Electron-transfer and -capture dissociations of doubly protonated peptides gave dramatically different product ions for a series of histidine-containing pentapeptides of both non-tryptic (AAHAL, ...AHAAL, AHADL, AHDAL) and tryptic (AAAHK, AAHAK, AHAAK, HAAAK, AAAHR, AAHAR, AHAAR, HAAAR) type. Electron transfer from gaseous Cs atoms and fluoranthene anions triggered backbone dissociations of all four N−Cα bonds in the peptide ions in addition to loss of H and NH3. Substantial fractions of charge-reduced cation-radicals did not dissociate on an experimental time scale ranging from 10−6 to 10−1 s. Multistage tandem mass spectrometric (MS n ) experiments indicated that the non-dissociating cation-radicals had undergone rearrangements. These were explained as being due to proton migrations from N-terminal ammonium and COOH groups to the C-2′ position of the reduced His ring, resulting in substantial radical stabilization. Ab initio calculations revealed that the charge-reduced cation-radicals can exist as low-energy zwitterionic amide π* states which were local energy minima. These states underwent facile exothermic proton migrations to form aminoketyl radical intermediates, whereas direct N−Cα bond cleavage in zwitterions was disfavored. RRKM analysis indicated that backbone N−Cα bond cleavages did not occur competitively from a single charge-reduced precursor. Rather, these bond cleavages proceeded from distinct intermediates which originated from different electronic states accessed by electron transfer. In stark contrast to electron transfer, capture of a free electron by the peptide ions mainly induced radical dissociations of the charge-carrying side chains and loss of a hydrogen atom followed by standard backbone dissociations of even-electron ions. The differences in dissociation are explained by different electronic states being accessed upon electron transfer and capture.
A gaseous nanocalorimetry approach is used to investigate effects of hydration and ion identity on the energy resulting from ion-electron recombination. Capture of a thermally generated electron by a ...hydrated multivalent ion results in either loss of a H atom accompanied by water loss or exclusively loss of water. The energy resulting from electron capture by the precursor is obtained from the extent of water loss. Results for large-size-selected clusters of Co(NH₃)₆(H₂O)Formula: see text and Cu(H₂O)Formula: see text indicate that the ion in the cluster is reduced on electron capture. The trend in the data for Co(NH₃)₆(H₂O)Formula: see text over the largest sizes (n greater-than-or-equal 50) can be fit to that predicted by the Born solvation model. This agreement indicates that the decrease in water loss for these larger clusters is predominantly due to ion solvation that can be accounted for by using a model with bulk properties. In contrast, results for Ca(H₂O)Formula: see text indicate that an ion-electron pair is formed when clusters with more than almost equal to20 water molecules are reduced. For clusters with n = almost equal to20-47, these results suggest that the electron is located near the surface, but a structural transition to a more highly solvated electron is indicated for n = 47-62 by the constant recombination energy. These results suggest that an estimate of the adiabatic electron affinity of water could be obtained from measurements of even larger clusters in which an electron is fully solvated.
Visual inspections of anatomical changes observed on daily cone-beam CT (CBCT) images are often used as triggers for radiotherapy plan adaptation to avoid unacceptable dose levels to the target or ...OARs. Direct CBCT dose calculations would improve the ability to adapt only those plans where dosimetric changes are observed. This study investigates the accuracy of dose calculations on CBCTs.
Calibration curves were obtained for CBCT imagers at nine identical accelerators. CBCT scans of a phantom with different density inserts were recorded for two scan modes (Head-Neck and Pelvis) and mean calibration curves were calculated. Subsequently, CBCT scans of the phantom with six different density inserts were recorded, the dose distributions on the CBCTs were calculated and compared to dose on the planning CT (pCT). The uncertainty was quantified by the dosimetric difference between the pCT and the CBCT. The two mean calibration curves were used to calculate the daily delivered CBCT dose for ten Head-Neck-, eleven Lung-, and ten pelvic patients. Additional patient calculations were performed using low-HU empirically corrected calibration curves. Patient doses were compared on target coverage and mean dose, and D1cc for OARs.
The dose differences between pCT and CBCT for phantom data were small for all DVH parameters, with mean deviations below ±0.6% for both CBCT modes. For patient data, it was found that low-HU corrected calibration curves performed the best. The mean deviations for the mean dose and coverage of the target were 0.2%±0.7% and 0.1%±0.6%, across all patient groups.
Dose calculation on CBCT images results in target coverage and mean dose with an accuracy of the order of 1%, which makes this acceptable for clinical use. The CBCT mode specific calibration curves can be used at all identical imaging devices and for all patient groups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We have performed density functional theory calculations for a range of neutral, singly, and multiply charged polycyclic aromatic hydrocarbons (PAHs), and their fragmentation products for H-, H(+)-, ...C(2)H(2)-, and C(2)H(2)(+)-emissions. The adiabatic and vertical ionization energies follow linear dependencies as functions of charge state for all five intact PAHs (naphthalene, biphenylene, anthracene, pyrene, and coronene). First estimates of the total ionization and fragmentation cross sections in ion-PAH collisions display markedly different size dependencies for pericondensed and catacondensed PAH species, reflecting differences in their first ionization energies. The dissociation energies show that the PAH(q+)-molecules are thermodynamically stable for q ≤ 2 (naphthalene, biphenylene, and anthracene), q ≤ 3 (pyrene), and q ≤ 4 (coronene). PAHs in charge states above these limits may also survive experimental time scales due to the presence of reaction barriers as deduced from explorations of the potential energy surface regions for H(+)-emissions from all five PAHs and for C(2)H(2)(+)-emission from naphthalene--the smallest PAH.
Chronic obstructive pulmonary disease (COPD) may, in some patients, be characterized by recurring acute exacerbations. Often these exacerbations are associated with airway infections. As ...immunoglobulins (Ig) are important parts of the immune defence against airway infections, the aim of this study was to relate the levels of circulating immunoglobulins to clinical features in unselected patients with COPD included in a Norwegian multicenter study.
Clinical and biological data, including circulating levels of immunoglobulins, were assessed in 262 prospectively included patients with COPD GOLD stage II-IV at five hospitals in south-eastern Norway. A revisit was done after one year, and survival was assessed after five years. Clinical features and survival of those with immunoglobulin levels below reference values were compared to those with normal levels.
In total, 11.5% of all COPD patients and 18.5% of those with GOLD stage IV had IgG concentrations below reference values. These patients were more likely to use inhaled or oral steroids, had lower BMI, and lower FEV1%. Moreover, they had significantly more COPD-related hospital admissions (2.8 vs 0.6), number of prednisolone courses (3.9 vs 1.2), and antibiotic treatments (3.7 vs 1.5) in the preceding year. Importantly, hypogammaglobulinemia was significantly associated with reduced survival in a log-rank analysis. In multivariate regression analysis, we found that the higher risk for acute exacerbations in these patients was independent of other risk factors and was associated with impaired survival.
In conclusion, our study suggests that hypogammaglobulinemia may be involved in poor outcome in COPD and may thus be a feasible therapeutic target for interventional studies in COPD.
Electron capture by both bare and microsolvated small peptide dications was investigated by colliding these ions with sodium vapor in an accelerator mass spectrometer to provide insight into ...processes that occur on the microsecond time frame. Survival of the intact peptide monocation after electron capture depends strongly on molecular size. For dipeptides, no intact reduced species were observed; the predominant ions correspond to loss of hydrogen and ammonia. In contrast, the intact reduced species was observed for larger peptides. Calculated structures indicate that the diprotonated dipeptide ions form largely extended structures with low probability of internal ionic hydrogen bonding (i.e., charge solvation) whereas internal ionic H-bonding occurs extensively for larger peptide dications. Solvation of the peptide ions with between one to seven methanol molecules reduces the total extent of H loss even for dipeptides where intact reduced species can survive more than a microsecond after electron capture. The yield of ions corresponding to cleavage of N
C
α bonds (
c
+ and
z
+· ions) does not depend strongly on peptide size but decreases with the extent of microsolvation for the dipeptide dications. H-bonding appears to play an important role for the survival of the intact reduced ions but less so for the formation of
c
+ and
z
+· ions. Our results indicate that electron capture predominantly occurs at the ammonium groups (at least 70 to 80%), and provides important new insights into the electron capture dissociation process.
Here we report on the charge partition between c and z fragments formed after femtosecond collisional electron-transfer from Cs atoms to charge-tagged peptide dications. Peptides chosen for study ...were Ala-Lys (AK) and Lys-Lys (KK) where one or both of the lysine ε-amino groups were trimethylated to provide one or two fixed charges. For peptides with only one charge tag, the other charge was obtained by protonation of an amino group. In some experiments the ammonium group was tagged by 18-crown-6-ether (CE). Since recombination energies decrease in the order: MeNH3+ > NMe4+ > MeNH3+(CE) > NMe4+(CE), it is possible to change the probability for the transferred electron to end up at either the N-terminal or the C-terminal residue by CE attachment. We find, however, that the individual recombination energies have little influence on the relative ratio between the yield of c and z ions as long as there are no mobile protons that can be transferred between the two fragments. Our results can be accounted for by the Utah-Washington model where the electron is captured into an amide π* orbital that weakens the N–Cα bond and causes its breakage, followed by proton, electron, or hydrogen transfer between the c and z fragments that stay together as an ion-molecule complex for some time. The data are also in accordance with the notion that an amide group competes with the charged groups for the electron. Electron capture by charged groups results in loss of small neutrals such as hydrogen and ammonia.
Charge partitioning between z and c fragments formed after electron capture by dipeptide dications is independent on the individual recombination energies of the charge sites.
In this work we have recorded synchrotron radiation circular dichroism (SRCD) spectra from 180 nm to 360 nm of cytosine strands (dC)(n), n = 1, 2, ..., 10 in aqueous solution at different pH values ...to reveal electronic coupling between bases in different ionisation states. The geometry of the strands is determined by the pH value and the strand length and the local organisation of the cytosines will determine the base-to-base interaction that impacts on the CD signal. At low pH where all bases are protonated, there is no signature of electronic coupling between the bases, and the SRCD spectrum is simply n times that of the n = 1 spectrum. At higher pH where all bases are neutral, the spectra for n > 1 differ from the monomer spectrum, which implies electronic coupling between bases. The correlation between the CD signal and n is linear, and the spatial extent of the excited state wavefunction is therefore over just two stacked bases both in the UV and VUV. At intermediate pH, the low-n spectra are different from the high-n spectra, and a transition is seen to occur at n = 6-8. We ascribe this behavior to the formation of i-motif structures between four (dC)(n) strands for high n.
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