Irvine, CA, United States

University of California at Irvine
Irvine, CA, United States

The University of California, Irvine , is a public research university located in Irvine, California, and one of the 10 general campuses in the University of California system. UCI has over 30,000 students, 1,100 faculty members and 9,000 staff. Times Higher Education in 2013 ranked UC Irvine 1st among all US universities and 5th among the top 100 global universities under 50 years old.UC Irvine is considered a Public Ivy and offers 80 undergraduate degrees and 98 graduate and professional degrees. The university is designated as having very high research activity in the Carnegie Classification of Institutions of Higher Education, and in fiscal year 2012 had $350 million in research and development expenditures according to the National Science Foundation. UC Irvine became a member of the Association of American Universities in 1996, and is the youngest university to hold membership. The university also administers the UC Irvine Medical Center, a large teaching hospital, and its affiliated health science system in the city of Orange; the University of California, Irvine, Arboretum; and a portion of the University of California Natural Reserve System.UCI was one of three new UC campuses established in the 1960s to accommodate growing enrollments across the UC system. A site in Orange County was identified in 1959, and in the following year the Irvine Company sold the University of California 1,000 acres of land for one dollar to establish the new campus. President Lyndon B. Johnson dedicated the campus in 1964.The UC Irvine Anteaters compete in 18 men's and women's sports in the NCAA Division I as members of the Big West Conference and the Mountain Pacific Sports Federation. The Anteaters have won 28 national championships in nine different team sports, 64 Anteaters have won individual national championships, and 53 Anteaters have competed in the Olympics. Wikipedia.

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Fruman D.A.,University of California at Irvine | Rommel C.,Amgen Inc.
Nature Reviews Drug Discovery | Year: 2014

The central role of phosphoinositide 3-kinase (PI3K) activation in tumour cell biology has prompted a sizeable effort to target PI3K and/or downstream kinases such as AKT and mammalian target of rapamycin (mTOR) in cancer. However, emerging clinical data show limited single-agent activity of inhibitors targeting PI3K, AKT or mTOR at tolerated doses. One exception is the response to PI3Kδ inhibitors in chronic lymphocytic leukaemia, where a combination of cell-intrinsic and -extrinsic activities drive efficacy. Here, we review key challenges and opportunities for the clinical development of inhibitors targeting the PI3K-AKT-mTOR pathway. Through a greater focus on patient selection, increased understanding of immune modulation and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anticancer agents..©2014 Macmillan Publishers Limited. All rights reserved.

Striedter G.F.,University of California at Irvine
Journal of Comparative Neurology | Year: 2016

Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions. J. Comp. Neurol. 524:496-517, 2016. © 2016 Wiley Periodicals, Inc.

Hickok G.,University of California at Irvine
Nature Reviews Neuroscience | Year: 2012

Speech production has been studied predominantly from within two traditions, psycholinguistics and motor control. These traditions have rarely interacted, and the resulting chasm between these approaches seems to reflect a level of analysis difference: whereas motor control is concerned with lower-level articulatory control, psycholinguistics focuses on higher-level linguistic processing. However, closer examination of both approaches reveals a substantial convergence of ideas. The goal of this article is to integrate psycholinguistic and motor control approaches to speech production. The result of this synthesis is a neuroanatomically grounded, hierarchical state feedback control model of speech production. © 2012 Macmillan Publishers Limited. All rights reserved.

Ehlert F.J.,University of California at Irvine
Trends in Pharmacological Sciences | Year: 2015

Contemporary analysis of the functional responses of G-protein-coupled receptors (GPCRs) usually addresses drug-receptor interactions from the perspective of the average behavior of the receptor population. This behavior is characterized in terms of observed affinity and efficacy. Efficacy is a measure of how well a drug activates the receptor population and observed affinity a measure of how potently a drug occupies the receptor population. The latter is quantified in terms of the dissociation constant of the ligand-receptor complex. At a deeper level of analysis, drug-receptor interactions are described in terms of ligand affinity constants for active and inactive receptor states. Unlike observed affinity and efficacy, estimates of receptor state affinity constants are unperturbed by G proteins, guanine nucleotides, or other signaling proteins that interact with the receptor. Recent advances in the analysis of the functional responses of GPCRs have enabled the estimation of receptor state affinity constants. These constants provide a more fundamental measure of drug-receptor interactions and are useful in analyzing structure-activity relationships and in quantifying allosterism, biased signaling, and receptor-subtype selectivity. © 2015 Elsevier Ltd. All rights reserved.

Lander A.D.,University of California at Irvine
Cell | Year: 2011

Systems biology seeks not only to discover the machinery of life but to understand how such machinery is used for control, i.e., for regulation that achieves or maintains a desired, useful end. This sort of goal-directed, engineering-centered approach also has deep historical roots in developmental biology. Not surprisingly, developmental biology is currently enjoying an influx of ideas and methods from systems biology. This Review highlights current efforts to elucidate design principles underlying the engineering objectives of robustness, precision, and scaling as they relate to the developmental control of growth and pattern formation. Examples from vertebrate and invertebrate development are used to illustrate general lessons, including the value of integral feedback in achieving set-point control; the usefulness of self-organizing behavior; the importance of recognizing and appropriately handling noise; and the absence of "free lunch." By illuminating such principles, systems biology is helping to create a functional framework within which to make sense of the mechanistic complexity of organismal development. © 2011 Elsevier Inc.

Poulos T.L.,University of California at Irvine
Chemical Reviews | Year: 2014

The review focuses on those enzymes that catalyze oxidation reactions and those for which crystal structures are available. There are two broad classes of heme enzyme oxidants: oxygenases that use O2 to oxidize, oxygenate, substrates and peroxidases that use 2O2 to oxidize. The review demonstrates that out of the oxidants molecular oxygen is the most unusual, as O2 is not a reactive molecule despite the oxidation of nearly all biological molecules by O2 being a thermodynamically favorable process. The reason is that there is a large kinetic barrier to these reactions owing to O2 being a paramagnetic molecule so that the reaction between a majority of biological molecules that have paired spins is a spin forbidden process.

Alicea J.,University of California at Irvine
Reports on Progress in Physics | Year: 2012

The 1937 theoretical discovery of Majorana fermions - whose defining property is that they are their own anti-particles - has since impacted diverse problems ranging from neutrino physics and dark matter searches to the fractional quantum Hall effect and superconductivity. Despite this long history the unambiguous observation of Majorana fermions nevertheless remains an outstanding goal. This review paper highlights recent advances in the condensed matter search for Majorana that have led many in the field to believe that this quest may soon bear fruit. We begin by introducing in some detail exotic topological one- and two-dimensional superconductors that support Majorana fermions at their boundaries and at vortices. We then turn to one of the key insights that arose during the past few years; namely, that it is possible to engineer such exotic superconductors in the laboratory by forming appropriate heterostructures with ordinary s-wave superconductors. Numerous proposals of this type are discussed, based on diverse materials such as topological insulators, conventional semiconductors, ferromagnetic metals and many others. The all-important question of how one experimentally detects Majorana fermions in these setups is then addressed. We focus on three classes of measurements that provide smoking-gun Majorana signatures: tunneling, Josephson effects and interferometry. Finally, we discuss the most remarkable properties of condensed matter Majorana fermions - the non-Abelian exchange statistics that they generate and their associated potential for quantum computation. © 2012 IOP Publishing Ltd.

Principe D.R.,University of California at Irvine
Journal of the National Cancer Institute | Year: 2014

Several mechanisms underlying tumor progression have remained elusive, particularly in relation to transforming growth factor beta (TGF-β). Although TGF-β initially inhibits epithelial growth, it appears to promote the progression of advanced tumors. Defects in normal TGF-β pathways partially explain this paradox, which can lead to a cascade of downstream events that drive multiple oncogenic pathways, manifesting as several key features of tumorigenesis (uncontrolled proliferation, loss of apoptosis, epithelial-to-mesenchymal transition, sustained angiogenesis, evasion of immune surveillance, and metastasis). Understanding the mechanisms of TGF-β dysregulation will likely reveal novel points of convergence between TGF-β and other pathways that can be specifically targeted for therapy.

Borovik A.S.,University of California at Irvine
Chemical Society Reviews | Year: 2011

The functionalization of C-H bonds has yet to achieve widespread use in synthetic chemistry in part because of the lack of synthetic reagents that function in the presence of other functional groups. These problems have been overcome in enzymes, which have metal-oxo active sites that efficiently and selectively cleave C-H bonds. How high-energy metal-oxo transient species can perform such difficult transformations with high fidelity is discussed in this tutorial review. Highlighted are the relationships between redox potentials and metal-oxo basicity on C-H bond activation, as seen in a series of bioinspired manganese-oxo complexes. © 2011 The Royal Society of Chemistry.

Grando S.A.,University of California at Irvine
Nature Reviews Cancer | Year: 2014

This Opinion article discusses emerging evidence of direct contributions of nicotine to cancer onset and growth. The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing. © 2014 Macmillan Publishers Limited.

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