Jan S. Bauer

Nanocrystalline FeNdB permanent magnets with enhanced remanence

Isotropic nanocrystalline exchange coupled FeNdB magnets with enhanced remanence were produced using the melt spinning procedure. Starting from nearly single phase Fe14Nd2B magnets, the content of additional α‐Fe in composite magnets was stepwise increased up to 40 vol % by reducing the Nd and B content. The maximum remanence of JR=1.25 T was found in composite magnets containing 30 vol % α‐Fe, the maximum energy product reaches the value (BH)max=185 kJ/m3, whereas the coercive field is μ0HC=0.53 T for this composition. The microstructural investigations of the composite magnets reveal two characteristic maxima in the grain size distribution at about 15 and 25 nm corresponding to the α‐Fe phase and to the Fe14Nd2B phase, respectively. The influence of the exchange coupling on the coercive field can be described by a microstructural parameter αex. From the temperature dependence of the coercive field the microstructural parameters αKαex and Neff are determined.

T‐ and B‐cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis

The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody‐mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re‐evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expressed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, inducing severe EAE in both rodents and primates. In rat and marmoset models of MOG‐induced EAE demyelination is antibody‐dependent and reproduces the immunopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG‐specific B cell response, although if present this will enhance disease severity and demyelination. Clinical studies indicate that autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG‐specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summary of our current understanding of MOG as a target autoantigen in EAE and MS, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual. GLIA 36:220–234, 2001.

The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (αMβ2, CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen–Mac-1 interaction in fibrinogen-γ390-396A knock-in mice or pharmacologically impeding fibrinogen–Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (γ377-395) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen–Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the γ377-395 fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation.

T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning.

In this study we evaluated the effects of intracellular compartmentalization of the ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 on its proton T1 and T2 relaxivities at 1.5 and 3T. Monocytes were labeled with ferumoxtran-10 by simple incubation. Decreasing quantities of ferumoxtran-10-labeled cells (2.5×107-0.3×107 cells/ml) and decreasing concentrations of free ferumoxtran-10 (without cells) in Ficoll solution were evaluated with 1.5 and 3T clinical magnetic resonance (MR) scanners. Pulse sequences comprised axial spin echo (SE) sequences with multiple TRs and fixed TE and SE sequences with fixed TR and increasing TEs. Signal intensity measurements were used to calculate T1 and T2 relaxation times of all samples, assuming a monoexponential signal decay. The iron content in all samples was determined by inductively coupled plasma atomic emission spectrometry and used for calculating relaxivities. Measurements at 1.5T and 3T showed higher T1 and T2 relaxivity values of free extracellular ferumoxtran-10 as opposed to intracellularly compartmentalized ferumoxtran-10, under the evaluated conditions of homogeneously dispersed contrast agents/cells in Ficoll solution and a cell density of up to 2.5×107 cells/ml. At 3T, differences in T1-relaxivities between intra- and extracellular USPIO were smaller, while differences in USPIO T2-relaxivities were similar compared with 1.5T. In conclusion, cellular compartmentalization of ferumoxtran-10 changes proton relaxivity.

Five Freely Circulating miRNAs and Bone Tissue miRNAs Are Associated With Osteoporotic Fractures

Osteoporosis as a systemic skeletal disorder is characterized by increased bone fragility and the risk of fractures. According to the World Health Organization, osteoporosis is one of the 10 most common diseases and affects approximately 75 million people in Europe, the United States, and Japan. In this context, the identification of specific microRNA (miRNA) signatures is an important step for new diagnostic and therapeutic approaches. The focus of interest on miRNAs as biomarkers came with new publications identifying free circulating extracellular miRNAs associated with various types of cancer. This study aimed to identify specific miRNAs in patients with osteoporotic fractures compared with nonosteoporotic fractures. For the array analysis, miRNAs were isolated from the serum of 20 patients with hip fractures, transcribed, and the samples were pooled into 10 osteoporotic and 10 nonosteoporotic specimens. With each pool of samples, human serum and plasma miRNA PCR arrays were performed, which are able to identify 83 different miRNAs. Subsequently, a separate validation analysis of each miRNA found to be regulated in the array followed with miRNA samples isolated from the serum of 30 osteoporotic and 30 nonosteoporotic patients and miRNA samples isolated from the bone tissue of 20 osteoporotic and 20 nonosteoporotic patients. With the validation analysis of the regulated miRNAs, we identified 9 miRNAs, namely miR‐21, miR‐23a, miR‐24, miR‐93, miR‐100, miR‐122a, miR‐124a, miR‐125b, and miR‐148a, that were significantly upregulated in the serum of patients with osteoporosis. In the bone tissue of osteoporotic patients, we identified that miR‐21, miR‐23a, miR‐24, miR‐25, miR‐100, and miR‐125b displayed a significantly higher expression. A total of 5 miRNAs display an upregulation both in serum and bone tissue. This study reveals an important role for several miRNAs in osteoporotic patients and suggested that they may be used as biomarkers for diagnostic purposes and may be a target for treating bone loss and optimizing fracture healing in osteoporotic patients.

Demonstration of interleukin-1β in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level

Interleukin-1 beta (IL-1) is a cytokine which exerts many biological effects during inflammation. In the present study, experimental allergic encephalomyelitis (EAE) was induced in Lewis rats. During the various stages of EAE, the presence of IL-1 in the brain was investigated using immunocytochemistry at both the light and ultrastructural level. Ten days after immunization, IL-1 immunoreactivity was found in brains of animals which at this time showed mild clinical signs. Outside the blood-brain barrier, IL-1 was localized in the cytoplasm of meningeal macrophages and perivascular cells. Within the brain parenchyma, IL-1 immunoreactivity was distributed in perivascular lesions in the cytoplasm of infiltrated macrophages and activated microglia. On day 13, animals had developed a full blown EAE. At this stage the number of lesions with IL-1-positive cells had increased. In the remission phase (day 25), lesions with IL-1-positive cells could still be detected but were less pronounced as compared to day 13. Other presumptive IL-1-producing cell types like endothelial cells or astrocytes were, at none of the various stages, found to stain for IL-1.

Advances in osteoporosis imaging.

In the assessment of osteoporosis, the measurement of bone mineral density (BMD(a)) obtained from dual energy X-ray absorptiometry (DXA; g/cm(2)) is the most widely used parameter. However, bone strength and fracture risk are also influenced by parameters of bone quality such as micro-architecture and tissue properties. This article reviews the radiological techniques currently available for imaging and quantifying bone structure, as well as advanced techniques to image bone quality. With the recent developments in magnetic resonance (MR) techniques, including the availability of clinical 3T scanners, and advances in computed tomography (CT) technology (e.g. clinical Micro-CT), in-vivo imaging of the trabecular bone architecture is becoming more feasible. Several in-vitro studies have demonstrated that bone architecture, measured by MR or CT, was a BMD-independent determinant of bone strength. In-vivo studies showed that patients with, and without, osteoporotic fractures could better be separated with parameters of bone architecture than with BMD. Parameters of trabecular architecture were more sensitive to treatment effects than BMD. Besides the 3D tomographic techniques, projection radiography has been used in the peripheral skeleton as an additional tool to better predict fracture risk than BMD alone. The quantification of the trabecular architecture included parameters of scale, shape, anisotropy and connectivity. Finite element analyses required highest resolution, but best predicted the biomechanical properties of the bone. MR diffusion and perfusion imaging and MR spectroscopy may provide measures of bone quality beyond trabecular micro-architecture.

Understanding junction breakdown in multicrystalline solar cells

Extensive investigations on industrial multicrystalline silicon solar cells have shown that, for standard 1 Ω cm material, acid-etched texturization, and in absence of strong ohmic shunts, there are three different types of breakdown appearing in different reverse bias ranges. Between −4 and −9 V there is early breakdown (type 1), which is due to Al contamination of the surface. Between −9 and −13 V defect-induced breakdown (type 2) dominates, which is due to metal-containing precipitates lying within recombination-active grain boundaries. Beyond −13 V we may find in addition avalanche breakdown (type 3) at etch pits, which is characterized by a steep slope of the I-V characteristic, avalanche carrier multiplication by impact ionization, and a negative temperature coefficient of the reverse current. If instead of acid-etching alkaline-etching is used, all these breakdown classes also appear, but their onset voltage is enlarged by several volts. Also for cells made from upgraded metallurgical grade materia...

Modelling of multiple sclerosis: lessons learned in a non-human primate.

The many, highly specific, biological therapies for immune-based diseases create a need for valid preclinical animal models. The wide immunological gap between human beings and laboratory mouse or rat models makes many disease models in these species invalid. In this review, we report a non-human-primate model of chronic multiple sclerosis (MS)-experimental autoimmune encephalitis (EAE) in the common marmoset (Callithrix jacchus)-that can help bridge this wide gap. The genetic and immunological similarity of marmosets and human beings and the clinical and neuropathological similarity of the EAE model to MS provide a unique experimental platform for research into basic immunopathogenetic mechanisms and for the development of more effective treatments for MS.

Inter-subject comparison of MRI knee cartilage thickness

In this paper, we present the development and application of current image processing techniques to perform MRI inter-subject comparison of knee cartilage thickness based on the registration of bone structures. Each point in the bone surface which is part of the bone-cartilage interface is assigned a cartilage thickness value. Cartilage and corresponding bone structures are segmented and their shapes interpolated to create isotropic voxels. Cartilage thicknesses are computed for each point in the bone-cartilage interfaces and transferred to the bone surfaces. Corresponding anatomic points are then computed for bone surfaces based on shape matching using 3D shape descriptors called shape contexts to register bones with affine and elastic transformations, and then perform a point to point comparison of cartilage thickness values. An alternative technique for cartilage shape interpolation using a morphing technique is also presented. The cartilage segmentation and morphing were validated visually, based on volumetric measurements of porcine knee images which cartilage volumes were measured using a water displacement method, and based on digital thickness values computed with an established technique. Shape matching using 3D shape contexts was validated visually and against manual shape matching performed by a radiologist. The reproducibility of intra- and inter-subject cartilage thickness comparisons was established, as well as the feasibility of using the proposed technique to build a mean femoral shape, cartilage thickness map, and cartilage coverage map. Results showed that the proposed technique is robust, accurate, and reproducible to perform point to point inter-subject comparison of knee cartilage thickness values.