Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged ...intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) the delivery of vaccine antigens in order to mount T cell immune responses and (2) the introduction of reprogramming factors into differentiated cells in order to induce pluripotency, that mRNAs tagged with the 3′ UTR elements discovered in this study outperform those with commonly used 3′ UTRs. This approach further leverages the utility of mRNA as a gene therapy drug format.
Orlandini von Niessen et al. describe a cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. They show in two examples of mRNA application that the discovered 3′ UTRs outperform commonly used regions. These findings leverage the utility of mRNA as a gene therapy drug format.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
What is the size of the atomic nucleus? This deceivably simple question is dicult to answer. Although the electric charge distributions in atomic nuclei were measured accurately already half a ...century ago, our knowledge of the distribution of neutrons is still decient. In addition to constraining the size of atomic nuclei, the neutron distribution also impacts the number of nuclei that can exist and the size of neutron stars. We present an ab initio calculation of the neutron distribution of the neutron-rich nucleus 48Ca. We show that the neutron skin (dierence between the radii of the neutron and proton distributions) is signicantly smaller than previously thought. We also make predictions for the electric dipole polarizability and the weak form factor; both quantities that are at present targeted by precision measurements. Based on ab initio results for 48Ca, we provide a constraint on the size of a neutron star.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
For detectors with resistive elements, the time dependence of the signals is not solely given by the movement of the charges in the drift medium but also by the time-dependent reaction of the ...resistive materials. In this report, we present a numerical way to capture this contribution by using the extended form of the Ramo–Shockley theorem for conductive media. As an example, the methodology will be applied to the MicroCAT two-dimensional interpolation readout to calculate the center of gravity position reconstruction distortion map of its readout cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron ...scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We describe the development of a position-sensitive Gas Electron Multiplier detector prototype, providing for each ionizing event three coordinates: the cartesian X and Y, and U at 45°. Simultaneous ...recording of the three projections permits ambiguity-free reconstruction of multiple tracks, and aims at operation in very high intensity radiation fields.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Developments in quantum technologies in the last decades have led to a wide range of applications, but have also resulted in numerous novel approaches to explore the low energy particle physics ...parameter space. The potential for applications of quantum technologies to high energy particle physics endeavors has however not yet been investigated to the same extent. In this paper, we propose a number of areas where specific approaches built on quantum systems such as low-dimensional systems (quantum dots, 2D atomic layers) or manipulations of ensembles of quantum systems (single atom or polyatomic systems in detectors or on detector surfaces) might lead to improved high energy particle physics detectors, specifically in the areas of calorimetry, tracking or timing.
Abstract
As demonstrated by the ATLAS New Small Wheel community with their MicroMegas (MM) design,
resistive electrodes are now used in different detector types within the Micro Pattern Gaseous
...Detector family to improve their robustness. The extended form of the Ramo-Shockley theorem for
conductive media has been applied to a 1 MΩ/□ 2D resistive strip bulk MM to calculate
the signal spreading over neighbouring channels using an 80 GeV/c muon track. For this geometry,
the dynamic weighting potential was obtained numerically using a finite element solver by applying
a junction condition and coordinate scaling technique to accurately represent the boundary
conditions of a 10 × 10 cm
2
active area. Using test beam measurements, the results of
this model will be used to benchmark this microscopic modelling methodology for signal induction
in resistive particle detectors.
Abstract Gas Electron Multipliers (GEMs) are used in many particle physics experiments, employing their `standard' configuration with amplification holes of 140 μ m pitch in a hexagonal pattern. ...However, the collection of the charge cloud from the primary ionisation electrons from the drift region of the detector into the GEM holes affects the position information from the initial interacting particle. In this paper, the results from studies with a triple-GEM detector with an X-Y-strip readout anode are presented. It is demonstrated that GEMs with a finer hole pitch of here 90 μ m improve the detector's spatial resolution. Within these studies, also the impact of the front-end electronics on the spatial resolution was investigated, which is briefly discussed in the paper.
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