Astrometric Methods and Instrumentation to Identify and Characterize Extrasolar Planets: A Review

I present a review of astrometric techniques and instrumentation utilized to search for, detect, and characterize extra-solar planets. First, I briefly summarize the properties of the present-day sample of extrasolar planets, in connection with predictions from theoretical models of planet formation and evolution. Next, the generic approach to planet detection with astrometry is described, with significant discussion of a variety of technical, statistical, and astrophysical issues to be faced by future ground-based as well as space-borne efforts in order to achieve the required degree of measurement precision. After a brief summary of past and present efforts to detect planets via milli-arcsecond astrometry, I then discuss the planet-finding capabilities of future astrometric observatories aiming at micro-arcsecond precision. Lastly, I outline a number experiments that can be conducted by means of high-precision astrometry during the next decade, to illustrate its potential for important contributions to planetary science, in comparison with other indirect and direct methods for the detection and characterization of planetary systems.Comment: 61 pages, 8 figures, PASP, accepted (October 2005 issue

Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!

Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the “code of conduct” of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens

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

Sun exposure and protection practices among Florida college marching band members and alumni: a cross-sectional study

In the USA, skin cancer is the most common cancer, more than all other cancers combined. Skin cancer may be prevented by using sun protection. This is particularly important in 18-29-year-olds who, compared to older individuals, experience sunburns more frequently. Moreover, in locations close to the equator, such as Florida, people are at an increased risk of developing melanoma. College marching band members spend a significant amount of time in the sun, as much as 25 h weekly practicing and performing at games, yet little is known about this population. We examined and compared sun exposure and protection practices among Florida college marching band members and alumni. In 2020, anonymous cross-sectional web-based surveys were distributed via email and private Facebook groups. A total of 859 members and alumni of five Florida university marching bands participated. Questionnaires assessed demographic characteristics, sun protection behaviors, as well as history of sunburn and skin cancer. Analyses of variance and multiple linear regression analyses were employed to compare sun protection practices between band members and alumni. During sunny day practices, only 16.1% (63/391) of alumni and 27.1% (127/468) of current band members always wore sunscreen. In the multiple linear regression, after adjusting for gender, race/ethnicity, and family history of skin cancer, alumni, who participated in marching band practices within the past 50 years, were significantly less likely to wear sunscreen or hats compared to current band members. Overall, men were less likely to wear sunscreen but were more likely to wear hats and shirts with sleeves that cover their shoulders compared to women. Compared to the general US population in 2017 (0.38%), alumni of Florida college marching bands in 2020 (2.04%) have a self-reported increase in melanoma prevalence of 1.66%. Of note, melanoma diagnoses were only reported by alumni who self-identified as non-Hispanic white; none of the non-Hispanic black, Hispanic, or other alumni reported a melanoma diagnosis. As skin cancer incidence continues to rise, it is critical that leaders in the marching band community continually address unprotected sun exposure, by promoting protective practices, as well as modifying attitudes and behaviors regarding sun exposure and protection