23 research outputs found

    Random polarization dynamics in a resonant optical medium

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    Random optical-pulse polarization switching along an active optical medium in the Λ\Lambda-configuration with spatially disordered occupation numbers of its lower energy sub-level pair is described using the idealized integrable Maxwell-Bloch model. Analytical results describing the light polarization-switching statistics for the single self-induced transparency pulse are compared with statistics obtained from direct Monte-Carlo numerical simulations.Comment: 7 pages, 3 figure

    A random map implementation of implicit filters

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    Implicit particle filters for data assimilation generate high-probability samples by representing each particle location as a separate function of a common reference variable. This representation requires that a certain underdetermined equation be solved for each particle and at each time an observation becomes available. We present a new implementation of implicit filters in which we find the solution of the equation via a random map. As examples, we assimilate data for a stochastically driven Lorenz system with sparse observations and for a stochastic Kuramoto-Sivashinski equation with observations that are sparse in both space and time

    Implicit particle methods and their connection with variational data assimilation

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    The implicit particle filter is a sequential Monte Carlo method for data assimilation that guides the particles to the high-probability regions via a sequence of steps that includes minimizations. We present a new and more general derivation of this approach and extend the method to particle smoothing as well as to data assimilation for perfect models. We show that the minimizations required by implicit particle methods are similar to the ones one encounters in variational data assimilation and explore the connection of implicit particle methods with variational data assimilation. In particular, we argue that existing variational codes can be converted into implicit particle methods at a low cost, often yielding better estimates, that are also equipped with quantitative measures of the uncertainty. A detailed example is presented

    Stochastic Pulse Switching in a Degenerate Resonant Optical Medium

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    Using the idealized integrable Maxwell-Bloch model, we describe random optical-pulse polarization switching along an active optical medium in the Lambda-configuration with disordered occupation numbers of its lower energy sub-level pair. The description combines complete integrability and stochastic dynamics. For the single-soliton pulse, we derive the statistics of the electric-field polarization ellipse at a given point along the medium in closed form. If the average initial population difference of the two lower sub-levels vanishes, we show that the pulse polarization will switch intermittently between the two circular polarizations as it travels along the medium. If this difference does not vanish, the pulse will eventually forever remain in the circular polarization determined by which sub-level is more occupied on average. We also derive the exact expressions for the statistics of the polarization-switching dynamics, such as the probability distribution of the distance between two consecutive switches and the percentage of the distance along the medium the pulse spends in the elliptical polarization of a given orientation in the case of vanishing average initial population difference. We find that the latter distribution is given in terms of the well-known arcsine law

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

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

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    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
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