid Globules. Microtubules. Ergastic Substances. References. CELL WALL. Macromolecular Components and Their Organization in the Wall. Cell Wall Layers. Intercellular Spaces. Pits, Primary Pit--Fields, and Plasmodesmata. Origin of Cell Wall During Cell Division. Growth of Cell Wall. References. PARENCHYMA AND COLLENCHYMA. Parenchyma. Collenchyma. References. SCLERENCHYMA. Sclereids. Fibers. Development of Sclereids and Fibers. References. EPIDERMIS. Composition. Developmental Aspects. Cell Wall. Stomata. Trichomes. References. XYLEM: GENERAL STRUCTURE AND CELL TYPES. Gross Structure of Secondary Xylem. Cell Types in the Secondary Xylem. Primary Xylem. Differentiation of Tracheary Elements. References. XYLEM: VARIATION IN WOOD STRUCTURE. Conifer Wood. Dicotyledon Wood. Some Factors in Development of Secondary Xylem. Identification of Wood. References. VASCULAR CAMBIUM. Organization of Cambium. Developmental Changes in the Initial Layer. Patterns and Causal Relations in Cambial Activity. References. PHLOEM. Cell Types. Primary Phloem. Secondary Phloem. References. PERIDERM. Structure of Periderm and Related Tissues. Development of Periderm. Outer Aspect of Bark in Relation to Structure. Lenticels. References. SECRETORY STRUCTURES. External Secretory Structures. Internal Secretory Structures. References. THE ROOT: PRIMARY STATE OF GROWTH. Types of Roots. Primary Structure. Development. References. THE ROOT: SECONDARY STATE OF GROWTH AND ADVENTITIOUS ROOTS. Common Types of Secondary Growth. Variations in Secondary Growths. Physiologic Aspects of Secondary Growth in Roots. Adventitious Roots. References. THE STEM: PRIMARY STATE OF GROWTH. External Morphology. Primary Structure. Development. References. THE STEM: SECONDARY GROWTH AND STRUCTURAL TYPES. Secondary Growth. Types of Stems. References. THE LEAF: BASIC STRUCTURE AND DEVELOPMENT. Morphology. Histology of Angiosperm Leaf. Development. Abscission. References. THE LEAF: VARIATIONS IN STRUCTURE. Leaf Structure and Environment. Dicotyledon Leaves. Monocotyledon Leaves. Gymnosperm Leaves. References. THE FLOWER: STRUCTURE AND DEVELOPMENT. Concept. Structure. Development. References. THE FLOWER: REPRODUCTIVE CYCLE. Microsporogenesis. Pollen. Male Gametophyte. Megasporogenesis. Female Gametophyte. Fertilization. References. THE FRUIT. Concept and Classification. The Fruit Wall. Fruit Types. Fruit Growths. Fruit Abscission. References. THE SEED. Concept and Morphology. Seed Development. Seed Coat. Nutrient Storage Tissues. References. EMBRYO AND SEEDLING. Mature Embryo. Development of Embryo. Classification of Embryos. Seedling. References. Glossary. Index.

1,454 citations

Journal ArticleDOI
TL;DR: A redshift quality parameter, -->Qz, is introduced, which provides a robust estimate of the reliability of the photometric redshift estimate, and is provided for the FIRES, MUSYC, and FIREWORKS surveys.
Abstract: We describe a new program for determining photometric redshifts, dubbed EAZY. The program is optimized for cases where spectroscopic redshifts are not available, or are only available for a biased subset of the galaxies. The code combines features from various existing codes: it can fit linear combinations of templates, it includes optional flux- and redshift-based priors, and its user interface is modeled on the popular HYPERZ code. A novel feature is that the default template set, as well as the default functional forms of the priors, are not based on (usually highly biased) spectroscopic samples, but on semianalytical models. Furthermore, template mismatch is addressed by a novel rest-frame template error function. This function gives different wavelength regions different weights, and ensures that the formal redshift uncertainties are realistic. We introduce a redshift quality parameter, -->Qz, which provides a robust estimate of the reliability of the photometric redshift estimate. Despite the fact that EAZY is not trained on spectroscopic samples, the code (with default parameters) performs very well on existing public data sets. For K-selected samples in CDF-South and other deep fields, we find a 1 ? scatter in -->? z/(1 + z) of 0.034, and we provide updated photometric redshift catalogs for the FIRES, MUSYC, and FIREWORKS surveys.

1,454 citations

Journal ArticleDOI
03 Oct 2008-Science
TL;DR: A comparative quality assessment of current yeast interactome data sets is carried out, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information.
Abstract: Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a "second-generation" high-quality, high-throughput Y2H data set covering approximately 20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.

1,452 citations


Authors

Showing all 91064 results

NameH-indexPapersCitations
Richard A. Flavell2311328205119
Eugene Braunwald2301711264576
Matthias Mann221887230213
Bruce S. McEwen2151163200638
Robert J. Lefkowitz214860147995
Edward Giovannucci2061671179875
Rakesh K. Jain2001467177727
Francis S. Collins196743250787
Lewis C. Cantley196748169037
Martin White1962038232387
Ronald Klein1941305149140
Thomas C. Südhof191653118007
Michael Rutter188676151592
David H. Weinberg183700171424
Douglas R. Green182661145944
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023381
20221,783
202112,465
202011,877
201910,264
20189,234