David W. Lewis

Effects of interleukin-18 on natural killer cells: Costimulation of activation through Fc receptors for immunoglobulin

The antitumor activity of monoclonal antibodies is mediated by effector cells, such as natural killer (NK) cells, that express Fc receptors for immunoglobulin. Efficacy of monoclonal antibodies, including the CD20 antibody rituximab, could be improved by agents that augment the function of NK cells. Interleukin (IL)-18 is an immunostimulatory cytokine that has antitumor activity in preclinical models. The effects of IL-18 on NK cell function mediated through Fcγ receptors were examined. Human NK cells stimulated with immobilized IgG in vitro secreted IFN-γ as expected; such IFN-γ production was partially inhibited by blocking CD16 with monoclonal antibodies. IL-18 augmented IFN-γ production by NK cells stimulated with immobilized IgG or CD16 antibodies. NK cell IFN-γ production in response to immobilized IgG and/or IL-18 was inhibited by chemical inhibitors of Syk and several other kinases involved in CD16 signaling pathways. IL-18 augmented antibody-dependent cellular cytotoxicity (ADCC) of human NK cells against rituximab-coated Raji cells in vitro. IL-18 and rituximab acted synergistically to promote regression of human lymphoma xenografts in SCID mice. Inasmuch as IL-18 costimulates IFN-γ production and ADCC of NK cells activated through Fc receptors in vitro and augments antitumor activity of rituximab in vivo, it is an attractive cytokine to combine with monoclonal antibodies for treatment of human cancer.

Soypeptide lunasin in cytokine immunotherapy for lymphoma.

Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. We have previously reported that post-transplant lymphoma patients have an acquired deficiency of signal transducer and activator of transcription 4, which results in defective IFNγ production during clinical immunotherapy. With the goal of further improving cytokine-based immunotherapy, we examined the effects of a soybean peptide called lunasin that synergistically works with cytokines on natural killer (NK) cells. Peripheral blood mononuclear cells of healthy donors and post-transplant lymphoma patients were stimulated with or without lunasin in the presence of IL-12 or IL-2. NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. Chromatin immunoprecipitation assay was performed to evaluate the histone modification of gene loci that are regulated by lunasin and cytokine. Adding lunasin to IL-12- or IL-2-stimulated NK cells demonstrated synergistic effects in the induction of IFNG and GZMB involved in cytotoxicity. The combination of lunasin and cytokines (IL-12 plus IL-2) was capable of restoring IFNγ production by NK cells from post-transplant lymphoma patients. In addition, NK cells stimulated with lunasin plus cytokines displayed higher tumoricidal activity than those stimulated with cytokines alone using in vitro and in vivo tumor models. The underlying mechanism responsible for the effects of lunasin on NK cells is likely due to epigenetic modulation on target gene loci. Lunasin represents a different class of immune modulating agent that may augment the therapeutic responses mediated by cytokine-based immunotherapy.

Reference in the Age of Wikipedia, Or Not...

The title of my talk today is purposefully provocative. But it is not because I believe that reference in the age of Wikipedia is dead, but rather that in the time of Wikipedia we need to be able to ask and answer the question implied by the, “or not...” We all know that the old models of reference work no longer are adequate. Our challenge is to be able to affirmatively explain what it is we do and how it adds value.

The Future of Academic Library Materials Expenditures: A Thought Experiment

For several decades academic library materials budgets have been increasing. ARL statistics show a 322% increase in Library Materials expenditures between 1986 and 2012 versus a 109% increase in the CPI. Data from the National Center for Educational Statistics shows growth in a way that is less precise, but still shows an increase of 133% increase in expenditures on information resources from a national total of

The 2.5% commitment

1,197,292,834 to

Measures of Change in Academic Library Behavior

2,790,039,494 between 1992 and 2012. The percentage of total library expenditures used for information resources increased from 32.8% in 1992 to 39.8% in 2012.

Clay Shirky on Newspapers and What It Can Teach Academic Libraries

In the end, libraries can point out the fact that their future role actually points in in two, apparently opposite, yet deeply complementary directions: on the one hand, they plunge deeply into the local production scenes since they aim at systematically sweeping, storing, preserving, and curating all that is produced in their hosting institution; at the same time, the libraries, with their sister institutions, are involved in the task of ensuring a vibrant knowledge-nurturing life for their documents: they will circulate, be discoverable, be interoperable, be evaluated, etc. With the first function, each library ensures its safe and strong function within its host institution; with the second function, the libraries connect to bring the knowledge infrastructure that we all really need. — Jean-Claude Guédon

The First Book Project: A Disruptive Process for Creating Scholarly Monographs in the Social Sciences and Humanities

Most of us working in academic libraries recognize that new strategies and practices are required given the changes technology has brought to higher education and scholarly communication. Many libraries are implementing these strategies and practices, but it is difficult to move often long-established ways of doing things and to know how much progress is being made. At least in part this is because we are in uncharted waters and the old markers no longer measure the things that matter. What we need now are new measures to help establish how we are doing. It is a management truism that what gets measured is what gets done, and so until we have measures that direct us toward the changes we know we should be making, we are unlikely to go fast enough or far enough.

A Strategy for Academic Libraries in the First Quarter of the 21st Century

In March 2009 Clay Shirky posted the essay, “Newspapers and Thinking the Unthinkable,” on his blog and in July 2011 he posted a second essay “Why We Need the New News Environment to be Chaotic.” These two essays are concerned with the newspapers and the news, but taken together they provide useful insights for academic librarians. Newspapers and libraries are in many ways quite different, but they share a common heritage, both born out of the technology of the printing press and its 19th century industrialization. Similar technologies drove economic and organizational structures and the values of libraries and newspapers. Both face similar challenges as the Internet unwinds their economic and technical underpinnings and by doing so stresses organizations and the professional values that have sustained them.

The Inevitability of Open Access

The usual explanation for demise of the scholarly monograph is the decline in the academic library resources available to purchase scholarly monographs that has resulted from the large increases in the cost of scientific journals. While this has certainly played a role, why is it that scientific journals have maintained their pricing power, while the scholarly monograph has not been able to do so? Christensen would argue that the customers for the scholarly monograph were overshot, that is the product had exceeded the needs of its customers — libraries and scholars — and they will no longer pay the price premium for the increased quality of the product. Because of this established academic publishers have attempted to move upmarket by producing higher quality books for smaller and more exclusive markets (soliciting philanthropic support for some projects) or to move into other markets. At this point both strategies have exhausted themselves and the scholarly monograph, and maybe academic presses, are an endangered species.