Nanophotonic Neural Probes for in vivo Light Sheet Imaging

We present implantable silicon neural probes with nanophotonic waveguide routing networks and grating emitters for light sheet imaging. Fluorescein beam profiles, fluorescent bead imaging, and fluorescence brain imaging in vivo are presented

Nanophotonic Neural Probes for in vivo Light Sheet Imaging

We present implantable silicon neural probes with nanophotonic waveguide routing networks and grating emitters for light sheet imaging. Fluorescein beam profiles, fluorescent bead imaging, and fluorescence brain imaging in vivo are presented

Beam-Steering Nanophotonic Phased-Array Neural Probes

We demonstrate the first implantable nanophotonic neural probes with integrated silicon nitride phased arrays. Coherent beam-steering is achieved in brain tissue by wavelength tuning. Beam profiles, optogenetic stimulation, and functional imaging are validated in vitro

Implantable photonic neural probes for light-sheet fluorescence brain imaging

Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for highspeed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200-mm-diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed, in vitro, and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses <16 μm for propagation distances up to 300 μm in free space. Imaging areas were as large as ≈240 μm × 490 μm in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals

Implantable photonic neural probes for light-sheet fluorescence brain imaging

Significance: Light-sheet fluorescence microscopy is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. Here, we demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200 mm diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed and in vitro mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 μm for propagation distances up to 300 μm in free space. Imaging areas were as large as ≈ 240 μm x 490 μm in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of light-sheet fluorescence microscopy for deep brain imaging and experiments in freely-moving animals

Observation of Fine Time Structures in the Cosmic Proton and Helium Fluxes with the Alpha Magnetic Spectrometer on the International Space Station

International audienceWe present the precision measurement from May 2011 to May 2017 (79 Bartels rotations) of the proton fluxes at rigidities from 1 to 60 GV and the helium fluxes from 1.9 to 60 GV based on a total of $1 \times 10^9$ events collected with the Alpha Magnetic Spectrometer aboard the International Space Station. This measurement is in solar cycle 24, which has the solar maximum in April 2014. We observed that, below 40 GV, the proton flux and the helium flux show nearly identical fine structures in both time and relative amplitude. The amplitudes of the flux structures decrease with increasing rigidity and vanish above 40 GV. The amplitudes of the structures are reduced during the time period, which started one year after solar maximum, when the proton and helium fluxes steadily increase. Above $\sim 3$  GV the p/He flux ratio is time independent. We observed that below $\sim 3$  GV the ratio has a long-term decrease coinciding with the period during which the fluxes start to rise

Experimental Apparatus for Nanophotonic Neuroprobe-enabled Fluorescence Imaging

Fluorescence imaging has the ability to resolve brain structure and activity, in real time and with single-cell resolution. Current techniques, however, remain slow and cannot penetrate deep into the brain. This thesis investigates the use of implantable silicon photonic neuroprobes for three dimensional neuroimaging at higher framerates than what is currently possible. We present the implementation of neuroprobes as a novel method to deliver excitation in a fluorescent light sheet microscopy setup, achieving higher contrast than epi-fluorescence. We also present the algorithm and calibration of a high speed volumetric imaging setup, to monitor multiple depths simultaneously. Imaging experiments were performed on mouse brain tissues in vitro and in vivo. The system may be extended to freely moving animals in the future.M.A.S

An investigation on possible links between risk management, performance measurement and reward schemes

The ongoing global financial crisis underlined the urgent need of changing traditional executives compensation schemes. Governments and authorities reacted through regulation and standards, while professionals and academics have suggested several new pay mechanisms. Given some limitations of the above-mentioned solutions, the paper aims at understanding whether they can be improved by introducing incentives strictly tied to companies’ risk metrics for executive members of the Boards and top managers with strategic responsibilities. The link between monetary incentives and the achievement of desired riskadjusted performance is thus proposed and explored. Following a qualitative methodology, four case studies were carried out using semi-structured interviews with Italian risk managers and human resources managers. Results show that a reward system based on risk measures is welcome and feasible, if not already adopted. It needs to be carefully tailored to each company. Lastly, its adoption and implementation rely on various contextual conditions and can be hindered by some difficulties in risk measurement. The paper contributes to the reward and risk management literature by investigating new tools to satisfy the need of sounder compensation practices

Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle- Invasive Bladder Cancer

International audienceBiomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Pro-filing tumor and blood samples, we found that follicular helper CD4+T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+TFH residing in bladder tissues cor-related with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. SIGNIFICANCE: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli– specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies