77 research outputs found

    Higher education needs a “new front door” for adults

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    This essay describes alternate paths for advanced education for adults. It stresses a certificate system that could be offered by a wide array of providers across the state. Standardized certificates would have clear meaning to employers and the new system would have the scale to be marketed effectively

    Using Indium-111 labeled radiopharmaceuticals to target the BB2 receptor on human prostate cancer cells [abstract]

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    Abstract only availableThe BB2 receptor, belonging to the Bombesin receptor family, has been shown to be highly over expressed in a variety of cancer cell lines, including human prostate cancer. Our laboratory have been involved, for over a decade, in synthesizing Bombesin analogues that target the BB2 receptor for the purpose of developing radiopharmaceuticals for diagnostic and/or therapeutic treatment of cancer. Radiopharmaceuticals based on Bombesin are typically composed of a chelator, isotope, linking group and targeting vector [See Bifunctional Conjugate Design [figure below]. Previous studies by our group and others have shown that variations in linking groups affect the retention time of the bifunctional conjugate in prostate cancer (PC-3) cells. Higher retention time allows for more efficacious therapeutic benefits and enhanced diagnostic imaging capabilities. In this study, we seek to determine the pharmacokinetic benefits achieved in altering the linking group using aliphatic and aromatic linking groups. In-vitro analysis of the radiopharmaceuticals studied found that the Bombesin derivative with the aliphatic linking group demonstrated a slightly higher affinity for the BB2 receptor compared to the Bombesin analogs containing aromatic linking groups. In vivo pharmacokinetic and imaging studies were performed using pre-clinical models of prostate cancer. The tumor uptake of the Bombesin derivatives with the aromatic linking groups were found to be significantly higher compared to that of the Bombesin derivative with the aliphatic linking group. In contrast, the aromatic Bombesin analogs also exhibited higher amounts of undesirable accumulation in the kidneys and other non-target tissues. In conclusion, we found that the aliphatic compounds were more appropriate for diagnostic imaging of prostate cancer due to the reduced non-target retention. The Bombesin analogs with aromatic linking groups showed potential for use as therapeutic agents for prostate cancer treatment.National Institutes of Health Molecular Imaging Progra

    Targeting the BB2 receptor on human prostate cancer cells using Indium-111 labeled radiopharmaceutical [abstract]

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    Abstract only availableFaculty Mentor: Dr. Timothy Hoffman, Internal MedicineThe BB2 receptor, belonging to the Bombesin receptor family, has been shown to be highly over expressed in a variety of cancer cell lines, including human prostate cancer. Over expression of the BB2 receptor offers an appealing target for the design of targeted radiopharmaceuticals.  The Hoffman laboratory and others have been involved, for over a decade, in synthesizing Bombesin analogues that target the BB2 receptor for the purpose of developing a viable radiopharmaceutical for diagnostic or therapeutic treatment of cancer. Radiopharmaceuticals based on Bombesin analogues are typically composed of a targeting vector, radioisotope, chelator and linking group [See Bifunctional Conjugate Design figure below]. Previous studies have shown that variations in linking groups may affect the retention time of the bifunctional conjugate in prostate cancer (PC-3) cells.  Higher retention time allows for more efficacious therapeutic benefits and enhanced diagnostic imaging capabilities.  In the work presented, we designed and synthesized a 111In-Bombesin analogue with a phenyl linker group in order to determine if the phenyl linker group would provide higher retention times in prostate cancer.  In-vitro analysis of the radiopharmaceutical was performed using PC-3 cells to determine the affinity of the new compound for the BB2 receptor to be 1.09 nM. In-vivo studies of the radiopharmaceutical were also conducted by injection of the radiopharmaceutical into CF-1 (“normal”) mice, as well as SCID (Severe Combined Immunodeficient) mice bearing 2-3 week old PC-3 tumors. Experimental results on SCID mice revealed uptakes of 6.36, 3.34, 2.42 and 1.69 % Injected Dose of radiopharmaceutical per gram of tumor tissue at 0.25, 1, 4 and 24 hours, respectively. Imaging using Micro-SPECT (Single-Photon Emission Computed Tomography) was performed to track the dispersion of the radiopharmaceutical throughout the mouse model and confirmed the targeted uptake of the radiopharmaceutical

    Reconciling end-to-end and population concepts for marine ecosystems

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    Author Posting. Š The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 83 (2010): 99-103, doi:10.1016/j.jmarsys.2010.06.006.The inherent complexities in the structure and dynamics of marine food webs have led to two major simplifying concepts, a species-centric approach focused on physical processes driving the population dynamics of single species and a trophic-centric approach emphasizing energy flows through broad functional groups from nutrient input to fish production. Here we review the two approaches and discuss their advantages and limitations. We suggest that these concepts are complementary: their applications involve different time scales and distinct aspects of population and community resilience, but their integration is necessary for ecosystem-based managementWe acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele) and NSF award OCE0217399 (D.J. Gifford)

    The effectiveness of interventions to change six health behaviours: a review of reviews

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    Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

    A major QTL located in chromosome 8 of Cucurbita moschata is responsible for resistance to tomato leaf curl New Delhi virus (ToLCNDV)

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    Tomato leaf curl New Delhi virus (ToLCNDV) is a bipartite whitefly transmitted begomovirus, responsible since 2013 of severe damages in cucurbit crops in Southeastern Spain. Zucchini (Cucurbita pepo) is the most affected species, but melon (Cucumis melo) and cucumber (Cucumis sativus) are also highly damaged by the infection. The virus has spread across Mediterranean basin and European countries, and integrated control measures are not being enough to reduce economic losses. The identification of resistance genes is required to develop resistant cultivars. In this assay, we studied the inheritance of the resistance to ToLCNDV previously identified in two Cucurbita moschata accessions. We generated segregating populations crossing both resistant pumpkins, an American improved cultivar Large Cheese (PI 604506) and an Indian landrace (PI 381814), with a susceptible C. moschata genotype (PI 419083). The analysis of symptoms and viral titers of all populations established the same monogenic recessive genetic control in both resistant accessions, and the allelism tests suggest the occurrence of alleles of the same locus. By genotyping with a single nucleotide polymorphism (SNP) collection evenly distributed along the C. moschata genome, a major quantitative trait locus (QTL) was identified in chromosome 8 controlling resistance to ToLCNDV. This major QTL was also confirmed in the interspecific C. moschata × C. pepo segregating populations, although C. pepo genetic background affected the resistance level. Molecular markers here identified, linked to the ToLCNDV resistance locus, are highly valuable for zucchini breeding programs, allowing the selection of improved commercial materials. The duplication of the candidate region within the C. moschata genome was studied, and genes with paralogs or single-copy genes were identified. Its synteny with the region of chromosome 17 of the susceptible C. pepo revealed an INDEL including interesting candidate genes. The chromosome 8 candidate region of C. moschata was also syntenic to the region in chromosome 11 of melon, previously described as responsible of ToLCNDV resistance. Common genes in the candidate regions of both cucurbits, with high- or moderate-impact polymorphic SNPs between resistant and susceptible C. moschata accessions, are interesting to study the mechanisms involved in this recessive resistance

    Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

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    Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

    The essential guide to computing

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