The modeling of neutrino-nucleus interactions constitutes a challenging source of systematic uncertainty for the extraction of precise values of neutrino oscillation parameters in long-baseline ...accelerator neutrino experiments. To improve such modeling and minimize the corresponding uncertainties, a new generation of detectors is being developed, which aim to measure the complete final state of particles resulting from neutrino interactions. In order to fully benefit from the improved detector capabilities, precise simulations of the nuclear effects on the final-state nucleons are needed. This article presents the study of the in-medium propagation of knocked-out protons, i.e., final-state interactions (FSI), comparing the NuWro and INCL cascade models. The INCL model is used here for the first time to predict exclusive final states of neutrino interactions. This study of INCL in the framework of neutrino interactions features various novelties, including the production of nuclear clusters (e.g., deuterons, \(\alpha\) particles) in the final state. The paper includes a complete characterization of the final state after FSI, comparisons to available measurements of single transverse variables, and an assessment of the observability of nuclear clusters.
beta2-Microglobulin (beta2m) is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). The natural turnover of MHC-I gives rise to the release of beta2m ...into plasmatic fluids and to its catabolism in the kidney. beta2m dissociation from the heavy chain of the complex is a severe complication in patients receiving prolonged hemodialysis. As a consequence of renal failure, the increasing beta2m concentrations can lead to deposition of the protein as amyloid fibrils. Here we characterize the His31-->Tyr human beta2m mutant, a non-natural form of beta2m that is more stable than the wild-type protein, displaying a ten-fold acceleration of the slow phase of folding. We report the 2.9A resolution crystal structure and the NMR characterization of the mutant beta2m, focussing on selected structural features and on the molecular packing observed in the crystals. Juxtaposition of the four mutant beta2m molecules contained in the crystal asymmetric unit, and specific hydrogen bonds, stabilize a compact protein assembly. Conformational heterogeneity of the four independent molecules, some of their mutual interactions and partial unpairing of the N-terminal beta-strand in one protomer are in keeping with the amyloidogenic properties displayed by the mutant beta2m.
The X-ray crystal structure of the human α-thrombin-hirunorm
IV complex has been determined at 2.5 Å resolution,
and refined to an R-factor of 0.173. The structure
reveals an inhibitor binding mode ...distinctive of a true
hirudin mimetic, which justifies the high inhibitory potency
and the selectivity of hirunorm IV. This novel inhibitor,
composed of 26 amino acids, interacts through the N-terminal
end with the α-thrombin active site in a nonsubstrate
mode, and binds specifically to the fibrinogen recognition
exosite through the C-terminal end. The backbone of the
N-terminal tripeptide Chg1"-Arg2"-2Nal3"
(Chg, cyclohexyl-glycine; 2Nal, β-(2-naphthyl)-alanine)
forms a parallel β-strand to the thrombin main-chain
segment Ser214–Gly216. The Chg1" side chain
occupies the S2 site, Arg2" penetrates into the S1
specificity site, while the 2Nal3" side chain occupies
the aryl binding site. The Arg2" side chain enters
the S1 specificity pocket from a position quite apart from
the canonical P1 site. This notwithstanding, the Arg2"
side chain establishes the typical ion pair with the carboxylate
group of Asp189.
In commercial medium-voltage vacuum contactors, widely used for grid management, the linear motion required for the actuation of contacts is often generated by a linear actuator. Aiming to ...investigate alternatives from an industrial point of view, a rotary actuation system based on a switched reluctance motor and a suited coupling mechanism was developed. The design process, based on a mechatronic approach using multi-physics modeling and simulation, is recalled first in this paper. A dedicated test rig designed and assembled for validation purposes is then described. Finally, experimental results obtained by testing the prototype motor and coupling mechanism are presented, confirming the expected performances.
In this paper we describe the performance of a prototype of the High Angle Time Projection Chambers (HA-TPCs) that are being produced for the Near Detector (ND280) upgrade of the T2K experiment. The ...two HA-TPCs of ND280 will be instrumented with eight Encapsulated Resistive Anode Micromegas (ERAM) on each endplate, thus constituting in total 32 ERAMs. This innovative technique allows the detection of the charge emitted by ionization electrons over several pads, improving the determination of the track position. The TPC prototype has been equipped with the first ERAM module produced for T2K and with the HA-TPC readout electronics chain and it has been exposed to the DESY Test Beam in order to measure spatial and dE/dx resolution. In this paper we characterize the performances of the ERAM and, for the first time, we compare them with a newly developed simulation of the detector response. Spatial resolution better than 800 \({\mu \rm m}\) and dE/dx resolution better than 10% are observed for all the incident angles and for all the drift distances of interest. All the main features of the data are correctly reproduced by the simulation and these performances fully fulfill the requirements for the HA-TPCs of T2K.
The surface loop which in the Bacillus subtilis neutral protease (NP) extends from amino acid residue 188 to residue 194 was replaced, by site-directed mutagenesis, with the 10-residue segment which ...in the homologous polypeptide chain of thermolysin (TLN) binds calcium-4 Matthews, B. W., Weaver, L. H., & Kester, W. R. (1974) J. Biol. Chem. 249, 8030-8044. The mutant NP was isolated to homogeneity, and its structural, functional, calcium-binding, and stability properties were investigated. Proteolytic fragmentation with Staphylococcus aureus V8 protease of mutant NP was used to isolate and analyze the protein fragment encompassing the site of mutation, unambiguously establishing the effective insertion of the new 10-residue segment. Atomic absorption measurements allowed us to demonstrate that mutant NP binds three calcium ions instead of the two ions bound to wild-type NP, showing that indeed the chain segment grafted from TLN to NP maintains its calcium-binding properties. The mutant NP showed kinetic parameters essentially similar to those of the wild-type NP with Z-Phe-Leu-Ala-OH as substrate. The enzyme inactivation of mutant vs wild-type NP was studied as a function of free Ca2+. It was found that mutant NP was much less stable than the wild-type NP when enzyme solutions were dialyzed at neutral pH in the presence of Ca2+ below 10(-3) M. On the other hand, the kinetic thermal stability to irreversible inactivation of mutant NP, when measured in the presence of 0.1 M CaCl2, was found to be increased about 2-fold over that of the wild-type NP. Thus, modulation of enzyme stability by free Ca2+ in mutant NP correlates with similar findings previously reported for thermolysin. Overall, the results obtained indicate that protein engineering experiments can be used to prepare hybrid proteins on the basis of sequence and function analysis of homologous protein molecules and show the feasibility of engineering metal ion binding sites into proteins.
Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus ...(EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.
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