Profiling of micrometer sized laser beams in restricted volumes

We present a method for determining the 3D intensity distribution of directed laser radiation with micrometer resolution in restricted volumes. Our method is based on in-coupling and guiding properties of optical fibers, with the current version requiring only few hundred micrometers. We characterize the performance of the method and experimentally demonstrate profiling of micrometer sized laser beams. We discuss the limiting factors and routes towards a further increase of the resolution and beam profiling in even more restricted volumes. Finally, as an application example, we present profiling of laser beams inside a micro ion trap with integrated optical fibers

Plasma sheet structure in the magnetotail: kinetic simulation and comparison with satellite observations

We use the results of a three-dimensional kinetic simulation of an Harris current sheet to propose an explanation and to reproduce the ISEE-1/2, Geotail, and Cluster observations of the magnetotail current sheet structure. Current sheet flapping, current density bifurcation, and reconnection are explained as the results of the kink and tearing instabilities, which dominate the current sheet evolution.Comment: Submitted to Geophys. Res. Lett. (2003

Magnetic field topology during July 14–16 2000 (Bastille Day) solar CME event

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95295/1/grl15382.pd

Does epigenetics play a role in the pathology of osteoarthritis?

Idiopathic osteoarthritis (OA) is a complex, late-onset disease whose causes are still unknown. In spite of tremendous efforts, the search for the genes pre-disposing towards osteoarthritis has so far met with little success. We hypothesize that epigenetic changes play a major role in the pathology of OA. Epigenetics refers to stable, heritable, but potentially reversible modifications of gene expression that do not involve mutations in the DNA sequence, for example DNA methylation or histone modification. Epigenetic changes are gene and cell-type specific, may arise sporadically with increasing age or be provoked by environmental factors. To investigate whether epigenetic changes are significant factors in OA, we examined the DNA methylation status of the promoter regions of three genes that are expressed by OA, but not by normal, articular chondrocytes, namely MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and MMP-13 (collagenase3). We hypothesized that these genes are silenced in normal chondrocytes by methylation of the cytosines of CpG dinucleotides in the respective promoter regions, but that abnormal expression is associated with a de-methylation, leading to eunsilencing f of gene expression. Cartilage was obtained from the femoral heads of 16 OA and 10 femoral neck fracture (#NOF) patients, which served as controls due to the inverse relationship between osteoporosis and OA. The cartilage was milled in a freezer mill with liquid nitrogen, DNA was extracted with a Qiagen kit, digested with methylation sensitive restriction enzymes, followed by PCR amplification. These enzymes will cut at their specific cleavage sites only if the CpGs is not methylated and thus allow us to determine methylation status of specific CpG sites.Results. Less than 5% of the chondrocytes in superficial layer from #NOF cartilage expressed degradative enzymes, whereas all cloned chondrocytes from advanced-stage OA cartilage were immunopositive. The overall % of CpG demethylation in the promoters of control patients (whose chondrocytes did not express the enzymes) was 20.1%, whereas 48.6% of CpG sites were demethylated in degradative chondrocytes of OA patients (p<0.001). For MMP-13, the increase in demethylation between control and OA was from 4 ..20%; for MMP-9 from 47 ..81% and for MMP-3 from 30 ..57%. However, not all available CpG sites were equally demethylated. Some sites were uniformly methylated in both OA and controls, others were demethylated even in controls. However, there was at least one crucial site for each degradative enzyme, where the differences in the degree of methylation were greatest and statistically different. These sites were at –110 for MMP-13; –36 for MMP-9; –635 for MMP-3. There was no relation between the % demethylation and the patient fs age and no apparent difference between males and females.Conclusions: We have demonstrated an association between abnormal gene expression of MMP-3, MMP-9 and MMP-13 and promoter DNA demethylation. This epigenetic dysregulation of genes appeared to be clonally inherited by daughter cells and may be typical for osteoarthritis and other complex, late-onset diseases.Correspondence should be addressed to Mr Carlos Wigderowitz, Honorary Secretary BORS, University Dept of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School, Dundee DD1 9SY.None of the authors have received anything of value from a commercial or other party related directly or indirectly to the subject of the presentatio

Atypical progressive multifocal leukoencephalopathy in HIV with a high CD4 count: the use of magnetic resonance imaging plus spectrometry studies

Progressive multifocal leukoencephalopathy (PML) is still a underinvestigated central nervous system infection, often linked to HIV-related immunodeficiency. We present an unusual case report characterized by motor involvement, which occurred as the first AIDS-defining event in the absence of appreciable immunodeficiency in a patient with previously undiagnosed HIV infection, who was also assessed by a functional-metabolic magnetic resonance imaging technique (MRI-spectrometry). A 45-year-old patient had HIV infection detected after the appearance of motor abnormalities, in the absence of other signs or symptoms. No significant immunodeficiency was found (initial CD4+ lymphocyte count of 566 cells/μL), and HIV viral load was 24,000 RNA copies/mL. Combination antiretroviral therapy was started with lamivudine, abacavir and lopinavir/ritonavir, with subsequent addition of efavirenz and enfuvirtide. Elevated cerebrospinal fluid levels of JC virus (JCV) (11,668 copies/μL) and consistent neuroradiological findings at contrast-enhanced computed tomography and MRI scans confirmed a diagnosis of PML. Despite the aggressive therapeutic approach, which achieved undetectable HIV viraemia, a CD4+ count above 700 cells/μL and disappearance of JCV after 20 days, the neurological motor involvement rapidly deteriorated, yet associated cognitive impairment never occurred. Clinical and neuroradiological deterioration occurred, and our patient died five months after the diagnosis due to respiratory failure. Combined MRI-spectrometry studies performed 10 days before death included proton ((1)H) spectrometry, and an MRI study-calculation of water diffusion and anisotropy: through this innovative technique combining morphological and metabolic findings, multiple abnormalities involving the subtentorial white matter were detected (with multiple encephalic trunk and ponto-bulbar lesions), which usually are not part of the PML course

Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart.

Morphological, electrophysiological, and biochemical properties of H9c2 cells, a permanent cell line derived from rat cardiac tissue, were studied. Although the lectin binding pattern revealed similar sugar residues in the surface coat ofH9c2 cells and isolated rat cardiocytes, heart-specific morphological structures could not be detected in H9c2 cells. Under physiological ionic conditions, H9c2 cells exhibited an outwardly rectifying, transient K ' current. When this current component was blocked by Ba2 ' and Cs+, we observed an inward current through Ca21 channels (15.8±2.2 pA/pF, n=18, measured as Ba21 current) that showed all characteristics of cardiac L-type currents. The activation kinetics were fast, and the current was stimulated by isoprotere-nol. The effect of isoproterenol was mimicked by forskolin or intracellularly applied cAMP. In radioligand binding experiments, we identified a specific, saturable, stereoselective and reversible high-affinity [3H]-(+)PN 200-110 binding with a dissociation constant Kd=0.53+0.28 nM and a maximal specific binding of Bm.=129.3+16.1 fmollmg protein. There was an additional low-affinity/high-capacity binding site, which is unlikely to be related to a Ca21 channel protein. Signal-transducing G proteins in membranes were characterized by [32P]ADP-ribosylation catalyzed by bacterial toxins and by the use of various antibodies. Cholera toxin substrates of 4