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Results for “crossover”

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At least 163 records · Page 9Linked to original sources

PubMed1998

Early complications of femorofemoral crossover bypass grafts after aorta uni-iliac endovascular repair of abdominal aortic aneurysms.

OBJECTIVE: The following procedures are the 3 main methods of endovascular repair (EVR) of abdominal aortic aneurysms (AAA): aorto-aortic bypass grafting, bifurcated bypass grafting, and aorta uni-iliac grafts. The latter method has the potential disadvantage of requiring an extra anatomic graft (ie, a femorofemoral crossover bypass graft) to maintain contralateral pelvic and limb perfusion. The aim of this study was to assess the complications associated with the femorofemoral crossover bypass graft after aorta uni-iliac EVR of AAA. METHOD: A prospective review was conducted of the complications attributable to the femorofemoral crossover bypass graft in 136 patients who underwent EVR of AAA with an aorta uni-iliac device. RESULTS: During a median follow-up of 7 months (range, 0 to 36 months), 4 patients had superficial wound infections that required antibiotic treatment and 2 patients had bypass graft infections. Nine hematomas developed: 7 (5%) groin hematomas (6 in patients with Dacron bypass grafts), 1 scrotal hematoma, and 1 perigraft hematoma. One bypass graft thrombus developed. CONCLUSION: The femorofemoral crossover bypass graft is a safe and a durable component of EVR of AAA with an aorta uni-iliac device. The results are similar to those with bifurcated devices.

Aorta, Abdominal↗

PubMed1998

High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot.

Little is known about the fine-scale distribution of meiotic crossovers in human chromosomes. Methods have therefore been developed for detecting and mapping recombination products directly in human sperm DNA. Analysis of crossovers adjacent to the GC-rich minisatellite MS32, which is known to mutate by conversion and crossover within the repeat array, revealed an intense and highly localized recombination hotspot centered upstream of the locus and extending into the beginning of the minisatellite. Allele-specific cosuppression of crossovers and repeat instability suggests that the hotspot is responsible for driving repeat turnover at MS32 and thus that minisatellites might evolve as by-products of localized meiotic recombination in the human genome.

Alleles↗

PubMed2003

Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis.

The double Holliday junction (dHJ) is generally regarded to be a key intermediate of meiotic recombination, whose resolution is critical for the formation of crossover recombinants. In fission yeast, the Mus81-Eme1 endonuclease has been implicated in resolving dHJs. Consistent with this role, we show that Mus81-Eme1 is required for generating meiotic crossovers. However, purified Mus81-Eme1 prefers to cleave junctions that mimic those formed during the transition from double-strand break to dHJ. Crucially, these junctions are cleaved by Mus81-Eme1 in precisely the right orientation to guarantee the formation of a crossover every time. These data demonstrate how crossovers could arise without forming or resolving dHJs using an enzyme that is widely conserved amongst eukaryotes.

Crossing Over, Genetic↗

PubMedDate not supplied

Intracoronary radiation for patients with refractory in-stent restenosis: an analysis from the WRIST-Crossover Trial. Washington Radiation for In-stent Restenosis Trial.

BACKGROUND: In-stent restenosis (ISR) is a limitation of intracoronary stent implantation. In animal models and clinical trials, ionizing radiation has been shown to decrease in-stent neointimal formation. METHODS AND MATERIALS: In the Washington Radiation for In-stent Restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized to gamma irradiation (l92Ir, 15 Gy at 2 mm from the source) or placebo. Patients randomized to placebo that developed recurrent ISR and presented with anginal symptoms were crossed-over to active therapy. We compared the clinical and angiographic outcomes of 39 patients in the crossover group with 65 patients treated primarily with radiation. The primary clinical endpoints were mortality, morbidity, and repeat target lesion revascularization (TLR) at 6 months. RESULTS: Procedural success was 100%. In-hospital and 30-day complications were minimal. At 6 months, the rate for any multiple adverse cardiac events (MACE: death, MI, or TLR) was 25.6% in the crossover group vs. 29.2% in the primary treatment group (p = 0.86). Three patients in the crossover group and four in the primary treatment group died (p = NS). There were no Q-wave myocardial infarction. Ten (9.6%) of the patients presented with late thrombosis and total occlusion: 6.2% (4/65) in the primary treatment group vs. 15.4% (6/39) in the crossover group (p = 0.13). CONCLUSIONS: Patients who fail conventional catheter-based intervention without radiation can be treated with 192Ir with results similar to those who initially receive brachytherapy. This is of specific importance with respect to patients initially assigned to the placebo arm of randomized clinical trials.

Brachytherapy↗

PubMed2002

Theoretical study of the Fe(phen)(2)(NCS)(2) spin-crossover complex with reparametrized density functionals.

The theoretical study of spin-crossover compounds is very challenging as those parts of the experimental findings that concern the electronic structure of these compounds can currently hardly be reproduced because of either technical limitations of highly accurate ab initio methods or because of inaccuracies of density functional methods in the prediction of low-spin/high-spin energy splitting. However, calculations with reparametrized density functionals on molecules of the thermal spin-crossover type can give improved results when compared with experiment for close-lying states of different spin and are therefore important for, e.g., transition metal catalysis. A classification of transition metal compounds within hybrid density functional theory is given to distinguish standard, critical, and complicated cases. From the class of complicated cases we choose the prominent spin-crossover compound Fe(phen)(2)(NCS)(2) and show in a first step how the electronic contribution to the energy splitting can be calculated. In a second step, the vibrational effects on the spin flip are investigated within the harmonic force-field approximation of the isolated-molecule approach. A main result of the study is the necessity of exact-exchange reduction in hybrid density functionals to arrive at reasonable electronic energy splittings. The study resolves problems that originated from the use of standard density functionals, which are not able to reproduce the electronic contribution to the low-spin/high-spin splitting correctly, and demonstrates to which extent reparametrized density functionals can be used for the prediction of the spin-crossover effect.

Journal Article↗

PubMed2005

Formation of third generation poly(pyrazolyl)borate ligands from alkyne coupling reactions of Fe[(p-IC6H4)B(3-Rpz)3]2 (R = H, Me; pz = pyrazolyl): pathways toward controlling an iron(II) electronic spin-state crossover.

Sonogashira coupling reactions of terminal alkynes with Fe[(p-IC6H4)B(3-Mepz)3]2 (pz = pyrazolyl ring) yield Fe[(p-PhC2C6H4)B(3-Mepz)3]2 (2), Fe[(p-Me3SiC2C6H4)B(3-Rpz)3]2 (R = H, 3a, R = Me, 3b), and Fe[(p-HC2C6H4)B(3-Mepz)3]2 (R = H, 4a, R = Me, 4b), a series of new complexes containing "third generation" poly(pyrazolyl)borate ligands. Complex 2 undergoes a fairly gradual iron(II) electronic spin-state crossover with a 30 K hysteresis, whereas complex 3b is an unusual example of a complex with equivalent iron(II) sites in the high-spin form that shows an abrupt 50% spin crossover. For complex 4b, 50% of the iron(II) sites undergo a gradual spin-state transition between 185 and 350 K with an activation energy of 1590 +/- 30 cm(-1) and a T(1/2) = 280 K and, for the remaining iron(II) sites, an abrupt cooperative spin-state crossover between 106 and 114 K. The crystal structures of 4b obtained for each of the three distinct electronic spin states reveal two crystallographically different iron(II) sites, and analysis of the molecular/supramolecular structures indicates that the difference in the degree of pyrazolyl ring tilting in the ligands between the two sites, rather than the strength of the intermolecular forces, play a prominent role in determining the temperature of the spin-state crossover.

Journal Article↗

PubMed2005

Observation of an Fe(II) spin-crossover in a cesium iron hexacyanochromate.

In this work, we observed a spin-crossover phenomenon in a cesium iron hexacyanochromate, which is a Prussian blue analogue. This compound showed a thermal phase transition with transition temperatures of 211 K (T1/2 downward arrow) and 238 K (T1/2 upward arrow) due to a spin-crossover on FeII sites. This spin-crossover phase transition is accompanied by a lattice contraction of 0.38 A, but maintains a face-centered cubic structure (F3m). This is the first observation of FeII spin-crossover in a series of Prussian blue analogues.

Journal Article↗

PubMed2001

Genetic crossover interference in the human genome.

Positive crossover interference refers to the phenomenon that the occurrence of a crossover reduces the probability of another crossover in its vicinity. There have been studies reporting the presence of positive interference in humans. Some studies have also found evidence suggesting within and between chromosomal interference heterogeneity on some of the chromosomes. However, there has been no systematic study of interference and interference heterogeneity in the whole human genome, using pedigree data without first inferring crossovers. In this paper, we studied the Chi-square interference model and other models extensively to compare the relative performance of each of these models for accounting for interference and measuring strength of interference. Our results showed that the Chi-square model consistently fitted the data well and provided easily interpretable estimates of interference strength. The Chi-square model was then used to study interference and interference heterogeneity within and between chromosomes. We found strong evidence of positive interference in the whole human genome. Our results also indicated that the level of interference was fairly constant in most parts of the genome, but there was some evidence suggesting that the levels of interference for two of the chromosomes were different from the rest. We also found evidence of within chromosomal interference heterogeneity for several of the chromosomes.

Chromosomes↗

PubMed2006

Orbital disproportionation and spin crossover as a pseudo Jahn-Teller effect.

It is shown that in systems with electronic half-closed-shell configurations of degenerate orbitals, e(2) and t(3) (which have totally symmetric charge distribution), ground state distortions from high-symmetry geometries may occur due to a strong pseudo Jahn-Teller effect (PJTE) in the excited states, resulting also in a novel phenomenon of PJT-induced spin crossover. There is no JTE neither in the ground state term nor in the excited terms (including degenerate terms) of these configurations but a strong PJT mixing between two excited states [((1)E+(1)A) [cross-filled circle] e and ((2)T(1)+(2)T(2)) [cross-filled circle] e in the e(2) and t(3) cases, respectively] pushes down the lower term to cross the ground state of the undistorted system and to form the global minimum with a distorted geometry. The analysis of the electronic structure of this distorted configuration shows that it is accompanied by orbital disproportionation: instead of proportional population of all degenerate orbitals by one electron each (as in the ground state of the undistorted system that follows Hund's rule), two electrons with opposite spins occupy one orbital, resulting in transformations of the type (e(theta);e(epsilon))-->(e(theta)e(theta)) for e(2) and (t(x);t(y);t(z))-->(t(x);t(x);t(z)) for t(3) systems. Since the two geometry configurations, undistorted and distorted, appertain to different electronic terms that have different spin states, the formation of the global minimum with the distorted configuration is accompanied by a spin crossover. Distinguished from the known spin-crossover phenomenon in some transition metal compounds, the two states with different spin in the PJT-induced spin crossover have also different nuclear configurations, undistorted and distorted, that coexist with a relatively small energy difference. The change of configuration reduces significantly the rate of relaxation between the two states; the relaxation is further reduced by the lower spin-orbital coupling in the light-atom systems as compared with transition metal compounds. This means that there may be systems for which the switch between the two states (in both directions) under perturbations may be observed as a single-molecule phenomenon. Systems with half-closed-shell electronic configurations e(2) and t(3) are available in a variety of molecules from different classes, organic and inorganic; the theory is illustrated here by ab initio calculations for a series of molecular systems, including Si(3), Si(3)C, CuF(3), Na(3), Si(4), Na(4), Na(4) (-), and C(60) (3-), which are in agreement with the experimental data available.

Journal Article↗

PubMed2006

A crossover from metal to plasma in dense fluid hydrogen.

Thermodynamic properties in dense fluid hydrogen are studied by using a density-functional theory for electron-proton binary mixtures that is called quantal hypernetted-chain (QHNC) integral equation. A nonlocal approximation for the exchange-correlation potential in a finite-temperature Kohn-Sham equation is presented. Results obtained from the QHNC with the nonlocal approximation are compared with those obtained from the QHNC with a local density approximation. Temperature variation of thermodynamic quantities between 10(4) and 10(6) K are investigated along an isochor specified by a dimensionless density parameter of rs=0.5. These quantities obtained from the QHNCs show that a crossover from metal to plasma occurs around a temperature of T=1.78 x 10(5) K. Electrical resistivity Re of the dense fluid hydrogen evaluated from a Ziman formula [The Properties of Liquid Metals, edited by S. Takenohi (Wiley, New York, 1973)] extended to finite temperature is about 0.7 muOmega cm at T=10(4) K. The dense fluid hydrogen at the temperature can be considered as a metallic fluid, because the value is smaller than typical values of Re in alkali metals at room temperature. The Re slightly increases with the temperature increase, and the temperature valuation of Re is monotonic. We clearly show that the contribution from the electronic excited states plays an important role for the sharp crossover from the metal to the plasma, and that the crossover is interpreted as a crossover from degenerate electron gas to nondegenerate electron gas.

Journal Article↗

PubMed2001

Creating multiple-crossover DNA libraries independent of sequence identity.

We have developed, experimentally implemented, and modeled in silico a methodology named SCRATCHY that enables the combinatorial engineering of target proteins, independent of sequence identity. The approach combines two methods for recombining genes: incremental truncation for the creation of hybrid enzymes and DNA shuffling. First, incremental truncation for the creation of hybrid enzymes is used to create a comprehensive set of fusions between fragments of genes in a DNA homology-independent fashion. This artificial family is then subjected to a DNA-shuffling step to augment the number of crossovers. SCRATCHY libraries were created from the glycinamide-ribonucleotide formyltransferase (GART) genes from Escherichia coli (purN) and human (hGART). The developed modeling framework eSCRATCHY provides insight into the effect of sequence identity and fragmentation length on crossover statistics and draws contrast with DNA shuffling. Sequence analysis of the naive shuffled library identified members with up to three crossovers, and modeling predictions are in good agreement with the experimental findings. Subsequent in vivo selection in an auxotrophic E. coli host yielded functional hybrid enzymes containing multiple crossovers.

Algorithms↗

PubMed1988

T4 endonuclease VII cleaves the crossover strands of Holliday junction analogs.

We have formed four-arm branched DNA junctions that contain no more than a single base pair of branch migratory freedom. Recently, we have shown that these Holliday junction analogs have twofold symmetric protection patterns in solution when probed with hydroxyl radicals: two opposite strands of one junction show extensive protection near the branch point, while the other pair of opposite strands is virtually as susceptible as a double helix. In a different junction, the hydroxyl radical protection pattern is reversed. These patterns suggest that a crossover-isomer bias exists in these molecules and that the protected strands form the crossover between helices. Here, we examine the cleavage pattern of these structures when they are resolved by T4 endonuclease VII. Junctions are formed from a single shamrock-shaped molecule, which contains 5', 3', or internal labels. The enzyme shows a preference for resolving these modified junctions at sites near those protected from hydroxyl radicals. This result suggests that only crossover strands in a Holliday junction are cleaved, and thus an odd number of crossover isomerizations must occur when flanking markers are exchanged.

Base Sequence↗

PubMed1992

On assessment of bioequivalence under a higher-order crossover design.

In bioavailability studies of two formulations of a drug, the standard two-sequence, two-period crossover design is usually considered to assess bioequivalence. The standard two-sequence, two-period crossover design, however, may not be useful when differential carryover effects are present. In addition, it does not provide independent estimates of intrasubject variabilities for the two formulations. To overcome these problems, alternatively, a higher-order crossover design may be considered. In this paper, we derive statistical methods based on Schuirmann's two one-sided tests procedure for assessing bioequivalence for some commonly used higher-order crossover designs. Four designs, including Balaam's design, the two-sequence dual design, and two four-period designs (with two and four sequences), are considered. The relative merits of these designs as compared to the standard two-sequence, two-period design are discussed. Two examples concerning bioequivalence are used to illustrate the use of these methods.

Biological Availability↗

PubMed1994

Evaluation of alternative statistical models for crossover studies to demonstrate caffeine adjuvancy in the treatment of tension headache.

This paper discusses alternative statistical models for the analysis of six crossover studies to determine whether better relief of tension headache occurs from treatment with an analgesic plus caffeine (C) than with the analgesic alone (A) or with placebo (P). Each patient in these crossover studies randomly received a pair of distinct medications in such a way as to treat the first two of four headaches with the initial medication in the pair and to treat the third and fourth headaches with the last medication in the pair. In order to have greater power for the C versus A comparison, three times as many patients were randomly assigned to the A:C and C:A sequence groups as to the A:P, C:P, P:A, and P:C sequence groups. An issue of statistical interest for these crossover studies is the extent to which the possibility of unequal carryover effects of the three medications influences the roles of alternative models for data analysis and the interpretation of results. When carryover effects for all three medications are equal, univariate analysis of variance for the difference scores between the average response for the first two headaches and the average response for the third and fourth headaches for each patient provides nearly the same power for pairwise treatment comparisons as more comprehensive multivariate methods for all four headaches. However, for comparisons concerning carryover effects and for treatment comparisons with adjustment for carryover effects, multivariate methods encompassing all four headaches jointly can provide greater power than univariate analysis for difference scores, particularly when there is low intraclass correlation for responses within the same patient. Another noteworthy role for multivariate methods in situations with potentially unequal carryover effects is their capacity to clarify whether multiple types of carryover effects occur across the second, third, and fourth headaches in the respective sequence groups. Multivariate models with alternative specifications of carryover effects are fit to the data from the six crossover studies to compare C, A, and P by weighted least squares. The role of potential variation among centers is addressed in these analyses by the use of stratified proportional means over centers, means of center means, and means ignoring centers. The primary focus of attention in the respective analyses is the evaluation of treatment comparisons with and without adjustment for potential differences among carryover effects of the treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

Caffeine↗

PubMed1999

Design and analysis issues for crossover designs in phase I clinical studies.

To assess the efficacy of potential new drugs in the initial phase of clinical research, one must use an efficient design that satisfies conditions to guarantee the safety of the subjects. For a parallel design, a two-period crossover design, two three-period crossover designs, and a Latin square design with three periods, we compared variances of estimators based on a mixed analysis of variance model. The proposed three-period crossover designs turned out to be only slightly less efficient than the Latin square design, which is not capable of satisfying the necessary safety conditions. The analysis of data from the crossover design poses several problems, including nonconstant variances for all observations and the possibility of carryover effects. To resolve these issues, we generalized the Box-Cox transformations to the mixed model at hand and, using simulation, investigated the sensitivity of the analysis to the presence of (first-order) carryover effects. This showed that results from the model without carryover are reliable for only very small carryover effects.

Clinical Trials, Phase I as Topic↗

PubMed2002

Tests for inter-subject and total variabilities under crossover designs.

In this paper, we consider statistical tests for inter-subject and total variabilities between treatments under crossover designs. Since estimators of variance components for inter-subject variability and total variability in crossover design are not independent, the usual F-test cannot be applied. Alternatively, we propose a test based on the concept of the extension of the modified large sample method to compare inter-subject variability and total variability between treatments under a 2 x 2 m replicated crossover design. An asymptotic power of the proposed test is derived. A sensitivity analysis is performed based on the asymptotic power to determine how the power changes with respect to various parameters such as inter-subject correlation and intra-class correlation. Also the two methods for sample size calculation for testing total variability under 2 x 4 crossover design are discussed. The method based on the Fisher-Cornish inversion shows better performance than the method based on the normal approximation. Several simulation studies were conducted to investigate the finite sample performance of the proposed test. Our simulation results show that the proposed test can control type I error satisfactorily.

Analysis of Variance↗

PubMed2005

Cocaine use and the occurrence of panic attacks in the community: a case-crossover approach.

The epidemiologic case-crossover method is a powerful tool for research on suspected hazards of illegal drug use, the advantage being a subject-as-own-control approach that constrains stable individual-level susceptibility traits. Here, we use the case-crossover method to estimate the magnitude of excess occurrence of panic attacks during months of cocaine use vs. months of no cocaine use, motivated by a prior estimate that cocaine users have three-fold excess risk of panic attack. The self-report data on cocaine and panic are from assessments of a nationally representative sample of 1071 recent panic cases age 18 years or older identified as part of the National Household Surveys on Drug Abuse conducted in the United States during 1994-1997. Based on case-crossover estimates, cocaine use is associated with a three- to- four-fold excess occurrence of panic attack (estimated relative risk (RR) = 3.3, p = 0.049; 95% confidence interval: 1.0, 13.7). Year-by-year, the RR estimates from four independent yearly replicates (1994-1997) are 5.0, 2.0, 3.0, and 3.0. While there are several important limitations, this study adds new evidence about a previously reported suspected causal association linking cocaine use to occurrence of panic attacks, and illustrates advantages of the epidemiologic case-crossover approach and new directions in research on hazards of illegal drug use.

Adolescent↗

PubMed2000

Unequal meiotic crossover: a frequent cause of NF1 microdeletions.

Neurofibromatosis type 1 is a common autosomal dominant disorder caused by mutations of the NF1 gene on chromosome 17. In only 5%-10% of cases, a microdeletion including the NF1 gene is found. We analyzed a set of polymorphic dinucleotide-repeat markers flanking the microdeletion on chromosome 17 in a group of seven unrelated families with a de novo NF1 microdeletion. Six of seven microdeletions were of maternal origin. The breakpoints of the microdeletions of maternal origin were localized in flanking paralogous sequences, called "NF1-REPs." The single deletion of paternal origin was shorter, and no crossover occurred on the paternal chromosome 17 during transmission. Five of the six cases of maternal origin were informative, and all five showed a crossover, between the flanking markers, after maternal transmission. The observed crossovers flanking the NF1 region suggest that these NF1 microdeletions result from an unequal crossover in maternal meiosis I, mediated by a misalignment of the flanking NF1-REPs.

Adolescent↗