University of North Carolina at Chapel Hill

About: University of North Carolina at Chapel Hill is a education organization based out in Chapel Hill, North Carolina, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 81393 authors who have published 185327 publications receiving 9948508 citations. The organization is also known as: University of North Carolina & North Carolina.

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

Abstract: Emerging viral infections are difficult to control because heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. Severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) successively emerged, causing severe epidemic respiratory disease in immunologically naive human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. We show that a nucleotide prodrug, GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems, including primary human airway epithelial cell cultures with submicromolar IC50 values. GS-5734 was also effective against bat CoVs, prepandemic bat CoVs, and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory function. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and, possibly most importantly, emerging CoV of the future.

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

Abstract: Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding Bristol-Myers Squibb.

Doping Metal–Organic Frameworks for Water Oxidation, Carbon Dioxide Reduction, and Organic Photocatalysis

Abstract: Catalytically competent Ir, Re, and Ru complexes H2L1–H2L6 with dicarboxylic acid functionalities were incorporated into a highly stable and porous Zr6O4(OH)4(bpdc)6 (UiO-67, bpdc = para-biphenyldicarboxylic acid) framework using a mix-and-match synthetic strategy. The matching ligand lengths between bpdc and L1–L6 ligands allowed the construction of highly crystalline UiO-67 frameworks (metal–organic frameworks (MOFs) 1–6) that were doped with L1–L6 ligands. MOFs 1–6 were isostructural to the parent UiO-67 framework as shown by powder X-ray diffraction (PXRD) and exhibited high surface areas ranging from 1092 to 1497 m2/g. MOFs 1–6 were stable in air up to 400 °C and active catalysts in a range of reactions that are relevant to solar energy utilization. MOFs 1–3 containing [Cp*IrIII(dcppy)Cl] (H2L1), [Cp*IrIII(dcbpy)Cl]Cl (H2L2), and [IrIII(dcppy)2(H2O)2]OTf (H2L3) (where Cp* is pentamethylcyclopentadienyl, dcppy is 2-phenylpyridine-5,4′-dicarboxylic acid, and dcbpy is 2,2′-bipyridine-5,5′-dicarboxylic a...

The Cost of Diversity: The Diversification Discount and Inefficient Investment

Abstract: We model the distortions that internal power struggles can generate in the allocation of resources between divisions of a diversified firm. The model predicts that if divisions are similar in the level of their resources and opportunities, funds will be transferred from divisions with poor opportunities to divisions with good opportunities. When diversity in resources and opportunities increases, however, resources can f low toward the most inefficient division, leading to more inefficient investment and less valuable firms. We test these predictions on a panel of diversified U.S. firms during the period from 1980 to 1993 and find evidence consistent with them. THE FUNDAMENTAL QUESTION IN THE THEORY of the firm, raised by Coase ~1937! more than 60 years ago, is how decisions taken inside a hierarchy differ from those taken in the marketplace. Coase suggested that decisions within a hierarchy are determined by power considerations rather than relative prices. If this is indeed the case, why, and when, does the hierarchy dominate the market? A major obstacle to progress in this area has been the lack of data. Data on internal decisions made by firms are generally proprietary. Even when they are available to researchers, it is difficult to find a comparable group of decisions taken in the market. A notable exception is the capital allocation decision in diversified firms. Since 1978, public U.S. companies have been forced to disclose their data on sales, profitability, and investments by major lines of business ~segments!. An analysis of a small sample of multisegment firms reveals that segments correspond, by and large, to distinct internal