Measured and predicted shock shapes for AFE configuration at Mach 6 in air and in CF4

Shock shapes and stand-off distances were obtained for the Aeroassist Flight Experiment configuration from Mach 6 tests in air and in CF4. Results were plotted for an angle-of attack range from -10 to 10 degrees and comparisons were made at selected angles with inviscid-flow predictions. Tests were performed in the Langley Research Center (LaRC) 20 inch Mach 6 Tunnel (air) at unit free-stream Reynolds numbers (N sub Re, infinity) of 2 million/ft and 0.6 million/ft and in the LaRC Hypersonic CF4 Tunnel at N sub Re, infinity = 0.5 million/ft and 0.3 million/ft. Within the range of these tests, N sub Re, infinity did not affect the shock shape or stand off distance, and the predictions were in good agreement with the measurements. The shock stand-off distance in CF4 was approximately half of that in air. This effect resulted from the differences in density ratio across the normal shock, which was approximately 12 in CF4 and 5 in air. In both test gases, the shock lay progressively closer to the body as angle of attack decreased

Resource‐based learning strategies: Implications for students and institutions

This paper reports some findings from a project in implementing resource‐based learning in economics, and identifies some implications for students and institutions. These include student responses to a mid‐semester evaluation and the views of the project team. The latter have been informed by action research which sought to recognize students’ individual differences, employ active learning methods and, above all, integrate IT into the curriculum. While innovative strategies are clearly welcomed, students show strong attachment to some traditional methods. Most of those who suggested changes to the range of activities asked for reinstatement of at least some lectures, generally as additions to existing activities. Implications include the need for students and staff to acquire a wide range of new skills, for large‐scale curriculum review if new learning technologies are to be fully integrated, and the need to acknowledge that, given student and staff perceptions of change, the process may be long and costly

Adjunct faculty experiences in a comprehensive development program: a single-site case study

2015 Spring.Includes bibliographical references.Adjunct faculty have come to represent an increasingly larger portion of the overall faculty population in American community colleges and according to recent studies now account for approximately 70% of the instructors in these institutions. Definitions of adjunct faculty vary considerably, but they are generally part-time instructors whose course load is less than the full-time faculty requirement. There has been limited attention paid in the literature to the training and development needs of this faculty group. In addition, we know even less about the needs of the individual types or categories of adjunct or part-time faculty and their experiences in training and development programs. This study examines the experiences of a sub-set of adjunct faculty who are practicing professionals outside of higher education and who teach on a part-time basis. I have labeled this group practitioner adjunct faculty. For this study, I chose to complete a single-site case study of a part-time faculty training and development program at community college in the southeastern United States. My primary data source came from interviews with 10 practitioner adjunct faculty who had completed either the 2010 or 2011 version of the college's centerpiece course in their efforts to support and develop their part-time faculty, the Summer Certification Program. In addition to interview data, I also collected data from internal college documents and the college web site, interviews with academic and professional development leaders, and my own direct observations of training and support programs for the college's part-time faculty. The data from this study have provided an overview of the practitioner adjunct faculty study participants' perspectives on their experiences with the college's training and support efforts. The results show that while these faculty are not fully aware of and are largely not taking advantage of many of the training and support programs offered by the college, the Summer Certification Program was seen as a valuable resource by most of the study participants and does appear to have had an impact on their classroom practice

Mosquitoes, West Nile Virus, Attractants, Competition, Environmental Conditions, and Insecticide Resistance

The six main objectives of this project were: 1) test for levels of West Nile Virus in mosquitoes collected at a Fulton County Recreational Facility, 2) assay various mosquito oviposition attractants on West Nile virus positive female mosquitoes, 3) test effects of distance between mosquito infusion attractants, 4) determine effects of study site location, treatment, and competition distances on mosquito collections, 5) test for any correlation between environmental factors and mosquito abundance, and 6) measure levels of enzymatic insecticide resistance present in species of female mosquitoes that tested positive for the presence of West Nile Virus. Ofthe two species that were collected, only Culex quinquefasciatus females were found to contain West Nile Virus. Of the three oviposition media tested, fescue grass infusion was the most effective for capturing both Cx. quinquefasciatus and Aedes albopictus females. The distance between the organic media attractants tested did not show any significant effect on attractancy of the media, when analyzed with the variation of location and treatment. A positive correlation was found between minimum air temperature, maximum air temperature, and average air temperature and mean mosquitoes collected A negative correlation was found between mean wind speed and mean mosquitoes collected. No correlation was found between mean dew point or mean precipitation and total mosquitoes collected. Assays of the enzymatic levels in Cx. quinquefasciatus females showed good evidence for presence of the A2B2 amplicon and B1 complex, and thus revealed the presence of insecticide resistance in the sampled mosquito population

The Dormancy Dilemma: Quiescence versus Balanced Proliferation

Metastatic dissemination with subsequent clinical outgrowth leads to the greatest part of morbidity and mortality from most solid tumors. Even more daunting is that many of these metastatic deposits silently lie undetected, recurring years to decades after primary tumor extirpation by surgery or radiation (termed metastatic dormancy). As primary tumors are frequently curable, a critical focus now turns to preventing the lethal emergence from metastatic dormancy. Current carcinoma treatments include adjuvant therapy intended to kill the cryptic metastatic tumor cells. Because such standard therapies mainly kill cycling cells, this approach carries an implicit assumption that metastatic cells are in the mitogenic cycle. Thus, the pivotal question arises as to whether clinically occult micrometastases survive in a state of balanced proliferation and death, or whether these cells undergo at least long periods of quiescence marked by cell-cycle arrest. The treatment implications are thus obvious—if the carcinoma cells are cycling then therapies should target cycling cells, whereas if cells are quiescent then therapies should either maintain dormancy or be toxic to dormant cells. Because this distinction is paramount to rational therapeutic development and administration, we investigated whether quiescence or balanced proliferation is the most likely etiology underlying metastatic dormancy. We recently published a computer simulation study that determined that balanced proliferation is not the likely driving force and that quiescence most likely participates in metastatic dormancy. As such, a greater emphasis on developing diagnostics and therapeutics for quiescent carcinomas is needed.National Institutes of Health (U.S.). National Center for Advancing Translational Sciences (Grant UH2TR000496

Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion

Background: Carcinoma cells must circumvent the normally suppressive signals to disseminate. While often considered ‘stop ’ signals for adherent cells, CXCR3-binding chemokines have recently been correlated positively with cancer progression though the molecular basis remains unclear. Results: Here, we examined the expression and function of two CXCR3 variants in human prostate cancer biopsies and cell lines. Globally, both CXCR3 mRNA and protein were elevated in localized and metastatic human cancer biopsies compared to normal. Additionally, CXCR3A mRNA level was upregulated while CXCR3B mRNA was downregulated in these prostate cancer specimens. In contrast to normal prostate epithelial cells (RWPE-1), CXCR3A was up to half the receptor in the invasive and metastatic DU-145 and PC-3 prostate cancer cells, but not in the localized LNCaP cells. Instead of inhibiting cell migration as in RWPE-1 cells, the CXCR3 ligands CXCL4/PF4 and CXCL10/IP10 promoted cell motility and invasiveness in both DU-145 and PC-3 cells via PLCb3 and μ-calpain activation. CXCR3-mediated diminution of cell motility in RWPE-1 cells is likely a result of cAMP upregulation and m-calpain inhibition via CXCR3B signal transduction. Interestingly, overexpression of CXCR3B in DU-145 cells decreased cell movement and invasion. Conclusion: These data suggest that the aberrant expression of CXCR3A and down-regulation of CXCR3B may switch a progression “stop ” to a “go ” signal to promote prostate tumor metastasis via stimulating cell migration and invasion

Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering. However, due to their low numbers upon harvesting, MSCs need to be expanded in vitro without biasing future differentiation for optimal utility. In this concept paper, we focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs. Soluble EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population, and thus did not induce differentiation. However, tethered form of EGF was shown to promote osteogenic differentiation. Soluble EGF was also shown to increase paracrine secretions including VEGF and HGF from MSC. Thus, soluble EGF can be used not only to expand MSC in vitro, but also to enhance paracrine secretion through drug-releasing MSC-encapsulated scaffolds in vivo. Tethered EGF can also be utilized to direct MSC towards osteogenic lineage both in vitro and in vivo

Cross-Talk between PPARs and the Partners of RXR: A Molecular Perspective

The PPARs are integral parts of the RXR-dependent signaling networks. Many other nuclear receptor subfamily 1 members also require RXR as their obligatory heterodimerization partner and they are often co-expressed in any given tissue. Therefore, the PPARs often complete with other RXR-dependent nuclear receptors and this competition has important biological implications. Thorough understanding of this cross-talk at the molecular level is crucial to determine the detailed functional roles of the PPARs. At the level of DNA binding, most RXR heterodimers bind selectively to the well-known “DR1 to 5” DNA response elements. As a result, many heterodimers share the same DR element and must complete with each other for DNA binding. At the level of heterodimerization, the partners of RXR share the same RXR dimerization interface. As a result, individual nuclear receptors must complete with each other for RXR to form functional heterodimers. Cross-talk through DNA binding and RXR heterodimerization present challenges to the study of these nuclear receptors that cannot be adequately addressed by current experimental approaches. Novel tools, such as engineered nuclear receptors with altered dimerization properties, are currently being developed. These tools will enable future studies to dissect specific RXR heterodimers and their signaling pathways

Growth factor regulation of proliferation and survival of multipotential stromal cells

Multipotential stromal cells (MSCs) have been touted to provide an alternative to conservative procedures of therapy, be it heart transplants, bone reconstruction, kidney grafts, or skin, neuronal and cartilage repair. A wide gap exists, however, between the number of MSCs that can be obtained from the donor site and the number of MSCs needed for implantation to regenerate tissue. Standard methods of MSC expansion being followed in laboratories are not fully suitable due to time and age-related constraints for autologous therapies, and transplant issues leave questions for allogenic therapies. Beyond these issues of sufficient numbers, there also exists a problem of MSC survival at the graft. Experiments in small animals have shown that MSCs do not persist well in the graft environment. Either there is no incorporation into the host tissue, or, if there is incorporation, most of the cells are lost within a month. The use of growth and other trophic factors may be helpful in counteracting these twin issues of MSC expansion and death. Growth factors are known to influence cell proliferation, motility, survival and morphogenesis. In the case of MSCs, it would be beneficial that the growth factor does not induce differentiation at an early stage since the number of early-differentiating progenitors would be very low. The present review looks at the effect of and downstream signaling of various growth factors on proliferation and survival in MSCs

Deciphering the molecular mechanism of enhanced tumor activity of the EGFR variant T790M/L858R using melanoma cell lines

IntroductionThe abnormal expression and mutagenesis of EGFR drives both the development and progression of a multitude of human cancers. Further mutations within the tyrosine kinase region of the EGFR subsequently contribute to resistance to targeted drugs. What is not known is how these mutations affect progression-related behaviors of cancer cells.MethodsThe mutagenesis of EGFR T790M, L858R, and T790M/L858R was performed via oligo primer-guided polymerase chain reaction (PCR). GFP-tagged mammalian expression vectors were constructed and confirmed. Stable melanoma cell lines WM983A and WM983B expressing WT or mutant EGFRs were generated for determining the functions of WT and mutant EGFRs in migration, invasion, and resistance to doxorubicin. Immunoblotting and immunofluorescence were performed to detect the transphosphorylation and autophosphorylation of WT and mutant EGFRs and other molecules.ResultsThe EGFR mutant T790M/L858R showed significantly higher basal autophosphorylation in melanoma cell lines WM983A and WM983B. Overexpression of WT EGFR significantly enhanced the protein level of E-cadherin (E-cad) via upregulating its mRNA. In contrast, L858R significantly downregulated E-cad. Biological activity assays show that T790M/L858R presented significant enhancement in vitro in invasion and migration, while WT and T790M moderately inhibited invasion and migration. In WM983A cells, enhanced invasion and migration by T790M/L858R required the downstream signaling pathways through Akt and p38. T790M/L858R dramatically triggers phosphorylation of actin cross-linking protein alpha-actinin-4 in the absence of EGF. This double mutant also conferred resistance to a general chemotherapy doxorubicin through Akt but not the p38 signaling pathway.ConclusionThese findings suggest that T790M/L858R not only confers enhanced therapeutic resistance in cancer cell lines but also may promote tumor metastasis via its boosted downstream signaling pathways and/or direct phosphorylation of other key proteins