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Thermodynamic analysis of the increased stability of major histocompatibility complex class II molecule I-Ek complexed with an antigenic peptide at an acidic pH.

The differential scanning calorimetry analysis of the murine major histocompatibility complex class II molecule, I-E(k), in complex with an antigenic peptide derived from mouse hemoglobin, showed that the thermal stability at the mildly acidic pH is higher than that at the neutral pH. Although the thermal unfolding of I-E(k)-hemoglobin was irreversible, we extracted the equilibrium thermodynamic parameters from the kinetically controlled heat capacity curves. Both the denaturation temperatures and the enthalpy changes were almost independent of the heating rate over 1 degrees C per min. The linear relation between the denaturation temperature and the calorimetric enthalpy change provided the heat capacity changes, which are classified into one for the mildly acidic pH region and another for the neutral pH region. The equilibrium thermodynamic parameters showed that the increased stability at the mildly acidic pH is because of the entropic effect. These thermodynamic data provided new insight into the current structural model of a transition to an open conformation at the mildly acidic pH, which is critical for the peptide exchange function of major histocompatibility complex class II in the endosome.

Acids↗

Correlation analysis of the structures and stability constants of gadolinium(III) complexes.

To simplify the abstraction of descriptors, for the correlation analysis of the stability constants of gadolinium(III) complexes and their ligand structures, aiming at gadolinium(III) complexes, we only considered the ligands and ignored the common parts of the structures, i.e., the metal ions. Quantum-chemical descriptors and topological indices were calculated to describe the structures of the ligands. Multiple regression analysis and neural networks were applied to construct the models between the ligands and the stability constants of gadolinium(III) complexes and satisfactory results were obtained.

Contrast Media↗

The shortened Study Process Questionnaire: an investigation of its structure and longitudinal stability using confirmatory factor analysis.

BACKGROUND: The Study Process Questionnaire (SPQ) is a widely used measure of learning approach and was proposed to have three orientations: surface, deep, and achieving, each with an underlying motive and strategy. AIMS: This study aimed to examine the factor structure and longitudinal stability over five to seven years of a modified shortened 18-item version of the SPQ. SAMPLES: A total of 1349 medical students completed the shortened SPQ at application and in their final year of medical school. Three additional cohorts of students completed the shortened SPQ during their third and fourth year of medical school (sample size: 194, 203, 174). METHOD: Confirmatory factor analysis was used to examine the dimensionality and longitudinal stability of the shortened SPQ. RESULTS: Like the full 42-item version, the shortened SPQ has six subscales and the data are best fit by three second order shared indicator factors (surface, deep and achieving) and a single higher order composite deep-achieving factor. The longitudinal analysis found 26.8%, 26.3%, and 18.7% of the non-attenuated variance of the surface, deep and achieving factor scores in the final year is predicted from the shortened SPQ completed at application to medical school. CONCLUSIONS: The shortened 18-item SPQ has the same six subscales as the full SPQ as well as three second order shared indicator factors (surface, deep, achieving) and one higher order deep-achieving factor similar to that suggested by Biggs (1987). The longitudinal analysis supports this hypothesis and suggests that these learning approaches are partly stable during medical school undergraduate training and partly modifiable under the influence of the educational environment.

Adult↗

Stability of finite difference deconvolution I: theoretical analysis.

Analysis of the stability of finite difference deconvolution (FDD) shows that it is dependent on the characteristics of the unit impulse response function and the sampling schedule of the input response function, and that stability properties are improved when the cumulative amount function is directly estimated rather than the rate function. The estimated input rate for an intravenous (iv) unit impulse response function and the release rate for an oral solution unit impulse response function are unstable for any sampling schedule of the input response function. However, for an iv unit impulse response function, the estimated cumulative amount absorbed is stable for any sampling schedule of the response function. For an oral unit impulse response function, the estimated cumulative amount released is unstable for all the sampling points of the input response function located before the time of the maximum of the oral unit impulse response function, but it can be made stable if an appropriately designed sampling schedule of the input response function is used. In addition, the theoretical basis for choosing a sampling schedule to overcome the instability of FDD has been established.

Algorithms↗

Monitoring of implant stability in grafted bone using resonance frequency analysis. A clinical study from implant placement to 6 months of loading.

The aim of this prospective study was to compare implants placed in grafted and normal non-grafted maxilla by means of resonance frequency analysis (RFA), clinical stability and implant failure. Twenty-nine patients with severe atrophy of the edentulous maxilla were treated with autogenous bone grafts as onlay (24 patients) or as interpositional grafts in conjunction with a Le Fort I osteotomy (five patients) 6 months prior to placement of 222 implants. Ten non-grafted patients treated with 75 Brånemark implants in the edentulous maxillae served as a control group. RFA was performed at implant placement, abutment connection and after 6 months of bridge loading. Seventeen (8%) implants were lost in the grafted bone and one (1%) in normal bone. RFA revealed a similar pattern in both grafted and normal maxillae, i.e. increasing resonance frequency (RF) with time (Wilcoxon Signed Rank test for paired data). Twenty implants that were rotation mobile (low primary stability) at the time of insertion showed a significantly lower value at implant placement according to RFA (Mann-Whitney U-test, P = 0.020). The RF for the failed implants revealed a tendency towards lower values (Mann-Whitney U-test, P = 0.072), compared to the successful implants. It is concluded that implants placed in grafted bone when using a two-stage technique achieve a stability similar to that of implants placed in normal non-grafted bone.

Aged↗

[Application of interactive virtual reality technique in biomechanical analysis of knee joint stability].

OBJECTIVE: To test the feasibility of using interactive virtual reality technique for three-dimensional reconstruction and image segmentation for biomechanical analysis of the knee joint structures. METHODS: The muscular and fat tissues along with the connective tissues were removed from the knee joint, and the femur and tibia were embedded in polymethacrylate gel. The knee joint was reconstructed with three-dimensional analysis system after calibration of the sequence of the three-dimensional markers attached to the femur and tibia. RESULTS: The knee joint model was reconstructed and verified by three-dimensional analysis. This model provided information of the motions of the internal and external knee joint structures. CONCLUSION: This method is useful for reconstructing human joints and provides a new and highly efficient experimental method for biomechanical simulation of human joints.

Adolescent↗

Long-term follow-up of post-acute traumatic brain injury rehabilitation: a statistical analysis to test for stability and predictability of outcome.

A high percentage of the estimated 500,000 traumatic brain injuries (TBI) in the US every year occur with young people who will face many years of neurobehavioral and economic consequences. This study examined the long-term stability of outcome after post-acute TBI rehabilitation and possible predictors of long-term outcome based on a 127-item survey of 332 clients up to 14 years post-discharge. Correlational, factor, and multiple regression analysis indicated positive long-term outcome stability following rehabilitation with the exception of vocational status, which decreased over the same time period. A number of possible explanations for this occupational anomaly are suggested. Rating scale scores and latency-to-rehabilitation proved to be better predictors of long-term outcome than demographic data.

Activities of Daily Living↗

The effect of anteversion on femoral component stability assessed by radiostereometric analysis.

Internal rotation of a femoral stem within the femur, with posterior migration of the femoral head (PHM) relative to the femur, is an important mode of failure. The relationship between anteversion and rotational stability for the Exeter (Howmedica International Ltd, London, UK) and Charnley Elite (DePuy International Ltd, Leeds, UK) stems was investigated using radiostereometric analysis (RSA). For the Elite, there was a significant (P=.01) correlation between anteversion and PHM, whereas for the Exeter, there was no significant correlation (P=.6). Increasing anteversion of the Elite was associated with decreasing PHM and increased stability. Of stems, 20% of the Elite and none of the Exeter were classified as having reduced rotational stability because their PHM was >2 SDs from the mean. All reduced rotational stability implants had anteversion substantially <20 degrees. Polished collarless tapered stems such as the Exeter seem to have enhanced rotational stability. For conventional stems, increasing anteversion increases stability. It is recommended that these stems are anteverted 20 degrees.

Hip Prosthesis↗

Intra-operative evaluation of cementless hip implant stability: a prototype device based on vibration analysis.

Cementless implants are mechanically stabilized during surgery by a press-fitting procedure. Good initial stability is crucial to avoid stem loosening and bone cracking, therefore, the surgeon must achieve optimal press-fitting. A possible approach to solve this problem and assist the surgeon in achieving the optimal compromise, involves the use of vibration analysis. The present study aimed to design and test a prototype device able to evaluate the primary mechanical stability of a cementless prosthesis, based on vibration analysis. In particular, the goal was to discriminate between stable and quasi-stable implants; thus the stem-bone system was assumed to be linear in both cases. For that reason, it was decided to study the frequency responses of the system, instead of the harmonic distortion. The prototype developed consists of a piezoelectric exciter connected to the stem and an accelerometer attached to the femur. Preliminary tests were performed on four composite femurs implanted with a conventional stem. The results showed that the input signal was repeatable and the output could be recorded accurately. The most sensitive parameter to stability was the shift in resonance frequency of the stem-bone system, which was highly correlated with residual micromotion on all four specimens.

Cementation↗

A novel technique for laminoplasty augmentation of spinal canal area using titanium miniplate stabilization. A computerized morphometric analysis.

STUDY DESIGN: Titanium miniplates are used to secure the posterior elements in the open position after expansive open-door laminoplasty. Preoperative and postoperative spinal canal dimensions are measured to assess the effectiveness of this technique. OBJECTIVES: To develop a simple yet effective technique to stabilize the posterior elements after laminoplasty and to compare preoperative and postoperative spinal canal dimensions to accepted normal values. SUMMARY OF BACKGROUND DATA: Expansive open-door laminoplasty has been offered as a simple alternative to laminectomy, which has been associated with postoperative kyphosis. Although the technique of laminoplasty is effective, a simple and reliable method of holding the posterior elements open has not been described. METHODS: Ten myelopathic patients with multilevel cervical canal stenosis secondary to spondylosis or ossification of the posterior longitudinal ligament were treated with an expansive open-door laminoplasty. The posterior elements were stabilized in the open position with titanium miniplates. Computer-assisted morphometric analysis was performed on preoperative and postoperative computed tomography scans to obtain spinal canal dimensions. Plain radiographs were used to monitor construct integrity. RESULTS: The preoperative sagittal canal diameter was 8.2 +/- 0.96 mm, and the canal area was 180.6 +/- 33.7 mm2. These dimensions increased after surgery to 16.6 +/- 1.5 mm and 321.9 +/- 29.7 mm2, respectively. The titanium miniplate constructs did not fail during the follow-up period (mean, 26.4 months), and the decompression was maintained. The single significant complication was transient C5 radiculopathy. CONCLUSIONS: Normal canal dimensions can be reestablished with open-door laminoplasty. Achieving and maintaining an increased sagittal canal diameter is probably the most important change in anatomic parameters to facilitate neurologic recovery. The use of titanium miniplates to stabilize the posterior elements after laminoplasty is a simple, durable, and effective technique to maintain the increased sagittal diameter of the spinal canal.

Adult↗

Inference and analysis of the relative stability of bacterial chromosomes.

The stability of genomes is highly variable, both in terms of gene content and gene order. Here I calibrate the loss of gene order conservation (GOC) through time by fitting a simple probabilistic model on pairwise comparisons involving 126 bacterial genomes. The model computes the probability of separation of pairs of contiguous genes per unit of time and fits the data better than previous ones while allowing a mechanistic interpretation for the loss of GOC with time. Although the information on operons is not used in the model, I observe, as expected, that most highly conserved pairs of genes are indeed within operons. However, even the other pairs are much more conserved than expected given the observed experimental rearrangement rates. After 500 Myr, about 50% of the originally contiguous orthologues remain so in the average genome. Hence, the large majority of rearrangements must be deleterious and random genome rearrangements are unlikely to provide for positively selected structural changes. I then use the deviations from the model to define an intrinsic measure of genome stability that allowed the comparison of distantly related genomes and the inference of ancestral states. This shows that clades differ in genome stability, with cyanobacteria being the least stable and gamma-proteobacteria the most stable. Without correction for phylogeny, free-living bacteria are the least stable group of genomes, followed by pathogens, and then endomutualists. However, after correction for phylogenetic inertia (or the removal of cyanobacteria from the analysis), there is no significant association between genome stability and lifestyle or genome size. Hence, although this method has allowed uncovering some of mechanisms leading to rearrangements, we still ignore the forces that differentially shape selection upon genome stability in different species.

Bacteria↗

High pressure effects on cellular expression profile and mRNA stability. A cDNA array analysis.

Hydrostatic pressure has a profound effect on cartilage tissue and chondrocyte metabolism. Depending on the type and magnitude of pressure various responses can occur in the cells. The mechanisms of mechanotransduction at cellular level and the events leading to specific changes in gene expression are still poorly understood. We have previously shown that induction of stress response in immortalized chondrocytes exposed to high static hydrostatic pressure increases the stability of heat shock protein 70 mRNA. In this study, our aim was to examine the effect of high pressure on gene expression profile and to study whether stabilization of mRNA molecules is a general phenomenon under this condition. For this purpose a cDNA array analysis was used to compare mRNA expression profile in pressurized vs. non-pressurized human chondrosarcoma cells (HCS 2/8). mRNA stability was analyzed using actinomycin-treated and nontreated samples collected after pressure treatment. A number of immediate-early genes, and genes regulating cell cycle and growth were up-regulated due to high pressure. Decrease in osteonectin, fibronectin, and collagen types VI and XVI mRNAs was observed. Also bikunin, cdc37 homologue and Tiam1, genes linked with hyaluronan metabolism, were down-regulated. In general, stability of down-regulated mRNA species appeared to increase. However, no increase in mRNA above control level due to stabilization was noticed in the genes available in the array. On the other hand, mRNAs of certain immediate-early genes, like c-jun, jun-B and c-myc, became destabilized under pressure treatment. Increased accumulation of mRNA on account of stabilization under high pressure conditions seems to be a tightly regulated, specific phenomenon.

Cartilage, Articular↗

The thermodynamic mechanism of protein stabilization by trehalose.

The stabilization of ribonuclease A by alpha-alpha-trehalose was studied by preferential interaction and thermal unfolding. The protein is stabilized by trehalose at pH 2.8 and pH 5.5. Wyman linkage analysis showed increased exclusion of trehalose from the protein domain on denaturation. Preferential interaction measurements were carried out at 52 degrees C at pH 5.5 and 2.8, where the protein is native and unfolded, respectively, and at 20 degrees C where the protein is native at both pH values. At the low temperature, the interaction was preferential exclusion. At 52 degrees C the interaction was that of preferential binding, greater to the native than the unfolded protein, the increment on denaturation being identical to that deduced from the Wyman analysis. The stabilizing effect of trehalose can be fully accounted by the change in transfer free energy on unfolding. The temperature dependence of the preferential interactions of 0.5 M trehalose with ribonuclease A showed that it is the smaller preferential binding to the unfolded protein than to the native one which gives rise to the stabilization. A thermodynamic analysis of the data led to approximate values of the transfer enthalpies and transfer entropies for the trehalose-ribonuclease A system.

Hydrogen-Ion Concentration↗

Synthesis of heterotrimeric collagen models containing Arg residues in Y-positions and analysis of their conformational stability.

An Arg residue incorporated into the Y-position of collagenous host-guest peptide Ac-(Gly-Pro-Hyp)(3)-Gly-Pro-Y-(Gly-Pro-Hyp)(4)-Gly-Gly-NH(2) is reported to stabilize the triple helical structure as well as a 4(R)-hydroxyproline (Hyp) residue. Here, we synthesized heterotrimeric collagen models containing Arg in Y-positions utilizing the cystine knot strategy. Analysis of their thermal transition temperatures using circular dichroism spectrometry demonstrated unexpected decrease in the triple helical stability as the number of Arg increased. The obtained results indicated that an Arg residue in a Y-position is not always an equivalent of a Hyp residue, and that it possesses a potential helix destabilizing effect.

Amino Acid Sequence↗

Multivariate analysis of EEG coherence: stability of the metric, individual differences in patterning and response to arousal.

When coherence is computed among all pairs of a multichannel EEG, the resultant matrix can be de-structured with conventional multivariate analysis procedures to characterize the patterning of electrophysiologic information at each frequency band of the EEG across brain regions. Six right-handed young men had EEG data recorded from left and right frontal, temporal, parietal, and occipital locations during three visits to the laboratory at one week intervals. During each session, data were recorded during a relaxation period, an alert resting period, and as loud white noise was presented. Factor analysis of coherence matrices showed a model pattern of a large posterior factor and an anterior factor, both of which were right-lateralized, plus a residual factor that was most often left-lateralized. Four of the six men showed this pattern on each occasion, particularly for the delta and the theta bands. Two men showed variant patterns, which were also stable over time. A priori de-structuring of the matrix into partial multiple intrahemispheric and inter-hemispheric coherences also showed generally higher coherences on the right side, with the exception of left occipital inter-hemispheric values. Effects of arousal manipulations were not striking, but the factor patterns suggested increases in right hemisphere coherence for the alpha and beta bands during high arousal.

Adult↗

Mast cells in cervical ripening--an immunohistochemical and biomechanical study in rats.

Cervical ripening purportedly involves different cell types and mediators normally associated with inflammatory reactions. The purpose of the present study was to determine the presence of mast cells in rat cervices during spontaneous and antigestagen induced ripening and to test whether a mast cell stabilizer was able to inhibit the antigestagen induced cervical ripening. Immunohistochemical examinations demonstrated an increased number of mast cells in pregnant and intrapartum rats. Furthermore, mast cell degranulation was found to be prominent after antigestagen treatment. The degranulation was completely abolished by co-treatment with the mast cell stabilizer. Biomechanical analysis showed that the mast cell stabilizer also inhibited the antigestagen induced cervical ripening to some extent. Thus, it is concluded that mast cell stabilizers might constitute a new approach in the treatment of preterm cervical ripening.

Animals↗

Studies on the stability of creatine kinase isozymes.

Research on the stabilizing properties of creatine kinase isozymes CK-BB, CK-MB, and CK-MM showed that minor alteration of their sequence and structure influenced their stability significantly. An analysis of the stability of the isozymes in storage after freeze drying indicates that creatine kinase isozymes are all in monomer form because of the loss of subunit interactions. Freeze-drying leads to the oxidization of CK-BB and rearrangement of CK-MB. There are also differences in the unfolding of the isozymes in urea. CK-BB and CK-MB are unfolded in lower urea concentrations than CK-MM. Differences in the thermal unfolding were also examined by differential scanning calorimetry. This paper discusses the potential biological significance of these results.

Animals↗

Desk-top analysis of the structural stability of various point mutations introduced into ribonuclease H.

The structural stability of Escherichia coli ribonuclease HI mutants was analyzed by a pseudo-energy potential developed for evaluating structure-sequence compatibility. From the structure profile, the energy changes of the folding of mutant proteins relative to that of the wild-type, which correspond to the changes of free energy differences, were estimated. They are weakly but significantly correlated with the experimentally determined changes in the melting temperature between the mutant proteins and the wild-type. The correlation coefficient between the experimental data and the computation, estimated for all the known data (96 point mutations) and for the buried site data (32 point mutations), are -0.51 and -0.68, respectively. Experimentally known mechanisms to increase the structural stability are explained by the method: the main contributor to the stability in mutations of Val74 to either Ile or Leu is the side-chain packing energy, and that of Lys95 to Gly is the local conformational energy. This analysis is easy to do on a desk-top computer, and allows one to consider all the sites of possible candidates for point mutations. From the profile, new promising sites to increase the structural stability are suggested.

Computer Simulation↗