Charge Radii of Neutron Deficient

Bunched-beam collinear laser spectroscopy is performed on neutron deficient ^{52,53}Fe prepared through in-flight separation followed by a gas stopping. This novel scheme is a major step to reach nuclides far from the stability line in laser spectroscopy. Differential mean-square charge radii δ⟨r^{2}⟩ of ^{52,53}Fe are determined relative to stable ^{56}Fe as δ⟨r^{2}⟩^{56,52}=-0.034(13) fm^{2} and δ⟨r^{2}⟩^{56,53}=-0.218(13) fm^{2}, respectively, from the isotope shift of atomic hyperfine structures. The multiconfiguration Dirac-Fock method is used to calculate atomic factors to deduce δ⟨r^{2}⟩. The values of δ⟨r^{2}⟩ exhibit a minimum at the N=28 neutron shell closure. The nuclear density functional theory with Fayans and Skyrme energy density functionals is used to interpret the data. The trend of δ⟨r^{2}⟩ along the Fe isotopic chain results from an interplay between single-particle shell structure, pairing, and polarization effects and provides important data for understanding the intricate trend in the δ⟨r^{2}⟩ of closed-shell Ca isotopes.

Bioluminescence tomography with CT/MRI co-registration.

We present a three-dimensional (3D) bioluminescence image reconstruction method with MRI and CT co-registration for small animal molecular imaging. The multi-spectral light intensity distribution of an optical luciferase-luciferin reporter system is measured at the tissue surface of a small animal for the purpose of 3D image reconstruction. The reporter probe distribution inside tissue is calculated with a linear matrix inversion method and a light propagation model based on the simplified spherical harmonics equations. The animal's surface geometry and anatomy is determined from co-registered CT and MR images in order to locate the reconstructed source distribution relative to the animal's anatomy. We present in vivo bioluminescence reconstruction results that demonstrate the performance of our co-registration method.

Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer's disease.

INTRODUCTION: Molecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level. IMAGING OF AD CHARACTERISTIC CHANGES BY microPET: The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research. In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimer's disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases.

In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-induced arthritis: the role of P-selectin.

OBJECTIVE: Platelets are thought to participate in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA). We showed recently an in vivo increase in platelet-endothelial cell interactions in mice with antigen-induced arthritis (AiA). The underlying mechanisms are not yet clear. The aim of this study was to investigate the impact of P-selectin in AiA by means of intravital fluorescence microscopy (IVM). METHODS: C57/Bl6 mice and P-selectin-deficient mice were divided into four groups (n = 7; control/AiA per strain). The extent of AiA was assessed by measuring knee joint swelling and by histological scoring. Rolling and adherent fluorescence-labelled platelets and leucocytes were investigated by IVM. RESULTS: In arthritic P-selectin-deficient mice (rolling: 0.05+/-0.01; adherent: 130+/-20 mm(-2)), compared to arthritic C57/Bl6 mice (rolling: 0.20+/-0.04; adherent: 1910+/-200 mm(-2)), platelet interaction was significantly reduced (p<0.05) and reached the level of both control groups without AiA. In addition, interaction of leucocytes in P-selectin-deficient arthritic animals (rolling: 0.12+/-0.06; adherent: 387+/-37 mm(-2)) was significantly decreased in comparison to arthritic C57/Bl6 animals (rolling: 0.21+/-0.06; adherent: 1492+/-284 mm(-2); p<0.05). Swelling of the knee joint and histological scoring were reduced in arthritic P-selectin-deficient mice compared to arthritic C57/Bl6 mice. CONCLUSION: We have demonstrated for the first time in vivo a significant decrease in the interaction of platelets and leucocytes with the endothelium in P-selectin-deficient mice with AiA and a reduction in clinical and histological symptoms of arthritis. These findings suggest that leucocyte-endothelial cell interactions depend at least partially on platelet P-selectin and therefore platelets may be responsible for the leucocyte tissue damage in AiA.

Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.

First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints.

OBJECTIVE: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. METHODS: 78 SLOT images of proximal interphalangeal joints II-IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. RESULTS: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. CONCLUSION: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.

Reduced antioxidant capacity in second-trimester pregnancies with pathological uterine perfusion.

OBJECTIVES: To examine whether pathological perfusion in the second trimester is characterized by an altered plasma antioxidant capacity and to investigate whether the total antioxidant capacity in maternal plasma is related to the clinical outcome of these high-risk pregnancies. METHODS: This was a prospective cohort study that included 25 pregnancies with normal and 25 pregnancies with pathological uterine perfusion. Doppler ultrasound measurement of uterine perfusion was performed between 18 and 23 weeks of gestation. Total antioxidant capacity in maternal plasma was measured using a specific photometric assay. RESULTS: Plasma antioxidant capacity of pregnant women with pathological uterine perfusion (227.3 +/- 4.0 micro mol/L) was significantly lower compared with the group with normal uterine perfusion (275.2 +/- 10.5 micro mol/L; P < 0.05). There was a significant negative correlation between antioxidant capacity and mean pulsatility index of the uterine arteries (r = -0.363; P < 0.05). Patients with pathological perfusion and a normal course of pregnancy did not show significantly changed values compared with those patients with later pre-eclampsia or intrauterine growth restriction (235.0 +/- 4.9 micro mol/L vs. 218.6 +/- 6.7 micro mol/L). CONCLUSIONS: Second-trimester pregnancies with pathological uterine perfusion are characterized by a decreased antioxidant capacity in maternal plasma. This reduction is related to the impaired uteroplacental blood flow, but does not reflect the changes characteristic of the oxidative status for diseases like pre-eclampsia since the reduction of the plasma antioxidant capacity is not related to the clinical outcome of these high-risk pregnancies.

Near-infrared diffuse optical tomography.

Diffuse optical tomography (DOT) is emerging as a viable new biomedical imaging modality. Using near-infrared (NIR) light, this technique probes absorption as well as scattering properties of biological tissues. First commercial instruments are now available that allow users to obtain cross-sectional and volumetric views of various body parts. Currently, the main applications are brain, breast, limb, joint, and fluorescence/bioluminescence imaging. Although the spatial resolution is limited when compared with other imaging modalities, such as magnetic resonance imaging (MRI) or X-ray computerized tomography (CT), DOT provides access to a variety of physiological parameters that otherwise are not accessible, including sub-second imaging of hemodynamics and other fast-changing processes. Furthermore, DOT can be realized in compact, portable instrumentation that allows for bedside monitoring at relatively low cost. In this paper, we present an overview of current state-of-the -art technology, including hardware and image-reconstruction algorithms, and focus on applications in brain and joint imaging. In addition, we present recent results of work on optical tomographic imaging in small animals.

Genetic variability and prevalence of Bartonella henselae in cats in Berlin, Germany, and analysis of its genetic relatedness to a strain from Berlin that is pathogenic for humans.

Nineteen Bartonella henselae strains and one Bartonella clarridgeiae strain were isolated from blood samples of 97 pet cats and 96 stray cats from Berlin, Germany, indicating prevalence rates of 1 and 18.7%, respectively, for B. henselae and 0 and 1%, respectively, for B. clarridgeiae. Eighteen of 19 B. henselae isolates corresponded to 16S rRNA type II. Pulsed-field gel electrophoresis (PFGE) analysis revealed seven different PFGE types among the feline B. henselae strains. Interestingly, all feline isolates displayed low genetic relatedness to B. henselae strain Berlin-1, which is pathogenic for humans.

[Initial studies of the application of the linear signal transfer theory in evaluating diaphanoscopic examinations exemplified by rheumatism diagnosis]. / Erste Untersuchungen zur Anwendung der linearen Signalübertragungstheorie in der Auswertung diaphanoskopischer Untersuchungen am Beispiel der Rheumadiagnostik.

Rheumatoid arthritis affecting the small joints--in particular the fingers--has advantageous geometry for the transmission of near-infrared (NIR) light. Examination of the optical properties of tissues has revealed that as a result of changes to the capsule and synovial fluid there is a considerable increase in photon scattering already in the early stages of the disease--in particular around 685 nm. This suggests the appropriateness of analysing the photon density profile resulting from punctiform irradiation of the joint. In a first approximation, the point spread function of transmitted photon density is confirmed to be proportional to a Gauss distribution, as suggested by Arridge. In accordance with the linear signal transfer theory, therefore, it is possible to establish a virtual transfer system described by a first-order differential equation. (The tissue optical conditions mu a << mu's and mu a = constant (mu a = absorption coefficient) were assumed). The parameter mu's (= reduced scattering coefficient) was determined by linear approximation of the Gauss distribution to the calculated or measured point spread function. For selected patient data, the mu's was determined in healthy and diseased finger joints (e.g. 10.1 cm-1 and 26.8 cm-1, respectively), and the results were in good agreement with those obtained experimentally.

Anatomical variations of landmarks for implantation at the cochlear nucleus.

A knowledge of the microanatomy of the cochlear nucleus complex and its variations is essential for successful implantation and for the design of stimulation devices. One hundred cerebellopontine angle specimens were dissected under surgical conditions using the Zeiss NC31 surgical microscope. The topographical anatomy of the exit of the vestibulocochlear nerve, the cochlear nucleus and the surface of the medulla and their relation to the surrounding structures was recorded and measured. The mean distances between the exits of the VIIth and VIIIth cranial nerves were 4.7 +/- 0.9 mm, between the VIIth and IXth 6.3 +/- 1.2 mm and between the VIIIth and IXth 5.5 +/- 1.0 mm. The visible area of the cochlear nucleus covered a square of 10.0 +/- 2.9 by 3.3 +/- 1.0 mm. A major AICA-loop had to be re-routed in 17 per cent of specimens. The taenia of the choroid plexus was present in 92 per cent and had to be cut in 51 per cent in order to enter the foramen of Luschka, that had a mean size of 3.5 by 2.0 mm. It was wide open in 24 per cent, open only after incision of the arachnoid in 53 per cent, functionally closed but opened by extensive dissection in 18 per cent and anatomically occluded in five per cent of the specimens. The typical straight vein at the cochlear nucleus leading to the entrance of the foramen of Luschka was found in 76 per cent of specimens. Constant anatomical landmarks are very helpful for finding the cochlear nucleus, but variations may endanger dissection and implantation in a remarkable number of cases.

Evolution strategies for optical tomographic characterization of homogeneous media.

The reconstruction problem in diffuse optical tomography can be formulated as an optimization problem, in which an objective function has to be minimized. Current model-based iterative image reconstruction schemes commonly use information about the gradient of the objective function to locate the minimum. These gradient-based search algorithms often find local minima close to an initial guess, or do not converge if the gradient is very small. If the initial guess is too far from the solution, gradient-based schemes prove inefficient for finding the global minimum. In this work we introduce evolution-strategy (ES) algorithms for diffuse optical tomography. These algorithms seek to find the global minimum and are less sensitive to initial guesses and regions with small gradients. We illustrate the fundamental concepts by comparing the performance of gradient-based schemes and ES algorithms in finding optical properties (absorption coefficient microa , scattering coefficient micros , and anisotropy factor g) of a homogenous medium.

Iterative reconstruction scheme for optical tomography based on the equation of radiative transfer.

We report on the development of an iterative image reconstruction scheme for optical tomography that is based on the equation of radiative transfer. Unlike the commonly applied diffusion approximation, the equation of radiative transfer accurately describes the photon propagation in turbid media without any limiting assumptions regarding the optical properties. The reconstruction scheme consists of three major parts: (1) a forward model that predicts the detector readings based on solutions of the time-independent radiative transfer equation, (2) an objective function that provides a measure of the differences between the detected and the predicted data, and (3) an updating scheme that uses the gradient of the objective function to perform a line minimization to get new guesses of the optical properties. The gradient is obtained by employing an adjoint differentiation scheme, which makes use of the structure of the finite-difference discrete-ordinate formulation of the transport forward model. Based on the new guess of the optical properties a new forward calculation is performed to get new detector predictions. The reconstruction process is completed when the minimum of the objective function is found within a defined error. To illustrate the performance of the code we present initial reconstruction results based on simulated data.

Gradient-based iterative image reconstruction scheme for time-resolved optical tomography.

Currently available tomographic image reconstruction schemes for optical tomography (OT) are mostly based on the limiting assumptions of small perturbations and a priori knowledge of the optical properties of a reference medium. Furthermore, these algorithms usually require the inversion of large, full, ill-conditioned Jacobian matrixes. In this work a gradient-based iterative image reconstruction (GIIR) method is presented that promises to overcome current limitations. The code consists of three major parts: 1) A finite-difference, time-resolved, diffusion forward model is used to predict detector readings based on the spatial distribution of optical properties; 2) An objective function that describes the difference between predicted and measured data; 3) An updating method that uses the gradient of the objective function in a line minimization scheme to provide subsequent guesses of the spatial distribution of the optical properties for the forward model. The reconstruction of these properties is completed, once a minimum of this objective function is found. After a presentation of the mathematical background, two- and three-dimensional reconstruction of simple heterogeneous media as well as the clinically relevant example of ventricular bleeding in the brain are discussed. Numerical studies suggest that intraventricular hemorrhages can be detected using the GIIR technique, even in the presence of a heterogeneous background.

Two independent mutations in a family with neurofibromatosis type 1 (NF1).

We report on two independent alterations of the NF1 gene in a three-generation kindred with neurofibromatosis type 1 (NF1). Using temperature gradient gel electrophoresis (TGGE) in a mutation analysis of exon 31 of the NF1 gene we detected the previously reported nonsense mutation R1947X. This C-to-T transition at codon 1947 in exon 31 is considered to represent a mutation "hot spot" of the NF1 gene due to 5mCpG deamination. All living family members together with their genomic DNA were included in this investigation. However, the mutation R1947X was absent from two undoubtedly affected siblings of the propositus. Another NF1 mutation (889-2A-->G) was identified in the two sibs by the protein truncation test (PTT). The novel splice site mutation 889-2A-->G results in a skip of NF1 exon 7 during splicing and protein truncation due to frameshift. The two NF1 alterations are linked to different paternal haplotypes. In our study of a three-generation kindred, R1947X represents a de novo mutation whereas 889-2A-->G is an inherited splice mutation. Implications for phenotype variation are discussed.

Selective disactivation of neurofibromin GAP activity in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common familial tumour syndrome with multiple clinical features such as neurofibromas, café-au-lait spots (CLS), iris Lisch nodules, axillary freckling, optic glioma, specific bone lesions and an increased risk of malignant tumours. It is caused by a wide spectrum of mutations affecting the NF1 gene. Most mutations result in the loss of one allele at the DNA, mRNA or protein level and thus in the loss of any function of the gene product neurofibromin. The idea of the simultaneous loss of several different neurofibromin functions has been postulated to explain the pleiotropic effects of its loss. However, we have identified a novel missense mutation in a family with a classical multi-symptomatic NF1 phenotype, including a malignant schwannoma, that specifically abolishes the Ras-GTPase-activating function of neurofibromin. In this family, Arg1276 had mutated into proline. Based on complex biochemical studies as well as the analysis of the crystal structure of the GTPase-activating protein (GAP) domain of p120GAP in the presence of Ras, we unequivocally identified this amino acid as the arginine finger of the neurofibromin GAP-related domain (GRD)-the most essential catalytic element for RasGAP activity. Here, we present data demonstrating that the mutation R1276P, unlike previously reported missense mutations of the GRD region, does not impair the secondary and tertiary protein structure. It neither reduces the level of cellular neurofibromin nor influences its binding to Ras substantially, but it does completely disable GAP activity. Our findings provide direct evidence that failure of neurofibromin GAP activity is the critical element of NF1 pathogenesis. Thus, therapeutic approaches aimed at the reduction of Ras.GTP levels in neural crest-derived cells can be expected to relieve most of the NF1 symptoms.

Two novel mutations in exons 19a and 20 and a BsaBI [correction of BsaI] polymorphism in a newly characterized intron of the neurofibromatosis type 1 gene.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. It is caused by mutations in the NF1 gene, which comprises 60 exons and is located on chromosome 17q11.2. A total of 170 unrelated NF1 patients were screened for mutations in four exons by temperature-gradient gel electrophoresis. Preparatory work revealed the presence of a previously uncharacterized intron (19a) in what was previously designated exon 19; this allowed us to develop assays for genomic mutation screening in the newly defined exons 19a and 19b. Two novel NF1 mutations were detected: a single-base insertion in exon 19a creating a frameshift, and a second mutation affecting the splice donor site of intron 20 and leading to skipping of exon 20. A novel BsaBI polymorphism was identified in intron 19a.

Effects of spatial frequency of a vertically striped rotating drum on vection-induced motion sickness.

PURPOSE: The present study investigated the effects of differential spatial frequencies of a vertically striped, horizontally rotating drum on the observer's frequency of eye nystagmus, perceived velocity of self-motion, and symptoms of motion sickness. METHODS AND RESULTS: Two experiments were conducted. In Experiment 1, each of 10 subjects viewed 1 min of an optokinetic rotating drum at the speed of 10 rpm covered with 6, 12, 24, 48, and 96 pairs of black and white stripes, presented in counterbalanced order. The results indicated that subjects perceived significantly stronger circular vection (p < 0.05) and generated significantly higher frequencies of eye nystagmus (p < 0.05) when they were viewing 24 pairs of black and white stripes than when they were viewing any of the other combinations of 6, 12, 48, or 96 black and white stripes. In Experiment 2, 100 highly susceptible subjects viewed 16 min of an optokinetic rotating drum covered with one of the five different numbers of black and white stripe pairs: 6, 12, 24, 48, and 96. The results indicated that subjects in the group viewing 24 moving contrasts perceived significantly stronger circular vection (p < 0.001), reported significantly more severe symptoms of motion sickness (p < 0.001), and showed significantly greater ratios of EGG 4-9 cycles per minute spectral intensity between drum rotation and baseline periods (p < 0.004) than those in the groups of viewing 6, or 96 moving contrasts. CONCLUSION: These results demonstrated that the severity of vection-induced motion sickness is affected by differential spatial frequencies of the stripes of the rotating drum and may be affected by number of horizontal eye movements.

Elucidation of an HIV-1 transmission from mother to child in west Africa by sequence analysis.

A pregnant woman living in Germany went to Ghana for several months, where she received 4 blood transfusions. Her newborn child also received one blood transfusion in West Africa. After return to Germany, HIV-1 infection was detected in both of them. Serotyping with V3 peptides revealed that the sera reacted only poorly with the subtype B-specific antigens. To investigate whether the child had been infected by vertical or parenteral transmission, we amplified different proviral HIV-1 gene segments from samples obtained 1-3 years after infection. Sequence analysis of the hypervariable regions V1 and V2 of the proviral env gene was misleading, since the viral population of the mother was highly heterogeneous, whereas only one predominant viral variant was found in the child. In contrast, sequences of the gag p17 gene and the regulatory genes nef and vif were homogeneous and revealed a very high homology, suggesting that the child had been infected by the mother. This was confirmed by phylogenetic tree analysis showing that sequences of mother and child clustered together and that both were infected by HIV-1 subtype A which is common in West Africa. The results suggest that sequence analysis of the hypervariable regions V1 and V2 alone can lead to unclear results, especially if not single genomes are analysed but a mixture of quasi-species. It is recommended that investigations into HIV transmission should be based on sequence analysis of several HIV genes.