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PubMed2004

A surgical stent for the Brånemark Novum bone reduction procedure.

BACKGROUND: The Brånemark Novum concept (Nobel Biocare AB, Göteborg, Sweden) was introduced to load implants immediately with a definitive fixed prosthesis in the edentulous mandible. This concept is based on the use of prefabricated templates to allow precise placement of three implants and a prefabricated bar structure for the prosthetic procedure. To obtain three-dimensional stability in these prefabricated templates, surgical bone reduction may be necessary to obtain a stable adaptation between the templates and the recipient bone site. PURPOSE: The aim of this work was to design a surgical stent for predictable reduction of the residual alveolar crest prior to the implant placement procedures. MATERIALS AND METHODS: A predetermined alveolar crest platform based essentially on a lateral cephalometric radiographic evaluation was simulated on a cast in order to design a transparent resin surgical guide. The predictability potential of the procedure was then evaluated in 10 patients. The prosthetic outcomes were compared with those of a similar group of 10 patients treated without the presented stent by evaluating two factors, namely, the anterior dimensions of the prostheses and the required posterior adjustments of the upper bar. RESULTS: Correlation analysis of our series suggested a good predictability potential for this procedure (r = 0.9215). The mean anterior prosthetic dimension was 32% lower and was more predictable (narrow range of 8-12 mm vs broad range of 8-21 mm) when the stent was used. Furthermore, since half as many posterior adjustments of the upper bar were required, the laboratory procedure was facilitated. CONCLUSION: This individualized guide allows appropriate bone reduction for obtaining a predictable surgery and prosthetic stage.

Adult↗
PubMed2003

Mechanism of growth reduction of the deceleration-phase ablative Rayleigh-Taylor instability.

The deceleration-phase (dp) ablative Rayleigh-Taylor instability (RTI) of igniting and nonigniting inertial fusion capsules is studied by high-resolution two-dimensional Lagrangian fluid simulations. It is found that growth reduction of the dp-RTI with respect to classical RTI results from the advection of perturbed fluid elements outside a thin unstable fluid layer. Within this layer, at fixed Lagrangian position, perturbations grow approximately classically.

Journal Article↗
PubMed1999

An electrochemical study of the factors responsible for modulating the reduction potential of putidaredoxin.

The gene coding for putidaredoxin has been synthesized using a combination of chemical and enzymatic methods and subsequently expressed in Escherichia coli. The recombinant protein characterized by electronic spectroscopy, mass spectrometry, and electrochemistry was found to be identical to putidaredoxin obtained from Pseudomonas putida. Polylysine was found to promote the fast and reversible electrochemistry of putidaredoxin at negatively charged electrodes such as indium-doped tin oxide or gold surfaces modified with mercaptoalkanoate groups. The value of the heterogeneous electron transfer rate constant obtained from solutions containing a mixture of putidaredoxin and polylysine (k(s) = 1.3 x 10(-3) cm/s) is one order of magnitude larger than the values reported previously at gold electrodes modified with mercaptoethylamine or at antimony-doped tin oxide semiconductor electrodes. It was observed that when the reduction potential of putidaredoxin is measured by cyclic voltammetry, the resultant value is consistently more positive (64 mV) than the reduction potential measured with potentiometric titrations. A comparison between the electrochemical responses of putidaredoxin and spinach ferredoxin, combined with the examination of their corresponding three-dimensional structures, indicates that the positive shift in the reduction potential of putidaredoxin originates from the formation of a transient complex between putidaredoxin and polylysine at the electrode surface. The formation of this transient complex modulates the reduction potential of putidaredoxin by lowering the value of the dielectric constant around its iron-sulfur cluster microenvironment, specifically by neutralizing negative charges surrounding the active site and by excluding water from the solvent exposed iron sulfur cluster. The observed positive shift in E degrees ', which is induced by complexation with polylysine at the electrode-surface, suggests that similar factors are likely to contribute to the anodic shift in the E degrees ' of cytochrome P450(cam)-bound putidaredoxin (+44 mV) with respect to the E degrees ' measured for free putidaredoxin.

Amino Acid Sequence↗
PubMed2005

Reduction of chemical reaction networks using quasi-integrals.

We present a numerical method to identify possible candidates for quasi-stationary manifolds in complex reaction networks governed by systems of ordinary differential equations. Inspired by singular perturbation theory, we examine the ratios of certain components of the reaction rate vector. Those ratios that rapidly approach a nearly constant value define a slow manifold for the original flow in terms of quasi-integrals, that is, functions that are nearly constant along the trajectories. The dimensionality of the original system is thus effectively reduced without reliance on a priori knowledge of the different time scales in the system. We also demonstrate the relation of our approach to singular perturbation theory which, in its simplest form, is just the well-known quasi-steady-state approximation. In two case studies, we apply our method to oscillatory chemical systems: the 6-dimensional hemin-hydrogen peroxide-sulfite pH oscillator and a 10-dimensional mechanistic model for the peroxidase-oxidase (PO) reaction system. We conjecture that the presented method is especially suited for a straightforward reduction of higher dimensional dynamical systems where analytical methods fail to identify the different time scales associated with the slow invariant manifolds present in the system.

Hemin↗
PubMed1989

Experimental evidence of an alpha helix in Desulfovibrio desulfuricans Norway ferredoxin I: a two-dimensional NMR study.

Desulfovibrio ferredoxins are small proteins involved in biological oxido-reduction reactions and contain either one or two (4Fe-4S) clusters. The conformation of D. desulfuricans Norway ferredoxin I in solution was studied by two-dimensional NMR and various conformational parameters (n.O.e. and J-coupling) indicate the presence of an alpha-helix involving residues 41 to 50. These data confirm an earlier proposal (Fukuyama et al, J. Mol. Biol. 199, 183 (1988] in which the space of the missing cluster in monocluster ferredoxins is occupied by an alpha-helix. The evolutionary relevance of this result is discussed in view of published sequences and structures of related ferredoxins.

Amino Acid Sequence↗
PubMed2006

The invariant constrained equilibrium edge preimage curve method for the dimension reduction of chemical kinetics.

This work addresses the construction and use of low-dimensional invariant manifolds to simplify complex chemical kinetics. Typically, chemical kinetic systems have a wide range of time scales. As a consequence, reaction trajectories rapidly approach a hierarchy of attracting manifolds of decreasing dimension in the full composition space. In previous research, several different methods have been proposed to identify these low-dimensional attracting manifolds. Here we propose a new method based on an invariant constrained equilibrium edge (ICE) manifold. This manifold (of dimension nr) is generated by the reaction trajectories emanating from its (nr-1)-dimensional edge, on which the composition is in a constrained equilibrium state. A reasonable choice of the nr represented variables (e.g., nr "major" species) ensures that there exists a unique point on the ICE manifold corresponding to each realizable value of the represented variables. The process of identifying this point is referred to as species reconstruction. A second contribution of this work is a local method of species reconstruction, called ICE-PIC, which is based on the ICE manifold and uses preimage curves (PICs). The ICE-PIC method is local in the sense that species reconstruction can be performed without generating the whole of the manifold (or a significant portion thereof). The ICE-PIC method is the first approach that locally determines points on a low-dimensional invariant manifold, and its application to high-dimensional chemical systems is straightforward. The "inputs" to the method are the detailed kinetic mechanism and the chosen reduced representation (e.g., some major species). The ICE-PIC method is illustrated and demonstrated using an idealized H2O system with six chemical species. It is then tested and compared to three other dimension-reduction methods for the test case of a one-dimensional premixed laminar flame of stoichiometric hydrogen/air, which is described by a detailed mechanism containing nine species and 21 reactions. It is shown that the error incurred by the ICE-PIC method with four represented species is small across the whole flame, even in the low temperature region.

Journal Article↗
PubMed2001

Redox changes accompanying the degradation of seed storage proteins in germinating rice.

The mobilization of storage proteins (glutelins) in germinating rice seeds was accompanied by an ordered sequential combination of proteolysis and reduction of disulfide groups. Mobilization was followed by application of non-reducing/reducing two dimensional-PAGE after monobromobimane labeling of the sulfhydryl groups of the proteins in intact seeds.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1994

Spiral CT-angiography of the aorta.

AIMS: To determine whether the new technique of CT-angiography was accurate in displaying the complex anatomy of the aorta and its major branches. METHODS: Seventeen patients with a variety of aortic pathology were examined. Using a spiral CT-scanner a volumetric scan was made during injection of 150 cc of i.v. contrast. Depending on the chosen CT technique, a body volume with a length ranging between 25-100 cm could be examined in one 50 second spiral scan. On the resulting transverse slices vascular lumina and extent of thrombus were studied. Subsequently, the transverse slices were reconstructed in the coronal or sagittal plane in order to appreciate the craniocaudal relations of the vascular anatomy. Finally, three-dimensional reconstructions were made of vascular lumina and thrombus. RESULTS: In aortic aneurysms the extent of the aneurysmal dilatation and of the adherent thrombus could be accurately located relative to the origins of renal and visceral branches proximally, and iliac bifurcation distally. In cases of severe elongation, dissection or complex anatomy, a detailed preoperative insight into the individual anatomy could be obtained. The two-dimensional axial and multiplanar reconstructions offered excellent anatomic detail. The three-dimensional reconstructions, being based on a considerable data reduction, offered an efficient means of providing an overall view of complex anatomic relations. CONCLUSION: The advantage of CT-angiography is that, based on a single spiral scan, the vascular structures in the examined body volume can be displayed in any desired plane using multiplanar reconstructions. Alternatively, three-dimensional renderings can be created. The combination of multiplanar reconstructions and three-dimensional reconstructions makes CT-angiography an accurate technique for displaying even the most complex aortic anatomy.

Aortic Dissection↗
PubMed2005

Computer-aided detection of lung nodules: false positive reduction using a 3D gradient field method and 3D ellipsoid fitting.

We are developing a computer-aided detection system to assist radiologists in the detection of lung nodules on thoracic computed tomography (CT) images. The purpose of this study was to improve the false-positive (FP) reduction stage of our algorithm by developing features that extract three-dimensional (3D) shape information from volumes of interest identified in the prescreening stage. We formulated 3D gradient field descriptors, and derived 19 gradient field features from their statistics. Six ellipsoid features were obtained by computing the lengths and the length ratios of the principal axes of an ellipsoid fitted to a segmented object. Both the gradient field features and the ellipsoid features were designed to distinguish spherical objects such as lung nodules from elongated objects such as vessels. The FP reduction performance in this new 25-dimensional feature space was compared to the performance in a 19-dimensional space that consisted of features extracted using previously developed methods. The performance in the 44-dimensional combined feature space was also evaluated. Linear discriminant analysis with stepwise feature selection was used for classification. The parameters used for feature selection were optimized using the simplex algorithm. Training and testing were performed using a leave-one-patient-out scheme. The FP reduction performances in different feature spaces were evaluated by using the area Az under the receiver operating characteristic curve and the number of FPs per CT section at a given sensitivity as accuracy measures. Our data set consisted of 82 CT scans (3551 axial sections) from 56 patients with section thickness ranging from 1.0 to 2.5 mm. Our prescreening algorithm detected 111 of the 116 solid nodules (nodule size: 3.0-30.6 mm) marked by experienced thoracic radiologists. The test Az values were 0.95 +/- 0.01, 0.88 +/- 0.02, and 0.94 +/- 0.01 in the new, previous, and combined feature spaces, respectively. The number of FPs per section at 80% sensitivity in these three feature spaces were 0.37, 1.61, and 0.34, respectively. The improvement in the test Az with the 25 new features was statistically significant (p<0.0001) compared to that with the previous 19 features alone.

Algorithms↗
PubMed2003

Variable-density spiral 3D tailored RF pulses.

A variable-density spiral method is presented for reducing three-dimensional tailored radiofrequency pulse duration. Pulse length reductions of 21-32% are possible, with only a small error in the desired excitation profile. The method is demonstrated using simulations, phantom experiments, and T(2)*-weighted images of brain regions with susceptibility-induced intravoxel dephasing. Four 19.7-ms shots were needed to excite a 5-mm-thick slice with reduced susceptibility artifacts in the sinus region at 3T.

Artifacts↗
PubMed1991

Schistosoma mansoni: influence of infection on levels of translatable mRNA and on polypeptide synthesis in the ovotestis and albumen gland of Biomphalaria glabrata.

Larval trematode infection causes a disruption of normal reproductive activity in the molluscan intermediate host. Because relatively little is known about the dynamics of this host-parasite interaction, the effect of Schistosoma mansoni infection on translatable mRNA pools and on polypeptide synthesis was examined in the ovotestis (OT) and albumen gland (AG) of Biomphalaria glabrata. Total RNA was isolated from OTs and AGs from uninfected control snails and snails at 14, 21, and 28 days postinfection (pi) with 20 S. mansoni miracidia and subjected to a rabbit reticulocyte in vitro translation system. Quantitative densitometry of autofluorograms of one-dimensional SDS-PAGE slab gels revealed reductions in quantities of total proteins synthesized in vitro from RNA isolated from infected OTs at 21 and 28 days pi, but not at Day 14 pi. Similar reductions were seen in 10 individual polypeptides selected for a more detailed analysis. In contrast to the OT, Day 14 pi-infected AGs exhibited an initial increase in total protein synthesized in the in vitro translation system utilized, followed by significant reductions at 21 and 28 days pi. Selective modulation of labeled polypeptides was evident in 11 polypeptides chosen for a more detailed analysis. This general pattern of parasite inhibitory effects was also seen in parallel pulse-chase studies using [35S]methionine metabolic labeling of in vitro-cultured OTs and AGs. In these experiments, significant reductions in the amounts of labeled polypeptides found in culture supernatants at 14, 21, and 28 days pi were evident. Total polypeptide synthesis also was solubilized AGs from infected snails at 21 and 28 days pi. Results indicate that larval trematode infection induced a generalized disruption of polypeptide metabolism in OTs and AGs of B. glabrata. Such inhibition may occur at both the transcriptional and the translational levels and is initially manifested early in infection, during the time that daughter sporocysts begin to migrate and colonize the digestive gland and OT.

Animals↗
PubMed1986

Cellular protein differences between nontumorigenic Ad5 and tumorigenic Ad12 transformed mouse cells.

Murine fibroblasts transformed by adenovirus 12 (Ad12) show reduced class I major histocompatibility complex (MHC) antigen synthesis and form tumors in syngeneic mice whereas those transformed by adenovirus 5 (Ad5) show no alteration in class I antigen synthesis and do not form tumors (K. B. Eager, J. Williams, D. Breiding, S. Pan, B. Knowles, E. Appella, and R. P. Ricciardi (1985) Proc. Natl. Acad. Sci. USA 82, 5525-5529). Nearly 1500 metabolically labeled polypeptides from the Ad5 and Ad12 transformed cell lines as well as polypeptides from a nontransformed murine line of the same haplotype were compared by two-dimensional gel electrophoresis. In addition to the reduction of the class I H-2 transplantation antigens seen in the Ad12-transformed lines, we detect few but reproducible polypeptide differences between the tumorigenic and nontumorigenic cell lines.

Adenoviridae↗
PubMed1990

Contribution of centrifugal innervation to choline acetyltransferase activity in the cat cochlear nucleus.

Using a quantitative microchemical mapping approach combined with surgical cuts of fiber tracts, the contributions of centrifugal pathways to choline acetyltransferase activity were mapped three-dimensionally in the cat cochlear nucleus. Large reductions of choline acetyltransferase activity, averaging 70%, were measured in almost all parts of the lesion-side nucleus following transection of virtually all its centrifugal connections. More superficial cuts, penetrating just through the olivocochlear bundle, also led to significant reductions of enzyme activity, especially most rostrally in the anteroventral cochlear nucleus and superficial granular region, where the reductions were similar to those following the complete cuts. Lesions encroaching upon the superior olivary complex gave bilateral effects. Transverse cuts between rostral and caudal parts of the cochlear nucleus gave some small effects. The results suggest that, as in rats, most choline acetyltransferase activity in the cat cochlear nucleus is associated with its centrifugal innervation. However, unlike the situation in rats, the enzyme activity in cats is related more to olivocochlear branches than to ventral fibers in the trapezoid body region. Also, the choline acetyltransferase activity related to olivocochlear collateral innervation is much less uniformly distributed within the cochlear nucleus in cats than in rats.

Animals↗
PubMed2005

Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy.

PURPOSE: To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. RESULTS: Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. CONCLUSIONS: Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity.

Adult↗
PubMed1999

Anxiogenic-like effects and reduced stereological counting of immunolabelled 5-hydroxytryptamine6 receptors in rat nucleus accumbens by antisense oligonucleotides.

The physiological role of 5-hydroxytryptamine6 receptors in the central nervous system has not yet been elucidated. The high affinity of various psychotropic drugs for 5-hydroxytryptamine6 receptors has led to the suggestion that this receptor type may be a novel target in neuropsychiatry. We have found that continuous intracerebroventricular administration of a 5-hydroxytryptamine6 receptor antisense oligonucleotide, but not of a missense oligonucleotide, produced an anxiogenic-like response in rats using two different models of anxiety, the social interaction test and the elevated plus-maze. Neither oligonucleotide treatment modified locomotor activity, rectal temperature or food intake, suggesting a low or null neurotoxicity. The effectiveness of the treatment with the designed antisense oligonucleotide to block the synthesis of the protein encoded by the target mRNA was assessed by immunolabelling 5-hydroxytryptamine6 receptors in the nucleus accumbens, where this receptor is highly expressed, using previously characterized specific antibodies. The density of the immunostaining was quantified by means of an unbiased three-dimensional stereologic procedure, which revealed a significant reduction (-25%) in the number of immunolabelled neuronal elements. These results suggest that, in addition to other 5-hydroxytryptamine receptor subtypes, 5-hydroxytryptamine6 receptors in the nucleus accumbens may participate in anxiety-related neurobiological mechanisms.

Animals↗
PubMed2003

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies.

The alpha-folate receptor (FR) is selectively overexpressed in 90% of nonmucinous ovarian carcinomas, whereas no expression is detectable in normal ovarian surface epithelium (OSE). Indirect evidence suggests that FR expression is associated with tumor progression and affects cell proliferation. To evaluate better the role of FR, we developed an approach based on intracellular expression of single-chain (sc) antibodies (intrabody) to downmodulate membrane expression of FR in ovary cancer cells. IGROV-1 and SKOV3 ovarian carcinoma cell lines were transfected with an anti-FR intrabody. Transfectants and parental cells were tested for FR, integrins and anti-FR intrabody expression by fluorescence-activated cell sorting (FACS), reverse transcription and polymerase chain reaction (RT-PCR) and/or immunoblotting. Cell growth characteristics and adhesion properties were evaluated in liquid, semisolid and organotypic cultures. The anti-FR scFv inhibited FR expression from 60 to 99%. At physiological concentrations of folate, proliferation varied directly as a function of FR expression. FR downmodulation was accompanied by reduced colony-forming ability in soft agar, morphological change of the cells, significant enhanced adhesion to laminin or Matrigel, a two- to three-fold increase in alpha6beta4 integrin expression, and a marked reduction in laminin production. In three-dimensional organotypic cultures, anti-FR intrabody-transfected IGROV1 cells grew as a single-ordered layer, reminiscent of normal OSE growth in vivo. In conclusion, the anti-FR intrabody reverses the transformed phenotype in ovary cancer cells and may provide an efficient means to inhibit selectively the growth of these cells.

Antibodies, Monoclonal↗
PubMed1999

Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen.

Dermatopontin is a recently discovered extracellular matrix protein with proteoglycan and cell-binding properties and is assumed to play important roles in cell-matrix interactions and matrix assembly. In this study we examined the expression of dermatopontin mRNA and protein in skin fibroblast cultures from patients with hypertrophic scar and patients with systemic sclerosis. Dermatopontin mRNA and protein levels were reduced in fibroblast cultures from hypertrophic scar lesional skin compared with fibroblasts from normal skin of the same hypertrophic scar patient. Fibroblast cultures from systemic sclerosis patient involved skin also showed significantly reduced expression of dermatopontin compared with normal skin fibroblasts from healthy individuals. We also investigated the effects of cytokines and matrix collagen on dermatopontin expression in normal cultured fibroblasts. Transforming growth factor-beta1 increased dermatopontin mRNA and protein levels, while interleukin-4 reduced dermatopontin expression. Substrate coated with type I collagen reduced dermatopontin mRNA levels, the reduction being more prominent in three-dimensional collagen matrices. Our results suggest that the decreased expression of dermatopontin is associated with the pathogenesis of fibrosis in hypertrophic scar and systemic sclerosis, and that the effect of the cytokines and matrix collagen on dermatopontin may have important implications for skin fibrosis.

Adolescent↗
PubMed2001

Two active site asparagines are essential for the reaction mechanism of the class III anaerobic ribonucleotide reductase from bacteriophage T4.

Class III ribonucleotide reductase is an anaerobic enzyme that uses a glycyl radical to catalyze the reduction of ribonucleotides to deoxyribonucleotides and formate as ultimate reductant. The reaction mechanism of class III ribonucleotide reductases requires two cysteines within the active site, Cys-79 and Cys-290 in bacteriophage T4 NrdD numbering. Cys-290 is believed to form a transient thiyl radical that initiates the reaction with substrate and Cys-79 to take part as a transient thiyl radical in later steps of the reductive reaction. The recently solved three-dimensional structure of class III ribonucleotide reductase (RNR) from bacteriophage T4 shows that two highly conserved asparagines, Asn-78 and Asn-311, are positioned close to the essential Cys-79. We have investigated the function of Asn-78 and Asn-311 by site-directed mutagenesis and measured enzyme activity and glycyl radical formation in five single (N78(A/C/D) and N311(A/C)) and one double (N78A/N311A) mutant proteins. Our results suggest that both asparagines are important for the catalytic mechanism of class III RNR and that one asparagine can partially compensate for the lack of the other functional group in the single Asn --> Ala mutant proteins. A plausible role for these two asparagines could be in positioning formate in the active site to orient it toward the proposed thiyl radical of Cys-79. This would also control the highly reactive carbon dioxide radical anion form of formate within the active site before it is released as carbon dioxide. A detailed reaction scheme including the function of the two asparagines and two formate molecules is proposed for class III RNRs.

Amino Acid Sequence↗