279 research outputs found

    Antitrust - Merger - Divestiture Action

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    The Supreme Court of the United States has held that the failing company doctrine cannot successfully be invoked as a defense to an anti-merger action unless defendant establishes both that the acquiring company is the only available purchaser and that there is dim or non-existent hope for reorganization of the failing company through bankruptcy procedures. Citizen Publishing Company v. United States, 89 S. Ct. 927 (1969)

    The Concept of Possession in Commercial Transactions: Chasing the Quick-Brown Fox

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    Condensate cosmology in O'Raifeartaigh models

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    Flat directions charged under an R-symmetry are a generic feature of O'Raifeartaigh models. Non-topological solitons associated with this symmetry, R-balls, are likely to form through the fragmentation of a condensate, itself created by soft terms induced during inflation. In gravity mediated SUSY breaking R-balls decay to gravitinos, reheating the universe. For gauge mediation R-balls can provide a good dark matter candidate. Alternatively they can decay, either reheating or cooling the universe. Conserved R-symmetry permits decay to gravitinos or gauginos, whereas spontaneously broken R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for publication in JHE

    Treg Depletion Inhibits Efficacy of Cancer Immunotherapy: Implications for Clinical Trials

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    Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients.Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs present in tumors, draining lymph nodes and spleen and improved long-term survival (50% of mice survived >150 days). No improvement in survival was observed when Tregs were depleted 24 days after tumor implantation, suggesting that tumor burden is an important factor for determining efficacy of Treg depletion in clinical trials. In a T cell dependent model of brain tumor regression elicited by intratumoral delivery of adenoviral vectors (Ad) expressing Fms-like Tyrosine Kinase 3 ligand (Flt3L) and Herpes Simplex Type 1-Thymidine Kinase (TK) with ganciclovir (GCV), we demonstrate that administration of PC61 24 days after tumor implantation (7 days after treatment) inhibited T cell dependent tumor regression and long term survival. Further, depletion with PC61 completely inhibited clonal expansion of tumor antigen-specific T lymphocytes in response to the treatment.Our data demonstrate for the first time, that although Treg depletion inhibits the progression/eliminates GBM tumors, its efficacy is dependent on tumor burden. We conclude that this approach will be useful in a setting of minimal residual disease. Further, we also demonstrate that Treg depletion, using PC61 in combination with immunotherapy, inhibits clonal expansion of tumor antigen-specific T cells, suggesting that new, more specific targets to block Tregs will be necessary when used in combination with therapies that activate anti-tumor immunity

    Spirituality during aging

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    This paper suggests that an understanding of spirituality during aging provides an important supplement for the developmental model in looking at the religious lives of older persons. Jung's perspective on the psychodynamics of human spirit is compared with Allport's description of mature religious sentiment in order to present a basis for looking at three case studies of nursing home residents. Each case addresses a major challenge faced in the later years of life: 1) self-worth, 2) the meaning of one's life, 3) losses in aging. An understanding of the developmental issues faced in late life supplemented with an appreciation for a person's spirituality may help us better minister to older persons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45470/1/11089_2005_Article_BF01760074.pd

    Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

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    Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis
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