Lentiviral vectors pseudotyped with glycoproteins from Ross River and vesicular stomatitis viruses: variable transduction related to cell type and culture conditions

HIV-1-derived lentiviral vectors have been pseudotyped with various envelope glycoproteins to alter their host range. Previously, we found that envelope glycoproteins derived from the alphavirus Ross River virus (RRV) can pseudotype lentiviral vectors and mediate efficient transduction of a variety of epithelial and fibroblast-derived cell lines. In this study, we have investigated transduction of hematopoietic cells using RRV-pseudotyped vectors encoding the enhanced green fluorescent protein (EGFP). RRV-mediated transduction of human CD34+ cord blood cells and progenitors was very inefficient, even at multiplicities of infection of 100 (0.4% EGFP-positive progenitor colonies). Inefficient transduction was also observed in a variety of hematopoietic cell lines. However, two erythroleukemia-derived cell lines and monocytic cells that were driven to macrophage-like differentiation were moderately transduced. Transduction of hematopoietic cells with a control VSV-G-pseudotyped lentiviral vector was generally efficient, but unexpectedly decreased up to threefold upon stimulation of lymphocytic cell lines or primary murine bone marrow cells. Also, the tested hematopoietic cell lines were essentially nonpermissive for adeno-associated type 2 (AAV) vectors, and this was not affected by lineage, activity, or differentiation. Treatment of permissive 293 cells with proteases revealed that transduction with both the RRV- and the VSV-G-pseudotyped vectors in part depends on the presence of cell surface proteins. These results show a severely restricted ability of RRV glycoproteins to mediate transduction in hematopoietic cells that is likely due to specific receptor requirements that differ from those of VSV-G and AAV. Conversely, transduction with the VSV glycoprotein is affected by cellular activation more than widely believed. Our findings suggest that the envelope glycoproteins and culture conditions employed need to be carefully evaluated for each application. Furthermore, the uniquely restricted host range of RRV-pseudotyped vectors may aid in the design of novel cell-selective transduction strategies

Agricultural producer perceptions of climate change and climate education needs for the Central Great Plains

Citation: Hibbs, Amber Campbell, Daniel Kahl, Lisa PytlikZillig, Ben Champion, Tarik Abdel-Monem, Timothy Steffensmeier, Charles W. Rice, and Kenneth Hubbard. “Agricultural Producer Perceptions of Climate Change and Climate Education Needs for the Central Great Plains.” Journal of Extension 52, no. 3 (June 2014). https://www.joe.org/joe/2014june/a2.php.The Central Great Plains Climate Education Partnership conducted focus groups throughout Kansas to gain a better understanding of farmer perceptions and attitudes towards climate change education. Results indicate concern about climatic changes, even if producers are unsure that "human caused climate change" is occurring. Participants indicated they would like access to information through Web-based programs that allow them to manipulate variables relevant to their area and situation. Participants prefer locally relevant information and identified Extension agents as trusted educators. The study provided an expanded understanding of agricultural producer perceptions that will be valuable to individuals or organizations providing climate education

An Integrated Toolkit for Modern Action Planning

Bützken M, Edelkamp S, Elalaoui A, et al. An Integrated Toolkit for Modern Action Planning. In: 19th Workshop on New Results in Planning, Scheduling and Design (PUK). 2005: 1-11.In this paper we introduce to the architecture and the abilities of our design and analysis workbench for modern action planning. The toolkit provides automated domain analysis tools together with PDDL learning capabilities. New optimal and suboptimal planners extend state-of-the-art technology. With the tool, domain experts assist solving hard combinatorial problems. Approximate or incremental solutions provided by the system are supervised. Intermediate results are accessible to improve domain modeling and to tune exploration in generating high quality plans, which, in turn, can be bootstrapped for domain inference

Age-related increases in parathyroid hormone may be antecedent to both osteoporosis and dementia

<p>Abstract</p> <p>Background</p> <p>Numerous studies have reported that age-induced increased parathyroid hormone plasma levels are associated with cognitive decline and dementia. Little is known about the correlation that may exist between neurological processing speed, cognition and bone density in cases of hyperparathyroidism. Thus, we decided to determine if parathyroid hormone levels correlate to processing speed and/or bone density.</p> <p>Methods</p> <p>The recruited subjects that met the inclusion criteria (n = 92, age-matched, age 18-90 years, mean = 58.85, SD = 15.47) were evaluated for plasma parathyroid hormone levels and these levels were statistically correlated with event-related P300 potentials. Groups were compared for age, bone density and P300 latency. One-tailed tests were used to ascertain the statistical significance of the correlations. The study groups were categorized and analyzed for differences of parathyroid hormone levels: parathyroid hormone levels <30 (n = 30, mean = 22.7 ± 5.6 SD) and PTH levels >30 (n = 62, mean = 62.4 ± 28.3 SD, p ≤ 02).</p> <p>Results</p> <p>Patients with parathyroid hormone levels <30 showed statistically significantly less P300 latency (P300 = 332.7 ± 4.8 SE) relative to those with parathyroid hormone levels >30, which demonstrated greater P300 latency (P300 = 345.7 ± 3.6 SE, p = .02). Participants with parathyroid hormone values <30 (n = 26) were found to have statistically significantly higher bone density (M = -1.25 ± .31 SE) than those with parathyroid hormone values >30 (n = 48, M = -1.85 ± .19 SE, p = .04).</p> <p>Conclusion</p> <p>Our findings of a statistically lower bone density and prolonged P300 in patients with high parathyroid hormone levels may suggest that increased parathyroid hormone levels coupled with prolonged P300 latency may become putative biological markers of both dementia and osteoporosis and warrant intensive investigation.</p

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves

Managerial Responses to Incentives: Control of Firm Risk, Derivative Pricing Implications, and Outside Wealth Management

We model a firm’s value process controlled by a manager maximizing expected utility from restricted shares and employee stock options. The manager also dynamically controls allocation of his outside wealth. We explore interactions between those controls as he partially hedges his exposure to firm risk. Conditioning on his optimal behavior, control of firm risk increases the expected time to exercise for his employee stock options. It also reduces the percentage gap between his certainty equivalent and the firm’s fair value for his compensation, but that gap remains substantial. Managerial control also causes traded options to exhibit an implied volatility smile

An Integrated Toolkit for Modern Action Planning

Abstract. In this paper we introduce to the architecture and the abilities of our design and analysis workbench for modern action planning. The toolkit provides automated domain analysis tools together with PDDL learning capabilities. New optimal and suboptimal planners extend state-of-the-art technology. With the tool, domain experts assist solving hard combinatorial problems. Approximate or incremental solutions provided by the system are supervised. Intermediate results are accessible to improve domain modeling and to tune exploration in generating high quality plans, which, in turn, can be bootstrapped for domain inference.