Institution
University of Hamburg
Education•Hamburg, Germany•
About: University of Hamburg is a education organization based out in Hamburg, Germany. It is known for research contribution in the topics: Population & Laser. The organization has 45564 authors who have published 89286 publications receiving 2850161 citations. The organization is also known as: Hamburg University.
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TL;DR: This study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts.
Abstract: The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts.
935 citations
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TL;DR: It is shown that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice, and functional circulating MICs and associated markers are described to aid the design of better tools to diagnose and treat metastatic breast cancer.
Abstract: It has been hypothesized that carcinoma metastasis is initiated by a subpopulation of circulating tumor cells (CTCs) found in the blood of patients. However, although the presence of CTCs is an indicator of poor prognosis in several carcinoma entities, the existence and phenotype of metastasis-initiating cells (MICs) among CTCs has not been experimentally demonstrated. Here we developed a xenograft assay and used it to show that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice. These MIC-containing CTC populations expressed EPCAM, CD44, CD47 and MET. In a small cohort of patients with metastases, the number of EPCAM(+)CD44(+)CD47(+)MET(+) CTCs, but not of bulk EPCAM(+) CTCs, correlated with lower overall survival and increased number of metastasic sites. These data describe functional circulating MICs and associated markers, which may aid the design of better tools to diagnose and treat metastatic breast cancer.
930 citations
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TL;DR: This review has summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.
Abstract: I. Introduction STEROID hormones are essential constituents of the intercellular communication system that maintains homeostasis in higher organisms. Glucocorticoids, a major subclass of steroid hormones, modulate a large number of metabolic, cardiovascular, immune, and behavioral functions (for a review see Refs. 1 and 2). Glucocorticoids are produced by the adrenal cortex under the regulatory influence of ACTH. The latter is produced by corticotrophs of the anterior pituitary, in turn, under the regulatory influence of hypothalamic CRH and arginine vasopressin (AVP). The hypothalamic-pituitary-adrenal (HPA) axis is kept in balance by the negative feedback effects of cortisol on the secretion of ACTH, CRH, and usually, to a lesser extent, AVP. In the resting state, basal levels of CRH, AVP, ACTH, and cortisol are released in a pulsatile and circadian fashion. At these baseline levels, the main function of cortisol is to sustain normoglycemia and to prevent arterial hypotension. Whether and to what extent...
930 citations
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TL;DR: The ability to obtain direct time-domain access to charge dynamics with attosecond resolution by probing photoelectron emission from single-crystal tungsten is demonstrated and illustrates thatAttosecond metrology constitutes a powerful tool for exploring not only gas-phase systems, but also fundamental electronic processes occurring on the attose Cond timescale in condensed-matter systems and on surfaces.
Abstract: Electrons move in solids at very high speed — traversing atomic layers and interfaces within tens to hundreds of attoseconds (an attosecond is a billionth of a billionth of a second). These astonishingly brief travel times will ultimately limit the speed of the electronics of the future. Physicists have now experimentally probed such electron dynamics in real time. The cover illustrates the first attosecond spectroscopic measurement in a solid, revealing a 110-attosecond difference in the travel time of two different types of electrons following photoexcitation in a tungsten crystal. The ability to time electrons moving in solids over merely a few interatomic distances makes it possible to probe the solid-state electronic processes occurring at the ultimate speed limit and thus helps to advance technologies such as computation, data storage and photovoltaics, which all rely on exquisite control of electron transport in ever smaller structures of solid matter. When exposing a tungsten crystal to intense light, the travel times of emitted electrons differ by 110 attoseconds, depending on whether they were originally tightly bound to one atom in the crystal or delocalized over many atoms. This ability to directly probe fundamental aspects of solid-state electron dynamics could aid the further development of modern technologies such as electronics, information processing and photovoltaics. Comprehensive knowledge of the dynamic behaviour of electrons in condensed-matter systems is pertinent to the development of many modern technologies, such as semiconductor and molecular electronics, optoelectronics, information processing and photovoltaics. Yet it remains challenging to probe electronic processes, many of which take place in the attosecond (1 as = 10-18 s) regime. In contrast, atomic motion occurs on the femtosecond (1 fs = 10-15 s) timescale and has been mapped in solids in real time1,2 using femtosecond X-ray sources3. Here we extend the attosecond techniques4,5 previously used to study isolated atoms in the gas phase to observe electron motion in condensed-matter systems and on surfaces in real time. We demonstrate our ability to obtain direct time-domain access to charge dynamics with attosecond resolution by probing photoelectron emission from single-crystal tungsten. Our data reveal a delay of approximately 100 attoseconds between the emission of photoelectrons that originate from localized core states of the metal, and those that are freed from delocalized conduction-band states. These results illustrate that attosecond metrology constitutes a powerful tool for exploring not only gas-phase systems, but also fundamental electronic processes occurring on the attosecond timescale in condensed-matter systems and on surfaces.
929 citations
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TL;DR: The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events.
Abstract: Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques. These experiments identify binding events either by looking at the resonance signals of the ligand or the protein. Ideally, both techniques together deliver a complete picture of ligand binding to a receptor. The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events. Also, characterization of the binding strength and kinetics is possible, competitive binding as well as allosteric effects can be identified, and it has even been possible to identify ligand binding to intact viruses and membrane-bound proteins.
927 citations
Authors
Showing all 46072 results
Name | H-index | Papers | Citations |
---|---|---|---|
Rudolf Jaenisch | 206 | 606 | 178436 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Stefan Schreiber | 178 | 1233 | 138528 |
Chris Sander | 178 | 713 | 233287 |
Dennis J. Selkoe | 177 | 607 | 145825 |
Daniel R. Weinberger | 177 | 879 | 128450 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Bradley Cox | 169 | 2150 | 156200 |
Anders Björklund | 165 | 769 | 84268 |
J. S. Lange | 160 | 2083 | 145919 |
Hannes Jung | 159 | 2069 | 125069 |
Andrew D. Hamilton | 151 | 1334 | 105439 |
Jongmin Lee | 150 | 2257 | 134772 |
Teresa Lenz | 150 | 1718 | 114725 |
Stefanie Dimmeler | 147 | 574 | 81658 |