32 research outputs found
The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance
The James Webb Space Telescope (JWST) is a large, infrared space telescope
that has recently started its science program which will enable breakthroughs
in astrophysics and planetary science. Notably, JWST will provide the very
first observations of the earliest luminous objects in the Universe and start a
new era of exoplanet atmospheric characterization. This transformative science
is enabled by a 6.6 m telescope that is passively cooled with a 5-layer
sunshield. The primary mirror is comprised of 18 controllable, low areal
density hexagonal segments, that were aligned and phased relative to each other
in orbit using innovative image-based wavefront sensing and control algorithms.
This revolutionary telescope took more than two decades to develop with a
widely distributed team across engineering disciplines. We present an overview
of the telescope requirements, architecture, development, superb on-orbit
performance, and lessons learned. JWST successfully demonstrates a segmented
aperture space telescope and establishes a path to building even larger space
telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25
figure
Sewer System Alternatives Evaluation for Potential Creswell Area Expansion in Harford County
Final project for ENCE422: Project Cost Accounting and Economics (Fall 2018).
University of Maryland, College Park.This report summarizes the findings of the ENCE422 Fall 2018 class term project. Students were
tasked with evaluating sewer system alternatives for the Creswell area expansion in Harford
County. Student groups were to consider environmental impacts, community/social impacts,
and perform financial analysis for the alternatives they chose to evaluate. This report extracts
information from 14 separate team presentations and synthesizes it around the following
structure; 1. Systems that Utilize Septic Tanks
a. Traditional Septic System
b. Orenco Effluent System
c. Small Diameter Gravity Sewer System
2. System that Do Not Utilize Septic Tanks
a. Traditional Gravity System
b. Vacuum System
c. Grinder Pump SystemHarford Count
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
Learning from multiple sources
We consider the problem of learning accurate models from multiple sources of “nearby ” data. Given distinct samples from multiple data sources and estimates of the dissimilarities between these sources, we provide a general theory of which samples should be used to learn models for each source. This theory is applicable in a broad decision-theoretic learning framework, and yields results for classification and regression generally, and for density estimation within the exponential family. A key component of our approach is the development of approximate triangle inequalities for expected loss, which may be of independent interest.
Learning from Data of Variable Quality
We initiate the study of learning from multiple sources of limited data, each of which may be corrupted at a different rate. We develop a complete theory of which data sources should be used for two fundamental problems: estimating the bias of a coin, and learning a classifier in the presence of label noise. In both cases, efficient algorithms are provided for computing the optimal subset of data