114,203 research outputs found
Personal Papers (MS 80-0002)
No full textLetter from Frank A. Richards to Robert H. Blocker introducing Blocker to Harris L. Kempner, the president of H. Kempner Cotton Company. Richards states Kempner is a gentleman of integrity and unquestioned financial responsibility
The β-blocker Nebivolol Is a GRK/β-arrestin Biased Agonist
No full textNebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker), AG1478 (EGFR inhibitor), indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2-AR, and likely β1-AR, GRK/β-arrestin biased agonist, which suggests that some of the unique clinically beneficial effects of nebivolol may be due to biased agonism at β1- and/or β2-ARs. © 2013 Erickson et al
Personal Papers (MS 80-0002)
No full textLetter from T. G. Blocker to I. H. Kempner discussing the Constitutional Amendments mentioned in Kempner's letter of February 13. He states that Dallas enthusiastically supports the amendment, and he knows of no opposition. He sees no reason to oppose the bill, even though it doesn't directly apply to their situation
Letter from W. L. Blocker, Pratt City, Alabama, to A. H. Woodward, Birmingham, Alabama, circa 1940
No full textThis item is from the Woodward Family Papers, an extensive collection, including business and personal correspondence, financial records, photographs, and other materials of this Birmingham, Alabama family which operated the Woodward Iron Company
On the Constructor-Blocker Game
No full textIn the Constructor-Blocker game, two players, Constructor and Blocker,
alternatively claim unclaimed edges of the complete graph . For given
graphs and , Constructor can only claim edges that leave her graph
-free, while Blocker has no restrictions. Constructor's goal is to build as
many copies of as she can, while Blocker attempts to stop this. The game
ends once there are no more edges that Constructor can claim. The score
of the game is the number of copies of in Constructor's graph at
the end of the game, when both players play optimally and Constructor plays
first. In this paper, we extend results of Patk\'os, Stojakovi\'c and Vizer on
to many pairs of and : We determine when
and , also when both and are odd cycles, using
Szemer\'edi's Regularity Lemma. We also obtain bounds of when
and .Comment: 16 page
Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease
No full textNaohiro Oda,1 Nobuaki Miyahara,1,2 Hirohisa Ichikawa,3 Yasushi Tanimoto,4 Kazuhiro Kajimoto,5 Makoto Sakugawa,6 Haruyuki Kawai,7 Akihiko Taniguchi,1 Daisuke Morichika,1 Mitsune Tanimoto,1 Arihiko Kanehiro,1 Katsuyuki Kiura1 1Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, 3Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, 4Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, 5Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, 6Department of Respiratory Medicine, Okayama Red Cross Hospital, 7Department of Respiratory Medicine, Okayama Saiseikai Hospital, Okayama, Japan Background: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD) is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. Patients and methods: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1) was assessed. Results: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years); 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD) stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC), FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6±93.5 mL/year vs -4.7±118.9 mL/year, P=0.671). After controlling for relevant confounders in multivariate analyses, it was found that beta-blocker use was not significantly associated with the annual decline in FEV1 (β=-0.019; 95% confidence interval: -0.073 to 0.036; P=0.503). Conclusion: Long-term beta-blocker use in Japanese COPD patients might not affect the FEV1, one of the most important parameters of lung function in COPD patients. Keywords: chronic obstructive pulmonary disease, beta-blocker, lung function, spirometry, forced expiratory volume in 1 second, long-ter
The Constructor-Blocker Game
No full textWe study the following game version of the generalized graph Tur\'an problem.
For two fixed graphs and , two players, Constructor and Blocker,
alternately claim unclaimed edges of the complete graph . Constructor can
only claim edges so that he never claims all edges of any copy of , i.e. his
graph must remain -free, while Blocker can claim unclaimed edges without
restrictions. The game ends when Constructor cannot claim further edges or when
all edges have been claimed. The score of the game is the number of copies of
with all edges claimed by Constructor. Constructor's aim is to maximize the
score, while Blocker tries to keep the score as low as possible. We denote by
the score of the game when both players play optimally and
Constructor starts the game.
In this paper, we obtain the exact value of when both and
are stars and when , . We determine the asymptotics of
when is a star and is a tree and when , , and we derive
upper and lower bounds on
The constructor-blocker game
No full textWe study the following game version of generalized graph Turán problems. For two fixed graphs F and H, two players, Constructor and Blocker, alternately claim unclaimed edges of the complete graph Kn. Constructor can only claim edges so that he never claims all edges of any copy of F , i.e. his graph must remain F -free, while Blocker can claim unclaimed edges without restrictions. The game ends when Constructor cannot claim further edges or when all edges have been claimed. The score of the game is the number of copies of H with all edges claimed by Constructor. Constructor’s aim is to maximize the score, while Blocker tries to keep the score as low as possible. We denote by g(n, H, F ) the score of the game when both players play optimally and Constructor starts the game. In this paper, we obtain the exact value of g(n, H, F ) when both F and H are stars and when F = P4, H = P3. We determine the asymptotics of g(n, H, F ) when F is a star and H is a tree and when F = P5, H = K3, and we derive upper and lower bounds on g(n, P4, P5)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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