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PubMed1998

Comparison between freestanding and tooth-connected partially stabilized zirconia implants after two years' function in monkeys: a clinical and histologic study.

STATEMENT OF PROBLEM: Partially stabilized zirconia implants placed by a 1-stage procedure have been previously shown to obtain initial osseointegration under clinically unloaded condition. However, it is unknown whether freestanding and tooth-connected partially stabilized zirconia implants can maintain a long-term direct bone-implant interface. PURPOSE: This study examined the possibility of the long-term stability of osseointegration around partially stabilized zirconia implants with a 1-stage procedure with different loading designs. MATERIAL AND METHODS: Thirty-two partially stabilized zirconia implants were placed into the mandibles of 8 monkeys. Three months after implant placement, 3 types of superstructure were provided in each animal to obtain different concepts of support as (1) single freestanding implant support, (2) connected freestanding implant support, and (3) a combination of implant and tooth support. At 12 and 24 months after loading, clinical, histologic, and histomorphometric evaluations of peri-implant tissues were performed on 28 implants. RESULTS: No clear difference in clinical features was observed among the different types of support. Direct bone apposition to the implant was generally seen in all groups. Histometrically, bone contact ratio ranged between 66% and 81%, and bone area ratio varied between 49% and 78% at 24 months after loading. These values showed almost no difference among single freestanding, connected freestanding, and implant-tooth supports of partially stabilized zirconia implants. CONCLUSION: In a primate model, partially stabilized zirconia implants placed with a 1-stage procedure achieve long-term stability of osseointegration with the use of single freestanding, connected freestanding, and implant-tooth supports.

Analysis of Variance↗
PubMed2004

Dynamic stabilization devices in the treatment of low back pain.

Soft stabilization has an important role in the treatment of the degenerative lumbar spine. Fusion of one or two motion segments may not make a big difference in the total range of motion of the lumbar spine, but preserving flexibility of a motion segment may prevent adjacent segment disease and may permit disc replacement, even when facet joints need to be excised. If a favorable environment is created in the motion segment by unloading the disc and permitting near normal motion, the disc may be able to repair itself or may supplement the reparative potential of gene therapy. Although soft stabilization seems promising, one should take a cautious approach to any new implant system. An implant for fusion only has to serve a temporary stabilization until fusion has taken place; on the other hand, a soft stabilization system has to provide stability throughout its life. Implant loosening following fusion surgery is common in the presence of pseudarthrosis. After soft stabilization, the implant has to stay anchored to the bone despite allowing movement. This sounds like a daunting task. The flexibility of the implant system, however, should be able to protect it from loosening at the anchor point into the bone. Finally, the soft stabilization system is intended to load-share with the disc and the facet joint only partially and unloads the motion segment. Any mismatch between the kinematics of the implant system and the motion segment, in particular any discrepancy between their IAR, would result in the implant bearing unexpected load at certain ranges of motion. If that happens, it would guarantee an early implant failure or loosening. The need for strict bench testing in the laboratory, therefore, cannot be over-emphasized. The few soft stabilization systems that have had clinical applications so far have produced a clinical outcome comparable to that of fusion. No prospective randomized controlled trial has been reported yet, which is an essential requirement for practice of evidence-based medicine.

Biomechanical Phenomena↗
PubMed1996

Stabilization of respiratory syncytial virus (RSV) against thermal inactivation and freeze-thaw cycles for development and control of RSV vaccines and immune globulin.

A high-titered and stable respiratory syncytial virus (RSV) is essential for the development of RSV vaccines and quality control of vaccines and RSV immune globulin. We increased the virus titer of RSV seed stock, and virus preparations made from this seed stock, 100 times by removing defective interfering particles using limiting dilution procedure. RSV preparations made from the new seed stock had infectivity titers ranging from 10(7.6) to 10(8.2) TCID50 per ml for five lots made over a period of 3 years. Unstabilized RSV lost most of its infectivity at -86 degrees C within 2-3 weeks, at 37 degrees C within 24 hr, at 56 degrees C within 3 min and after five freeze-thaw cycles. The high titered virus was stabilized at -86 degrees C for 3 years, at 37 degrees C for 3 days, at 56 degrees C for 6 min and against five freeze-thaw cycles. Most effective stabilizers included 25% sucrose, 10% trehalose and 45% fetal bovine serum (FBS) in Medium 199 whereas 3.5% dimethyl sulfoxide, > or = 45% FBS in phosphate buffered saline, 40% glycerol and 10% sorbitol also stabilized RSV to lesser and variable degrees. A mixture of 0.5% gelatine and 0.3% sodium glutamate stabilized the virus for a short period whereas 0.1 M MgCl2 and 25% FBS did not stabilize the virus. The stabilized high-titered virus is very useful for achieving reproducibility in serologic assays. A broad spectrum of stabilizers, such as those evaluated in this study, would be useful in choosing the most suitable formulation for stabilizing a live RSV vaccine.

Cryopreservation↗
PubMed1998

Stability of external circular fixation: a multi-variable biomechanical analysis.

OBJECTIVE: To determine how the manipulation of the parameters of fixation and components of the circular external frame could improve and maintain optimal stability of bone fragments. DESIGN: We performed a multi-parametric biomechanical analysis of the extrinsic parameters effecting bone fragment stabilization. Results of testing are presented as a percent change in stiffness due to the manipulation of frame components and their interaction with other fixation parameters. BACKGROUND: Although there have been investigations of the biomechanical characteristics of circular external fixation, they have been limited to either individual frame components or full frame comparisons. Therefore, these studies did not provide a comprehensive understanding of how the manipulation of circular fixator components influences bone fragment stability. METHODS: Mechanical testing was performed in three phases examining the effect of numerous components including ring diameter, wire angle, ring separation, etc. on axial, torsional and bending stiffness. RESULTS: For phase I (single ring) and phase II (double-ring block), ring diameter was the most significant factor affecting axial and torsional stiffness, while wire angle, ring separation, and their interaction had the most influence on bending stiffness. Phase III (two double-ring blocks) showed that ring positioning with respect to the osteotomy site had the most affect on bending and torsional stiffness while axial stiffness was non-linear and dependent upon the applied load. CONCLUSIONS: The stability of bone fragments within a circular external fixator is affected by manipulation of the parameters of fixation or individual components of the frame. The contribution of each component to overall bone fragment stability is dependent upon the mode of loading. The changes in overall stability of bone fragments are dependent not only on the individual frame components but also upon their interaction with other parameters of fixation. RELEVANCE: Understanding how the manipulation of individual frame components will affect overall bone fragment stabilization will allow the surgeon to better control the stability of bone fragments for each clinical situation.

Journal Article↗
PubMed2002

The thermal stability of RNA duplexes containing modified base pairs placed at internal and terminal positions of the oligoribonucleotides.

The presence of various modifications within oligomers changes their thermodynamic stability. To get more systematic data, we measured effects of 5- and 6-substituted uridine on thermal stability of (AUCU(Mod.)AGAU)2 and (AUCUAGAU(Mod.))2. Collected results lead to the following conclusions: (i) 5-halogenated and 5-alkylated substituents of the uridine affect thermal stability of the RNA duplexes differently. Moreover, the 5-fluorouridine changes stability of the RNA duplexes opposite to remaining 5-halogenouridines; (ii) for oligomers containing 5-chloro, 5-bromo or 5-iodouridine stronger hydrogen bond formed between oxygen-4 of the 5-halogenated uracil and 6-amino group of the adenine is presumably responsible for stabilizing effect; (iii) placing of A-U(5R) base pairs closer to the end of the duplex enhance thermal stability relatively to oligomer with central position of this base pair; (iv) the effects of 5-substituents are additive, particularly for substituents which stabilize RNA duplexes; (v) 6-methyluridines (N1 and N3 isomers) as well as 3N-methyluridine present at internal position of A-U(Mod.) inhibit duplexes formation; (vi) 6-methyluridines (N1 and N3 isomers) as well as 3N-methyluridine placed as terminal base pairs stabilize the duplexes mostly via 3'-dangling end effect.

Hot Temperature↗
PubMed1997

NL(q) Theory: A Neural Control Framework with Global Asymptotic Stability Criteria.

In this paper a framework for model-based neural control design is presented, consisting of nonlinear state space models and controllers, parametrized by multilayer feedforward neural networks. The models and closed-loop systems are transformed into so-called NL(q) system form. NL(q) systems represent a large class of nonlinear dynamical systems consisting of q layers with alternating linear and static nonlinear operators that satisfy a sector condition. For such NL(q)s sufficient conditions for global asymptotic stability, input/output stability (dissipativity with finite L(2)-gain) and robust stability and performance are presented. The stability criteria are expressed as linear matrix inequalities. In the analysis problem it is shown how stability of a given controller can be checked. In the synthesis problem two methods for neural control design are discussed. In the first method Narendra's dynamic backpropagation for tracking on a set of specific reference inputs is modified with an NL(q) stability constraint in order to ensure, e.g., closed-loop stability. In a second method control design is done without tracking on specific reference inputs, but based on the input/output stability criteria itself, within a standard plant framework as this is done, for example, in H( infinity ) control theory and &mgr; theory. Copyright 1997 Elsevier Science Ltd.

Journal Article↗
PubMed1993

Cytosine-cytosine+ base pairing stabilizes DNA quadruplexes and cytosine methylation greatly enhances the effect.

Previous spectroscopic studies demonstrated that the oligodeoxynucleotide d(CGC G3 GCG) undergoes a reversible cation-dependent transition between Watson-Crick (WC) hairpin and parallel-stranded "G-DNA" quadruplex structures [Hardin, C.C., Watson, T., Corregan, M., & Bailey, C. (1992) Biochemistry 31, 833-841]. The relative stabilities of the structures were assessed as a function of pH, and it was found that the quadruplex was substantially stabilized (delta Tm = +15 degrees C) when the pH was shifted from 7.5 to 6 (apparent pKa = 6.8). In the present study, the effects of different cations and pH on four specific sequence varients were determined to test the proposal that this stabilization is due to C.C+ base pair formation mediated by N3-protonation of cytosine. Characteristically large differences in stability were observed when structures formed by d(TAT G3 ATA) and d(TAT G4 ATA) were thermally dissociated at pH 7 in the presence of different cations, verifying that Gn tracts bordered by TAT- and -ATA sequences form quadruplex structures. Imino proton NMR results indicate that the d(m5C G m5C G3 G m5C G)4 and d(TAT G4 ATA)4 quadruplex structures are parallel-stranded. It was necessary to increase the K+ concentration from 40 mM to ca. 200 mM to stabilize d(TAT G3 ATA)4, while the d(TAT G4 ATA)4 complex was nearly as stable as the quadruplex formed by d(CGC G3 GCG) under the same conditions. The d(TAT G4 ATA)4 quadruplex was only slightly stabilized at pH 6 relative to pH 7.5 (delta Tm = +3 degrees C), confirming that the unique stabilization that occurs in the pH 6.8 range with [d(CGC Gn GCG)4.ionn] complexes is due to the C residues. The sequence d(m5C G m5C G3 G m5C G) was found to form a very stable quadruplex in K+ or Ca2+. As with the quadruplex formed by the unmethylated analog, the stability is greatly enhanced when the pH is decreased below about 7.2 (pKa,obs = 6.8). Dissociation kinetic constants and activation energies were determined for quadruplexes formed by d(CGC G3 GCG), d(m5C G m5C G3 G m5C G) and d(TAT G4 ATA). Quantitative comparisons showed that methylation produces a complex that is much more stable at pH 7 in 40 mM Na+ than either of the unmodified structures; the rate-limiting activation energy for dissociation of d(CGC G3 GCG)4 was 22 kcal mol-1 less than for the methylated analog.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Composition↗
PubMed2000

Contribution of salt bridges near the surface of a protein to the conformational stability.

Salt bridges play important roles in the conformational stability of proteins. However, the effect of a surface salt bridge on the stability remains controversial even today; some reports have shown little contribution of a surface salt bridge to stability, whereas others have shown a favorable contribution. In this study, to elucidate the net contribution of a surface salt bridge to the conformational stability of a protein, systematic mutant human lysozymes, containing one Glu to Gln (E7Q) and five Asp to Asn mutations (D18N, D49N, D67N, D102N, and D120N) at residues where a salt bridge is formed near the surface in the wild-type structure, were examined. The thermodynamic parameters for denaturation between pH 2.0 and 4.8 were determined by use of a differential scanning calorimeter, and the crystal structures were analyzed by X-ray crystallography. The denaturation Gibbs energy (DeltaG) of all mutant proteins was lower than that of the wild-type protein at pH 4, whereas there was little difference between them near pH 2. This is caused by the fact that the Glu and Asp residues are ionized at pH 4 but protonated at pH 2, indicating a favorable contribution of salt bridges to the wild-type structure at pH 4. Each contribution was not equivalent, but we found that the contributions correlate with the solvent inaccessibility of the salt bridges; the salt bridge contribution was small when 100% accessible, while it was about 9 kJ/mol if 100% inaccessible. This conclusion indicates how to reconcile a number of conflicting reports about role of surface salt bridges in protein stability. Furthermore, the effect of salts on surface salt bridges was also examined. In the presence of 0.2 M KCl, the stability at pH 4 decreased, and the differences in stability between the wild-type and mutant proteins were smaller than those in the absence of salts, indicating the compensation to the contribution of salt bridges with salts. Salt bridges with more than 50% accessibility did not contribute to the stability in the presence of 0.2 M KCl.

Amino Acid Substitution↗
PubMed1993

Engineering stability of the insulin monomer fold with application to structure-activity relationships.

To evaluate the possible relationship between biological activity and structural stability in selected regions of the insulin molecule, we have analyzed the guanidine hydrochloride induced reversible unfolding of a series of mutant insulins using a combination of near- and far-UV circular dichroism (CD). The unfolding curves are reasonably described on the basis of a two-state denaturation scheme; however, the observation of subtle differences between near- and far-UV CD detected unfolding indicates that intermediates may be present. Three regions of the insulin molecule are analyzed in detail with respect to their contribution to folding stability, i.e., the central B-chain helix, the NH2-terminal A-chain helix, and the B25-B30 extended chain region. Considerable enhancement of folding stability is engineered by mutations at the N-cap of the central B-chain helix and at the C-cap of the NH2-terminal A-chain helix. Mutations that confer increased stability in these regions are identical to those that lead to enhanced biological activity. In contrast, for insulin species modified in the B25-B30 region of the molecule, we observe no correlation between global folding stability and bioactivity. Mutations in the three regions examined are found to affect stability in a nearly independent fashion, and stabilizing mutations are generally found to enhance the cooperativity of the unfolding transition. We conclude that highly potent insulins (i.e., HisA8, ArgA8, GluB10, and AspB10) elicit enhanced activity because these mutations stabilize structural motifs of critical importance for receptor recognition.

Amino Acid Sequence↗
PubMed2002

N-terminus of the photosystem II manganese stabilizing protein: effects of sequence elongation and truncation.

The importance of the N-terminal domain of manganese stabilizing protein in binding to photosystem II has been previously demonstrated [Eaton-Rye and Murata (1989) Biochim. Biophys. Acta 977, 219-226; Odom and Bricker (1992) Biochemistry 31, 5616-5620]. In this paper, we report results from a systematic study of functional and structural consequences of N-terminal elongation and truncation of manganese stabilizing protein. Precursor manganese stabilizing protein is the unprocessed wild-type protein, which carries an N-terminal extension of 84 amino acids in the form of its chloroplastic signal peptide. Despite its increased size, this protein is able to reconstitute O(2) evolution activity to levels observed with the mature, processed protein, but it also binds nonspecifically to PSII. Truncation of wild-type manganese stabilizing protein by site-directed mutagenesis to remove three N-terminal amino acids, resulting in a mutant called DeltaG3M, causes no loss of activity reconstitution, but this protein also exhibits nonspecific binding. Further truncation of the wild-type protein by ten N-terminal amino acids, producing DeltaE10M, limits binding of manganese stabilizing protein to 1 mol/mol of photosystem II and decreases activity reconstitution to about 65% of that obtained with the wild-type protein. Because two copies of wild type normally bind to photosystem II, amino acids in the domain (4)K-(10)E must be involved in the binding of one copy of manganese stabilizing protein to photosystem II. Spectroscopic analysis (CD and UV spectra) reveals that N-terminal elongation and deletion of manganese stabilizing protein influence its overall conformation, even though secondary structure content is not perturbed. Our data suggest that the solution structure of manganese stabilizing protein attains a more compact solution structure upon removal of N-terminal amino acids.

Amino Acid Sequence↗
PubMed2004

Inverse electrostatic effect: electrostatic repulsion in the unfolded state stabilizes a leucine zipper.

The pH-dependent stability of a protein is strongly affected by electrostatic interactions between ionizable residues in the folded as well as unfolded state. Here we characterize the individual contributions of charged Glu and His residues to stability and determine the NMR structure of the designed, heterodimeric leucine zipper AB consisting of an acidic A chain and a basic B chain. Thermodynamic parameters are compared with those of the homologous leucine zipper AB(SS) in which the A and B chains are disulfide-linked. NMR structures of AB based on (1)H NMR data collected at 600 MHz converge, and formation of the same six interchain salt bridges found previously in disulfide-linked AB(SS) [Marti, D. N., and Bosshard, H. R. (2003) J. Mol. Biol. 330, 621-637] is indicated. While the structures of AB and AB(SS) are very similar, their pH-dependent relative stabilities are strikingly different. The stability of AB peaks at pH approximately 4.5 and is higher at pH 8 than at pH 2. In contrast, AB(SS) is most stable at acidic pH where no interhelical salt bridges are formed. The different energetic contributions of charged Glu and His residues to stability of the two coiled coil structures were evaluated from pK(a) shifts induced by folding. The six charged Glu residues involved in salt bridges stabilize leucine zipper AB by 4.5 kJ/mol yet destabilize disulfide-linked AB(SS) by -1.1 kJ/mol. Two non-ion-paired Glu charges destabilize AB by only -1.8 kJ/mol but AB(SS) by -5.6 kJ/mol. The higher relative stability of AB at neutral pH is not caused by more favorable electrostatic interactions in the folded leucine zipper. It is due mainly to unfavorable electrostatic interactions in the unfolded A and B chains and may therefore be called an inverse electrostatic effect. This study illustrates the importance of residual interactions in the unfolded state and how the energetics of the unfolded state affect the stability of the folded protein.

Amino Acid Sequence↗
PubMed2006

Mechanism of presynaptic filament stabilization by the bacteriophage T4 UvsY recombination mediator protein.

UvsY is the recombination mediator protein (RMP) of bacteriophage T4, which promotes homologous recombination by facilitating presynaptic filament assembly. The results of previous studies suggest that UvsY promotes the assembly of presynaptic filaments in part by stabilizing interactions between T4 UvsX recombinase and single-stranded DNA (ssDNA). To test this hypothesis, we studied the interactions of UvsX and UvsY with a fluorescein-derivatized oligonucleotide. This assay distinguishes between bipartite UvsX- or UvsY-ssDNA and tripartite UvsX-UvsY-ssDNA complex formation via differential fluorescence quenching effects. Salt stabilities of the three complexes were measured at equilibrium in the presence and absence of various nucleotide ligands of the UvsX protein and also under steady-state conditions for UvsX-catalyzed ssDNA-dependent ATP hydrolysis. The results demonstrate that UvsY globally stabilizes UvsX-ssDNA complexes, consistent with an increase in the apparent equilibrium binding affinity, K(ss)omega, of the UvsX-ssDNA interactions. The UvsY-mediated affinity increase is observed at equilibrium in the presence of ADP, ATPgammaS, or in the absence of the nucleotide and also at steady-state in the presence of ATP. Intriguingly, the stabilizing effects of UvsY and ATPgammaS on UvsX-ssDNA interactions are synergistic, indicating nonredundant mechanisms for UvsX-ssDNA complex stabilization by RMP versus nucleoside triphosphate effectors. Experiments with UvsY missense mutants defective in ssDNA binding demonstrate that UvsY-ssDNA interactions are of major importance in stabilizing UvsX-ssDNA complexes, whereas UvsY-UvsX protein-protein interactions provide residual stabilization energy. Together, the data is consistent with a mechanism in which UvsY stabilizes presynaptic filaments by organizing the ssDNA lattice into a structure that is favorable for UvsX-ssDNA interactions.

Adenine Nucleotides↗
PubMed1999

Selectivity of polyamines on the stability of RNA-DNA hybrids containing phosphodiester and phosphorothioate oligodeoxyribonucleotides.

RNA-DNA hybrid stabilization is an important factor in the efficacy of oligonucleotide-based antisense gene therapy. We studied the ability of natural polyamines, putrescine, spermidine, and spermine, and a series of their structural analogues to stabilize RNA-DNA hybrids using melting temperature (Tm) measurements, circular dichroism (CD) spectroscopy, and the ethidium bromide (EB) displacement assay. Phosphodiester (PO) and phosphorothioate (PS) oligodeoxyribonucleotides (ODNs) (21-mer) targeted to the initiation codon region of c-myc mRNA and the corresponding complementary RNA oligomer were used for this study. In the absence of polyamines, the Tm values of RNA-PODNA and RNA-PSDNA helices were 41 +/- 1 and 35 +/- 1 degrees C, respectively, in 10 mM sodium cacodylate buffer. In the presence of a hexamine analogue of spermine at a concentration of 25 microM, the hybrids were stabilized with Tm values of 80 and 78 degrees C, for RNA-PODNA and RNA-PSDNA, respectively. The d(Tm)/d(log[polyamine]) values, representing the concentration-dependent stabilization of hybrid helices by polyamines, increased from 10 to 24 for both the RNA-PODNA and RNA-PSDNA helices. Bisethyl substitution of the primary amino groups of the polyamines reduced the hybrid stabilizing potential of the polyamines. Among the homologues of spermidine [H2N(CH2)3NH(CH2)nNH2, where n = 2-8; n = 4 for spermidine] and spermine [H)N(CH2)3NH(CH2)nNH(CH2)3NH2, where n = 2-8; n = 4 for spermine], spermidine and spermine were the most effective agents for stabilizing the hybrid helices. At a physiologically compatible concentration of 150 mM NaCl, the hybrid helix formed from PODNA was more stable than that formed from PSDNA in the presence of polyamines. CD spectroscopic studies showed that the hybrids were stabilized in a conformation close to A-DNA in the presence of polyamines. The relative binding affinity of the polyamine homologues for the hybrid helices, as measured by the EB displacement assay, followed the same order in which they stabilized the hybrids. These results are important in the antisense context and in the general context of polyamine-nucleic acid interactions, and suggest that pentamine and hexamine analogues of spermine might be useful in improving the efficacy of therapeutic ODNs.

Binding, Competitive↗
PubMed2000

Thermodynamic analysis of cavity creating mutations in an engineered leucine zipper and energetics of glycerol-induced coiled coil stabilization.

Protein stability in vitro can be influenced either by introduction of mutations or by changes in the chemical composition of the solvent. Recently, we have characterized the thermodynamic stability and the rate of folding of the engineered dimeric leucine zipper A(2), which has a strengthened hydrophobic core [Dürr, E., Jelesarov, I., and Bosshard, H. R. (1999) Biochemistry 38, 870-880]. Here we report on the energetic consequences of a cavity introduced by Leu/Ala substitution at the tightly packed dimeric interface and how addition of 30% glycerol affects the folding thermodynamics of A(2) and the cavity mutants. Folding could be described by a two-state transition from two unfolded monomers to a coiled coil dimer. Removal of six methylene groups by Leu/Ala substitutions destabilized the dimeric coiled coil by 25 kJ mol(-1) at pH 3.5 and 25 degrees C in aqueous buffer. Destabilization was purely entropic at around room temperature and became increasingly enthalpic at elevated temperatures. Mutations were accompanied by a decrease of the unfolding heat capacity by 0.5 kJ K(-1) mol(-1). Addition of 30% glycerol increased the free energy of folding of A(2) and the cavity mutants by 5-10 kJ mol(-1) and lowered the unfolding heat capacity by 25% for A(2) and by 50% for the Leu/Ala mutants. The origin of the stabilizing effect of glycerol varied with temperature. Stabilization of the parent leucine zipper A(2) was enthalpic with an unfavorable entropic component between 0 and 100 degrees C. In the case of cavity mutants, glycerol induced enthalpic stabilization below 50 degrees C and entropic stabilization above 50 degrees C. The effect of glycerol could not be accounted for solely by the enthalpy and entropy of transfer or protein surface from water to glycerol/water mixture. We propose that in the presence of glycerol the folded coiled coil dimer is better packed and displays less intramolecular fluctuations, leading to enhanced enthalpic interactions and to an increase of the entropy of folding. This work demonstrates that mutational and solvent effects on protein stability can be thermodynamically complex and that it may not be sufficient to only analyze changes of enthalpy and entropy at the unfolding temperature (T(m)) to understand the mechanisms of protein stabilization.

Acids↗
PubMed2005

Effects of substituents on the stability of phosphoranyl radicals.

The effect of substituents on the geometries, apicophilicities, radical stabilization energies, and bond dissociation energies of (*)P(CH(3))(3)X (X = CH(3), SCH(3), OCH(3), OH, CN, CF(3), Ph) were studied via high-level ab initio molecular orbital calculations. Two alternative definitions for the radical stabilization energy (RSE) were considered: the standard RSE, in which radical stability is measured relative to H-P(CH(3))(3)X, and a new definition, the alpha-RSE, which measures stability relative to P(CH(3))(2)X. We show that these alternative definitions yield almost diametrically opposed trends; we argue that alpha-RSE provides a reasonable qualitative measure of relative radical stability, while the standard RSE qualitatively reflects the relative strength of the P-H bonds in the corresponding H-P(CH(3))(3)X phosphines. The (*)P(CH(3))(3)X radicals assume a trigonal-bipyramidal structure, with the X-group occupying an axial position, and the unpaired electron distributed between a 3p(sigma)-type orbital (that occupies the position of the "fifth ligand"), and the sigma orbitals of the axial bonds. Consistent with this picture, the radical is stabilized by resonance (along the axial bonds) with configurations such as X(-) P(*+)(CH(3))(3) and X(*) P(CH(3))(3). As a result, substituents that are strong sigma-acceptors (such as F, OH, or OCH(3)) or have weak P-X bonds (such as SCH(3)) stabilize these configurations, resulting in the largest apicophilicities and alpha-RSEs. Unsaturated pi-acceptor substituents (such as phenyl or CN) are weakly stabilizing and interact with the 3p(sigma)-type orbital via a through-space effect. As part of this work, we challenge the notion that phosphorus-centered radicals are more stable than carbon-centered radicals.

Free Radicals↗
PubMed2003

Causes of stability of aggression from early childhood to adolescence: a longitudinal genetic analysis in Dutch twins.

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.

Aggression↗
PubMed1997

mRNA stability is regulated by a coding-region element and the unique 5' untranslated leader sequences of the three Synechococcus psbA transcripts.

The psbAI and psbAIII transcripts in Synechococcus sp. strain PCC 7942 are subject to accelerated turnover when cells are exposed to high light intensities, but psbAII message stability is unaffected. We used a psbAI 'minigene' which has a part of the coding sequence removed as a reporter gene in order to identify the cis-acting elements of the transcript that determine stability. While engineering the minigene to optimally mimic the native gene, we identified a stabilizer element within the open reading frame, corresponding to the coding region for the first membrane span of the D1 protein, the presence of and translation through which was essential for normal psbA mRNA stability. We propose that this stabilizer is a site for ribosome pausing, and that accumulation of ribosomes on the transcript upstream of the pause site increases stability. To identify the elements that regulate the differential responses of the psbA transcripts to high-light growth, sequences from psbAII and psbAIII were substituted in the psbAI minigene reporter. The chimeric reporter transcripts established that the psbAI and psbAIII untranslated leaders determine the faster turnover of these messages. The untranslated leader regions of the psbA transcripts may regulate mRNA stability by modulating translation and thereby stability, or by recruiting RNA-binding proteins that affect mRNA turnover more directly.

Cyanobacteria↗
PubMed2002

Combined use of morphology discrimination, sudden onset, and stability as discriminating algorithms in single chamber cardioverter defibrillators.

Morphology Discrimination (MD) is a rhythm discriminator based on QRS morphology analysis that can be combined with other discriminators like Stability, with or without Sinus Interval History (SIH) and Sudden Onset. Thirty-five patients implanted with a St. Jude Medical single chamber ICD were evaluated during exercise testing, during induced AF, and during follow-up for 14 +/- 5 months. At exercise testing (60 episodes detected) MD had a specificity (SP) of 96.7% and Sudden Onset a SP of 91.7%; during induced AF (25 episodes) both MD and Stability had a SP of 96.0%. The diagnostic performance on spontaneous arrhythmias was as follows: for ventricular tachycardia (126 episodes) a sensitivity (SE) of 94.4% for MD, 92.1% for Sudden Onset, 89.7% for Stability without SIH and 79.4% for Stability + SIH; for sinus tachycardia (44 episodes) a SP of 86.4% for MD, 97.7% for Sudden Onset, 2.3% for Stability and of 95.5% for Stability + SIH. For AF (165 cases) a SP of 67.9% for MD, 69.1% for Stability and 90.3% for Stability + SIH, 44.8% for Sudden Onset. Use of MD alone provided a SE of 94.4% and a SP of 71.4% for spontaneous arrhythmias and combined use of the discriminators in a "2 of 3" diagnostic logic implied a SP of 90.9% with maintenance of 96.0% of SE. In single chamber ICDs a wide range of SE/SP ratios may be obtained by use of multiple discriminators, but use of the algorithm in a 2 of 3 diagnostic logic may achieve a SP of 90.9% and a SE of 96.0%.

Algorithms↗