| 1. |
- Simonds, Erin F., et al.
(författare)
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Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
- 2021
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Glioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.Methods We used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.Results ICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.Conclusions Our data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.
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| 2. |
- Bimbot, F, et al.
(författare)
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An overwiev of the CAVE project research activities in speaker verification
- 2000
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Ingår i: Speech Communication. - 0167-6393 .- 1872-7182. ; 31:2-3, s. 155-180
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Tidskriftsartikel (refereegranskat)abstract
- This article presents an overview of the research activities carried out in the European CAVE project, which focused on text-dependent speaker verification on the telephone network using whole word Hidden Markov Models. It documents in detail various aspects of the technology and the methodology used within the project. In particular, it addresses the issue of model estimation in the context of limited enrollment data and the problem of a posteriori decision threshold setting. Experiments are carried out on the realistic telephone speech database SESP. State-of-the-art performance levels are obtained, which validates the technical approaches developed and assessed during the project as well as the working infrastructure which facilitated cooperation between the partners.
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| 3. |
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| 4. |
- Genoud, Guillaume, et al.
(författare)
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Increasing energy coupling into plasma waves by tailoring the laser radial focal spot distribution in a laser wakefield accelerator
- 2013
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:6
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Tidskriftsartikel (refereegranskat)abstract
- By controlling the focal spot quality with a deformable mirror, we are able to show that increasing the fraction of pulse energy contained within the central part of the focal spot, while keeping the total energy and central spot size constant, significantly increases the amount of energy transferred to the wakefield: Our measurements show that the laser loses significantly more laser energy and undergoes greater redshifting and that more charge is produced in the accelerated beam. Three dimensional particle in cell simulations performed with accurate representations of the measured focal spot intensity distribution confirm that energy in the wings of the focal spot is effectively wasted. Even though self-focusing occurs, energy in the wings of the focal spot distribution is not coupled into the wakefield, emphasising the vital importance of high quality focal spot profiles in experiments. (C) 2013 AIP Publishing LLC.
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| 5. |
- Genoud, Guillaume, et al.
(författare)
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Laser-plasma electron acceleration in dielectric capillary tubes
- 2011
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 105:2, s. 309-316
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Tidskriftsartikel (refereegranskat)abstract
- Electron beams and betatron X-ray radiation generated by laser wakefield acceleration in long plasma targets are studied. The targets consist of hydrogen filled dielectric capillary tubes of diameter 150 to 200 microns and length 6 to 20 mm. Electron beams are observed for peak laser intensities as low as 5x10(17) W/cm(2). It is found that the capillary collects energy outside the main peak of the focal spot and contributes to keep the beam self-focused over a distance longer than in a gas jet of similar density. This enables the pulse to evolve enough to reach the threshold for wavebreaking, and thus trap and accelerate electrons. No electrons were observed for capillaries of large diameter (250 mu m), confirming that the capillary influences the interaction and does not have the same behaviour as a gas cell. Finally, X-rays are used as a diagnostic of the interaction and, in particular, to estimate the position of the electrons trapping point inside the capillary.
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| 6. |
- Heusermann, W, et al.
(författare)
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Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER
- 2016
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 213:2, s. 173-184
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.
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| 7. |
- Lindberg, Johan, et al.
(författare)
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Techniques for a priori decision threshold estimation in speaker verification
- 1998
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Konferensbidrag (refereegranskat)abstract
- A key problem for field applications in speaker verification is the issue of a priori threshold setting. In the context of the CAVE project several methods for estimating speakerindependent and speaker-dependent decision thresholds were compared. Relevant parameters are estimated from development data only, i.e. without resorting to additional client data. The various approaches were tested on the Dutch SESP database.
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| 8. |
- Mangles, S. P. D., et al.
(författare)
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Controlling the spectrum of x-rays generated in a laser-plasma accelerator by tailoring the laser wavefront
- 2009
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 95:18
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Tidskriftsartikel (refereegranskat)abstract
- By tailoring the wavefront of the laser pulse used in a laser-wakefield accelerator, we show that the properties of the x-rays produced due to the electron beam's betatron oscillations in the plasma can be controlled. By creating a wavefront with coma, we find that the critical energy of the synchrotronlike x-ray spectrum can be significantly increased. The coma does not substantially change the energy of the electron beam, but does increase its divergence and produces an energy-dependent exit angle, indicating that changes in the x-ray spectrum are due to an increase in the electron beam's oscillation amplitude within the wakefield.
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| 9. |
- Mangles, S. P. D., et al.
(författare)
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Self-injection threshold in self-guided laser wakefield accelerators
- 2012
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Ingår i: Physical Review Special Topics. Accelerators and Beams. - 1098-4402. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- A laser pulse traveling through a plasma can excite large amplitude plasma waves that can be used to accelerate relativistic electron beams in a very short distance-a technique called laser wakefield acceleration. Many wakefield acceleration experiments rely on the process of wave breaking, or self-injection, to inject electrons into the wave, while other injection techniques rely on operation without self-injection. We present an experimental study into the parameters, including the pulse energy, focal spot quality, and pulse power, that determine whether or not a wakefield accelerator will self-inject. By taking into account the processes of self-focusing and pulse compression we are able to extend a previously described theoretical model, where the minimum bubble size k(p)r(b) required for trapping is not constant but varies slowly with density and find excellent agreement with this model.
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| 10. |
- Petrovska, D., et al.
(författare)
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Polycost : A telephone-speech database for speaker recognition
- 2020
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Ingår i: RLA2C 1998 - Speaker Recognition and its Commercial and Forensic Applications. - : International Speech Communication Association. ; , s. 211-214
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Konferensbidrag (refereegranskat)abstract
- This article presents an overview of the POLYCOST database dedicated to speaker recognition applications over the telephone network. The main characteristics of this database are: large mixed speech corpus size (> 100 speakers), English spoken by foreigners, mainly digits with some free speech, collected through international telephone lines, and more than eight sessions per speaker.
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