115 research outputs found
Formation and immunomodulatory function of meningeal B-cell aggregates in progressive CNS autoimmunity
No full textMeningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic Multiple Sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of Multiple Sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T cell- and B cell-receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of α4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of α4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with α4 integrin-sufficient T cells. B cell-conditional ablation of α4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with α4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20 percent of B cells in organised meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in Multiple Sclerosis
The Campfire as Pentecostal Vision in Hemingway\u27s Works
No full textErnest Hemingway\u27s main concern in representing human life through fictional forms, has consistently been to see man against the background of his world and universe, to examine the human situation from various points of view. The author\u27s prime goal is to depict the education of his hero. Within the text and the time of a given story Hemingway allows his hero to either accept or to reject the proper attitude in life. That portrayal of the acceptance or rejection enunciates another portion of the Hemingway code
A New Pulsed Co2 Laser Yielding New Fir Laser Lines From Ch 3od Pumped By The 10p And 10hp Lines
No full textUsing a novel CO2 pulsed laser that presents high peak power (several hundreds of watts) together with high spectral purity, we have reinvestigated the CH3OD isotopomer of methanol as a source of far infrared laser emissions pumped by the 10P and 10HP CO2 laser lines. Thirty-five new lines have been observed and characterized for wavelength, offset, relative polarization, optimum operation pressure and relative intensity.37919791984Chang, T.Y., Bridges, T.J., (1970) Opt. Commun., 1, p. 423Carelli, G., Ioli, N., Moretti, A., Pereira, D., Strumia, F., (1987) Appl. Phys. B, 44, p. 111Viscovini, R.C., Telles, E.M., Scalabrin, A., Pereira, D., (1997) Appl. Phys. B, 65, p. 33Bertolini, A., Beverini, N., Carelli, G., Francesconi, M., Ioli, N., Nannizzi, M., Moretti, A., Strumia, F., (2004) Rev. Sci. Instrum., , submittedDyubko, S.F., Svich, V.A., Fesenko, L.D., (1974) Sov. Phys. Tech. Phys., 18, p. 1121Pereira, D., Moraes, J.C.S., Telles, E.M., Scalabrin, A., Strumia, F., Moretti, A., Carelli, G., Massa, C.A., (1994) Int. J. Infrared Millim. Waves, 15, p. 1Zerbetto, S.C., Vasconcellos, E.C.C., (1994) Int. J. Infrared Millim. Waves, 15, p. 889Telles, E.M., Zink, L.R., Evenson, K.M., (1999) Int. J. Infrared Millim. Waves, 20, p. 741Vasconcellos, E.C.C., Zerbetto, S.C., Zink, L.R., Evenson, K.M., (2000) Int. J. Infrared Millim. Waves, 21, p. 477Vasconcellos, E.C.C., Dirocco, C., Chuzles, B., Knier, J., Schwalbe, J., Sutton, D., Jackson, M., (2003) Appl. Phys. B, 77, p. 97Costa, L.F.L., Cruz, F.C., Moraes, J.C.S., Pereira, D., (2004) IEEE J. Quantum Electron., , submittedFourrier, M., Kreisler, A., (1986) Appl. Phys. B, 41, p. 57Inguscio, M., Moretti, A., Strumia, F., (1979) Opt. Commun., 30, p. 355Ni, Y.C., Heppner, J., (1980) Opt. Commun., 32, p. 45
Reinvestigation of far-infrared laser emissions from hydrazine and deuterated isotopes of difluoromethane and methanol
No full textHydrazine (N2H4) and the deuterated isotopes of difluoromethane (CD2F2) and methanol (CH3OD and CD3OH) have been reinvestigated as sources of far-infrared (FIR) laser emissions using an optically pumped molecular laser system designed for wavelengths below 150 microns. With this system, seven FIR laser emissions from optically pumped N2H4, CH3OD and CD3OH were discovered with wavelengths ranging from 54.0 to 185.0 mum. In addition, the polarizations of eight previously observed laser emissions from optically pumped N2H4, CH3OD and CD2F2 were measured for the first time. All laser emissions are reported with their operating pressures, relative polarizations and wavelengths, measured to +/-0.5 mum. The effectiveness of this particular system in generating short-wavelength laser emissions has been further demonstrated by the improvement in output power observed from nine known FIR laser emissions.771979
Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study
No full textObjective: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. Methods: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. Results: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). Interpretation: Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618–629
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Automatic Generation of Strong, Light, Multi-Functional Structures from FEA Output
No full textAn automated process is being developed that will generate a minimal-mass lattice structure that
is fabrication-ready for a selected solid-freeform-fabrication (SFF) process. The results of a
standard, structural, finite-element analysis (FEA) are processed to define the selection,
alignment and sizing of unit lattice elements, such that a minimal-mass structure can be defined.
This process will allow for considerations of structural performance (e.g. safety factor), multiple
loads, as well as process parameters (e.g. materials and min./max. sizes). Further development
would lead to the definitions of composites and multi-functionality, as well as high-performance-computing (HPC) capabilities.Mechanical Engineerin
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Effective Thermal Conductivities of Unit-Lattice Structures for Multi-Functional Components
No full textApproaching the goal of automatically generating optimized multi-functional
components, previously-identified unit-lattice structures are being characterized for their
geometry-dependent, effective, thermal conductivities. This knowledge base will allow for the
definition of low-mass, load-bearing, thermal-management structures. One application is a
wearable power source for a custom, portable, active orthosis. The function of this structure is to
bear mechanical load while dissipating heat from the source, without burning the wearer.
Additive manufacturing affords the capability of fabricating the resultant complex structures.
Current research efforts are using finite-element analysis and physical testing to validate the
characteristic models, and determining the scale dependence of internal-convective-flow
development. Future work will include composites.Mechanical Engineerin
Neural System and Behavior course photograph 1984
No full textFaculty and students in the 1984 Neural Systems and Behavior course at the Marine Biological Laboratory in Woods Hole, MAOne multi-image tiff file comprised of six images and six jpeg images.NEURALSYSTEMSBEHAVIOR_1984-1.jpeg: Black and white group photo of the Neural System and Behavior course in 1984. Thirty-nine people posing next to water. Handwritten and circled numbers denoting identities of people and "NS&B 1984"NEURALSYSTEMSBEHAVIOR_1984-3.jpeg: Washed out copy of group photo "Neural Systems & Behavior (Doug Falls)NEURALSYSTEMSBEHAVIOR_1984-5.jpeg: Typed roster "NS & B 1984 Class Photo" followed by "1. Sabine Schafer, 2. Kip Keller, 3.Ron Hoy, 4. Tom Carew, 5. Eduardo Macagno, 6. Birgit Zipser, 7. Margy Nelson, 8. Lee Miller, 9. Blair Simpson, 10. Francisco Cervantes-Perez, 11. Don O'Malley, 12. Andy Bass, 13. David Lerner, 14. Doris Stoffers, 15. Eva Harris, 16. Cindy Sims, 17. Robin Ralls, 18. Julie Knier, 19. Matt Grober, 20. Doug Falls, 21. Robert Norgren,22. Elizabeth Gould, 23. Ed Arbus, 24. George Feher, 25. Neal Fischbach, 26. John Walsh, 27. Patricia Flynn, 28. Jackie Perex, 29. Neil Segil, 30. Dewey Meyers, 31. Weiqiang Gao, 32. Joe Fetcho, 33. Martha Tobia, 34. Laurie Miller, 35. Darcy Kelley, 36. Bruce Mendelson, 37. Richard Dunia, 38. Jack Byrne, 39. Ron Calabrese. Not pictured: Kenneth West, Gayne Bablanian, Susan DeRiemer, Ron Haris-Warrick, Bruce Johnson, Midge Marchaterre, Eve Marder, Dave Yager"photograph
Unusual catalytic activity of analogues of 2-iodoxybenzoic acid in the hydrolysis of active phosphates
No full textMyeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity
No full textPolymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE. The frequency of CD138+ B cells in the cerebrospinal fluid (CSF) of human subjects with multiple sclerosis was negatively correlated with the frequency of PMN-MDSCs in the CSF. Thus PMN-MDSCs might selectively control the accumulation and cytokine secretion of B cells in the inflamed CNS
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