2,932 research outputs found
Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective
This essay is inspired by the ideas and research examined in the special section on âStakeholder Marketingâ of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing âprosocietyâ and âproenvironmentâ perspectivesâorientations that are also in keeping with the public policy focus of this journal. Under the âhard formâ of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society
Optical and magneto-optical properties of ferromagnetic full-Heusler films: experiments and first-principles calculations
We report a joint theoretical and experimental study focused on understanding
the optical and magneto-optical properties of Co-based full-Heusler compounds.
We show that magneto-optical spectra calculated within ab-initio density
functional theory are able to uniquely identify the features of the
experimental spectra in terms of spin resolved electronic transitions. As
expected for 3d-based magnets, we find that the largest Kerr rotation for these
alloys is of the order of 0.3o in polar geometry. In addition, we demonstrate
that (i) multilayered structures have to be carefully handled in the
theoretical calculations in order to improve the agreement with experiments,
and (ii) combined theoretical and experimental investigations constitute a
powerful approach to designing new materials for magneto-optical and
spin-related applicationsComment: 20 pages, including 6 figures and 1 table. 40 refs. To be published
in Phys. Rev.
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PD-1 Blockade in Chronically HIV-1-Infected Humanized Mice Suppresses Viral Loads
An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012), with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV) loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus) humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus
Introducing Competition to The Middle Level Classroom: Providing for Success
Competition is a significant reality of life, but the decision to compete is a personal one, say these writers, who assert that competition must be introduced carefully to middle level students.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors
PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management
Mapping the Galactic Halo I. The `Spaghetti' Survey
We describe a major survey of the Milky Way halo designed to test for
kinematic substructure caused by destruction of accreted satellites. We use the
Washington photometric system to identify halo stars efficiently for
spectroscopic followup. Tracers include halo giants (detectable out to more
than 100 kpc), blue horizontal branch stars, halo stars near the main sequence
turnoff, and the ``blue metal-poor stars'' of Preston et al (1994). We
demonstrate the success of our survey by showing spectra of stars we have
identified in all these categories, including giants as distant as 75 kpc. We
discuss the problem of identifying the most distant halo giants. In particular,
extremely metal-poor halo K dwarfs are present in approximately equal numbers
to the distant giants for V fainter than 18, and we show that our method will
distinguish reliably between these two groups of metal-poor stars. We plan to
survey 100 square degrees at high galactic latitude, and expect to increase the
numbers of known halo giants, BHB stars and turnoff stars by more than an order
of magnitude. In addition to the strong test that this large sample will
provide for the question `was the Milky Way halo accreted from satellite
galaxies?', we will improve the accuracy of mass measurements of the Milky Way
beyond 50 kpc via the kinematics of the many distant giants and BHB stars we
will find. We show that one of our first datasets constrains the halo density
law over galactocentric radii of 5-20 kpc and z heights of 2-15 kpc. The data
support a flattened power-law halo with b/a of 0.6 and exponent -3.0. More
complex models with a varying axial ratio may be needed with a larger dataset.Comment: 55 pages, 22 figures, to appear in the Astronomical Journa
Neurophysiology
Contains reports on seven research projects.National Institutes of Health (Grant 5 RO1 EY01149-02)Bell Telephone Laboratories, Inc. (Grant)National Institutes of Health (Grant 1 TO1 EY00090-01
\u3cem\u3eDENND5B\u3c/em\u3e Regulates Intestinal Triglyceride Absorption and Body Mass
Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5bâ/â mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common DENND5B variant, p.(R52K), is correlated with body mass index. These studies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism
Treatment outcomes of patients on Second-line Antiretroviral Therapy in resource-limited settings: A Systematic Review and Meta-Analysis
A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings
Leukotriene antagonists as first-line or add-on asthma controller therapy
Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group
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