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Isoforms of murine and human serum amyloid P component.

Isoelectric focusing (IEF) and immunofixation of murine serum amyloid P component (SAP), purified and in serum, showed a distinct and strain-dependent isoform pattern with up to seven bands (pI 5.1-5.7). Neuraminidase treatment caused a shift of the isoforms to more basic pI values, but did not affect their number. When the acute-phase response was analysed in three mouse strains, CBA/J and C3H/HeN initially showed seven SAP isoforms in serum and C57BL/6 J three or four. The responses in all three strains peaked at day 2 and were normalized within 14 days. On days 2 and 4, CBA/J and C3H/HeN mice showed one more acidic isoform and an increase in the concentration of the most basic isoform. C57BL/6 J mice exhibited two to three new isoforms during the acute-phase response. This appears to be the first demonstration of the physiological existence of SAP isoforms. In contrast, demonstration of isoforms of human SAP required the presence of urea and higher SAP concentrations. TEF and immunofixation of SAP monomers showed five to eight isoforms, ranging from pI 4.7-5.7. IEF of SAP in human serum resulted in a less distinct pattern and more acidic isoforms. As with murine SAP, neuraminidase treatment caused a shift of the isoforms, but no reduction in isoform number. Two-dimensional gel electrophoresis confirmed the existence of multiple isoforms of human SAP monomers.

Animals↗

Investigation of the dynamics of two coupled oscillators with mixed quantum-classical methods.

The dynamics of two coupled oscillators can become quite complex if anharmonic potential energy functions are employed. This type of system therefore represents a good model for an investigation of the performance of mixed quantum-classical methods. In this work, the motion of two coupled particles with a mass ratio of one to ten is studied with three different mixed quantum-classical methods in the presence of anharmonic potential terms for a comparison with exact quantum mechanical calculations. The mixed quantum-classical approaches include the multitrajectory Ehrenfest, the mixed quantum-classical Bohmian (MQCB), and the so-called coupled Schrödinger equations (CSE) formalisms. The analysis shows that while the description of a weakly anharmonic system by the Ehrenfest and MQCB schemes is accurate if proper sampling techniques are applied, both approximations break down rapidly if the anharmonic terms are increased. The performance of the simple CSE prescription, which corresponds to a reduction of the full two-dimensional wave function to two one-dimensional wave functions representing two quantum oscillators coupled via the potential energy in a classical fashion, decreases if the width of the initial wave packet is enlarged. The dependence of the CSE method on the diffuseness of the initial wave packet is therefore opposite to that of the MQCB method, which is more accurate for wide wave packets. Overall, the multitrajectory Ehrenfest ansatz is found to be most successful in reproducing the exact quantum results.

Algorithms↗

Integrity of mitochondria in a mammalian cell mutant defective in mitochondrial protein synthesis.

A defect in mitochondrial protein synthesis has previously been identified in the respiration-deficient Chinese hamster lung fibroblast mutant V79-G7. The present work extends the characterization of this mutant. A more sensitive analysis has shown that mutant mitochondria synthesize all mitochondrially encoded peptides, but in significantly reduced amounts. This difference is also seen when isolated mitochondria are tested for in vitro protein synthesis. To distinguish between a defect in the translational machinery and a defect in the transcription of mitochondrial DNA, we investigated the synthesis of the 16S and 12S mitochondrial rRNA species and found them to be made in normal amounts in G7 mitochondria. These rRNA species appear to be assembled into subunits whose sedimentation behavior is virtually indistinguishable from that of the wild-type subunits. We also examined the consequences of the defect in mitochondrial protein synthesis on mutant cells and their mitochondria-utilizing techniques of electron microscopy, two-dimensional gel electrophoresis and immunochemical analysis. G7 mitochondria have a characteristic ultrastructure distinguished by predominantly tubular cristae, but the overall biochemical composition of mitochondrial membrane and matrix fractions appears essentially unaltered except for the absence of a few characteristic peptides. Specifically, we identify the absence of two mitochondrially encoded subunits of cytochrome c oxidase on two-dimensional gels and demonstrate a drastic reduction of both cytoplasmically and mitochondrially synthesized subunits of enzyme in immunoprecipitates of G7 mitochondria.

Animals↗

Nucleation and growth on a superhydrophobic grooved surface.

The growth dynamics of water drops condensed on a superhydrophobic geometrically patterned surface were studied. Drop size evolution at early and intermediate times is self-similar. Drop growth laws do not differ for a flat surface because of a reduction of both drop and substrate dimensionality. A striking observation is the instantaneous drying of the top surface of grooves at a point in time due to coalescence of the drops with a completely filled channel. At late times, only a few large drops grow connected to the channels, in a mixed Wenzel-penetration regime.

Journal Article↗

Reduced complexity rotation invariant texture classification using a blind deconvolution approach.

In this paper, we present a texture classification procedure that makes use of a blind deconvolution approach. Specifically, the texture is modeled as the output of a linear system driven by a binary excitation. We show that features computed from one-dimensional slices extracted from the two-dimensional autocorrelation function (ACF) of the binary excitation allows representing the texture for rotation-invariant classification purposes. The two-dimensional classification problem is thus reconduced to a more simple one-dimensional one, which leads to a significant reduction of the classification procedure computational complexity.

Algorithms↗

Modeling of finite-amplitude sound beams: second order fields generated by a parametric loudspeaker.

The nonlinear interaction of sound waves in air has been applied to sound reproduction for audio applications. A directional audible sound can be generated by amplitude-modulating the ultrasound carrier with an audio signal, then transmitting it from a parametric loudspeaker. This brings the need of a computationally efficient model to describe the propagation of finite-amplitude sound beams for the system design and optimization. A quasilinear analytical solution capable of fast numerical evaluation is presented for the second-order fields of the sum-, difference-frequency and second harmonic components. It is based on a virtual-complex-source approach, wherein the source field is treated as an aggregation of a set of complex virtual sources located in complex distance, then the corresponding fundamental sound field is reduced to the computation of sums of simple functions by exploiting the integrability of Gaussian functions. By this result, the five-dimensional integral expressions for the second-order sound fields are simplified to one-dimensional integrals. Furthermore, a substantial analytical reduction to sums of single integrals also is derived for an arbitrary source distribution when the basis functions are expressible as a sum of products of trigonometric functions. The validity of the proposed method is confirmed by a comparison of numerical results with experimental data previously published for the rectangular ultrasonic transducer.

Acoustics↗

Destructiveness, atrocities and healing: epistemological and clinical reflections.

In this paper, destructiveness is approached as a multi-dimensional phenomenon where the mental health perspective addresses only one of these dimensions. An attempt is made to locate this phenomenon in the context of epistemological and societal considerations. Critical of mono-dimensional explanations based on causal-reductive epistemology, the paper instead proposes the idea of an 'ecology of destructiveness', according to which mental health professionals cannot possibly continue to assume the role of detached observers. The ordinariness and archetypal fascination of destructiveness are discussed as preventing the psychologizing and pathologizing of it. In addition, it is suggested that 'destructiveness may be a tragic facet of the human condition', without this implying any justification of it. Based on my work with a group of Bosnian ex-camp prisoners, some basic principles of how one can work with survivors of atrocities are derived and discussed. A central feature of this work is the attempt to create an appropriate therapeutic context within which a 'therapeutic presence' and 'therapeutic witnessing' can be developed. Finally, the relevance of Jungian insights to this kind of work is reviewed and the emergence of new types of defences of the self is identified.

Humans↗

Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism.

OBJECTIVE: To screen cDNA for NLGN3 and NLGN4 from lymphoblastoid cells from autistic subjects. METHODS AND RESULTS: 10 young autistic females and 30 non-autistic subjects were studied for alterations in two X linked genes, NLGN3 and NLGN4. A novel NLGN4 isoform lacking exon 4, which occurred de novo on the paternal allele, was identified in one of the autistic females. Monoallelic expression of NLGN4 was seen in this subject and in 11 of 14 informative autistic and non-autistic females using a single nucleotide polymorphism found at 3' UTR. Additionally, the NLGN3 transcript was present in two isoforms (with and without exon 7) in nine of 10 autistic females and in 30 non-autistic subjects, including parents of the autistic female having only the complete transcript with exon 7, and from the whole brain of a control. The novel truncated NLGN3 product may have a regulatory role, as reported in other proteins (for example, vasopressin receptor) by attenuating the function of the full length isoform, resulting in a reduction of the mature protein. Three dimensional protein structures were characterised using comparative modelling, and significant changes were suggested in the protein cores for these two neuroligin isoforms. CONCLUSIONS: Splice variants may lead to potentially abnormal neuroligins in the causation of autism spectrum disorders.

Alleles↗

Helical CT: practical considerations and potential pitfalls.

Helical (spiral) computed tomography (CT) is having a dramatic impact on body imaging. Unlike conventional CT, helical CT provides continued volumetric acquisition as the patient moves through the gantry. Advantages of helical CT include dramatically shortened examination times, improved visibility of vascular structures, better enhancement of parenchymal organs, the capability for retrospective imaging and three-dimensional (3D) vascular studies, and potential reduction in use of contrast material. However, helical CT requires one to be more cognizant of the relationship between contrast material administration and scanning, since the optimal temporal window for detection of disease can be missed. Factors unique to helical technology can produce artifacts, which one must be aware of when interpreting helically generated scans. Many of these artifacts relate to accentuation of vascular or parenchymal enhancement. Others occur during production of high-quality 3D images. Additional artifacts are sure to be identified with increased experience with helical CT.

Aortic Dissection↗

Soluble heparin-binding peptides regulate chemokinesis and cell adhesive forces.

The ability of a soluble heparin-binding peptide sequence derived from fibronectin to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells was assessed using a novel glass microsphere centrifugation assay and automated time-lapse fluorescence videomicroscopy, respectively. Treatment of cells grown on fibronectin-coated substrates with the soluble heparin-binding peptide resulted in the disassembly of focal adhesions, as assessed by immunohistochemical staining. These observations were consistent with an observed dose-dependent two- to fivefold reduction in cell-substrate adhesive strength (P < 0.001) and a biphasic effect on migration speed (P < 0.05). Moreover, heparin-binding peptides induced a twofold reduction (P < 0.01) in two-dimensional cell dispersion in the presence of a non-heparin-binding growth factor, platelet-derived growth factor-AB (PDGF-AB). Heparin-binding peptides were unable to mediate these effects when cells were grown on substrates lacking a heparin-binding domain. These data support the notion that competitive interactions between cell surface heparan sulfates with heparin-binding peptides may modulate chemokinetic cell migration behavior and other adhesion-related processes.

Animals↗

Differentiation of dementia with Lewy bodies from Alzheimer's disease using brain SPECT.

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.

Aged↗

Regression of carotid plaques during low density lipoprotein cholesterol elimination.

We performed serial prospective ultrasound examinations of four flat and 17 soft carotid plaques during an average of 17 months in seven patients with heterozygous hypercholesterolemia during heparin-induced extracorporeal low density lipoprotein elimination on precipitation from plasma. By means of a specially designed quantitative three-dimensional ultrasound analysis, significant plaque volume reduction could be evaluated in all subjects, along with a marked reduction of total and low density lipoprotein cholesterol and fibrinogen serum levels.

Adult↗

Reduction of operating time and blood transfusion for craniosynostosis by simulated surgery using three-dimensional solid models.

Preoperative planning of craniofacial synostosis can be achieved through the use of two- or three-dimensional (3D) computed tomography (CT) images and by 3D solid models. The advantage of using 3D models was evaluated by calculating the amount of blood transfused and the operating time for 36 craniosynostosis procedures, 21 planned with 3D models and 15 with CT images performed in the past 7 years. The use of 3D models reduced both blood loss and operating time for fronto-orbital advancement with reshaping, LeFort III advancement, and LeFort IV minus Glabellar advancement; blood loss for fronto-orbital advancement without reshaping; and operating time for total cranial reshaping.

Adolescent↗

Crossover cutting during hamstring fatigue produces transverse plane knee control deficits.

OBJECTIVE: To assess the effects of eccentric work-induced hamstring fatigue on sagittal and transverse plane (axial) knee and ankle biodynamics and kinetics during a running crossover cut directional change (functional pivot shift). DESIGN AND SETTING: A pretest-posttest, single-group intervention experimental design was employed. All data were collected in a biodynamics laboratory. SUBJECTS: Twenty healthy athletic females were trained for 3 weeks in crossover cutting before testing. MEASUREMENTS: Data were sampled during 3 unfatigued and 3 fatigued (20% eccentric isokinetic knee-flexor torque reduction) crossover cut trials. Three-dimensional kinematic and ground reaction-force data were sampled at 200 Hz and 1000 Hz, respectively, and joint moment estimates were calculated. Data were standardized to initial force-plate heelstrike for comparisons of mean differences between conditions using paired t tests with Bonferroni adjustments. Pearson product-moment correlations compared kinematic and eccentric hamstring-torque relationships. RESULTS: During internal rotation phase 1, between heelstrike and impact absorption, mean internal rotation velocity increased by 21.2 degrees /s +/- 114 degrees /s. During internal rotation phase II, mean peak transverse plane knee rotation during propulsion decreased by 3.1 degrees +/- 9 degrees . During internal rotation phase II, mean peak ankle plantar flexor moment onsets occurred 12.7 +/- 53 milliseconds earlier, and this activation demonstrated a moderately positive relationship with the onset of mean peak knee internal rotation during propulsion and a weak negative relationship with mean peak hamstring torque/lean body weight. CONCLUSIONS: The increased knee internal rotation velocity during phase I indicates transverse plane dynamic knee-control deficits during hamstring fatigue. Earlier peak ankle plantar-flexor moments and decreased internal rotation during phase II in the presence of hamstring fatigue may represent compensatory attempts at dynamic knee stabilization from the posterior lower leg musculature during the pivot shift portion of the crossover cut. The weak relationship between decreased hamstring torque/lean body weight and delayed knee internal rotation during propulsion further supports greater dependence on ankle plantar flexors for dynamic knee stabilization compensation.

Journal Article↗

Retinoic acid acylation (retinoylation) of a nuclear protein in the human acute myeloid leukemia cell line HL60.

all-trans-Retinoic acid is a potent inducer in vitro of the differentiation of the human acute myeloid leukemia cell line HL60 and of fresh cells from patients with acute promyelocytic leukemia. The recent discovery of nuclear retinoic acid receptors provides a basis for understanding how retinoic acid acts at the genetic level. We have now found that retinoic acid is incorporated into HL60 cells in a form that is not removed by extraction with CHCl3:CH3OH. About 90% of this labeled retinoic acid is trichloroacetic acid-soluble after digestion with proteinase K or after hydrolysis with either NH2OH or CH3OH:KOH under mild conditions. Methyl retinoate is the major product of hydrolysis with CH3OH:KOH. These results are consistent with retinoylation of protein with the formation of an ester, probably thioester, bond. The extent of the retinoylation of HL60 protein is dependent on both time and retinoic acid concentration. A major fraction of the retinoylation is of protein that has a molecular mass of 55 kDa after reduction with dithiothreitol. On two-dimensional gels, the retinoylated protein has a pI of about 4.9 and a molecular mass of 55-60 kDa. These characteristics and its localization in the cell nucleus are consistent with retinoylation of the HL60 nuclear retinoic acid receptor or a closely related protein.

Acylation↗

[High-resolution 2-dimensional gel electrophoresis: a method for the clinical chemistry laboratory].

The working instructions, reagents and instruments for the performance of high resolution two dimensional gel electrophoresis are described. Size reduction of the gel slabs allows the two electrophoretic separation steps to be run within an 8-hour-working-day. The description also includes a well adapted method for silver staining and a photographic procedure for the documentation of the gels. The method is specially developed and designed for use in the clinical chemistry laboratory.

Chemistry, Clinical↗

Volume effects and epithelial regeneration in irradiated mouse colorectum.

The use of three-dimensional treatment planning and volume-reduction techniques in radiotherapy has prompted the development of a number of mathematical models to describe the effect of changing treatment volume on the probability of associated complications in normal tissues. However, limited data are available to test or support these models. One prediction of the Probability model and analogous models, which describe the volume-effect relationship for late end points in tissues with a series-type arrangement of functional subunits, is that there is no threshold volume in the development of the end point. This hypothesis was tested in mouse colorectum, a normal tissue with functional subunits suggested to be arranged in series, using the incidence of obstructions due to consequential fibrosis as the end point of damage. Various lengths of the colorectum of C3Hf/Kam mice were irradiated with single doses of 250 kVp X rays. A threshold length between 10 and 15 mm was observed after 32 Gy. The Probability model could not describe the data adequately, but a modified version that included a threshold volume term (the Threshold Probability model) provided an excellent fit. In a separate experiment, epithelial regeneration (migration, extracryptal proliferation and formation of new crypts) was examined as a possible mechanism for the threshold length. Re-epithelialization was complete after 32 Gy was delivered to lengths below (5 or 10 mm) but not above (20 mm) the threshold for consequential obstruction. Proliferation of epithelial cells outside the crypt on the mucosal surface (i.e. extracryptal proliferation) may contribute to the regeneration process. The data indicate that regeneration of the epithelium after irradiation results in a threshold length of the colorectum in the development of consequential fibrosis, in contradiction to predictions of the Probability model.

Animals↗

[Virtual simulation of dental surgery using a three-dimensional computer model with a force feedback system].

BACKGROUND: Selective reduction of bone without injuring inner structures is an essential part of surgical techniques, especially during dental surgery. Virtual drilling is possible using a new simulator. The following illustrates simulation of an apicectomy. MATERIAL AND METHODS: Using the VOXEL-MAN system, a virtual three-dimensional model of a skull was created based on CT data. Both inferior alveolar nerves and apical inflammations of teeth 23, 25, 36, and 35 were virtually simulated. To achieve a realistic drilling effect with the force feedback system, special tools were integrated into VOXEL-MAN to obtain a high resolution of collision recognition. Adding drilling noises further improved the simulation. Spatial 3D perception was possible with the help of shutter glasses. RESULTS: The presented computer model enabled the visual and haptic observation of complex volume-based models and virtual interaction with them. The haptic feeling proved to be convincing because of collision recognition, consideration of drilling parameters, and addition of drilling noises. Via postoperative reconstructions, polydimensional verification of performed drilling routes is possible. CONCLUSION: Using apicectomies as examples, realistic simulation of dental surgical procedures, even in complex anatomical models, is possible. Generally, it is possible to add virtual pathologies in data sets and/or to use anonymous patient data sets to extend the range of simulated surgical procedures.

Apicoectomy↗