Show & Tell What Fun Can Do

ÂUmwelt is a German word meaning Âenvironments, or Âsurroundings. In English, we use the word to describe the world as it is perceived by a given organism. As sighted people, we can only imagine the disconnect that arises when another personÂs Umwelt doesnÂt include sight

Evaluating the Causes and Consequences of Climate Migration in Morocco

Migration caused by climate change has already affected many communities, but has only recently been recognized as a problem. While climate change can cause migration, other factors such as political and socioeconomic issues can also provoke migration. Our goal was to gather research from a variety of sources to determine potential risks and impacts of climate migration on different areas in Morocco. We identified regions that are vulnerable to climate migration. We identified potential strategies for adaptation to climate change

Effective Treatment of Established GL261 Murine Gliomas through Picornavirus Vaccination-Enhanced Tumor Antigen-Specific CD8+ T Cell Responses.

Glioblastoma (GBM) is among the most invasive and lethal of cancers, frequently infiltrating surrounding healthy tissue and giving rise to rapid recurrence. It is therefore critical to establish experimental model systems and develop therapeutic approaches that enhance anti-tumor immunity. In the current study, we have employed a newly developed murine glioma model to assess the efficacy of a novel picornavirus vaccination approach for the treatment of established tumors. The GL261-Quad system is a variation of the GL261 syngeneic glioma that has been engineered to expresses model T cell epitopes including OVA257-264. MRI revealed that both GL261 and GL261-Quad tumors display characteristic features of human gliomas such as heterogeneous gadolinium leakage and larger T2 weighted volumes. Analysis of brain-infiltrating immune cells demonstrated that GL261-Quad gliomas generate detectable CD8+ T cell responses toward the tumor-specific Kb:OVA257-264 antigen. Enhancing this response via a single intracranial or peripheral vaccination with picornavirus expressing the OVA257-264 antigen increased anti-tumor CD8+ T cells infiltrating the brain, attenuated progression of established tumors, and extended survival of treated mice. Importantly, the efficacy of the picornavirus vaccination is dependent on functional cytotoxic activity of CD8+ T cells, as the beneficial response was completely abrogated in mice lacking perforin expression. Therefore, we have developed a novel system for evaluating mechanisms of anti-tumor immunity in vivo, incorporating the GL261-Quad model, 3D volumetric MRI, and picornavirus vaccination to enhance tumor-specific cytotoxic CD8+ T cell responses and track their effectiveness at eradicating established gliomas in vivo

Loss of CD8+ T cell cytotoxicity abrogates the effects of picornavirus vaccination against GL261-Quad gliomas.

<p>(A) Mean bioluminescence intensity (p/sec) of wild type C57BL/6 or perforin deficient (<i>Prf</i>^<i>-/-</i><i>)</i> GL261 glioma-bearing mice demonstrates no difference in the rate of tumor progression in the absence of treatment (N = 18 mice/group). (B) Mean BLI (p/sec) and (C) survival curve of C57BL/6 (N = 10 mice/group) or <i>Prf</i>^<i>-/-</i> (N = 7 mice) GL261-Quad glioma-bearing mice following picornavirus vaccination demonstrates a complete loss of vaccine efficacy in the absence of functional cytotoxic CD8+ T cell activity. Error bars indicate SEM. * denotes p<0.05, ** denotes p<0.01, ***denotes p<0.001. Arrow denotes time of vaccine administration.</p

GL261-Quad gliomas elicit an endogenous K^b:OVA_257–264 restricted CD8+ T cell response.

<p>Immune cells from whole brain tissue of glioma-bearing mice were isolated and gated based on CD45 expression. CD45^Hi cells were further analyzed for CD8, CD4, CD11b, GR-1 and K^b:OVA_{<b>257–264</b>} tetramer positivity. (A) The inflammatory profile of a representative GL261-bearing mouse. (B) Relative percentages of immune cell subsets in GL261 glioma-bearing mice confirm defined populations of CD8+, CD4+, and CD11b+,GR-1+ cells (N = 3 mice). (C) The inflammatory profile of a representative GL261-Quad glioma-bearing mouse. (D) K^b:OVA_{<b>257–264</b>} tetramer staining shows the presence of endogenous tumor antigen-restricted CD8+ T cell responses in the absence of treatment in mice bearing GL261-Quad gliomas (N = 5 mice).</p

Volumetric analysis of GL261 gliomas through quantification of T2 and T1 gadolinium enhanced MRI <i>in vivo</i>.

<p>(A,B) Volumetric analysis and 3D rendering of a representative live mouse bearing a GL261 glioma as visible by T2 weighted MRI using Analyze 11.0 software. (C) Quantification of mean tumor volumes demonstrates larger values from T2 weighted MRI than T1 gadolinium-enhanced MRI for both GL261 (N = 3 mice) and GL261-Quad (N = 4 mice) gliomas 4 weeks post tumor injection compared to PBS sham controls (N = 2 mice). (D) T2 weighted and T1 gadolinium-enhanced MRIs with corresponding bioluminescence images of representative small and large GL261-Quad gliomas. (E) Tumor volumes obtained from MRI plotted against bioluminescence intensity demonstrate a strong correlation for both T2 weighted (R² = 0.9045) and T1 gadolinium-enhanced (R² = 0.9296) imaging (N = 15 mice/group). (F,G) Representative H&E stained sections at 4X and 10X magnification of cortical brain tissue from mice bearing GL261 or GL261-Quad gliomas demonstrate similarities in histopathologic features of the two models.</p

Vaccination with TMEV Xho1-OVA8 enhances tumor antigen-restricted CD8+ T cell responses in the CNS, delays tumor progression, and extends survival in mice bearing GL261-Quad gliomas.

<p>Two weeks post-GL261-Quad tumor introduction, mice were treated with control or recombinant picornavirus. (A,B) At five weeks, brain infiltrating lymphocytes were isolated, gated based on CD45 expression, and analyzed for CD8 and K^b:OVA_{<b>257–264</b>} tetramer positivity. (A) Representative FACS plots and (B) mean percent of K^b:OVA_{<b>257–264</b>}+ cells per CD8+ cells demonstrate a significant increase in tumor antigen-restricted CD8+ T cells infiltrating the brain following intracranial (N = 9) or intraperitoneal (N = 10 mice) TMEV Xho1-OVA8 vaccine administration compared to TMEV-wt. Percent of K^b:OVA_{<b>257–264</b>}+ / CD8+ calculated as Q2-2/(Q2-2+Q4-2)*100. (C,E) Mean bioluminescence intensity (p/sec) of GL261-Quad glioma-bearing mice treated with TMEV-wt or recombinant TMEV Xho1-OVA8 picornavirus. Mice receiving (C) intracranial (N = 15 mice) or (E) intraperitoneal (N = 13 mice) TMEV Xho1-OVA8 treatment displayed significantly delayed progression of established gliomas compared to TMEV-wt treated controls. (D,F) Delayed tumor progression is accompanied by a significant increase in survival for mice treated with TMEV Xho1-OVA8 via (D) intracranial or (F) intraperitoneal administration. Arrow denotes time of vaccine administration. (G) RT-PCR analysis of RNA isolated from brains of glioma-bearing mice demonstrates a significant reduction in transgene expression following treatment with TMEV Xho1-OVA8 compared to TMEV-wt treated controls. Error bars indicate SEM. * denotes p<0.05, ** denotes p<0.01, ***denotes p<0.001.</p

Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment

International audienceA primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the O(10)  MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the νe component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section σ(Eν) for charged-current νe absorption on argon. In the context of a simulated extraction of supernova νe spectral parameters from a toy analysis, we investigate the impact of σ(Eν) modeling uncertainties on DUNE’s supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on σ(Eν) must be substantially reduced before the νe flux parameters can be extracted reliably; in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10% bias with DUNE requires σ(Eν) to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of σ(Eν). A direct measurement of low-energy νe-argon scattering would be invaluable for improving the theoretical precision to the needed level

The DUNE Far Detector Vertical Drift Technology, Technical Design Report

International audienceDUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals