Principles And Practices Fostering Inclusive Excellence: Lessons From The Howard Hughes Medical Institute’s Capstone Institutions

Best-practices pedagogy in science, technology, engineering, and mathematics (STEM) aims for inclusive excellence that fosters student persistence. This paper describes principles of inclusivity across 11 primarily undergraduate institutions designated as Capstone Awardees in Howard Hughes Medical Institute’s (HHMI) 2012 competition. The Capstones represent a range of institutional missions, student profiles, and geographical locations. Each successfully directed activities toward persistence of STEM students, especially those from traditionally underrepresented groups, through a set of common elements: mentoring programs to build community; research experiences to strengthen scientific skill/identity; attention to quantitative skills; and outreach/bridge programs to broaden the student pool. This paper grounds these program elements in learning theory, emphasizing their essential principles with examples of how they were implemented within institutional contexts. We also describe common assessment approaches that in many cases informed programming and created traction for stakeholder buy-in. The lessons learned from our shared experiences in pursuit of inclusive excellence, including the resources housed on our companion website, can inform others’ efforts to increase access to and persistence in STEM in higher education

Active Hydrothermal Features as Tourist Attractions

Tourists are looking increasingly for adventurous experiences by exploring unusual and interesting landscapes. Active volcanic and hydrothermal landscapes and their remarkable manifestations of geysers, fumaroles and boiling mud ponds are some of the surface features that fascinate visitors of National Parks, Geoparks and World Heritage areas worldwide. The uniqueness of hydrothermal activity based on volcanism has provided popular tourist attractions in many countries for several thousand years. The Romans for example have used hydrothermal springs on the Italian island Ischia and visited the Campi Flegrei for recreational purposes. In Iceland the original Geysir already attracted international visitors over 150 years ago, who came to observe this spectacular hydrothermal phenomenon. In Greece and Turkey volcanic hot springs have historically provided attractive destinations, as well as in New Zealand, Japan and the Americas. The fact that locations with hydrothermal activity based on active volcanism have acquired various forms of protected site status, adds a further dimension to their attraction and demonstrates a significant contribution to sustainable and nature based tourism. Countries such as Iceland, New Zealand and Japan have a long tradition of using hydrothermal activity in its various forms to offer tourists a unique natural experience. These environments however are also known for their unpredictable and potentially hostile nature, as the use of hydrothermal features as a natural resource for tourism does harbour certain risks with the potential to affect human health and safety. Hydrothermal systems have erupted in the past, thereby causing the destruction of their immediate environment. Depending on the level of magnitude explosions of super heated water and steam mixed with fractured rocks and hot mud can be violent enough to create craters varying in size from a few metres to several hundred metres in diameter. Apart from unexpected eruptions of hydrothermal vents with the potential to cause thermal burns, further risk factors include seismic activity such as earthquakes, lethal gas emissions of hydrogen sulphide (H2S) as well as ground instability through hydrothermal alteration. While it is essential to prevent injuries to tourists the management of hydrothermal hazards remains problematic. Precursory signs are not well understood by the general public and the communication of imminent danger is frequently unachievable. As a consequence serious thought needs to be given to the risk factors and the potential danger of areas in the proximity of active hydrothermal manifestations such as extreme hot springs and geysers. To improve the safety standards in hydrothermal landscapes that are used as main features in tourism, strategic guidelines for best practice management must cover ALL active volcanic and hydrothermal areas. This chapter looks at management issues at hydrothermal destinations with special consideration of areas where these unique features are integrated as tourist attractions. Examples from destinations traditionally based on active volcanic and hydrothermal phenomena are presented as case studies to highlight the risk management processes in individual countries. Potential hazards in volcanic and hydrothermal areas are assessed with a focus on the prevention of accidents and injuries to tourists

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Natural Transformation in Mesophilic and Thermophilic Bacteria: Identification and Characterization of Novel, Closely Related Competence Genes in Acinetobacter sp. Strain BD413 and Thermus thermophilus HB27

The mesophile Acinetobacter sp. strain BD413 and the extreme thermophile Thermus thermophilus HB27 display high frequencies of natural transformation. In this study we identified and characterized a novel competence gene in Acinetobacter sp. strain BD413, comA, whose product displays significant similarities to the competence proteins ComA and ComEC in Neisseria and Bacillus species. Transcription of comA correlated with growth phase-dependent transcriptional regulation of the recently identified pilin-like factors of the transformation machinery. This finding strongly suggests that comA is part of a competence regulon. Examination of the genome sequence of T. thermophilus HB27 led to detection of a comA/comEC-like open reading frame (ORF) which is flanked by an ORF whose product shows significant similarities to the Bacillus subtilis competence protein ComEA. To examine whether these two ORFs, designated comEC and comEA, are implicated in natural transformation of T. thermophilus HB27, both were disrupted by using a thermostable kanamycin resistance marker. Natural transformation in comEC mutants was reduced 1,000-fold, whereas in comEA mutants the natural transformation phenotype was completely eliminated. These results strongly suggest that both genes, comEC and comEA, are required for natural transformation in T. thermophilus HB27. Several transmembrane α-helices are predicted based on the amino acid sequences of ComA in Acinetobacter sp. strain BD413 and ComEC in T. thermophilus HB27, which suggests that ComA and ComEC are located in the inner membrane and function in DNA transport through the cytoplasmic membrane