36 research outputs found
What Is An Innovative Educational Leader?
This paper outlined the traits of an innovative educational leader in our changing society. It discussed the difference in a manager and leader, as well as the specific dispositions that differentiate the innovative educational leader from what many consider the average leader. The authors used the acronym âHELPSSâ to highlight the leadership skills and traits that many practitioners believe are necessary to qualify a person as an innovative leader
Fabrication techniques for very fast diffractive lenses
Aspheric lenses with arbitrary phase functions can be fabricated on thin light weight substrates via the binary optics fabrication technique. However, it is difficult and costly to fabricate a fast lens (f/number less than 1) for use as the shorter wavelengths. The pitch of the masks and the alignment accuracy must be very fine. For a large lens, the space-bandwidth product of the element can also become impractically large. In this paper, two alternate approaches for the fabrication of fast aspheric diffractive lenses are described. The first approach fabricates the diffractive lens interferometrically, utilizing a spherical wavefront to provide the optical power of the lens and a computer generated hologram to create the aspheric components. The second approach fabricates the aspheric diffractive lens in the form if a higher order kinoform which trades groove profile fidelity for coarser feature size. The design and implementation issues for these two fabrication techniques are discussed
Automated inspection of turbine blades: Challenges and opportunities
Current inspection methods for complex shapes and contours exemplified by aircraft engine turbine blades are expensive, time-consuming and labor intensive. The logistics support of new manufacturing paradigms such as integrated product-process development (IPPD) for current and future engine technology development necessitates high speed, automated inspection of forged and cast jet engine blades, combined with a capability of retaining and retrieving metrology data for process improvements upstream (designer-level) and downstream (end-user facilities) at commercial and military installations. The paper presents the opportunities emerging from a feasibility study conducted using 3-D holographic laser radar in blade inspection. Requisite developments in computing technologies for systems integration of blade inspection in production are also discussed
Joint and individual analysis of breast cancer histologic images and genomic covariates
A key challenge in modern data analysis is understanding connections between
complex and differing modalities of data. For example, two of the main
approaches to the study of breast cancer are histopathology (analyzing visual
characteristics of tumors) and genetics. While histopathology is the gold
standard for diagnostics and there have been many recent breakthroughs in
genetics, there is little overlap between these two fields. We aim to bridge
this gap by developing methods based on Angle-based Joint and Individual
Variation Explained (AJIVE) to directly explore similarities and differences
between these two modalities. Our approach exploits Convolutional Neural
Networks (CNNs) as a powerful, automatic method for image feature extraction to
address some of the challenges presented by statistical analysis of
histopathology image data. CNNs raise issues of interpretability that we
address by developing novel methods to explore visual modes of variation
captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features.
Our results provide many interpretable connections and contrasts between
histopathology and genetics
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
Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.
BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised