SINEUPs are modular antisense long non-coding RNAs that increase synthesis of target proteins in cells

Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs) and unveiling their functions in a wide range of biological processes their applications as biotechnological or therapeutic tools are still at their infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the Parkinson's disease-associated gene Ubiquitin carboxyl-terminal esterase L1 (Uchl1), is able to increase UchL1 protein synthesis at post-transcriptional level. Its activity requires two RNA elements: an embedded inverted SINEB2 sequence to increase translation and the overlapping region to target its sense mRNA. This functional organization is shared with several mouse lncRNAs antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs as enhancers of target mRNA translation remains unexplored. Here we define AS Uchl1 as the representative member of a new functional class of natural and synthetic antisense lncRNAs that activate translation. We named this class of RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to UP-regulate translation in a gene-specific manner. The overlapping region is indicated as the Binding Doman (BD) while the embedded inverted SINEB2 element is the Effector Domain (ED). By swapping BD, synthetic SINEUPs are designed targeting mRNAs of interest. SINEUPs function in an array of cell lines and can be efficiently directed toward N-terminally tagged proteins. Their biological activity is retained in a miniaturized version within the range of small RNAs length. Its modular structure was exploited to successfully design synthetic SINEUPs targeting endogenous Parkinson's disease-associated DJ-1 and proved to be active in different neuronal cell lines. In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies

Overview on electrical issues faced during the SPIDER experimental campaigns

SPIDER is the full-scale prototype of the ion source of the ITER Heating Neutral Beam Injector, where negative ions of Hydrogen or Deuterium are produced by a RF generated plasma and accelerated with a set of grids up to ~100 keV. The Power Supply System is composed of high voltage dc power supplies capable of handling frequent grid breakdowns, high current dc generators for the magnetic filter field and RF generators for the plasma generation. During the first 3 years of SPIDER operation different electrical issues were discovered, understood and addressed thanks to deep analyses of the experimental results supported by modelling activities. The paper gives an overview on the observed phenomena and relevant analyses to understand them, on the effectiveness of the short-term modifications provided to SPIDER to face the encountered issues and on the design principle of long-term solutions to be introduced during the currently ongoing long shutdown.Comment: 8 pages, 12 figures. Presented at SOFT 202

Microwave Photon Emission in Superconducting Circuits

Quantum computing requires a novel approach to store data as quantum states, opposite to classical bits. One of the most promising candidates is entangled photons. In this manuscript, we show the photon emission in the range of microwave frequencies of three different types of superconducting circuits, a SQUID, a JPA, and a JTWPA, often used as low-noise parametric amplifiers. These devices can be operated as sources of entangled photons. We report the experimental protocol used to produce and measure microwave radiation from these circuits, as well as data simulations. The collected spectra are obtained by performing single-tone measurements with a direct rf pump on the devices; the output spectra at low powers (below −100 dBm) are well interpreted by the dynamical Casimir model, while at high powers (above −100 dBm) the system is well described by the Autler–Townes fluorescence of a three-level atom

The role of the comprehensive complication index for the prediction of survival after liver transplantation.

In the last years, several scoring systems based on pre- and post-transplant parameters have been developed to predict early post-LT graft function. However, some of them showed poor diagnostic abilities. This study aims to evaluate the role of the comprehensive complication index (CCI) as a useful scoring system for accurately predicting 90-day and 1-year graft loss after liver transplantation. A training set (n = 1262) and a validation set (n = 520) were obtained. The study was registered at https://www.ClinicalTrials.gov (ID: NCT03723317). CCI exhibited the best diagnostic performance for 90 days in the training (AUC = 0.94; p < 0.001) and Validation Sets (AUC = 0.77; p < 0.001) when compared to the BAR, D-MELD, MELD, and EAD scores. The cut-off value of 47.3 (third quartile) showed a diagnostic odds ratio of 48.3 and 7.0 in the two sets, respectively. As for 1-year graft loss, CCI showed good performances in the training (AUC = 0.88; p < 0.001) and validation sets (AUC = 0.75; p < 0.001). The threshold of 47.3 showed a diagnostic odds ratio of 21.0 and 5.4 in the two sets, respectively. All the other tested scores always showed AUCs < 0.70 in both the sets. CCI showed a good stratification ability in terms of graft loss rates in both the sets (log-rank p < 0.001). In the patients exceeding the CCI ninth decile, 1-year graft survival rates were only 0.7% and 23.1% in training and validation sets, respectively. CCI shows a very good diagnostic power for 90-day and 1-year graft loss in different sets of patients, indicating better accuracy with respect to other pre- and post-LT scores.Clinical Trial Notification: NCT03723317

Modeling of Josephson Traveling Wave Parametric Amplifiers

The recent developments in quantum technologies, as well as advanced detection experiments, have raised the need to detect extremely weak signals in the microwave frequency spectrum. To this aim, the Josephson travelling wave parametric amplifier, a device capable of reaching the quantum noise limit while providing a wide bandwidth, has been proposed as a suitable cryogenic front-end amplifier. This work deals with the numerical study of a Josephson travelling wave parametric amplifier, without approximations regarding the nonlinearity of the key elements. In particular, we focus on the investigation of the system of coupled nonlinear differential equations representing all the cells of the Josephson travelling wave parametric amplifier, with proper input and output signals at the boundaries. The investigation of the output signals generated by the parametric amplification process explores the phase-space and the Fourier spectral analysis of the output voltage, as a function of the parameters describing the pump and signal tones that excite the device. Beside the expected behavior, i.e., the signal amplification, we show that, depending on the system operation, unwanted effects (such as pump tone harmonics, incommensurate frequency generation, and noise rise), which are not accounted for in simple linearized approaches, can be generated in the whole nonlinear system

Characterization of Traveling-Wave Josephson Parametric Amplifiers at T = 0.3 K

The growing interest in quantum technologies, from fundamental physics experiments to quantum computing, demands for extremely performing electronics only adding the minimum amount of noise admitted by quantum mechanics to the input signal (i.e., quantum-limited electronics). Superconducting microwave amplifiers, due to their dissipationless nature, exhibit outstanding performances in terms of noise (quantum limited), and gain. However, bandwidth and saturation power still show space for substantial improvement. Within the DARTWARS 1 1 DARTWARS (Detector Array Readout with Traveling Wave AmplifieRS), funded by Italian National Nuclear Institute (INFN), is a quantum technologies project targeted at the development of wideband superconducting amplifiers with noise at the quantum limit and the implementation of a quantum-limited readout in different types of superconducting detectors and qubit. We are developing state-of-the-art microwave superconducting amplifiers based on Josephson junction arrays and on distributed kinetic inductance transmission lines. Here we report the realization of a setup for the characterization of the performances of Josephson traveling-wave parametric amplifiers at a temperature of 300 mK. Although in the final experimental setup, these amplifiers will operate at a base temperature of about 20 mK, their characterization at 300 mK allows to evidence the main aspects of their performances, but the ultimate noise level. This represents a quick and relatively inexpensive way to test these superconductive devices that can be of help to improve their design and fabrication

Coherent quantum network of superconducting qubits as a highly sensitive detector of microwave photons for searching of galactic axions

We propose a novel approach to detect a low power microwave signal with a frequency of the order of several GHz based on a coherent collective response of quantum states occurring in a superconducting qubits network (SQN). An SQN composes of a large number of superconducting qubits embedded in a low-dissipative superconducting resonator. Our theory predicts that an SQN interacting with the off-resonance microwave radiation, demonstrates the collective alternating current Stark effect that can be measured even in the limit of single photon counting. A design of the layout of three terminals SQN detectors containing 10 flux qubits weakly coupled to a low-dissipative R-resonator and T-transmission line was developed. The samples were fabricated by Al-based technology with Nb resonator. The SQN detector was tested in terms of microwave measurements of scattering parameters and two-tone spectroscopy. A substantial shift of the frequency position of the transmission coefficient drop induced by a second tone pump signal was observed, and this effect clearly manifests a nonlinear multiphoton interaction between the second-tone microwave pump signal and an array of qubits.</p

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