Signal and noise of Diamond Pixel Detectors at High Radiation Fluences

CVD diamond is an attractive material option for LHC vertex detectors because of its strong radiation-hardness causal to its large band gap and strong lattice. In particular, pixel detectors operating close to the interaction point profit from tiny leakage currents and small pixel capacitances of diamond resulting in low noise figures when compared to silicon. On the other hand, the charge signal from traversing high energy particles is smaller in diamond than in silicon by a factor of about 2.2. Therefore, a quantitative determination of the signal-to-noise ratio (S/N) of diamond in comparison with silicon at fluences in excess of 10$^{15}$ n$_{eq}$ cm$^{-2}$, which are expected for the LHC upgrade, is important. Based on measurements of irradiated diamond sensors and the FE-I4 pixel readout chip design, we determine the signal and the noise of diamond pixel detectors irradiated with high particle fluences. To characterize the effect of the radiation damage on the materials and the signal decrease, the change of the mean free path $\lambda_{e/h}$ of the charge carriers is determined as a function of irradiation fluence. We make use of the FE-I4 pixel chip developed for ATLAS upgrades to realistically estimate the expected noise figures: the expected leakage current at a given fluence is taken from calibrated calculations and the pixel capacitance is measured using a purposely developed chip (PixCap). We compare the resulting S/N figures with those for planar silicon pixel detectors using published charge loss measurements and the same extrapolation methods as for diamond. It is shown that the expected S/N of a diamond pixel detector with pixel pitches typical for LHC, exceeds that of planar silicon pixels at fluences beyond 10$^{15}$ particles cm$^{-2}$, the exact value only depending on the maximum operation voltage assumed for irradiated silicon pixel detectors

Broad Efficacy of a Computationally Designed ACE2 Decoy Against SARS-CoV-2 Omicron Variants and Related Viruses In Vitro and In Vivo

Background: The SARS-CoV-2 omicron variant (B.1.1.529) and its sublineages are currently the dominant variants in the United States accounting for 100% of COVID-19 cases. Problem: The S protein receptor-binding domain (RBD), located in the S1 subunit of the S protein, binds the human angiotensin-converting enzyme 2 (hACE2) leading to S1 shedding and proteolytic processing of S2 that is important for membrane fusion and release of viral RNA. Various neutralizing therapeutics including protein minibinders, peptides, monoclonal antibodies, and nanobodies have been developed to block the critical interaction between the RBD and hACE2. However, these therapeutics are often developed against the S protein of wildtype or a specific variant of SARSCoV- 2, making them highly susceptible to mutational escape.1 Solution: A strategy employed by our group includes using sACE2 (soluble dimeric ACE2 that contains both the protease and dimerization domains) with enhanced S RBD affinity to outcompete native ACE2 expressed on host cells, acting as a ‘decoy’ to block the interaction between the RBD and hACE2 (Figure 1). sACE2 has moderate affinity for the S protein (~20 nM)2. Therefore, sACE2 must be engineered (by introducing affinity enhancing mutations) to bind with tighter affinity to outcompete membrane bound ACE2-S interaction and rival the potency of mAbs. These sACE2 derivatives maintain close similarity to the native ACE2 receptor making them extremely resistant to virus escape. Any mutation in the RBD that limits binding to the sACE2 derivative will likely have reduced binding towards native ACE2 receptors potentially making the virus unfit to propagate.https://jdc.jefferson.edu/aoa_research_symposium_posters/1000/thumbnail.jp

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Decision making in advanced heart failure: A scientific statement from the american heart association

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient. The top 10 things to know about decision making in advanced heart failure care are listed in Table 1

Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter

We present a study of showers initiated by electrons, pions, kaons, and protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE scintillator-tungsten analogue hadronic calorimeter. The data were recorded at the CERN Super Proton Synchrotron in 2011. The analysis includes measurements of the calorimeter response to each particle type as well as measurements of the energy resolution and studies of the longitudinal and radial shower development for selected particles. The results are compared to Geant4 simulations (version 9.6.p02). In the study of the energy resolution we include previously published data with beam momenta from 1 GeV to 10 GeV recorded at the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table

Hadron shower decomposition in the highly granular CALICE analogue hadron calorimeter

The spatial development of hadronic showers in the CALICE scintillator-steel analogue hadron calorimeter is studied using test beam data collected at CERN and FNAL for single positive pions and protons with initial momenta in the range from 10 to 80 GeV/c. Both longitudinal and radial development of hadron showers are parametrised with two-component functions. The parametrisation is fit to test beam data and simulations using the QGSP_BERT and FTFP_BERT physics lists from Geant4 version 9.6. The parameters extracted from data and simulated samples are compared for the two types of hadrons. The response to pions and the ratio of the non-electromagnetic to the electromagnetic calorimeter response, h/e, are estimated using the extrapolation and decomposition of the longitudinal profiles.Comment: 38 pages, 19 figures, 5 tables; author list changed; submitted to JINS

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS

The Time Structure of Hadronic Showers in highly granular Calorimeters with Tungsten and Steel Absorbers

The intrinsic time structure of hadronic showers influences the timing capability and the required integration time of hadronic calorimeters in particle physics experiments, and depends on the active medium and on the absorber of the calorimeter. With the CALICE T3B experiment, a setup of 15 small plastic scintillator tiles read out with Silicon Photomultipliers, the time structure of showers is measured on a statistical basis with high spatial and temporal resolution in sampling calorimeters with tungsten and steel absorbers. The results are compared to GEANT4 (version 9.4 patch 03) simulations with different hadronic physics models. These comparisons demonstrate the importance of using high precision treatment of low-energy neutrons for tungsten absorbers, while an overall good agreement between data and simulations for all considered models is observed for steel.Comment: 24 pages including author list, 9 figures, published in JINS

Performance of the first prototype of the CALICE scintillator strip electromagnetic calorimeter

A first prototype of a scintillator strip-based electromagnetic calorimeter was built, consisting of 26 layers of tungsten absorber plates interleaved with planes of 45x10x3 mm3 plastic scintillator strips. Data were collected using a positron test beam at DESY with momenta between 1 and 6 GeV/c. The prototype's performance is presented in terms of the linearity and resolution of the energy measurement. These results represent an important milestone in the development of highly granular calorimeters using scintillator strip technology. This technology is being developed for a future linear collider experiment, aiming at the precise measurement of jet energies using particle flow techniques

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13