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CyberKnife is the most advanced form of stereotactic body radiotherapy (SBRT) system that uses a robotic arm to deliver highly focused beams of radiation; however, a limitation is that it only irradiates from ceiling to floor direction. In patients with posterior lungs tumour who are positioned supine, normal lung tissue may suffer undesirable radiation injuries. This study compares the treatment planning between the prone set-up and the supine set-up for lung cancer in CyberKnife SBRT to decrease normal lung dose to avoid radiation side effects.
Materials and methods:
A human phantom was used to generate 108 plans (54 for prone and 54 for supine) using the CyberKnife planning platform. The supine and prone plans were compared in terms of the dosimetric characteristics, delivery efficiency and plan efficiency.
For posterior targets, the area of low-dose exposure to normal lungs was smaller in the prone set-up than in the supine set-up. V10 of the lungs was 7·53% and 10·47% (p < 0·001) in the anterior region, and 10·78% and 8·03% (p < 0·001) in the posterior region in the supine and prone set-up plans, respectively.
The comparison between the prone set-up and the supine set-up was investigated with regard to target coverage and dose to organs at risk. Our results may be deployed in CyberKnife treatment planning to monitor normal tissue dose by considering patient positioning. This may assist in the design of better treatment plans and prevention of symptomatic radiation pneumonitis in lung cancer patients.
To modify the final dose delivered to superficial tissues and to modulate dose distribution near irradiated surface, different boluses are used. Air gaps often form under the bolus affecting dose distribution. This study aimed to evaluate the effect of an air gap under the bolus radiation on dose delivery.
Materials and methods:
To evaluate the impact of the air gap, both helical tomotherapy (HT) and direct tomotherapy (DT) were performed in a simulation study.
The maximum dose to bolus in DT plans was bigger than that used in HT plans. The maximum dose delivered to the bolus depended on the air gap size. However, the maximum dose to bolus in all HT plans was within the acceptable value range. Acceptable value was set to up to 107% of the prescription dose. In the simulation performed in this study, the acceptable air gap under bolus was up to 15 mm and below 5 mm in HT and DT plans, respectively.
HT technique is a good choice, but DT technique can be also used if the bolus position can be reproduced accurately. Thus, the reproducibility of the bolus position between planning and treatment is very important.
The pressure-induced changes in 15N
enriched HPr from Staphylococcus carnosus were
investigated by two-dimensional (2D) heteronuclear NMR
spectroscopy at pressures ranging from atmospheric pressure
up to 200 MPa. The NMR experiments allowed the simultaneous
observation of the backbone and side-chain amide protons
and nitrogens. Most of the resonances shift downfield with
increasing pressure indicating generalized pressure-induced
conformational changes. The average pressure-induced shifts
for amide protons and nitrogens are 0.285 ppm GPa−1
at 278 K and 2.20 ppm GPa−1, respectively.
At 298 K the corresponding values are 0.275 and 2.41 ppm
GPa−1. Proton and nitrogen pressure coefficients
show a significant but rather small correlation (0.31)
if determined for all amide resonances. When restricting
the analysis to amide groups in the β-pleated sheet,
the correlation between these coefficients is with 0.59
significantly higher. As already described for other proteins,
the amide proton pressure coefficients are strongly correlated
to the corresponding hydrogen bond distances, and thus
are indicators for the pressure-induced changes of the
hydrogen bond lengths. The nitrogen shift changes appear
to sense other physical phenomena such as changes of the
local backbone conformation as well. Interpretation of
the pressure-induced shifts in terms of structural changes
in the HPr protein suggests the following picture: the
four-stranded β-pleated sheet of HPr protein is the
least compressible part of the structure showing only small
pressure effects. The two long helices a and c show intermediary
effects that could be explained by a higher compressibility
and a concomitant bending of the helices. The largest pressure
coefficients are found in the active center region around
His15 and in the regulatory helix b which includes the
phosphorylation site Ser46 for the HPr kinase. This suggests
that this part of the structure occurs in a number of different
structural states whose equilibrium populations are shifted
by pressure. In contrast to the surrounding residues of
the active center loop that show large pressure effects,
Ile14 has a very small proton and nitrogen pressure coefficient.
It could represent some kind of anchoring point of the
active center loop that holds it in the right place in
space, whereas other parts of the loop adapt themselves
to changing external conditions.
A 20-residue peptide E5 containing five glutamates, an
analog of the fusion peptide of influenza virus hemagglutinin
(HA) exhibiting fusion activity at acidic pH lower than
6.0–6.5 was studied by circular dichroism (CD), Fourier
transform infrared, and 1H-NMR spectroscopy
in water, water/trifluoroethanol (TFE) mixtures, dodecylphosphocholine
(DPC) micelles, and phospholipid vesicles. E5 became structurally
ordered at pH ≤6 and the helical content in the peptide
increased in the row: water < water/TFE < DPC ∼
phospholipid vesicle while the amount of β-structure
was approximately reverse. 1H-NMR data and line-broadening
effect of 5-, 16-doxylstearates on proton resonances of
DPC bound peptide showed E5 forms amphiphilic α-helix
in residues 2–18, which is flexible in 11–18
part. The analysis of the proton chemical shifts of DPC
bound and CD intensity at 220 nm of phospholipid bound
E5 showed that the pH dependence of helical content is
characterized by the same pKa ≈5.6.
Only Glu11 and Glu15 in DPC bound peptide showed such elevated
pKas, presumably due to transient hydrogen
bond(s) Glu11 (Glu15) δCOO−(H+)
… HN Glu15 that dispose(s) the side chain of Glu11
(Glu15) residue(s) close to the micelle/water interface.
These glutamates are present in the HA-fusion peptide and
the experimental half-maximal pH of fusion for HA and E5
peptides is ∼5.6. Therefore, a specific anchorage of
these peptides onto membrane necessary for fusion is likely
driven by the protonation of the carboxylate group of Glu11
(Glu15) residue(s) participating in transient hydrogen
The effect of pressure on amide 15N
chemical shifts was studied in uniformly 15N-labeled
basic pancreatic trypsin inhibitor (BPTI) in 90%1H2O/10%2H2O,
pH 4.6, by 1H-15N heteronuclear correlation
spectroscopy between 1 and 2,000 bar. Most 15N
signals were low field shifted linearly and reversibly
with pressure (0.468 ± 0.285 ppm/2 kbar), indicating
that the entire polypeptide backbone structure is sensitive
to pressure. A significant variation of shifts among different
amide groups (0–1.5 ppm/2 kbar) indicates a heterogeneous
response throughout within the three-dimensional structure
of the protein. A tendency toward low field shifts is correlated
with a decrease in hydrogen bond distance on the order
of 0.03 Å/2 kbar for the bond between the amide nitrogen
atom and the oxygen atom of either carbonyl or water. The
variation of 15N shifts is considered to reflect
site-specific changes in φ, ψ angles. For β-sheet
residues, a decrease in ψ angles by 1–2°/2
kbar is estimated. On average, shifts are larger for helical
and loop regions (0.553 ± 0.343 and 0.519 ±
0.261 ppm/2 kbar, respectively) than for β-sheet (0.295
± 0.195 ppm/2 kbar), suggesting that the pressure-induced
structural changes (local compressibilities) are larger
in helical and loop regions than in β-sheet. Because
compressibility is correlated with volume fluctuation,
the result is taken to indicate that the volume fluctuation
is larger in helical and loop regions than in β-sheet.
An important aspect of the volume fluctuation inferred
from pressure shifts is that they include motions in slower
time ranges (less than milliseconds) in which many biological
processes may take place.
We have performed a detailed study of methanol-induced
conformational transitions of horse heart apomyoglobin
(apoMb) to investigate the existence of the compact and
expanded denatured states. A combination of far- and near-ultraviolet
circular dichroism, NMR spectroscopy, and small-angle X-ray
scattering (SAXS) was used, allowing a phase diagram to
be constructed as a function of pH and the methanol concentration.
The phase diagram contains four conformational states,
the native (N), acid-denatured (UA),
compact denatured (IM), and expanded
helical denatured (H) states, and indicates that
the compact denatured state (IM) is
stable under relatively mild denaturing conditions, whereas
the expanded denatured states (UA and
H) are realized under extreme conditions of pH
(strong electric repulsion) or alcohol concentration (weak
hydrophobic interaction). The results of this study, together
with many previous studies in the literature, indicate
the general existence of the compact denatured states not
only in the salt-pH plane but also in the alcohol-pH plane.
Furthermore, to determine the general feature of the H
conformation we used several proteins including ubiquitin,
ribonuclease A, α-lactalbumin, β-lactoglobulin,
and Streptomyces subtilisin inhibitor (SSI) in
addition to apoMb. SAXS studies of these proteins in 60%
methanol showed that the H states of these all
proteins have expanded and nonglobular conformations. The
qualitative agreement of the experimental data with computer-simulated
Kratky profiles also supports this structural feature of
the H state.
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