Methodology for registration of distended recutms in pelvic CT studies

Purpose: Accurate delineation of the rectum is of high importance in off-line adaptive radiation therapy since it is a major dose-limiting organ in prostate cancer radiotherapy. The intensity-based deformable image registration (DIR) methods cannot create a correct spatial transformation if there is no correspondence between the template and the target images. The variation of rectal filling, gas, or feces, creates a noncorrespondence in image intensities that becomes a great obstacle for intensity-based DIR. Methods: In this study the authors have designed and implemented a semiautomatic method to create a rectum mask in pelvic computed tomography (CT) images. The method, that includes a DIR based on the demons algorithm, has been tested in 13 prostate cancer cases, each comprising of two CT scans, for a total of 26 CT scans. Results: The use of the manual segmentation in the planning image and the proposed rectum mask method (RMM) method in the daily image leads to an improvement in the DIR performance in pelvic CT images, obtaining a mean value of overlap volume index = 0.89, close to the values obtained using the manual segmentations in both images. Conclusions: The application of the RMM method in the daily image and the manual segmentations in the planning image during prostate cancer treatments increases the performance of the registration in presence of rectal fillings, obtaining very good agreement with a physician's manual contours.

Methodology for registration of distended rectums in pelvic CT studies

Purpose: Accurate delineation of the rectum is of high importance in off-line adaptive radiation therapy since it is a major dose-limiting organ in prostate cancer radiotherapy. The intensity-based deformable image registration (DIR) methods cannot create a correct spatial transformation if there is no correspondence between the template and the target images. The variation of rectal filling, gas, or feces, creates a noncorrespondence in image intensities that becomes a great obstacle for intensity-based DIR. Methods: In this study the authors have designed and implemented a semiautomatic method to create a rectum mask in pelvic computed tomography (CT) images. The method, that includes a DIR based on the demons algorithm, has been tested in 13 prostate cancer cases, each comprising of two CT scans, for a total of 26 CT scans. Results: The use of the manual segmentation in the planning image and the proposed rectum mask method (RMM) method in the daily image leads to an improvement in the DIR performance in pelvic CT images, obtaining a mean value of overlap volume index = 0.89, close to the values obtained using the manual segmentations in both images. Conclusions: The application of the RMM method in the daily image and the manual segmentations in the planning image during prostate cancer treatments increases the performance of the registration in presence of rectal fillings, obtaining very good agreement with a physician's manual contours.

Stabilization of hillside in the work terraces of Alcaidesa in San Roque(Cádiz)

In the locality of The Hills of Alcaidesa in San Roque (Cádiz) has been constructed three blocks of housing called "The Terraces Alcaidesa" in a hillside in part virgin and in part with a refilling terrain without compaction with a width of 50 m and with a difference of levels between the most extreme points of 10 m.

Dynamic stabilization of L2 periodic orbits using attitude-orbit coupling effects

Numerical explorations show how the known periodic solutions of the Hill problem are modified in the case of the attitude-orbit coupling that may occur for large satellite structures. We focus on the case in which the elongation is the dominant satellite’s characteristic and find that a rotating structure may remain with its largest dimension in a plane parallel to the plane of the primaries. In this case, the effect produced by the non-negligible physical length is dynamically equivalent to the perturbation produced by an oblate central body on a mass-point satellite. Based on this, it is demonstrated that the attitude-orbital coupling of a long enough body may change the dynamical characteristics of a periodic orbit about the collinear Lagrangian points.

Dynamic stabilization of L2 periodic orbits using attitude-orbit coupling effects

Numerical explorations show how the known periodic solutions of the Hill problem are modified in the case of the attitude-orbit coupling that may occur for large satellite structures. We focus on the case in which the elongation is the dominant satellite?s characteristic and find that a rotating structure may remain with its largest dimension in a plane parallel to the plane of the primaries. In this case, the effect produced by the non-negligible physical dimension is dynamically equivalent to the perturbation produced by an oblate central body on a masspoint satellite. Based on this, it is demonstrated that the attitude-orbital coupling of a long enough body may change the dynamical characteristics of a periodic orbit about the collinear Lagrangian points.

Pelvic Floor Muscle Training Included in a Pregnancy Exercise Program Is Effective in Primary Prevention of Urinary Incontinence: A Randomized Controlled Trial

AIMS: To investigate the effect of pelvic floor muscle training (PFMT) taught in a general exercise class during pregnancy on the prevention of urinary incontinence (UI) in nulliparous continent pregnant women. METHODS: This was a unicenter two armed randomized controlled trial. One hundred sixty-nine women were randomized by a central computer system to an exercise group (EG) (exercise class including PFMT) (n = 73) or a control group (CG) (n = 96). 10.1% loss to follow-up: 10 from EG and 7 from CG. The intervention consisted of 70-75 sessions (22 weeks, three times per week, 55-60 min/session including 10 min of PFMT). The CG received usual care (which included follow up by midwifes including information about PFMT). Questions on prevalence and degree of UI were posed before (week 10-14) and after intervention (week 36-39) using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). RESULTS: At the end of the intervention, there was a statistically significant difference in favor of the EG. Reported frequency of UI [Never: CG: 54/60.7%, EG: 60/95.2% (P < 0.001)]. Amount of leakage [None: CG: 45/60.7%, EG: 60/95.2% (P < 0.001)]. There was also a statistically significant difference in ICIQ-UI SF Score between groups after the intervention period [CG: 2.7 (SD 4.1), EG: 0.2 (SD 1.2) (P < 0.001)]. The estimated effect size was 0.8. CONCLUSION: PFMT taught in a general exercise class three times per week for at least 22 weeks, without former assessment of ability to perform a correct contraction was effective in primary prevention of UI in primiparous pregnant women.

Stabilization works at Olvés Church (Zaragoza-Spain)

The Olvés Church is a Lhree naves basilica. From its construction in 1767, it sufTercd important damages and successivc reparations. The church is built on a claycy hillock on top of the village with vcry fort slopcs. The retaining walls Lhat surround the church havc sufTered movements. A soil sludy was done to know its propcrtics and the reason of the movement. Also, the structural roof is broken and it is not fixed to thc walls that can movc. Thc first phase is done, with a pavcd squa rc ovcr an ancient cemetery. The next phase is a new roof structure to support the lean walls. Al'ter that done, the repair inside can start.

Stabilization of embankments on inclined surfaces by micropiles

Embankments constructed on hillsides can have serious problems of stability, generally created by the action of water com-bined with the inclination of the hillside. In order to increase the stability or correct problems of instability already present, there are various methods that can be used: surface and deep drainage, reinforcements with anchored beams, medium and large diameter piles, etc. Standing out among these systems (for its versatility) is the use of micropiles which ?sew? the embankment to a non-unstable area of the hillside. This paper presents research undertaken by means of a finite element code for studying the effect and stress of the micropiles, comparing the results with real measurements taken in the south of Spain.

Efficiency of hysteresis rods in small spacecraft attitude stabilization

A semiempirical method for predicting the damping efficiency of hysteresis rods on-board small satellites is presented. It is based on the evaluation of dissipating energy variation of different ferromagnetic materials for two different rod shapes: thin film and circular cross-section rods, as a function of their elongation. Based on this formulation, an optimum design considering the size of hysteresis rods, their cross section shape, and layout has been proposed. Finally, the formulation developed was applied to the case of four existing small satellites, whose corresponding in-flight data are published. A good agreement between the estimated rotational speed decay time and the in-flight data has been observed.

A molecular level picture of the stabilization of A-DNA in mixed ethanol–water solutions

Advances in computer power, methodology, and empirical force fields now allow routine “stable” nanosecond-length molecular dynamics simulations of DNA in water. The accurate representation of environmental influences on structure remains a major, unresolved issue. In contrast to simulations of A-DNA in water (where an A-DNA to B-DNA transition is observed) and in pure ethanol (where disruption of the structure is observed), A-DNA in ≈85% ethanol solution remains in a canonical A-DNA geometry as expected. The stabilization of A-DNA by ethanol is likely due to disruption of the spine of hydration in the minor groove and the presence of ion-mediated interhelical bonds and extensive hydration across the major groove.

Stabilization of microtubule dynamics by estramustine by binding to a novel site in tubulin: A possible mechanistic basis for its antitumor action

The cellular targets for estramustine, an antitumor drug used in the treatment of hormone-refractory prostate cancer, are believed to be the spindle microtubules responsible for chromosome separation at mitosis. Estramustine only weakly inhibits polymerization of purified tubulin into microtubules by binding to tubulin (Kd, ≈30 μM) at a site distinct from the colchicine or the vinblastine binding sites. However, by video microscopy, we find that estramustine strongly stabilizes growing and shortening dynamics at plus ends of bovine brain microtubules devoid of microtubule-associated proteins at concentrations substantially below those required to inhibit polymerization of the microtubules. Estramustine strongly reduced the rate and extent both of shortening and growing, increased the percentage of time the microtubules spent in an attenuated state, neither growing nor shortening detectably, and reduced the overall dynamicity of the microtubules. Significantly, the combined suppressive effects of vinblastine and estramustine on the rate and extent of shortening and dynamicity were additive. Thus, like the antimitotic mechanisms of action of the antitumor drugs vinblastine and taxol, the antimitotic mechanism of action of estramustine may be due to kinetic stabilization of spindle microtubule dynamics. The results may explain the mechanistic basis for the benefit derived from combined use of estramustine with vinblastine or taxol, two other drugs that target microtubules, in the treatment of hormone-refractory prostate cancer.

Chromosomal aberrations in PARP−/− mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA

Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP−/− mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP−/−mice and immortalized PARP−/−fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP−/− cells stably transfected with PARP cDNA [PARP−/−(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP−/− cells, p53 expression was partially restored in PARP−/− (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP−/− mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.

Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage

Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a protein that targets p53 for degradation in the proteasome. Dissociation of p53 from Mdm2 could be caused by DNA damage-induced p53 posttranslational modifications. The ATM and ATR kinases, whose activation in response to ionizing radiation (IR) and UV light, respectively, is required for p53 stabilization, directly phosphorylate p53 on Ser-15. However, phosphorylation of Ser-15 is critical for the apoptotic activity of p53 and not for p53 stabilization. Thus, whether any p53 modifications, and which, underlie disruption of the p53–Mdm2 complex after DNA damage remains to be determined. We analyzed the IR- and UV light-induced stabilization of p53 proteins with substitutions of Ser known to be posttranslationally modified after DNA damage. Substitution of Ser-20 was sufficient to abrogate p53 stabilization in response to both IR and UV light. Furthermore, both IR and UV light induced phosphorylation of p53 on Ser-20, which involved the majority of nuclear p53 protein and weakened the interaction of p53 with Mdm2 in vitro. ATM and ATR cannot phosphorylate p53 on Ser-20. We therefore propose that ATM and ATR activate an, as yet unidentified, kinase that stabilizes p53 by phosphorylating it on Ser-20.

Inhibiting transthyretin amyloid fibril formation via protein stabilization

Transthyretin (TTR) amyloid fibril formation is observed systemically in familial amyloid polyneuropathy and senile systemic amyloidosis and appears to be the causative agent in these diseases. Herein, we demonstrate conclusively that thyroxine (10.8 μM) inhibits TTR fibril formation efficiently in vitro and does so by stabilizing the tetramer against dissociation and the subsequent conformational changes required for amyloid fibril formation. In addition, the nonnative ligand 2,4,6-triiodophenol, which binds to TTR with slightly increased affinity also inhibits TTR fibril formation by this mechanism. Sedimentation velocity experiments were employed to show that TTR undergoes dissociation (linked to a conformational change) to form the monomeric amyloidogenic intermediate, which self-assembles into amyloid in the absence, but not in the presence of thyroxine. These results demonstrate the feasibility of using small molecules to stabilize the native fold of a potentially amyloidogenic human protein, thus preventing the conformational changes, which appear to be the common link in several human amyloid diseases. This strategy and the compounds resulting from further development should prove useful for critically evaluating the amyloid hypothesis—i.e., the putative cause-and-effect relationship between TTR amyloid deposition and the onset of familial amyloid polyneuropathy and senile systemic amyloidosis.

Physical reasons for the unusual α-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptides

We have carried out conformational energy calculations on alanine-based copolymers with the sequence Ac-AAAAAXAAAA-NH2 in water, where X stands for lysine or glutamine, to identify the underlying source of stability of alanine-based polypeptides containing charged or highly soluble polar residues in the absence of charge–charge interactions. The results indicate that ionizable or neutral polar residues introduced into the sequence to make them soluble sequester the water away from the CO and NH groups of the backbone, thereby enabling them to form internal hydrogen bonds. This solvation effect dictates the conformational preference and, hence, modifies the conformational propensity of alanine residues. Even though we carried out simulations for specific amino acid sequences, our results provide an understanding of some of the basic principles that govern the process of folding of these short sequences independently of the kind of residues introduced to make them soluble. In addition, we have investigated through simulations the effect of the bulk dielectric constant on the conformational preferences of these peptides. Extensive conformational Monte Carlo searches on terminally blocked 10-mer and 16-mer homopolymers of alanine in the absence of salt were carried out assuming values for the dielectric constant of the solvent ɛ of 80, 40, and 2. Our simulations show a clear tendency of these oligopeptides to augment the α-helix content as the bulk dielectric constant of the solvent is lowered. This behavior is due mainly to a loss of exposure of the CO and NH groups to the aqueous solvent. Experimental evidence indicates that the helical propensity of the amino acids in water shows a dramatic increase on addition of certain alcohols, such us trifluoroethanol. Our results provide a possible explanation of the mechanism by which alcohol/water mixtures affect the free energy of helical alanine oligopeptides relative to nonhelical ones.