60 research outputs found
Thermal leptogenesis in a model with mass varying neutrinos
In this paper we consider the possibility of neutrino mass varying during the
evolution of the Universe and study its implications on leptogenesis.
Specifically, we take the minimal seesaw model of neutrino masses and introduce
a coupling between the right-handed neutrinos and the dark energy scalar field,
the Quintessence. In our model, the right-handed neutrino masses change as the
Quintessence scalar evolves. We then examine in detail the parameter space of
this model allowed by the observed baryon number asymmetry. Our results show
that it is possible to lower the reheating temperature in this scenario in
comparison with the case that the neutrino masses are unchanged, which helps
solve the gravitino problem. Furthermore, a degenerate neutrino mass patten
with larger than the upper limit given in the minimal leptogenesis
scenario is permitted.Comment: 18 pages, 7 figures, version to appear in PR
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
Rhizopus microsporus and Mucor racemosus coinfection following COVID-19 detected by metagenomics next-generation sequencing: A case of disseminated mucormycosis
Mucormycosis is an invasive opportunistic fungal infection, which may be lethal and mostly affects patients with immunodeficiency or diabetes mellitus. Among Mucorales fungi, Rhizopus spp. is the most common cause of mucormycosis, followed by genera such as Mucor and Lichtheimia. Here we report a patient with severe COVID-19 infection who developed nasal pain, facial swelling, prominent black eschar on the nasal root. CT scan revealed pansinusitis along the maxillary, ethmoidal, and sphenoid sinuses. Mixed mold infection with Rhizopus microsporus and Mucor racemosus was detected by blood metagenomics next-generation sequencing (mNGS) and later nasal mucosa histological investigation confirmed mucormycosis. Severe COVID-19 infection led to the patient's thrombocytopenia and leukopenia. Later disseminated mucormycosis aggravated the infection and sepsis eventually resulted in death.It is the first case report of mucormycosis in which R. microsporus and M. racemosus as the etiologic agents were found simultaneously in one patient. COVID-19 infection combined with disseminated mucormycosisis can be fatal and mNGS is a fast, sensitive and accurate diagnostic method for fungi detection
Scattering Points in Parallel Coordinates
In this paper, we present a novel parallel coordinates design integrated with points (Scattering Points in Parallel Coordinates, SPPC), by taking advantage of both parallel coordinates and scatterplots. Different from most multiple views visualization frameworks involving parallel coordinates where each visualization type occupies an individual window, we convert two selected neighboring coordinate axes into a scatterplot directly. Multidimensional scaling is adopted to allow converting multiple axes into a single subplot. The transition between two visual types is designed in a seamless way. In our work, a series of interaction tools has been developed. Uniform brushing functionality is implemented to allow the user to perform data selection on both points and parallel coordinate polylines without explicitly switching tools. A GPU accelerated Dimensional Incremental Multidimensional Scaling (DIMDS) has been developed to significantly improve the system performance. Our case study shows that our scheme is more efficient than traditional multi-view methods in performing visual analysis tasks
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