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At least 307 records · Page 17Linked to original sources

Compensating bends in a 16-base-pair DNA oligomer containing a T(3)A(3) segment: A NMR study of global DNA curvature.

In-phase ligated DNA containing T(n)A(n) segments fail to exhibit the retarded polyacrylamide gel electrophoresis (PAGE) migration observed for in-phase ligated A(n)T(n) segments, a behavior thought to be correlated with macroscopic DNA curvature. The lack of macroscopic curvature in ligated T(n)A(n) segments is thought to be due to cancellation of bending in regions flanking the TpA steps. To address this issue, solution-state NMR, including residual dipolar coupling (RDC) restraints, was used to determine a high-resolution structure of [d(CGAGGTTTAAACCTCG)2], a DNA oligomer containing a T3A3 tract. The overall magnitude and direction of bending, including the regions flanking the central TpA step, was measured using a radius of curvature, Rc, analysis. The Rc for the overall molecule indicated a small magnitude of global bending (Rc = 138 +/- 23 nm) towards the major groove, whereas the Rc for the two halves (72 +/- 33 nm and 69 +/- 14 nm) indicated greater localized bending into the minor groove. The direction of bending in the regions flanking the TpA step is in partial opposition (109 degrees), contributing to cancellation of bending. The cancellation of bending did not correlate with a pattern of roll values at the TpA step, or at the 5' and 3' junctions, of the T3A3 segment, suggesting a simple junction/roll model is insufficient to predict cancellation of DNA bending in all T(n)A(n) junction sequence contexts. Importantly, Rc analysis of structures refined without RDC restraints lacked the precision and accuracy needed to reliably measure bending.

Bacterial Proteins↗

Control of protein functional dynamics by peptide linkers.

Control of structural flexibility is essential for the proper functioning of a large number of proteins and multiprotein complexes. At the residue level, such flexibility occurs due to local relaxation of peptide bond angles whose cumulative effect may result in large changes in the secondary, tertiary or quaternary structures of protein molecules. Such flexibility, and its absence, most often depends on the nature of interdomain linkages formed by oligopeptides. Both flexible and relatively rigid peptide linkers are found in many multidomain proteins. Linkers are thought to control favorable and unfavorable interactions between adjacent domains by means of variable softness furnished by their primary sequence. Large-scale structural heterogeneity of multidomain proteins and their complexes, facilitated by soft peptide linkers, is now seen as the norm rather than the exception. Biophysical discoveries as well as computational algorithms and databases have reshaped our understanding of the often spectacular biomolecular dynamics enabled by soft linkers. Absence of such motion, as in so-called molecular rulers, also has desirable functional effects in protein architecture. We review here the historic discovery and current understanding of the nature of domains and their linkers from a structural, computational, and biophysical point of view. A number of emerging applications, based on the current understanding of the structural properties of peptides, are presented in the context of domain fusion of synthetic multifunctional chimeric proteins.

Amino Acid Sequence↗

Influence of point mutations on the flexibility of cytochrome b5: molecular dynamics simulations of holoproteins.

Two membrane-bound isoforms of cytochrome b5 have been identified in mammals, one associated with the outer mitochondrial membrane (OM b5) and the other with the endoplasmic reticulum (microsomal, or Mc b5). The soluble heme binding domains of OM and Mc b5 have highly similar three-dimensional structures but differ significantly in physical properties, with OM b5 exhibiting higher stability due to stronger heme association. In this study, we present results of 8.5-ns length molecular dynamics simulations for rat Mc b5, bovine Mc b5, and rat OM b5, as well as for two rat OM b5 mutants that were anticipated to exhibit properties intermediate between those of rat OM b5 and the two Mc proteins: the A18S/I32L/L47R triple mutant (OM3M) and the A18S/I25L/I32L/L47R/L71S quintuple mutant (OM5M). Analysis of the structure, fluctuations, and interactions showed that the five b5 variants used in this study differed in organization of their molecular surfaces and heme binding cores in a way that could be used to explain certain experimentally observed physical differences. Overall, our simulations provided qualitative microscopic explanations of many of the differences in physical properties between OM and Mc b5 and two mutants in terms of localized changes in structure and flexibility. They also reveal that opening of a surface cleft between hydrophobic cores 1 and 2 in bovine Mc b5, observed in two previously reported simulations (E. M. Storch and V. Daggett, Biochemistry, 1995, Vol. 34, pp. 9682-9693; A. Altuve, Biochemistry, 2001, Vol. 40, pp. 9469-9483), probably resulted from removal of crystal contacts and likely does not occur on the nanosecond time scale. Finally, the MD simulations of OM5M b5 verify that stability and dynamic properties of cytochrome b5 are remarkably resistant to mutations that dramatically alter the stability and structure of the apoprotein.

Animals↗

Kinematics of the toe touching test: an investigation using motion analysis.

We describe a technique for measuring dynamic motion at the low back along with the major lower limb joints during the toe touching maneuver. This type of motion analysis was carried out on eight normal volunteers. Flexion during the toe touching maneuver involves not only low back and hip movement but also ankle plantar flexion and a varying degree of knee movement. The low back and ankle movements were highly correlated within each subject to an extent that suggests a functional connection between the lower limb and low back movements. The significance of our work is two-fold. First, we emphasize that the toe touching test represents a combined movement of the low back, the hips, the knees, and the ankles and it is reasonable to suggest that abnormalities of these joints may affect the clinical relevance of the test as an indicator of back movement. Second, we point out that the guidelines of the American Medical Association in using the test to determine hip movement are incorrect as they do not take into account the effect of knee and ankle movements on the estimation of hip movement.

Adult↗

Assessment of the trackability, flexibility, and conformability of coronary stents: a comparative analysis.

The efficacy and safety of coronary stent implantation depend on the mechanical features of these devices when deployed in atheromatous lesions of various morphologies. We evaluated the trackability, flexibility, and conformability of 17 coronary stents using specific mechanical bench tests. The quantifications used a dynamometer for assessment of trackability (maximal strength) and flexibility (stiffness) and a 3D optical gauging machine for assessment of conformability (distance between stent and arterial wall in a curvature). The maximal strength (measuring the trackability) ranged respectively from 0.24 +/- 0.06 and 0.38 +/- 0.03 N (Seaquest) to 1.31 +/- 0.42 and 1.34 +/- 0.35 N (Carbostent), concerning respectively curvatures of 90 degrees (P < 0.0001) and 135 degrees (P < 0.0001). The stiffness (measuring the flexibility) ranged from 0.53 +/- 0.16 (Seaquest) to 1.28 +/- 0.10 N/mm (NIR Royal; P < 0.0001). The mean distance between stent and external curvature (external conformability) ranged from 0.15 +/- 0.06 mm (S7) to 0.57 +/- 0.4 mm (NIR Royal; P < 0.0001). The mean distance between stent and internal curve (internal conformability) ranged from 0.26 +/- 0.13 (S7) to 0.44 +/- 0.12 mm (S670; P < 0.0001). These results may influence the choice of a particular stent adapted to a specific coronary anatomy.

Blood Vessel Prosthesis↗

Flexible but with a defined turn-influence of the template on the binding properties of two-armed receptors.

Combinatorial binding studies revealed that the di(trans-4-aminoproline)diketopiperazine is an ideal template for two-armed receptors with highly selective binding properties towards peptides. It is not only superior to structurally very different diamines but also to the diastereomeric di(cis-4-aminoproline)diketopiperazine. These empiric results are rationalized by the analysis of the conformation of the diastereomeric diketopiperazines in the solid state, by X-ray crystal structure analysis, as well as by NMR studies in solution: to observe highly selective binding, the template needs to be not only conformationally rigid but it must have a specific turn geometry. The combination of combinatorial binding studies, X-ray crystal structure analysis, and NMR spectroscopy gave insight into why the trans,trans-diketopiperazine is a superior template compared to other diamines. Additionally, the results provide a guide for the rational design of two-armed receptors with good binding properties towards peptidic guests.

Binding Sites↗

Mesoporous hybrid thin films: the physics and chemistry beneath.

Mesoporous films containing organic or biological functions within an organised array of cavities are produced by combining sol-gel, self-assembly of supramolecular templates and surface chemistry. This paper reviews the essential physics and chemical concepts behind the synthesis of these complex multifunctional materials.

Biological Products↗

The effect of glass fibre-reinforcement on the transverse strength, deflection and modulus of elasticity of repaired acrylic resins.

AIM: To test the effect of reinforcement qualities of glass fibre in the repair of acrylic fractures. METHODS: Four types of heat-curing acrylic resin test specimens were fabricated. The bottom and sides of the specimens were placed in stone to form a repair template. Lines were drawn 3.5 mm on each side of the centring mark. The 45 degree-bevel joint margins were cut at these lines to simulate fracture and the centre section was discarded. A 1 mm gap was created between the margins before repair with autopolymerising acrylic resin with and without glass fibre. OUTCOME MEASURES: A three-point loading test was used to measure transverse strength, deflection and the modulus of elasticity of repaired acrylic resin joints. RESULTS: The transverse strength of acrylic resins was increased with fibres. CONCLUSION: Glass fibre-reinforcement significantly increased resistance to deflection and increased the modulus of elasticity.

Acrylic Resins↗

Flexural strength distribution of a PMMA-based bone cement.

Polymethylmethacrylate bone cement containing either no added antibiotic or 0.5 g of Gentamicin was prepared and stored either in air at room temperature or in a 37 degree C water bath for 48 h. An additive-free cement stored in air at room temperature was also tested for purposes of comparison. Following storage the specimens were tested in flexure. Weibull statistics demonstrated to fit the flexural strength distribution of all the materials tested with regression coefficients of at least 0.98. The presence of a BaSO(4) radiopacifier markedly reduced the mean flexural strength and increased the data scatter in the air-stored specimens. On the other hand, the flexural strength of both impregnated and nonimpregnated antibiotic increased when those materials were stored in water at 37 degree C, compared with the same material stored in air, as a consequence of the water ingress. The water-stored antibiotic-impregnated cement displayed lower flexural strength, increased data scatter, and a remarkably higher number of weak specimens compared with the antibiotic-free cement. The influence of the load type on the flexural behavior was studied by testing the air-stored specimens in three-point bending and four-point bending. Cements tested in four-point bending resulted in lower flexural strength than that tested in three-point bending. The ratio of mean strength measured in the different load arrangements was satisfactory, as predicted by the Weibull model.

Anti-Bacterial Agents↗

In vivo evaluation of a bioactive scaffold for bone tissue engineering.

Revision cases of total hip implants are complicated by the significant amount of bone loss. New materials and/or approaches are needed to provide stability to the site, stimulate bone formation, and ultimately lead to fully functional bone tissue. Porous bioactive glasses (prepared from 45S5 granules, 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5) have been developed as scaffolds for bone tissue engineering and have been studied in vitro. In this study, we investigated the incorporation of tissue-engineered constructs utilizing these scaffolds in large, cortical bone defects in the rat simulating revision conditions. With implantation times of 2, 4, and 12 weeks the results were compared to those using the bioactive ceramic scaffold alone. Two tissue-engineered constructs were studied: osteoprogenitor cells that were either seeded onto the scaffold prior to implantation ("primary") or those that were culture expanded to form bonelike tissue on the scaffold prior to implantation ("hybrid"). Defects treated with the hybrid had the greatest amount of bone in the available pore space of the defect over all other groups at 2 weeks (p < 0.05). For both the primary and hybrid groups, woven and lamellar bone was present along the interface of the scaffold and the host cortex and within the porous space of the scaffold at 2 weeks. By 4 weeks, very uniform, lamellar bone was present throughout the scaffold for both tissue-engineered groups. The amount of bone significantly increased over time for all groups while the bioactive ceramic gradually resorbed by 40% at 12 weeks (p < 0.05). Structural properties of the treated long bones improved over time. Long bones treated with the hybrid had an early return in torsional stiffness by 2 weeks. Both tissue-engineered constructs achieved normal torsional strength and stiffness by 4 weeks as compared to the scaffold alone, which achieved this by 12 weeks. Porous, surface modified bioactive ceramic is a promising scaffold material for tissue-engineered bone repair.

Animals↗

Mechanical properties and three-body wear of veneering composites and their matrices.

Fatigue as one of the major factors affecting three-body wear of resin composites is influenced by mechanical properties of the resin matrix. The aim of this in vitro study was to determine three-body wear (ACTA methodology), fracture strength, and Young's modulus of four veneering composites (Artglass old and new formula, Vita Zeta LC Composite, Targis) and one direct restorative composite (Z 100). Furthermore, three-body wear of the pure matrices of the materials was tested. The wear results were compared to Amalgam as reference material. It should be computed whether there exists a correlation between the wear results of resin composite and matrix alone. Wear of the veneering composites was significantly higher than of Z100 (13 microm) and Amalgam (14 microm; p < 0.01, Mann-Whitney U-test). Mean fracture strengths of indirect composites ranged from 127.5 MPa (Targis) to 71.6 MPa (Vita Zeta LC). The elastic moduli of the composites were between 2.9 and 12.8 GPa. The matrix wear rates did not differ significantly. Three-body wear results of complex resin composites are highly influenced by their filler content, filler particle size distribution, kind of filler particles, shape, and their silanization to the matrix. Due to this fact, three-body wear testing is an essential testing method and cannot be replaced by testing single material components.

Composite Resins↗

Augmentation of acrylic bone cement with multiwall carbon nanotubes.

Acrylic bone cement, based on polymethylmethacrylate (PMMA), is a proven polymer having important applications in medicine and dentistry, but this polymer continues to have less than ideal resistance to mechanical fatigue and impact. A variety of materials have been added to bone cement to augment its mechanical strength, but none of these augmentative materials has proven successful. Carbon nanotubes, a new hollow multiwalled tubular material 10-40 nm in diameter, 10-100 microm long, and 50-100 times the strength of steel at 1/6 the weight, have emerged as a viable augmentation candidate because of their large surface area to volume ratio. The objective of this study was to determine if the addition of multiwall carbon nanotubes to bone cement can alter its static or dynamic mechanical properties. Bar-shaped specimens made from six different (0-10% by weight) concentrations of multiwall carbon nanotubes were tested to failure in quasi-static 3-point bending and in 4-point bending fatigue (5 Hz). Analyses of variance and the 3-Parameter Weibull model were used to analyze the material performance data. The 2 wt % MWNT concentration enhanced flexural strength by 12.8% (p=0.003) and produced a 13.1% enhancement in yield stress (p=0.002). Bending modulus increased slightly with the smaller (<5 wt % MWNT) concentrations, but increased 24.1% (p<0.001) in response to the 10 wt % loading. While the 2 wt % loading produced slightly improved quasi-static test results, it was associated with clearly superior fatigue performance (3.3x increase in the Weibull mean fatigue life). Weibull minimum fatigue life (No), Weibull modulus (alpha), and characteristic fatigue life (beta) for bone cement augmented with carbon nanotubes were enhanced versus that observed in the control group. These data unambiguously showed that the bone cement-MWNT polymer system has an enhanced fatigue life compared to "control" bone cement (no added nanotubes). It is concluded that specific multiwall carbon nanotube loadings can favorably improve the mechanical performance of bone cement.

Biocompatible Materials↗

Control of material stiffness during degradation for constructs made of absorbable polymer fibers.

Augmentation devices for cruciate ligament surgery should provide gradually decreasing mechanical properties with a half-time strength of at least 6 months to temporarily protect healing tendon grafts or sutured ligaments against high tensile loads during the postoperative healing period. The absorbable material of choice that shows such slow degradation kinetics is poly(L-lactide). However, previous studies have shown that poly(L-lactide) fulfills the requirement of a long half-time strength, while the corresponding stiffness decreases at a much slower rate. An augmentation stiffness that does not change much versus time cannot provide a gradual increase in graft load, which is important to stimulate the orientation of the collagenous tissue. Therefore a new augmentation device was designed, which should decrease both in strength and stiffness during degradation. The cord was braided out of two fibers made of poly(L-lactide) and poly(L-lactide-co-glycolide), which degrade at different rates. The cord prototype was degraded in vitro and the rupture force and stiffness was tested at eight different time points up to 60 weeks. The initial rupture force and stiffness was 522.7 +/- 2.8 N and 104.1 +/- 3.8 N/%, respectively. Both strength and stiffness decreased continuously with a half-time strength of 18 weeks and a half-time stiffness of 39 weeks. The gradually decreasing stiffness was achieved by the breakdown of the faster-degrading fiber component made of poly(L-lactide-co-glycolide). Thus the new augmentation device can provide a continuous increase of forces in a tendon graft or in a healing ligament.

Biocompatible Materials↗

Design of braided composite cardiovascular catheters based on required axial, flexural, and torsional rigidities.

Cardiovascular catheterization is a common medical procedure. A single braided catheter with different rigidities at the proximal and distal ends can, if properly designed, provide the necessary control and flexibility and thus replace the current two-piece (external catheter/internal guidewire) system. An analytical model based on classical laminate plate theory was developed in order to predict the elastic properties of angle-plied, single-overlap two-dimensional fiber composite tubular braids, which are required for the determination of the axial, flexural, and torsional rigidities. In this work the analytical model has been used to design one-piece cardiovascular catheters with axial, flexural, and torsional rigidities similar to those values for existing two-piece catheters, thus validating the model as a tool for designing braided cardiovascular catheters.

Biocompatible Materials↗

Tape-casting technique can prepare beta-TCP sheets with uniform thickness and flexibility.

The objective of this study is to propose a new fabrication technology for bone substitutes. In this study, a tape-casting method was used to prepare flexible beta-tricalcium phosphate (beta-TCP) sheets. A beta-TCP slurry containing a binder and plasticizer was used in a doctor blade system. The beta-TCP sheet obtained by this tape-casting method was highly flexible, enabling twisting and free-form shaping. The beta-TCP sheet was approximately 0.21 mm thick. X-ray diffraction and Fourier transform infrared spectrometry revealed that the structure of the beta-TCP component in the sheet is the same as that of the original beta-TCP powder. Observation by field-emission scanning electron microscopy showed that the beta-TCP sheet had a flat, microgranular surface. During the early stages, the tensile stress-strain curves of the beta-TCP sheet showed a nonlinear behavior until reaching the point of final fracture. This result was derived from the ductile property of the prepared beta-TCP sheet. In conclusion, a flexible beta-TCP sheet was easily prepared using a tape-casting technique. Fabrication using tape casting offers the advantages of enabling the preparation of ceramic sheets with precise thickness and not requiring expensive fabrication facilities.

Biocompatible Materials↗

Manufacturing, mechanical characterization, and in vitro performance of bioactive glass 13-93 fibers.

Fibers were manufactured from the bioactive glass 13-93 by melt spinning. The fibers were further characterized by measuring their tensile and flexural strength, and their in vitro performance was characterized by immersing them in simulated body fluid, which analyzed changes in their mass, their flexural strength, and surface reactions. The strength of glass fibers is highly dependent on fiber diameter, test method, and possible surface flaws, for example, cracks due to abrasion. In this study, the thinnest fibers (diameter between 24 and 33 microm) possessed the highest average tensile strength of 861 MPa. The flexural strength was initially 1353.5 MPa and it remained at that level for 2 weeks. The Weibull modulus for both tensile and flexural strength values was initially about 2.1. The flexural strength started to decrease and was only approximately 20% of the initial strength after 5 weeks. During the weeks 5-40, only a slight decrease was detected. The flexural modulus decreased steadily from 68 to 40 GPa during this period. The weight of the samples initially decreased due to leaching of ions and further started to increase due to precipitation of calcium phosphate on the fiber surfaces. The mass change of the bioactive glass fibers was dependent on the surface area rather than initial weight of the sample. The compositional analysis of the fiber surface after 24 h and 5 weeks immersion did confirm the initial leaching of ions and later the precipitation of a calcium phosphate layer on the bioactive glass 13-93 fiber surface in vitro.

Biocompatible Materials↗

Relationship between fracture toughness and flexural strength in dental porcelains.

The aim of this study was to investigate the correlation between fracture toughness (K(Ic)) and flexural strength (FS) in dental porcelains. Porcelains with different leucite contents and clinical indications were used (A, B, C, D, and E). K(Ic) was determined by surface crack in flexure method (SCF) and FS was determined by four-point-bending test. Microstructural characterization was also carried out. The leucite contents of porcelains A, B, C, D, and E were, respectively, 22, 22, 6, 15, and 0%. Materials with higher leucite content (A and B) presented significantly higher K(Ic) values compared to materials with lower leucite content (C and E). The Weibull moduli (m) of porcelains A and B were statistically higher than those of the other three materials. Regarding characteristic strength (sigma(0)), porcelains D and E showed similar values and statistically higher than those of the other materials which were statistically different from each other. According to the regression analysis, sigma(0) increased with the increase of K(Ic) until approximately 0.75 MPa m(1/2). After that, the increase in K(Ic) was accompanied by a decrease in sigma(0). However, the Weibull modulus increased with the increase in K(Ic), especially for values greater than 0.80 MPa m(1/2).

Aluminum Silicates↗