373 research outputs found
Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo.
No full text"Self" melanocyte differentiation antigens are potential targets for specific melanoma immunotherapy. Vaccination against murine tyrosinase-related protein (TRP)-1/gp75 was shown recently to cause melanoma rejection, which was accompanied by autoimmune skin depigmentation (vitiligo). To further explore the linkage between immunotherapy and autoimmunity, we studied the response to vaccination with a related antigen, TRP-2. i.m. inoculation of plasmid DNA encoding murine trp-2 elicited antigen-specific CTLs that recognized the B16 mouse melanoma and protected the mice from challenge with tumor cells. Furthermore, mice bearing established s.c. B16 melanomas rejected the tumor upon vaccination with a recombinant vaccinia virus encoding trp-2. Depletion experiments showed that CD8+ lymphocytes and natural killer cells were crucial for the antitumor activity of the trp-2-encoding vaccines. Mice that rejected the tumor did not develop generalized vitiligo, indicating that protective immunity can be achieved in the absence of widespread autoimmune aggression
Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo
No full text"Self" melanocyte differentiation antigens are potential targets for specific melanoma immunotherapy. Vaccination against murine tyrosinase-related protein (TRP)-1/gp75 was shown recently to cause melanoma rejection, which was accompanied by autoimmune skin depigmentation (vitiligo). To further explore the linkage between immunotherapy and autoimmunity, we studied the response to vaccination with a related antigen, TRP-2. i.m. inoculation of plasmid DNA encoding murine trp-2 elicited antigen-specific CTLs that recognized the B16 mouse melanoma and protected the mice from challenge with tumor cells. Furthermore, mice bearing established s.c. B16 melanomas rejected the tumor upon vaccination with a recombinant vaccinia virus encoding trp-2. Depletion experiments showed that CD8+ lymphocytes and natural killer cells were crucial for the antitumor activity of the trp-2-encoding vaccines. Mice that rejected the tumor did not develop generalized vitiligo, indicating that protective immunity can be achieved in the absence of widespread autoimmune aggression
Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells.
No full textFollowing an infection or immunization, a primary CD8+ T cell response generally rises then falls rapidly before giving rise to a "memory" response. When we immunized mice with recombinant viral immunogens optimized to enhance the lytic capability of CD8+ T cells, we measured a profound depression in Ag-specific effector function after early restimulation. Indeed, a "mirror image" cytolytic capability was observed: the most powerful immunogens, as measured by cytolytic capacity 6 days after immunization, elicited the weakest secondary immune response when evaluated following an additional 6 days after restimulation. To understand the mechanism of this suppression, we examined the fate of splenocytes immunized with a vaccinia virus encoding Ag and IL-2 then restimulated ex vivo. We found that these splenocytes underwent an apoptotic cell death, upon early restimulation, that was not dependent on the engagement of the FasR (CD95). Unlike previously described mechanisms of "propriocidal cell death" and "clonal exhaustion," the cell death we observed was not an inherent property of the CD8+ T cells but rather was due to a population of splenocytes that stained positive for both the Mac-1 and Gr-1 surface markers. Deletion of these cells in vitro or in vivo completely abrogated the observed suppression of cytolytic reactivity of Ag-specific CD8+ T cells. These observations could account for the apparent absence of Ag-specific immune responses after some current vaccination regimens employing powerful immunogens. Finally, our results may shed new light on a mechanism for the suppression of CD8+ T cell responses and its effect on vaccine efficacy and on immune memory
The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis
No full textDepression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP-D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP-D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit
Modern approaches to marine antifouling coatings
No full textMarine structures such as platforms, jetties and ship hulls are subject to diverse and severe biofouling. Methods for inhibiting both organic and inorganic growth on wetted substrates are varied but most antifouling systems take the form of protective coatings. Biofouling can negatively affect the hydrodynamics of a hull by increasing the required propulsive power and the fuel consumption. This paper reviews the development of antifouling coatings for the prevention of marine biological fouling. As a result of the 2001 International Maritime Organization (IMO) ban on tributyltin (TBT), replacement antifouling coatings have to be environmentally acceptable as well as maintain a long life. Tin-free self-polishing copolymer (SPC) and foul release technologies are current applications but many alternatives have been suggested. Modern approaches to environmentally effective antifouling systems and their performance are highlighted
The impact of nuclear masses near on -process abundances
No full textWe have performed for the first time a complete -process mass sensitivity
study in the region. We take into account how an uncertainty in a single
nuclear mass propagates to influence important quantities of neighboring
nuclei, including Q-values and reaction rates. We demonstrate that nuclear mass
uncertainties of MeV in the region result in up to an order of
magnitude local change in -process abundance predictions. We identify key
nuclei in the study whose mass has a substantial impact on final -process
abundances and could be measured at future radioactive beam facilities.Comment: 7 pages, 3 figures, submitte
Evolution of single particle strengths in tin isotopes and impacts on neutron capture
No full textAtomic nuclei with a few nucleons beyond shell closures are important in understanding the evolution of single-particle structure, which is critical to the benchmarking of nuclear models. With radioactive ion beams, studies near the double closed shell nucleus 132Sn have been made possible. While the single-neutron states in 133Sn with N = 83 and 131Sn with N = 81 have recently been verified to be highly pure, it is important to study further from the N = 82 neutron shell closure. Level energies and spectroscopic information for neutron-rich nuclei also provide important input for the rapid neutron capture r-process nucleosynthesis calculations. Specifically, it is important to know the location and strength of single-neutron states with orbital angular momentum l= 1 when calculating neutron-capture rates. Surman and collaborators have performed sensitivity studies to show that varying neutron-capture rates can significantly alter final r-process abundances. However, there are many nuclei important to the r-process that cannot be studied. Extending studies to more neutron-rich nuclei will help constrain the nuclear shell model in extrapolating to nuclei even further from stability. The (d, p) neutron transfer reaction has been measured in inverse kinematics with radioactive ion beams of 126Sn and 128Sn and a stable beam of 124Sn, all in inverse-kinematics at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory, utilizing the SuperORRUBA (Oak Ridge Rutgers University Barrel Array) of silicon detectors. The present work is combined with previous studies to complete the set of (d, p) studies on even mass tin isotopes from doubly-magic 132Sn to stable 124Sn and the systematics of l = 1 and l = 3 strengths. The results of the (d, p) study are used to map the fragmentation of single-neutron strengths in N ≤ 82 tin isotopes and to calculate the direct-semidirect neutron capture on these even mass tin isotopes that are important for the astrophysical r-process.Ph.D.Includes bibliographical referencesby Brett Montgomery Mannin
Reconstructing Masses of Merging Neutron Stars from Stellar r-process Abundance Signatures
No full textAbstract
Neutron star mergers (NSMs) are promising astrophysical sites for the rapid neutron-capture (“r”) process, but can their integrated yields explain the majority of heavy-element material in the Galaxy? One method to address this question implements a forward approach that propagates NSM rates and yields along with stellar formation rates and compares those results with observed chemical abundances of r-process-rich, metal-poor stars. In this work, we take the inverse approach by utilizing r-process-element abundance ratios of metal-poor stars as input to reconstruct the properties—especially the masses—of their neutron star (NS) binary progenitors. This novel analysis provides an independent avenue for studying the population of the original NS binary systems that merged and produced the r-process material now incorporated in Galactic metal-poor halo stars. We use ratios of elements typically associated with the limited-r-process and the actinide region to those in the lanthanide region (i.e., Zr/Dy and Th/Dy) to probe the NS masses of the progenitor merger. We find that NSMs can account for all r-process material in metal-poor stars that display r-process signatures, while simultaneously reproducing the present-day distribution of double-NS systems. Notably, with our model assumptions and the studied stellar sample, we postulate that the most r-process enhanced stars (the r–II stars) on their own would require progenitor NSMs of asymmetric systems that are distinctly different from present ones in the Galaxy. We also explore variations to the model and find that the predicted degree of asymmetry is most sensitive to the electron fraction of the remnant disk wind.</jats:p
Do we owe our existence to gravitational waves?
No full textTwo heavy elements essential to human biology are thought to have been produced by the astrophysical r-process, which occurs in neutron-rich environments: iodine is a constituent of thyroid hormones that affect many physiological processes including growth and development, body temperature and heart rate, and bromine is essential for tissue development and architecture. Collisions of neutron stars (kilonovae) have been identified as sources of r-process elements including tellurium, which is adjacent to iodine in the periodic table, and lanthanides. Neutron-star collisions arise from energy loss due to gravitational-wave emission from binary systems, leading us to suggest that gravitational waves have played a key role in enabling human life by producing iodine and bromine. We propose probing this proposal by searching in lunar material for live 129I deposited by a recent nearby kilonova explosion.Two heavy elements essential to human biology are thought to have been produced by the astrophysical -process, which occurs in neutron-rich environments: iodine is a constituent of thyroid hormones that affect many physiological processes including growth and development, body temperature and heart rate, and bromine is essential for tissue development and architecture. Collisions of neutron stars (kilonovae) have been identified as sources of -process elements including tellurium, which is adjacent to iodine in the periodic table, and lanthanides. Neutron-star collisions arise from energy loss due to gravitational-wave emission from binary systems, leading us to suggest that gravitational waves have played a key role in enabling human life by producing iodine and bromine. We propose probing this proposal by searching in lunar material for live I deposited by a recent nearby kilonova explosion
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