116 research outputs found

    Das Kluftsystem im Bereich des Naturdenkmals "Saurierfährten Münchehagen"

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    The joints at the site of the dinosaur tracks in Muenchehagen form a conspicuous rhomboid pattern in a widely exposed bedding surface of the local quarry. An approximately west-trending set of joints is radially orientated with regard to the shape of the Rehburg salt pillow indicating a genetic relation to salt flow. The second set of joints trends approximately NW and is associated with arrays of dextral shear joints. Its formation is attributed to salt pillow formation and/or a regional deformation plan. This deformation plan presumably existed during the Alpine orogeny. The preservation potential of the dinosaur tracks is considerably decreased by the joint System.Die Klüfte im Bereich des Naturdenkmals „Saurierfährten Münchehagen" bilden auf der örtlichen Steinbruchsohle ein auffälliges, rautenförmiges Muster. Eine etwa westlich streichende Kluftschar ist radial um den durch Salzkissenbildung entstandenen Rehburger Sattel angeordnet, so daß ihre Genese in Zusammenhang mit der Salzwanderung gesehen wird. Die Entstehung der zweiten Kluftschar, die etwa nordwestlich streicht und von dextralen Scherkluftstaffeln begleitet wird, läßt sich auf die Salzkissenbildung beziehungsweise einen regionalen Beanspruchungsplan zurückführen, der vermutlich während der Alpenorogenese bestand. Das Erhaltungspotential der im Naturdenkmal aufgeschlossenen Fährtenplatte wird durch das Kluftsystem erheblich verringert

    Kinematics of Post-obduction Deformation of the Tertiary Ridge at Al-Khod Village (Muscat, Oman)

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    Structural investigations in post-obductional Paleocene to Eocene limestones of the Tertiary Ridge reveal a ~1 km long WNW-ESE striking strike-slip fault system within the ridge, consisting of two main sub-parallel, strike-slip faults. Considering the geometry of the Harding Strain Ellipse, the orientation of structures between the two strike-slip faults (e.g., Riedel shears, folds, reverse faults) point to left-lateral motion. The abundance of large-scale folds (up to 100 m in wave length and amplitude) between the two strike-slip faults led us to the interpretation of transpressive conditions in a first approximation. Moreover, the Tertiary Ridge of the study area consists of three distinct structural domains. The faults of Domain A and C are oriented WNW-ESE, but the trend of the faults in the central Domain B differs by ~10°. The left-lateral strike-slip fault system exists only in Domain B. We propose that the direction of greatest stress during Miocene plate convergence (sigma 1) was oriented 032°/212°. Considering the trend of the strike-slip zone and the orientation of sigma 1, the left-lateral motion must have been transpressive. Sigma 1 is perpendicularly oriented to the domains A and C. Prior to the Miocene D2 compressional event the study area was affected by a D1 extensional event, related to the opening of the Red Sea and the Gulf of Aden or to gravity-driven normal faulting. The D2 compressional/transpressional structures of the Miocene are reactivating the D1 structures of the Oligocene

    Magnetic nanoparticle-gel materials for development of joint phantoms for MPI and MRI

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    To evaluate the performance of commercial as well as custom-made scanners, dedicated phantoms with defined magnetic nanoparticle (MNP) distributions are required. Prerequisite for the development of such phantoms is the establishment of suitable MNP-matrix combinations. In this study, two different gel types were investigated as potential matrix materials: water-based biopolymers and synthetic polymers. These materials exhibit similar imaging behaviour to body tissue in MRI and MPI. Aqueous suspensions of MNP coated with different types of functionalized dextranes were used for embedding particles into the biopolymers, and organic fluids with oleic acid coated MNP for synthetic polymers, respectively. The obtained MNP-matrix combinations were tested for their shape stability. The homogeneity of MNP distribution and immobilization within the matrix was determined by optical investigation of the samples with a microscope, and the magnetic properties of the composite materials measured by vibrating sample magnetometry. From the tested combinations of MNP and matrix material, oleic acid coated MNP embedded in Permagel was found to be the most suitable for the construction of MPI phantoms. This was based on the reliable and homogeneous fixation of the MNP within the matrix without agglomeration of the particles

    Implications of quantitative susceptibility mapping at 7 Tesla MRI for microbleeds detection in cerebral small vessel disease

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    Background: Cerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications. Aims: We explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD. Methods: Both 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM. Results: 48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T−QSM = 2.5; Mdn3T−T2 = 0; z = 4.90; p < 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group. Conclusions: Our observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed

    Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

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    Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

    Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

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    Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed

    Safety and Efficacy of Combining Sunitinib with Bevacizumab + Paclitaxel/Carboplatin in Non-small Cell Lung Cancer

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    Bevacizumab (B) improves survival of patients with metastatic, nonsquamous non-small cell lung cancer. Based on encouraging results from preclinical studies combining B with sunitinib (S), a phase II, randomized, open-label study (Study Assessing the Blockade of both VEGF Receptor and ligand to enhance Efficacy in Lung) was initiated to assess clinical outcomes of adding S to paclitaxel (P)/carboplatin (C) + B (PCB) for first-line treatment of locally advanced, metastatic, or recurrent nonsquamous non-small cell lung cancer.Study enrollment was to occur in three phases. In the first phase, patients received PC + B (15 mg/kg every 3 weeks), ±S (25 mg daily, 2 weeks on, 1 week off). If tolerated, the second phase would include a third cohort receiving 37.5 mg S. The third phase would consist of PCB ± highest tolerable dose S.Between March 2007 and January 2008, 26 patients were randomized to receive PCB and 30 to PCB + S 25 mg. Because of poor tolerability, none of the patients were escalated to 37.5 mg S. Median treatment duration was 10.3 weeks for PCB and 6.0 weeks for PCB + S. Thirty-five percent of patients on PCB + S required S dose reduction, 52% required S treatment interruption, and 59% discontinued S because of adverse events, most frequently hematologic events (neutropenia, thrombocytopenia, and leukopenia) and fatigue. Patients receiving PCB + S required more B interruptions (38% versus 19% for PCB) and discontinuation (52% versus 35%) because of adverse events. Survival data were limited by small sample sizes and limited treatment duration. Overall survival was not mature at time of analysis: median 6.6 months for PCB + S and not reached for PCB. Two out of 25 efficacy-evaluable patients randomized to the PCB + S cohort had confirmed partial responses, compared with 5 of 19 randomized to the PCB cohort.The addition of S to PCB was not well tolerated because of toxicities. This combination should not be studied further at these doses and schedules

    Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

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    Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides
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