Activated Ion Electron Capture Dissociation (AI ECD) of proteins: synchronization of infrared and electron irradiation with ion magnetron motion.

Here, we show that to perform activated ion electron capture dissociation (AI-ECD) in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer equipped with a CO(2) laser, it is necessary to synchronize both infrared irradiation and electron capture dissociation with ion magnetron motion. This requirement is essential for instruments in which the infrared laser is angled off-axis, such as the Thermo Finnigan LTQ FT. Generally, the electron irradiation time required for proteins is much shorter (ms) than that required for peptides (tens of ms), and the modulation of ECD, AI ECD, and infrared multiphoton dissociation (IRMPD) with ion magnetron motion is more pronounced. We have optimized AI ECD for ubiquitin, cytochrome c, and myoglobin; however the results can be extended to other proteins. We demonstrate that pre-ECD and post-ECD activation are physically different and display different kinetics. We also demonstrate how, by use of appropriate AI ECD time sequences and normalization, the kinetics of protein gas-phase refolding can be deconvoluted from the diffusion of the ion cloud and measured on the time scale longer than the period of ion magnetron motion

Medication errors at hospital admission and discharge in Type 1 and 2 diabetes

International audienceAIMS: To assess the prevalence and characteristics of medication errors at hospital admission and discharge in people with Type 1 and Type 2 diabetes, and identify potential risk factors for these errors. METHODS: This prospective observational study included all people with Type 1 (n~=~163) and Type 2 diabetes (n~=~508) admitted to the Diabetology-Department of the University Hospital of Montpellier, France, between 2013 and 2015. Pharmacists conducted medication reconciliation within 24~h of admission and at hospital discharge. Medication history collected from different sources (patient/family interviews, prescriptions/medical records, contact with community pharmacies/general practitioners/nurses) was compared with admission and discharge prescriptions to detect unintentional discrepancies in medication indicating involuntary medication changes. Medication errors were defined as unintentional medication discrepancies corrected by physicians. Risk factors for medication errors and serious errors (i.e. errors that may cause harm) were assessed using logistic regression. RESULTS: A total of 322 medication errors were identified and were mainly omissions. Prevalence of medication errors in Type 1 and Type 2 diabetes was 21.5% and 22.2% respectively at admission, and 9.0% and 12.2% at discharge. After adjusting for age and number of treatments, people with Type 1 diabetes had nearly a twofold higher odds of having medication errors (odds ratio (OR) 1.72, 95% confidence interval (CI) 1.02-2.94) and serious errors (OR 2.17, 95% CI 1.02-4.76) at admission compared with those with Type 2 diabetes. CONCLUSIONS: Medication reconciliation identified medication errors in one third of individuals. Clinical pharmacists should focus on poly-medicated individuals, but also on other high-risk people, for example, those with Type 1 diabetes

The Role of the D13 (1520) Resonance in eta Electroproduction

We investigate the electroproduction of eta mesons below a center of momentum energy of 1.6 GeV, with particular emphasis on the roles of the N*(1535) and N*(1520) resonances. Using the effective Lagrangian approach, we show that the transverse helicity amplitude of the N*(1535) can be extracted with good accuracy from the new eta electroproduction data, under reasonable assumptions for the strength of the longitudinal helicity amplitude. In addition, although the differential cross section is found to to have a small sensitivity to the N*(1520) resonance, it is shown that a recently completed double polarization experiment is very sensitive to this resonance.Comment: 7 pages, Revtex, 3 figure

A hydrogen beam to characterize the ASACUSA antihydrogen hyperfine spectrometer

The antihydrogen programme of the ASACUSA collaboration at the antiproton decelerator of CERN focuses on Rabi-type measurements of the ground-state hyperfine splitting of antihydrogen for a test of the combined Charge-Parity-Time symmetry. The spectroscopy apparatus consists of a microwave cavity to drive hyperfine transitions and a superconducting sextupole magnet for quantum state analysis via Stern-Gerlach separation. However, the small production rates of antihydrogen forestall comprehensive performance studies on the spectroscopy apparatus. For this purpose a hydrogen source and detector have been developed which in conjunction with ASACUSA's hyperfine spectroscopy equipment form a complete Rabi experiment. We report on the formation of a cooled, polarized, and time modulated beam of atomic hydrogen and its detection using a quadrupole mass spectrometer and a lock-in amplification scheme. In addition key features of ASACUSA's hyperfine spectroscopy apparatus are discussed.

The relativistic impulse approximation for the exclusive electrodisintegration of the deuteron

The electrodisintegration of the deuteron in the frame of the Bethe-Salpeter approach with a separable kernel of the nucleon-nucleon interaction is considered. This conception keeps the covariance of a description of the process. A comparison of relativistic and nonrelativistic calculations is presented. The factorization of the cross section of the reaction in the impulse approximation is obtained by analytical calculations. It is shown that the photon-neutron interaction plays an important role.Comment: 31 pages, 14 figures, 1 tabl

The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes

Mass spectrometry can be used to characterize multiprotein complexes, defining their subunit stoichiometry and composition following solution disruption and collision-induced dissociation (CID). While CID of protein complexes in the gas phase typically results in the dissociation of unfolded subunits, a second atypical route is possible wherein compact subunits or subcomplexes are ejected without unfolding. Because tertiary structure and subunit interactions may be retained, this is the preferred route for structural investigations. How can we influence which pathway is adopted? By studying properties of a series of homomeric and heteromeric protein complexes and varying their overall charge in solution, we found that low subunit flexibility, higher charge densities, fewer salt bridges, and smaller interfaces are likely to be involved in promoting dissociation routes without unfolding. Manipulating the charge on a protein complex therefore enables us to direct dissociation through structurally informative pathways that mimic those followed in solution

Quasifree Pion Electroproduction from Nuclei in the Δ\Delta Region

We present calculations of the reaction $A(e,e^\prime \pi N)B$ in the distorted wave impulse approximation. The reaction allows for the study of the production process in the nuclear medium without being obscured by the details of nuclear transition densities. First, a pion electroproduction operator suitable for nuclear calculations is obtained by extending the Blomqvist-Laget photoproduction operator to the virtual photon case. The operator is gauge invariant, unitary, reference frame independent, and describes the existing data reasonably well. Then it is applied in nuclei to predict nuclear cross sections under a variety of kinematic arrangements. Issues such as the effects of gauge-fixing, the interference of the $\Delta$ resonance with the background, sensitivities to the quadrupole component of the $\Delta$ excitation and to the electromagnetic form factors, the role of final-state interactions, are studied in detail. Methods on how to experimentally separate the various pieces in the coincidence cross section are suggested. Finally, the model is compared to a recent SLAC experiment.Comment: 27 pages in REVTEX, plus 22 PS figures embedded using psfig.sty (included), uuencode

A mini-twister variant and impact of residues/cations on the phosphodiester cleavage of this ribozyme class.

Nucleolytic ribozymes catalyze site-specific cleavage of their phosphodiester backbones. A minimal version of the twister ribozyme is reported that lacks the phylogenetically conserved stem P1 while retaining wild-type activity. Atomic mutagenesis revealed that nitrogen atoms N1 and N3 of the adenine-6 at the cleavage site are indispensable for cleavage. By NMR spectroscopy, a pKa value of 5.1 was determined for a 13C2-labeled adenine at this position in the twister ribozyme, which is significantly shifted compared to the pKa of the same adenine in the substrate alone. This finding pinpoints at a potential role for adenine-6 in the catalytic mechanism besides the previously identified invariant guanine-48 and a Mg2+ ion, both of which are directly coordinated to the non-bridging oxygen atoms of the scissile phosphate; for the latter, additional evidence stems from the observation that Mn2+ or Cd2+ accelerated cleavage of phosphorothioate substrates. The relevance of this metal ion binding site is further emphasized by a new 2.6 Å X-ray structure of a 2′-OCH3-U5 modified twister ribozyme