Irvine, CA, United States
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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Dewan S.,University of California at Irvine | Ren F.,Peking University
Information Systems Research | Year: 2011

In this paper, we empirically investigate the impact of information technology (IT) investment on firm return and risk financial performance, emphasizing the moderating role of the firm boundary strategies of diversification and vertical integration. Our results indicate a sharp contrast between the direct and interactive effects of IT on both the return (profitability) and risk (variability of returns) dimensions. Although the direct effect of IT capital is to increase firm risk for a given level of return, we find that suitable boundary strategies can moderate the impact of IT on firm performance in a way that increases return and decreases risk, at the margin. This interaction effect is strongest in service firms, in firms with high levels of IT investment intensity, and in more recent time periods. Our results are robust to alternative proxies for firm risk, including an ex ante risk measure (variability of analysts' earnings estimates), and alternative risk-return specifications. Put together, our results provide new insights into how IT and firm boundary strategies interact to affect the risk and return performance of firms. © 2011 INFORMS.

Spasojevic M.J.,University of California at Irvine | Spasojevic M.J.,University of California at Davis | Suding K.N.,University of California at Berkeley
Journal of Ecology | Year: 2012

Many studies of community assembly focus on two mechanisms: environmental filtering and competitive interactions. This focus ignores the importance of other assembly processes such as equalizing fitness processes and facilitation. The contribution of different processes to community assembly can be elucidated by examining functional diversity patterns of traits that differ in their contribution to different assembly processes. In alpine tundra, we explored trait patterns along a stress-resource gradient that varied in productivity, nitrogen availability and soil moisture. We explore whether functional diversity is low in abiotic stressful environments and increases in more benign environments as competition becomes more important, and if equalizing fitness processes and facilitation affect functional diversity. We calculated community-weighted mean trait values and functional diversity for specific leaf area (SLA), leaf area, stomatal conductance, plant height and chlorophyll content as well as multivariate functional diversity and phylogenetic diversity. At the community level, functional diversity increased at both ends of the gradient: high resource availability was associated with greater functional diversity in height and leaf area, and lower resource availability was associated with greater functional diversity in SLA, stomatal conductance, and chlorophyll content. As a result of this trade-off in functional diversity among traits, multivariate functional diversity did not change across the gradient. Phylogenetic diversity increased with increasing resource availability. We find evidence for at least three assembly processes along the gradient. Abiotic filtering by wind and cold exposure may reduce functional diversity in height and leaf area at the low resource end of the gradient. Also at low resource availability, increasing functional diversity in the other three traits suggests competition for below-ground resources. At the resource-rich end of the gradient, increased functional diversity in height and leaf area suggests increased competition for light or facilitation. Synthesis:Our results suggest that multiple assembly processes (abiotic filtering, above-ground competition, and below-ground competition) operate simultaneously to structure plant communities along a stress-resource gradient. These processes would be obscured by a single multivariate trait index or phylogenetic diversity and are only evident by analysing functional diversity patterns of individual traits. © 2011 The Authors. Journal of Ecology © 2011 British Ecological Society.

McKenney R.J.,Columbia University | Vershinin M.,University of California at Irvine | Kunwar A.,University of California at Davis | Vallee R.B.,Columbia University | Gross S.P.,University of California at Irvine
Cell | Year: 2010

Cytoplasmic dynein is responsible for many aspects of cellular and subcellular movement. LIS1, NudE, and NudEL are dynein interactors initially implicated in brain developmental disease but now known to be required in cell migration, nuclear, centrosomal, and microtubule transport, mitosis, and growth cone motility. Identification of a specific role for these proteins in cytoplasmic dynein motor regulation has remained elusive. We find that NudE stably recruits LIS1 to the dynein holoenzyme molecule, where LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle. NudE abrogates dynein force production, whereas LIS1 alone or with NudE induces a persistent-force dynein state that improves ensemble function of multiple dyneins for transport under high-load conditions. These results likely explain the requirement for LIS1 and NudE in the transport of nuclei, centrosomes, chromosomes, and the microtubule cytoskeleton as well as the particular sensitivity of migrating neurons to reduced LIS1 expression. © 2010 Elsevier Inc.

Kaplinghat M.,University of California at Irvine | Linden T.,University of Chicago | Yu H.-B.,University of California at Riverside
Physical Review Letters | Year: 2015

Observations by the Fermi Large-Area Telescope have uncovered a significant γ-ray excess directed toward the Milky Way Galactic Center. There has been no detection of a similar signal in the stacked population of Milky Way dwarf spheroidal galaxies. Additionally, astronomical observations indicate that dwarf galaxies and other faint galaxies are less dense than predicted by the simplest cold dark matter models. We show that a self-interacting dark matter model with a particle mass of roughly 50 GeV annihilating to the mediator responsible for the strong self-interaction can simultaneously explain all three observations. The mediator is necessarily unstable, and its mass must be below about 100 MeV in order to decrease the dark matter density of faint galaxies. If the mediator decays to electron-positron pairs with a cross section on the order of the thermal relic value, then we find that these pairs can up-scatter the interstellar radiation field in the Galactic center and produce the observed γ-ray excess. © 2015 American Physical Society.

Agency: GTR | Branch: EPSRC | Program: | Phase: Research Grant | Award Amount: 100.46K | Year: 2016

Nowadays, one of the focal approaches to pursue next generation low power consumption, multifunctional, and green nanoelectronics is to advance the electric field control of lattice, charge, orbital, and spin degrees of freedom. More sophisticated control of these degrees of freedom in new functional materials by external stimuli are desired. In order to control these degrees of freedom, a medium possessing the coupling between these degrees has to be established. The successful incorporation of ferroelectric and magnetic materials has led to a variety of technologies. To further enhance functionalities, as compared with conventional information storage and computer processing electronic devices, electric-field control of ferromagnetism/spin becomes an exciting new paradigm with the potential to impact data storage, spintronics and high-frequency devices. Promising solutions and a rich field of physics reside in the use of magnetoelectric multiferroics, in which the electric field can be employed to switch its magnetic order. Multiferroics that support both strong ferroelectric and magnetic orders are typically insulators with an antiferromagnetic spin arrangement. To achieve electric-field control of ferromagnetism, multiferroics have been used in the form of ferromagnet-multiferroic heterostructures. Among numerous multiferroic systems being explored, BiFeO3 (BFO) is currently the most studied and best understood. BFO exhibits large ferroelectric polarization and G-type antiferromagnetism with weak canted magnetic moment at room temperature making it appealing for applications in non-volatile logic and memory devices. The presence of ferroelectric-antiferromagnetic multiferroic BFO has offered an exciting opportunity for controlling spin through the application of an electric field. Although BFO sets an ideal template of manipulating the spin degree of freedom via electric field, before the realization of new devices, several key issues have to be solved. The primary control parameter is the ferroelectric switching. Solving the ferroelectric reliability issues, such as imprint, retention, and fatigue has to be made prior to realizing a practical device. For example, retention can be addressed to thermodynamic instability of the domain. Asymmetric free energy landscapes between polarizations directed away and toward the substrates result in at least one unstable polarization state. Effects of depolarization fields in the unstable domain become significant when the polarization bound charges are not fully screened. Although efforts on related studies have shown their ways to reduce the energy difference of the polarization double-well by controlling chemical environment, breaking the out-of-plane compositional symmetry, or using strain gradient, ferroelectric retention is still a key issue yet to be dealt with. In order to shed light on the retention problem, we intend to induce the elastic energy term to improve ferroelectric retention of BFO, since the ferroelectric switching of BFO involves a ferroelastic deformation. In our previous study, an observation on a giant improvement of retention in the mixed-phase region of a strained BFO film was found. By taking the advantages of periodic potential distribution, the T/R mixed phase boundaries act as pinning centers of domain walls in the relaxation process. Compared to the reversed domains written by SPM tips in other ferroelectrics, the symmetric potential design based on the BFO periodic strain suggests a possible solution to use elastic energy to improve ferroelectric retention. In this proposal, self-assembled BFO mesocrystal will serve as a model system. We expect the elastic coupling between BFO mesocrystal and surrounding matrix plays an important role to diminish the retention of BFO. The achievement of great improvement on the retention in this system will open a new avenue to ferroelectric retention and possible applications in non-volatile memory and spintronics.

Agency: GTR | Branch: AHRC | Program: | Phase: Research Grant | Award Amount: 312.28K | Year: 2015

This project assesses the architectural legacy of The Troubles, the social-historical phenomenon between 1969 and 1994 when the sectarian conflict in Northern Ireland was at its most extreme. The influence of The Troubles was such that it has had a profound impact on the social, political, economic, cultural and spatial structures of Northern Ireland. There are many visible architectural remnants of the Troubles in contemporary Belfast, most notably the peace-walls between a number of Protestant and Roman Catholic residential communities. Quite distinct from this recognised architectural legacy, this research encapsulates a specific, discrete and barely recognised aspect of the cultural structures of The Troubles: a range of distinct and divisive architecture within individual communities in Belfast, now embedded in the contemporary urban fabric. As Northern Ireland moves forward in a post-Troubles era, a plethora of housing, roads, landscaping and related artefacts continue to divide and spatially fragment communities. The research conceives of a community as a construct of People and Architecture, an intrinsic inter-relationship between people and their built environment. Community, housing, and security in Belfast are intricately linked. During The Troubles 70% of bombings were aimed at housing in the Belfast Urban Area. The residential inner-city was subject to fundamental architectural alterations by both civilian and security authorities. These interventions resulted in a profound material impact upon inner-city communities, creating architectural and spatial disconnection that has promoted deprivation and disenfranchisement within these communities. These areas that are at now at the focus of the Together: Building a United Community Strategy, the core policy framework for post-conflict Northern Ireland, which emphasises the role communities will have to play in shaping their own future. Whilst there has been much work in the areas of planning policy, sociology and human geography concerning The Troubles, there is a distinct lack of architectural research in this area, particularly concerning architectural design and the relationship to communities during conflict. This study addresses this gap in knowledge, and equip local communities and policy makers with a crucial knowledge-base that is pertinent to contemporary policy formulation. The overarching aim of this research is to effect material change in the community life of some of Belfasts most deprived urban areas. The research conceives of a city-wide study that will examine the architectural legacy of The Troubles and engage local communities with these findings in order to inclusively inform related policy formulation. This suggests four questions: What do these architectural artefacts look like? What do communities have to say about this architecture? How can this research inform the related and relevant policy discussions? What are the lessons for other communities, at both national and international level? These questions formulate the following objectives: to engage this area of arts & humanities research with community and policy stakeholders; to foster community empowerment through structured, active inclusion with policy makers; to illuminate and illustrate the urban impact of conflict in Belfasts communities; and, to develop a transferable method to engage local communities as active-researchers of their built environment. A community as a construct of People and Architecture involves a complex inter-relationship between community, design practice and policy ambition. A cross-disciplinary research team addresses this research context. Academics from architecture, photography, social policy, planning policy and conflict studies are working with community project partners and government agencies. This team have developed a co-designed, collaborative methodology with embedded pathways to community, policy, public and academic impact.

Whooley M.A.,University of California at San Francisco | Wong J.M.,University of California at Irvine
Annual Review of Clinical Psychology | Year: 2013

During the past two decades, research in the field of depression and cardiovascular disorders has exploded. Multiple studies have demonstrated that depression is more prevalent in populations with cardiovascular disease, is a robust risk factor for the development of cardiovascular disease in healthy populations, and is predictive of adverse outcomes (such as myocardial infarction and death) among populations with preexisting cardiovascular disease. Mechanistic studies have shown that poor health behaviors, such as physical inactivity, medication nonadherence, and smoking, strongly contribute to this association. Small randomized trials have found that antidepressant therapies may improve cardiac outcomes. Based on this accumulating evidence, the American Heart Association has recommended routine screening for depression in all patients with coronary heart disease. This review examines the key epidemiological literature on depression and cardiovascular disorders and discusses our current understanding of the mechanisms responsible for this association. We also examine current recommendations for screening, diagnosis, and management of depression. We conclude by highlighting new research areas and discussing therapeutic management of depression in patients with cardiovascular disorders. Copyright © 2013 by Annual Reviews.

Martiny J.B.H.,University of California at Irvine | Jones S.E.,University of Notre Dame | Lennon J.T.,Indiana University Bloomington | Martiny A.C.,University of California at Irvine
Science | Year: 2015

A focus on the phenotypic characteristics of microorganisms-their traits-offers a path for interpreting the growing amount of microbiome data.We review key aspects of microbial traits, as well as approaches used to assay their phylogenetic distribution. Recent studies reveal that microbial traits are differentially conserved across the tree of life and appear to be conserved in a hierarchical fashion, possibly linked to their biochemical complexity. These results suggest a predictive framework whereby the genetic (or taxonomic) resolution of microbiome variation among samples provides information about the traits under selection. The organizational parallels seen among human and free-living microbiomes seem to support this idea. Developments in this framework may offer predictions not only for how microbial composition responds to changing environmental conditions, but also for how these changes may alter the health or functioning in human, engineered, and environmental systems.

Lott I.T.,University of California at Irvine | Dierssen M.,CIBER ISCIII
The Lancet Neurology | Year: 2010

Improvements in medical interventions for people with Down's syndrome have led to a substantial increase in their longevity. Diagnosis and treatment of neurological complications are important in maintaining optimal cognitive functioning. The cognitive phenotype in Down's syndrome is characterised by impairments in morphosyntax, verbal short-term memory, and explicit long-term memory. However, visuospatial short-term memory, associative learning, and implicit long-term memory functions are preserved. Seizures are associated with cognitive decline and seem to cause additional decline in cognitive functioning, particularly in people with Down's syndrome and comorbid disorders such as autism. Vision and hearing disorders as well as hypothyroidism can negatively impact cognitive functioning in people with Down's syndrome. Dementia that resembles Alzheimer's disease is common in adults with Down's syndrome. Early-onset dementia in adults with Down's syndrome does not seem to be associated with atherosclerotic complications. © 2010 Elsevier Ltd. All rights reserved.

Said H.M.,University of California at Irvine | Said H.M.,Medical Center
Biochemical Journal | Year: 2011

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of themechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society.

Laskin A.,Environmental Molecular science Laboratory | Laskin J.,Pacific Northwest National Laboratory | Nizkorodov S.A.,University of California at Irvine
Chemical Reviews | Year: 2015

The chemistry of atmospheric brown carbon (BrC) is reviewed. BrC is now recognized as an important component in the atmosphere that affects climate forcing through a combination of direct effects on the transmission of solar and terrestrial radiation and indirect effects resulting from changes in cloud formation and microphysics. In addition, long-range transport and deposition of BrC most likely play a role in carbon and nitrogen cycling between atmosphere, land, and water and contribute to the formation of colored dissolved organic matter (CDOM). The existing evidence suggests that even a very small weight fraction of strongly absorbing BrC chromophores may have a distinct effect on organic aerosols (OA) optical properties. Because of the low concentrations of light-absorbing molecules in complex organic mixtures composing both laboratory-generated and ambient OA, identification of BrC chromophores is a very challenging task. Despite the analytical difficulties, several classes of compounds have been identified as potential contributors to light absorption by BrC. These include nitroaromatic compounds, such as nitrophenols, imidazole-based and other N-heterocyclic compounds, and quinines. The identification and structural characterization of BrC chromophores clearly require highly sensitive molecular characterization approaches capable of detecting both strongly and weakly absorbing species.

Tita G.E.,University of California at Irvine | Radil S.M.,University of Illinois at Urbana - Champaign
Journal of Quantitative Criminology | Year: 2011

The majority of spatial studies of crime employ an inductive approach in both the modeling and interpretation of the mechanisms of influence thought to be responsible for the patterning of crime in space and time. In such studies, the spatial weights matrix is specified without regard to the theorized mechanisms of influence between the units of analysis. Recently, a more deductive approach has begun to gain traction in which the theory of influence is used to model influence in geographic space. Using data from Los Angeles, we model the spatial distribution of gang violence by considering both the relative location of the gangs in space while simultaneously capturing their position within an enmity network of gang rivalries. We find that the spatial distribution of gang violence is more strongly associated with the socio-spatial dimensions of gang rivalries than it is with adjacency-based measures of spatial autocorrelation. © 2011 Springer Science+Business Media, LLC.

Agency: Department of Defense | Branch: Navy | Program: STTR | Phase: Phase I | Award Amount: 79.71K | Year: 2011

In this proposal, the team of Archinoetics and UCI define a program of research and development to develop a data collection and analysis system for human performance measurement that is (1) inexpensive, (2) modular, (3) easily extensible, and (4) that facilitates easy data analysis. Furthermore, in creating such a system, we will be leveraging know-how, lessons learned, as well as some technical building blocks from several similar multi-million dollar projects under both government and private funding; leverage that will substantially reduce the risks associated with this effort.

Chang Y.B.,Ulsan National Institute of Science and Technology | Gurbaxani V.,University of California at Irvine
MIS Quarterly: Management Information Systems | Year: 2012

Firms are increasingly sourcing internal information systems functions from external service providers. However, there is limited empirical evidence of the economic impact of this delivery option and, more specifically, of the productivity gains accruing to firms that have outsourced. Moreover, there is little evidence of the role and contributions of the individual mechanisms by which service providers create value for client firms. We are particularly interested in whether client firms benefit from the accumulated knowledge held by information technology (IT) service firms. In this paper, we examine the impact of IT outsourcing on the productivity of firms that choose this mode of services delivery focusing, on the role of IT-related knowledge. Since firms self-select into their optimal sourcing mode, we use a variety of econometric techniques including propensity score-based matching and switching regression to control for potential bias arising from endogenously determined sourcing modes. We demonstrate that IT outsourcing does lead to productivity gains for firms that select this mode of service delivery. Our results also suggest that IT-related knowledge held by IT services vendors enables these productivity gains, the magnitude of which is moderated by a firm's IT intensity. Moreover, the value of outsourcing to a client firm increases with its propensity for outsourcing, which in turn depends on firm-specific attributes including efficiency level, financial leverage, and variability in business conditions. Our analyses also show that firms that outsource have been able to achieve additional productivity gains from contracting out compared with their counterfactuals.

Agency: Department of Defense | Branch: Navy | Program: STTR | Phase: Phase I | Award Amount: 79.95K | Year: 2013

The NAVY solicits new non-destructive inspection (NDI) methods to address detection and evaluation of kissing bonds and bondline integrity in aerospace composites since no currently accepted standard exists. In response AS & T Inc. propose, the Conformal Array Laser Imager for Bondline Evaluation and Repair (CALIBER), designed expressly for this purpose. The novelty of the proposed approach lies in the integration of a new sensor technology developed by AS & T with a new NDI method, both of which have been independently developed well beyond the conceptual stage. The development of CALIBER will provide an NDI sensor whose output images reveal bondline adhesive strength and the lower threshold which qualify as kissing bonds. In form and function, CALIBER is geared towards field deployment. Founded on a previously successful NDI sensor developed for detection of hidden delaminations, disbonds and crushed core damage in composites, this effort therefore builds upon and broadens the applicability of a new NDI technology. The proposed development is anticipated to lead to a portable, non-contact inspection instrument for rapid detection and evaluation of kissing bonds in aerospace composites in addition to a broader range of flight-line composite NDI tasks.

Bai Y.,University of Wisconsin - Madison | Bai Y.,SLAC | Tait T.M.P.,University of California at Irvine
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

We explore the implications of the mono-lepton plus missing transverse energy signature at the LHC, and point out its significance on understanding how dark matter interacts with quarks, where the signature arises from dark matter pair production together with a leptonically decaying W boson radiated from the initial state quarks. We derive limits using the existing W' searches at the LHC, and find an interesting interference between the contributions from dark matter couplings to up-type and down-type quarks. Mono-leptons can actually furnish the strongest current bound on dark matter interactions for axial-vector (spin-dependent) interactions and iso-spin violating couplings. Should a signal of dark matter production be observed, this process can also help disentangle the dark matter couplings to up- and down-type quarks. © 2013 Elsevier B.V.

DeVries T.,University of California at Los Angeles | Primeau F.,University of California at Irvine
Journal of Physical Oceanography | Year: 2011

A data-constrained ocean circulation model is used to characterize the distribution of water masses and their ages in the global ocean. The model is constrained by the time-averaged temperature, salinity, and radiocarbon distributions in the ocean, as well as independent estimates of the mean sea surface height and sea surface heat and freshwater fluxes. The data-constrained model suggests that the interior ocean is ventilated primarily by water masses forming in the Southern Ocean. Southern Ocean waters, including those waters forming in the Antarctic and subantarctic regions, make up about 55% of the interior ocean volume and an even larger percentage of the deep-ocean volume. In the deep North Pacific, the ratio of Southern Ocean to North Atlantic waters is almost 3:1. Approximately 65% of interior ocean waters make first contact with the atmosphere in the Southern Ocean, further emphasizing the central role played by the Southern Ocean in the regulation of the earth's climate. Results of the age analysis suggest that the mean ventilation age of deep waters is greater than 1000 yr throughout most of the Indian and Pacific Oceans, reaching a maximum of about 1400-1500 yr in the middepth North Pacific. The mean time for deep waters to be reexposed at the surface also reaches a maximum of about 1400-1500 yr in the deep North Pacific. Together these findings suggest that the deep North Pacific can be characterized as a "holding pen" of stagnant and recirculating waters. © 2011 American Meteorological Society.

Loma Linda University, University of California at Los Angeles, University of California at Irvine and North Carolina State University | Date: 2015-04-02

A substance for treating a cerebral amyloid angiopathy related condition or disease affecting cerebrovasculature in a patient, comprising an inhibitor that causes inhibition of the formation of membrane attack complex of the complement system; and a vehicle for transporting the inhibitor into the cerebrovasculature; where the inhibition by the inhibitor is sufficient to decrease the incidence of or to prevent the incidence of cytolysis of the smooth muscle cells. A method for treating a cerebral amyloid angiopathy related condition or disease affecting cerebrovasculature in a patient, comprising: a) identifying a patient with a cerebral amyloid angiopathy related condition or disease; b) providing one or more than one substance that comprises an inhibitor that causes inhibition of the formation of membrane attack complex of the complement system, c) administering one or more than one dose of the one or more than one substance to the patient.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 1.31M | Year: 2011

DESCRIPTION (provided by applicant): The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries and veins to the blood vessels at the recipient site. These procedures enable reconstructive surgery after trauma, as well as after surgical resection of cancer. Flap transfer surgery is subject to failure via a number of modes including vascular insufficiency caused by mechanical obstruction of the artery or vein, injury caused to the transferred tissues due to the lack of blood flow during the flap transfer, or due to ischemia-reperfusion injury. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a free flap is a devastating experience to both the surgeon and the patient. Tissue oxygenation and maintenance of microvascular blood flow in grafted tissues are crucial for flap viability. Several studies have demonstrated that frequent monitoring and early detection of compromise results in earlier intervention which reduces the number of devastating complications that lead to tissue loss. Early in the era of microsurgery, flap monitoring was performed with only clinical observation of skin color, capillary refill, and dermal bleeding. However, issues related to staffing and subjective variations in clinical assessment of a flap's perfusion have led to the search for objective methods of flap monitoring. One promising technology for measuring local tissue oxygenation in-vivo is diffuse optical spectroscopy (DOS). DOS is a quantitative near-infrared (NIR) spectroscopy technique that can determine absolute concentrations of chromophores such as oxy and deoxy hemoglobin, fat and water. Modulated Imaging (MI) is a NIR imaging method invented at BLI that is based on the principles of DOS and employs patterned illumination to interrogate biological tissues. This non-contact approach enables rapid quantitative determination of the optical properties and in-vivo concentrations of chromophores over a wide field-of-view. The central aim of the proposed research is to further the development of Modulated Imaging and to assess the viability of this as a means to determine status of tissue reconstruction flaps. In Phase I, we carried out an in-vivo MI study using a dorsal pedicle flap rodent model. The dorsal pedicle flap is easily implemented to establish controlled ischemia and re-perfusion of the wounds. This allowed us to employ MI to deduce spatially resolved maps of tissue hemoglobin, oxygenation and hydration over the course of several days. In Phase II we propose to develop and validate an MI instrument for clinical use. Investigations will first evaluate the performance of MI in a controlled model of partial vascular congestion using adult Yorkshire pigs. This will be followed by a study in which MI and a potentially competing FDA cleared device will be employed in a clinical situation in order to assess local flap status. In parallelwith the Phase II research outlined herein, we will aggressively pursue commercialization of a medical device based on MI. PUBLIC HEALTH RELEVANCE: The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries and veins to the blood vessels at the recipient site. The medical utility of this process is to allow for reconstructive surgery after trauma, as well as after surgical resection of cancer. This type of reconstructive surgery is subject to failure caused by to mechanical obstruction of the artery or vein; injury caused to the transferred tissues due to the lack of blood flow when a free tissue flap is performed, (the tissue is disconnected prior to re-attaching the blood vessels); or due to a type of injury call ischemia- reperfusion injury, which is a type of injury that results after blood flow has been returned to the transferred tissue. Tissue oxygenation and maintenance of microvascular blood flow in grafted tissues are crucial for flap to survive. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a free flap is a devastating experience to both the surgeon and the patient. In this proposal we will develop and validate an instrument that has the potential to identify flap failure earlier than is currently achievable. A successful effort has the potential to enable development of a new medical device thatwill have the capability to guide reconstructive surgery and post-surgical recovery, both reducing post-surgery complication rate and reducing uncertainty in flap healing. This may shorten the duration of hospital stay and associated heath care costs in addition to improving surgical outcomes.

Coppari R.,University of Texas Southwestern Medical Center | Coppari R.,University of Geneva | Coppari R.,University of California at Irvine | Bjorbaek C.,Beth Israel Deaconess Medical Center
Nature Reviews Drug Discovery | Year: 2012

Since the discovery of leptin in 1994, we now have a better understanding of the cellular and molecular mechanisms underlying its biological effects. In addition to its established anti-obesity effects, leptin exerts antidiabetic actions that are independent of its regulation of body weight and food intake. In particular, leptin can correct diabetes in animal models of type 1 and type 2 diabetes. In addition, long-term leptin replacement therapy improves glycaemic control, insulin sensitivity and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. These results have spurred enthusiasm for the use of leptin therapy to treat diabetes. Here, we review the current understanding of the glucoregulatory functions of leptin, emphasizing its central mechanisms of action and lessons learned from clinical studies, and discuss possible therapeutic applications of leptin in the treatment of type 1 and type 2 diabetes. © 2012 Macmillan Publishers Limited. All rights reserved.

Tibayrenc M.,IRD Montpellier | Ayala F.J.,University of California at Irvine
PLoS Pathogens | Year: 2014

An abundant literature dealing with the population genetics and taxonomy of Giardia duodenalis, Cryptosporidium spp., Pneumocystis spp., and Cryptococcus spp., pathogens of high medical and veterinary relevance, has been produced in recent years. We have analyzed these data in the light of new population genetic concepts dealing with predominant clonal evolution (PCE) recently proposed by us. In spite of the considerable phylogenetic diversity that exists among these pathogens, we have found striking similarities among them. The two main PCE features described by us, namely highly significant linkage disequilibrium and near-clading (stable phylogenetic clustering clouded by occasional recombination), are clearly observed in Cryptococcus and Giardia, and more limited indication of them is also present in Cryptosporidium and Pneumocystis. Moreover, in several cases, these features still obtain when the near-clades that subdivide the species are analyzed separately ("Russian doll pattern"). Lastly, several sets of data undermine the notion that certain microbes form clonal lineages simply owing to a lack of opportunity to outcross due to low transmission rates leading to lack of multiclonal infections ("starving sex hypothesis"). We propose that the divergent taxonomic and population genetic inferences advanced by various authors about these pathogens may not correspond to true evolutionary differences and could be, rather, the reflection of idiosyncratic practices among compartmentalized scientific communities. The PCE model provides an opportunity to revise the taxonomy and applied research dealing with these pathogens and others, such as viruses, bacteria, parasitic protozoa, and fungi. © 2014 Tibayrenc, Ayala.

Tewari K.S.,University of California at Irvine | Monk B.J.,Creighton University
Clinical Cancer Research | Year: 2014

Cervical cancer remains unique among solid tumor malignancies. Persistent infection with oncogenic subtypes of the human papillomavirus (HPV) results in carcinogenesis, predominantly occurring at the cervical transformation zone where endocervical columnar cells undergo metaplasia to a stratified squamous epithelium. The molecular cascade involving viral oncoproteins, E6 and E7 and their degradative interactions with cellular tumor suppressor gene products, p53 and pRb, respectively, has been precisely delineated. The precursor state of cervical neoplasia may last for years allowing for ready detection through successful screening programs in developed countries using cervical cytology and/or high-risk HPV DNA testing. Prophylactic HPV L1 capsid protein vaccines using virus-like-particle technology have been developed to prevent primary infection by the most common high-risk HPVs (16 and 18). Women who lack access to health care and those who undergo sporadic screening remain at risk. Although radical surgery (including fertility-sparing surgery) is available for patients with early-stage cancers, and chemoradiation plus high-dose-rate brachytherapy can cure the majority of those with locally advanced disease, patients with metastatic and nonoperable recurrent cervical cancer constitute a high-risk population with an unmet clinical need. On August 14, 2014, the FDA approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer. This review will highlight advances in translational science, antiangiogenesis therapy and immunotherapy for advanced disease. © 2014 AACR.

Treseder K.K.,University of California at Irvine | Lennon J.T.,Indiana University Bloomington
Microbiology and Molecular Biology Reviews | Year: 2015

Fungi contribute extensively to a wide range of ecosystem processes, including decomposition of organic carbon, deposition of recalcitrant carbon, and transformations of nitrogen and phosphorus. In this review, we discuss the current knowledge about physiological and morphological traits of fungi that directly influence these processes, and we describe the functional genes that encode these traits. In addition, we synthesize information from 157 whole fungal genomes in order to determine relationships among selected functional genes within fungal taxa. Ecosystem-related traits varied most at relatively coarse taxonomic levels. For example, we found that the maximum amount of variance for traits associated with carbon mineralization, nitrogen and phosphorus cycling, and stress tolerance could be explained at the levels of order to phylum. Moreover, suites of traits tended to co-occur within taxa. Specifically, the genetic capacities for traits that improve stress tolerance - β-glucan synthesis, trehalose production, and cold-induced RNA helicases-were positively related to one another, and they were more evident in yeasts. Traits that regulate the decomposition of complex organic matter - lignin peroxidases, cellobiohydrolases, and crystalline cellulases - were also positively related, but they were more strongly associated with free-living filamentous fungi. Altogether, these relationships provide evidence for two functional groups: stress tolerators, which may contribute to soil carbon accumulation via the production of recalcitrant compounds; and decomposers, which may reduce soil carbon stocks. It is possible that ecosystem functions, such as soil carbon storage, may be mediated by shifts in the fungal community between stress tolerators and decomposers in response to environmental changes, such as drought and warming. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Agency: GTR | Branch: NERC | Program: | Phase: Research Grant | Award Amount: 250.09K | Year: 2015

The hydroxyl radical (OH) is the dominant oxidizing agent in the troposphere, as such its concentration controls the abundances and lifetimes of most atmospheric pollutants, including the important greenhouse gas methane (CH4). Ozone (O3) is also an important oxidant and is itself a greenhouse gas. The concentrations of OH and O3 are interdependent, both being determined by a complex series of reactions involving CH4, carbon monoxide (CO), non-methane volatile organic compounds (NMVOCs) and nitrogen oxides (NOX = NO + NO2). As emissions of these compounds have changed substantially since pre-industrial times, the tropospheric budgets of OH and O3 will also have changed. However, there are large uncertainties associated with current understanding of these past changes and consequently very large uncertainties in projected future changes and associated climate impacts. Most of this uncertainty in past trends comes from lack of observations to constrain studies. Whilst there are a few direct observational data sets which indicate how O3 concentrations changed through the 20th century, there are none for OH. Direct observational data sets of CH4, NMVOCs, CO and NOX, extend, at best, from the 1980s. These time series can be extended backward in time through the analysis of air trapped in firn (unconsolidated snow). Whilst such historic time series have been available for CH4 for some time, only recently have they become available for CO and for some NMVOCs, in particular alkanes. Furthermore, we have also recently determined, from firn analysis, historic time series of alkyl nitrates. Alkyl nitrates are products of the chemistry involving NOX and as such can be used as a diagnostic of the changes in NOX. These new (and in the case of the alkyl nitrates, unique), historic time series provide an exciting opportunity to investigate the changing OH and O3 budgets of the northern hemisphere troposphere since 1950 with observational constraints never available before. Very interestingly, the simple analyses carried out on these time series to date suggest that substantial changes in the atmospheric chemistry have occurred. To exploit the full value of these time series a detailed study is required with a comprehensive chemistry-climate model. Here we propose the first such study. The outcomes of this study will be: 1) a better understanding of the impact of changing anthropogenic emissions on the OH and O3 budgets of the northern hemisphere troposphere; 2) an improved modelling capability with which to project future changes and better inform climate policy. This proposal brings together experts in firn air data interpretation with experts in chemistry-climate modelling. Both groups also have considerable expertise in organic (including alkyl) nitrate chemistry. This proposal specifically builds on past NERC funded work on the trends of alkanes and alkyl nitrates in firm air using simply relationships and models.

Agency: Department of Defense | Branch: Army | Program: STTR | Phase: Phase I | Award Amount: 149.99K | Year: 2014

The goal of the proposed research is to develop self-healing embedded communication antennas to be used in transparent armori.e., ground vehicle windows. Embedded antennas are known to delaminate from their host structures after impact; this allows an empty space to form around the antenna and as a result detunes the antenna. A sandwich structure will be designed, fabricated, and tested whereby the antenna is embedded in a self-healing transparent armor. Upon delamination the antenna will reform its seal the armor materials. This effort will demonstrate that these near-kissing joint interfaces will heal after they have delaminated. NextGen Aeronautics will team with the University of California, Irvine to co-develop this innovate damage-resistant self-healing transparent antenna. We will deliver a self-healing antenna sandwich structure (nominally 4"x4") for eventual transition into transparent armorincluding bulletproof windows and self-repairing armor composites. We will consult with armor manufacturers to ensure full compatibility with existing bulletproof and ballistic glass laminates

Ramanan D.,University of California at Irvine | Baker S.,Microsoft
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2011

We present a taxonomy for local distance functions where most existing algorithms can be regarded as approximations of the geodesic distance defined by a metric tensor. We categorize existing algorithms by how, where, and when they estimate the metric tensor. We also extend the taxonomy along each axis. How: We introduce hybrid algorithms that use a combination of techniques to ameliorate overfitting. Where: We present an exact polynomial-time algorithm to integrate the metric tensor along the lines between the test and training points under the assumption that the metric tensor is piecewise constant. When: We propose an interpolation algorithm where the metric tensor is sampled at a number of references points during the offline phase. The reference points are then interpolated during the online classification phase. We also present a comprehensive evaluation on tasks in face recognition, object recognition, and digit recognition. © 2006 IEEE.

Tibayrenc M.,French National Center for Scientific Research | Ayala F.J.,University of California at Irvine
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria lactamica are often regarded as highly recombining bacteria. N. meningitidis has been considered a paradigmatic case of the "semiclonal model" or of "epidemic clonality," demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N. meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (i) the proposed way to distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N. meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model. © 2015, National Academy of Sciences. All rights reserved.

Steenbeek W.,Netherlands Institute for the Study of Crime and Law Enforcement NSCR | Hipp J.R.,University of California at Irvine
Criminology | Year: 2011

Social disorganization theory holds that neighborhoods with greater residential stability, higher socioeconomic status, and more ethnic homogeneity experience less disorder because these neighborhoods have higher social cohesion and exercise more social control. Recent extensions of the theory argue that disorder in turn affects these structural characteristics and mechanisms. Using a data set on 74 neighborhoods in the city of Utrecht in the Netherlands spanning 10 years, we tested the extended theory, which to date only a few studies have been able to do because of the unavailability of neighborhood-level longitudinal data. We also improve on previous studies by distinguishing between the potential for social control (feelings of responsibility) and the actual social control behavior. Cross-sectional analyses replicate earlier findings, but the results of longitudinal cross-lagged models suggest that disorder has large consequences for subsequent levels of social control and residential instability, thus leading to more disorder. This is in contrast to most previous studies, which assume disorder to be more a consequence than a cause. This study underlines the importance of longitudinal data, allowing for simultaneously testing the causes and consequences of disorder, as well as the importance of breaking down social control into the two dimensions of the potential for social control and the actual social control behavior. © 2011 American Society of Criminology.

Allison S.D.,University of California at Irvine | Wallenstein M.D.,Colorado State University | Bradford M.A.,Yale University
Nature Geoscience | Year: 2010

Most ecosystem models predict that climate warming will stimulate microbial decomposition of soil carbon, producing a positive feedback to rising global temperatures. Although field experiments document an initial increase in the loss of CO 2 from soils in response to warming, in line with these predictions, the carbon dioxide loss from soils tends to decline to control levels within a few years. This attenuation response could result from changes in microbial physiological properties with increasing temperature, such as a decline in the fraction of assimilated carbon that is allocated to growth, termed carbon-use efficiency. Here we explore these mechanisms using a microbial-enzyme model to simulate the responses of soil carbon to warming by 5 C. We find that declines in microbial biomass and degradative enzymes can explain the observed attenuation of soil-carbon emissions in response to warming. Specifically, reduced carbon-use efficiency limits the biomass of microbial decomposers and mitigates the loss of soil carbon. However, microbial adaptation or a change in microbial communities could lead to an upward adjustment of the efficiency of carbon use, counteracting the decline in microbial biomass and accelerating soil-carbon loss. We conclude that the soil-carbon response to climate warming depends on the efficiency of soil microbes in using carbon. © 2010 Macmillan Publishers Limited.

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