Institution
University of California, Irvine
Education•Irvine, California, United States•
About: University of California, Irvine is a education organization based out in Irvine, California, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 47031 authors who have published 113602 publications receiving 5521832 citations. The organization is also known as: UC Irvine & UCI.
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TL;DR: There is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody.
Abstract: Many effective vaccines act by inducing neutralizing antibodies, and this approach is a top priority in work on HIV vaccines. But a new study suggests that anti-HIV antibodies are most effective when they act in two ways: through neutralization — killing the virus outright and blocking its entry into T cells — and by killing infected cells. The use of engineered versions of a neutralizing human antibody that protects against HIV in a monkey model shows that protection is dependent not only the antibody's neutralizing activity, but also on its interaction with Fc receptors on effector cells, which may act to reduce virus yield from infected cells. This work suggests that the best results might be achieved with vaccines that recruit both neutralizing antibodies and cell-mediated immunity via agents such as macrophages and cytokinins, rather than antibodies. Passively administered neutralizing antibodies have been shown to protect macaques against challenge by the HIV/SIV chimeric SHIV. The antiviral effects of the monoclonal antibody b12 are crucially dependent on antibody effector mechanisms. Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine1,2. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge3,4. However, the mechanism(s) by which neutralizing antibodies afford protection against HIV is not understood and, in particular, the role of antibody Fc-mediated effector functions is unclear. Here we report that there is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody. No loss of antibody protective activity is associated with the elimination of complement binding alone. Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complexed infected cells is important in reducing virus yield from infected cells. Overall, the data suggest the potential importance of activity against both infected cells and free virus for effective protection against HIV.
882 citations
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TL;DR: This paper makes three points: long-established intellectual perspectives on innovation from neoclassical economics and organization theory are inadequate to explain the dynamics of actual innovative change in the IT domain, and institutional policy formation regarding IT innovation is facilitated by an understanding of the multifaceted role of institutions in the innovative process, and on the contingencies governing any given institution/innovation mix.
Abstract: Innovation in information technology is well established in developed nations; newly industrializing and developing nations have been creating governmental interventions to accelerate IT innovation within their borders. The lack of coherent policy advice for creating government policy for IT innovation signals a shortfall in research understanding of the role of government institutions, and institutions more broadly, in IT innovation. This paper makes three points. First, long-established intellectual perspectives on innovation from neoclassical economics and organization theory are inadequate to explain the dynamics of actual innovative change in the IT domain. A broader view adopted from economic history and the new institutionalism in sociology provides a stronger base for understanding the role of institutions in IT innovation. Second, institutional intervention in IT innovation can be constructed at the intersection of the influence and regulatory powers of institutions and the ideologies of supply-push and demand-pull models of innovation. Examples of such analysis are provided. Third, institutional policy formation regarding IT innovation is facilitated by an understanding of the multifaceted role of institutions in the innovative process, and on the contingencies governing any given institution/innovation mix.
882 citations
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TL;DR: It is proposed that this entropically unfavorable process is offset by an enthalpy gain due to an increase in molecular contacts at dispersed nanoparticle surfaces as compared with the surfaces of phase-separated nanoparticles.
Abstract: Traditionally the dispersion of particles in polymeric materials has proven difficult and frequently results in phase separation and agglomeration. We show that thermodynamically stable dispersion of nanoparticles into a polymeric liquid is enhanced for systems where the radius of gyration of the linear polymer is greater than the radius of the nanoparticle. Dispersed nanoparticles swell the linear polymer chains, resulting in a polymer radius of gyration that grows with the nanoparticle volume fraction. It is proposed that this entropically unfavorable process is offset by an enthalpy gain due to an increase in molecular contacts at dispersed nanoparticle surfaces as compared with the surfaces of phase-separated nanoparticles. Even when the dispersed state is thermodynamically stable, it may be inaccessible unless the correct processing strategy is adopted, which is particularly important for the case of fullerene dispersion into linear polymers.
881 citations
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TL;DR: Systems integration for global sustainability is poised for more rapid development, and transformative changes aimed at connecting disciplinary silos are needed to sustain an increasingly telecoupled world.
Abstract: Global sustainability challenges, from maintaining biodiversity to providing clean air and water, are closely interconnected yet often separately studied and managed. Systems integration—holistic approaches to integrating various components of coupled human and natural systems—is critical to understand socioeconomic and environmental interconnections and to create sustainability solutions. Recent advances include the development and quantification of integrated frameworks that incorporate ecosystem services, environmental footprints, planetary boundaries, human-nature nexuses, and telecoupling. Although systems integration has led to fundamental discoveries and practical applications, further efforts are needed to incorporate more human and natural components simultaneously, quantify spillover systems and feedbacks, integrate multiple spatial and temporal scales, develop new tools, and translate findings into policy and practice. Such efforts can help address important knowledge gaps, link seemingly unconnected challenges, and inform policy and management decisions.
881 citations
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Monash University1, Kaiser Permanente2, Pennington Biomedical Research Center3, Copenhagen University Hospital4, Ewha Womans University5, Norwegian Institute of Public Health6, Michigan State University7, Dankook University8, University of Antwerp9, Katholieke Universiteit Leuven10, University of California, Irvine11
TL;DR: More than 1 million pregnant women had gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.
Abstract: Importance Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear. Objective To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI Data Sources and Study Selection Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. Data Extraction and Synthesis Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. Main Outcomes and Measures Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. Results Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, −2% [−10% to −6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, −2% [−3% to −1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [−2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, −3%; [−4% to −2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, −2% [−2% to −1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. Conclusions and Relevance In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.
881 citations
Authors
Showing all 47751 results
Name | H-index | Papers | Citations |
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Daniel Levy | 212 | 933 | 194778 |
Rob Knight | 201 | 1061 | 253207 |
Lewis C. Cantley | 196 | 748 | 169037 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Joseph Biederman | 179 | 1012 | 117440 |
John R. Yates | 177 | 1036 | 129029 |
John A. Rogers | 177 | 1341 | 127390 |
Avshalom Caspi | 170 | 524 | 113583 |
Yang Gao | 168 | 2047 | 146301 |
Carl W. Cotman | 165 | 809 | 105323 |
John H. Seinfeld | 165 | 921 | 114911 |
Gregg C. Fonarow | 161 | 1676 | 126516 |
Jerome I. Rotter | 156 | 1071 | 116296 |
David Cella | 156 | 1258 | 106402 |