ABSTRACT
The Facility for Antiproton and Ion Research (FAIR) is in its ï¬nal construction stage next to the campus of the Gesellschaft für Schwerionenforschung Helmholtzzentrum for heavy-ion research in Darmstadt, Germany. Once it starts its operation, it will be the main nuclear physics research facility in many basic sciences and their applications in Europe for the coming decades. Owing to the ability of the new fragment separator, Super-FRagment Separator, to produce high-intensity radioactive ion beams in the energy range up to about 2 GeV/nucleon, these can be used in various nuclear reactions. This opens a unique opportunity for various nuclear structure studies across a range of ï¬elds and scales: from low-energy physics via the investigation of multi-neutron systems and halos to high-density nuclear matter and the equation of state, following heavy-ion collisions, fission and study of short-range correlations in nuclei and hypernuclei. The newly developed reactions with relativistic radioactive beams (R3B) set up at FAIR would be the most suitable and versatile for such studies. An overview of highlighted physics cases foreseen at R3B is given, along with possible future opportunities, at FAIR. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.
ABSTRACT
Experimental studies of nuclear fission induced by fusion, transfer, spallation, fragmentation, and electromagnetic reactions in combination with state-of-the-art calculations are successful to investigate the nuclear dissipation mechanism in normal nuclear matter, containing only nucleons. The dissipation mechanism has been widely studied by the use of many different fission observables and nowadays the dissipation coefficients involved in transport theories are well constrained. However, the existence of hypernuclei and the possible presence of hyperons in neutron stars make it necessary to extend the investigation of the nuclear dissipation coefficient to the strangeness sector. In this Letter, we use fission reactions of hypernuclei to constrain for the first time the dissipation coefficient in hypernuclear matter, observing that this coefficient increases a factor of 6 in the presence of a single Λ hyperon with respect to normal nuclear matter.
ABSTRACT
Taking benefit of the R3B/SOFIA setup to measure the mass and the nuclear charge of both fission fragments in coincidence with the total prompt-neutron multiplicity, the scission configurations are inferred along the thorium chain, from the asymmetric fission in the heavier isotopes to the symmetric fission in the neutron-deficient thorium. Against all expectations, the symmetric scission in the light thorium isotopes shows a compact configuration, which is in total contrast to what is known in the fission of the heavier thorium isotopes and heavier actinides. This new main symmetric scission mode is characterized by a significant drop in deformation energy of the fission fragments of about 19 MeV, compared to the well-known symmetric scission in the uranium-plutonium region.
ABSTRACT
Spectroscopic factors of neutron-hole and proton-hole states in ^{131}Sn and ^{131}In, respectively, were measured using one-nucleon removal reactions from doubly magic ^{132}Sn at relativistic energies. For ^{131}In, a 2910(50)-keV γ ray was observed for the first time and tentatively assigned to a decay from a 5/2^{-} state at 3275(50) keV to the known 1/2^{-} level at 365 keV. The spectroscopic factors determined for this new excited state and three other single-hole states provide first evidence for a strong fragmentation of single-hole strength in ^{131}Sn and ^{131}In. The experimental results are compared to theoretical calculations based on the relativistic particle-vibration coupling model and to experimental information for single-hole states in the stable doubly magic nucleus ^{208}Pb.
ABSTRACT
Fifty-five inclusive single nucleon-removal cross sections from medium mass neutron-rich nuclei impinging on a hydrogen target at â¼250 MeV/nucleon are measured at the RIKEN Radioactive Isotope Beam Factory. Systematically higher cross sections are found for proton removal from nuclei with an even number of protons as compared to odd-proton number projectiles for a given neutron separation energy. Neutron removal cross sections display no even-odd splitting, contrary to nuclear cascade model predictions. Both effects are understood through simple considerations of neutron separation energies and bound state level densities originating in pairing correlations in the daughter nuclei. These conclusions are supported by comparison with semimicroscopic model predictions, highlighting the enhanced role of low-lying level densities in nucleon-removal cross sections from loosely bound nuclei.
ABSTRACT
Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.
ABSTRACT
The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.
Subject(s)
Cryptogenic Organizing Pneumonia/complications , Leukemia, T-Cell/complications , Leukemia, T-Cell/diagnosis , Adult , Anti-Inflammatory Agents/therapeutic use , Bronchoalveolar Lavage Fluid/cytology , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Cryptogenic Organizing Pneumonia/blood , Cryptogenic Organizing Pneumonia/drug therapy , Humans , Leukemia, T-Cell/classification , Male , Prednisolone/therapeutic useABSTRACT
Superantigens (SAg) are bacterial exotoxins that provoke extreme responses in the immune system; for example, the acute hyperactivation of SAg-reactive T cells that leads to toxic shock syndrome is followed within days by strong immunosuppression. The gamma interferon (IFN-gamma) response is deeply affected in both extremes. The implication of IFN-gamma in the pathophysiology of lethal shock induced in mice after a secondary challenge with the SAg staphylococcal enterotoxin B (SEB) prompted us to study the regulation of IFN-gamma secretion and the intracellular response. We demonstrate in this study that a rechallenge with SEB becomes lethal only when given inside a critical time window after SEB priming and is associated with an increase of IFN-gamma serum release 72 h after priming. However, at this time, a selective blockade of IFN-gamma/STAT1 signaling develops in spleen cells, correlating with a lack of expression of the IFN-gamma receptor beta subunit and STAT1 in the T-cell population. Selective blockade of the STAT1 signaling pathway--while simultaneously maintaining STAT3 signaling and expression--may be a protective mechanism that shortens IFN-gamma production during the Th1 effector response. This blockade may also have consequences on switching towards a suppressor phenotype with chronic exposure to the superantigen.
Subject(s)
Antigens, Bacterial/immunology , Enterotoxins/immunology , Receptors, Interferon/biosynthesis , STAT1 Transcription Factor/metabolism , Signal Transduction/immunology , Th1 Cells/immunology , Animals , Electrophoretic Mobility Shift Assay , Escherichia coli/immunology , Immune Tolerance , Interferon-gamma/biosynthesis , Ligands , Lymphocyte Activation/immunology , Mice , Mice, Inbred BALB C , Reverse Transcriptase Polymerase Chain Reaction , STAT1 Transcription Factor/immunology , Shock, Septic/immunology , Superantigens/immunology , Interferon gamma ReceptorABSTRACT
During the effector phase of graft-versus-host disease (GvHD) response, donor T cells play an essential role and they are believed to change the expression of activation and co-stimulatory markers associated with functional alloreactivity. We analysed the expression of CD25, CD69, HLA-DR, CD154 and CD134 on CD4+ and CD8+ T cells by flow cytometry during acute GvHD (aGvHD) in 24 patients receiving human leucocyte antigen (HLA)-identical stem cell transplants. Expression of these molecules in nine patients with stages I-IV aGvHD was compared with 15 patients without aGvHD (n = 15). Serial analysis showed that peripheral blood of aGvHD patients presented a significant increase of CD4+ CD25+ cells (P < 0.03), CD4+ CD69+ (P < 0.04) and CD4+ CD134+ cells (P < 0.01). Additionally, there was a significant increase in CD8+ cells expressing CD134 (P = 0.007) and CD154 (P = 0.02). After resolution of aGvHD, the increased expression of these molecules returned to values comparable to patients without aGvHD. Only two of the 15 patients without clinical signs of aGvHD presented activated T cells that could not be attributed to development of aGvHD. In summary, our data show that multiple activation molecules are preferentially up-regulated on CD4+ and CD8+ T cells from patients with aGvHD. These patients had a significant increase in the expression of the co-stimulatory molecules CD134 and CD154.
Subject(s)
CD3 Complex/immunology , Graft vs Host Disease/immunology , T-Lymphocytes/immunology , Acute Disease , Adult , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Biomarkers/blood , CD4-Positive T-Lymphocytes/immunology , CD40 Ligand/analysis , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Female , Flow Cytometry , HLA-DR Antigens/analysis , Humans , Lectins, C-Type , Lymphocyte Activation/immunology , Male , Middle Aged , Receptors, Interleukin-2/analysis , Receptors, OX40 , Receptors, Tumor Necrosis Factor/analysis , Statistics, NonparametricABSTRACT
The activation of STAT1 and STAT3 in response to SEB was analyzed in spleen of Balb/c mice. The intraperitoneal injection of the superantigen SEB activated STAT1 and STAT3 in spleen. Activated STAT1 almost completely disappeared in 24 h even though activated STAT3 was present for more than 48 h after SEB injection. Cyclosporine A was able to block the initial STAT1 activation, but STAT3 activation was only partially affected. SEB also increased the mRNA levels for STAT1, STAT3 and SOCS1. When a second injection with SEB was given 72 h after the first stimulus, STAT1 activation was much lower than that observed after the first stimulation with SEB and no increase in the STAT1 mRNA level was observed. Nevertheless, after this second injection, STAT3 was again activated without any significant interference from the first stimulus and the STAT3 and SOCS1 mRNA levels again increased. These data indicate that a first stimulation with superantigen re-programs cells so that they respond to a second stimulation in a different way. Understanding the mechanisms implicated in this re-programming is basic for designing therapeutic strategies in processes such as septic shock.
Subject(s)
DNA-Binding Proteins/immunology , Superantigens/immunology , Trans-Activators/immunology , Transcription Factors/immunology , Animals , Carrier Proteins/genetics , Carrier Proteins/immunology , Carrier Proteins/metabolism , Cyclosporine/pharmacology , Cytokines/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Dimerization , Enterotoxins/pharmacology , Female , Kinetics , Mice , Mice, Inbred BALB C , RNA, Messenger/metabolism , Repressor Proteins/genetics , Repressor Proteins/immunology , Repressor Proteins/metabolism , STAT1 Transcription Factor , STAT3 Transcription Factor , Spleen/drug effects , Spleen/immunology , Superantigens/pharmacology , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
A cord blood unit from the Umbilical Cord Bank of Barcelona was initially typed by sequence-based typing (SBT) as DRB1* 0701. However, the subsequent confirmation by sequence-specific oligonucleotide probes (SSOP) revealed an unusual hybridization pattern that did not fit any of the known HLA-DRB1 alleles or allelic combinations. Molecular cloning and sequencing with primers located at introns 1 and 2 provided the definitive identification of a novel DRB1*1446 allele. It was similar to DRB1*1402 at exon 2 except for nucleotide substitutions at codons 10, 11 and 12 (from YST to LRK) that coincide with the 5'-end group specific site for the annealing of common amplification primers used by SBT and sequence-specific primers.
Subject(s)
Alleles , DNA Primers , Genetic Variation , HLA-DR Antigens/genetics , Fetal Blood , HLA-DQ Antigens/genetics , HLA-DRB1 Chains , Heterozygote , Humans , Molecular ProbesABSTRACT
We report here the sequence of an HLA B*15 allele, B*1573. Initially, a cord blood unit from the Umbilical Cord Bank of Barcelona was typed by sequence-specific oligonucleotide hybridization and revealed an unusual hybridization pattern. After the cloning, the sequence-based typing assigned two different alleles: B*07021, and a second allele identical to B*1558 in exons 2 and 3, except for a single nucleotide substitution in exon 3, which changed codon 140 from Phe to Leu (TTX-->TTA).
Subject(s)
Alleles , HLA-B Antigens/genetics , Base Sequence , Exons , Fetal Blood/immunology , HLA-B Antigens/immunology , HLA-B15 Antigen , Histocompatibility Testing , Humans , Molecular Sequence Data , Nucleic Acid Hybridization , Polymerase Chain Reaction , Sequence AlignmentABSTRACT
We report here a novel DRB1 allele identified during sequence-based HLA-DRB typing. This allele was detected during routine HLA typing of a patient and his family prior to bone marrow transplantation. The new allele, DRB1*0108, was found in the patient and in a brother. Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*0101 at exon 2 except for a single nucleotide substitution at codon 37 (TauCC-->TauAlphaC), changing the encoded serine to tyrosine. This position of the beta1 domain lies in the floor of the antigen-binding groove and shows the highest polymorphism among DRB1 alleles.
Subject(s)
Alleles , HLA-DR Antigens/genetics , Base Sequence , HLA-DRB1 Chains , Humans , SiblingsABSTRACT
The DRB1* polymorphism in 941 randomly selected individuals from the Umbilical Cord Blood Bank of Barcelona (92.75% of Spanish origin) was determined by sequence-based typing. The HLA profile was similar to that of other Mediterranean populations, with DRB1*0701 and *0301 being the most frequent alleles. This may be a consequence of the mixture of alleles as a result of migration from contiguous geographical areas.
Subject(s)
HLA-DR Antigens/genetics , Polymorphism, Genetic , Alleles , Gene Frequency , HLA-DRB1 Chains , Humans , SpainABSTRACT
CD8 glycoproteins play an important role in both the maturation and function of MHC class I-restricted T lymphocytes. A 25-year-old man, from a consanguineous family, with recurrent bacterial infections and total absence of CD8(+) cells, was studied. Ab deficiencies and ZAP-70 and TAP defects were ruled out. A missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene was shown to correlate with the absence of CD8 expression found in the patient and two sisters. Conversely, high percentages of CD4(-)CD8(-)TCR alpha beta(+) T cells were found in the three siblings. A novel autosomal recessive immunologic defect characterized by absence of CD8(+) cells is described. These findings may help to further understanding of the role of CD8 molecules in human immune response.
Subject(s)
Amino Acid Substitution , CD8 Antigens/genetics , Immunologic Deficiency Syndromes/genetics , Mutation, Missense , Adult , Animals , Antibody Formation , Bacterial Infections/etiology , CD8 Antigens/chemistry , COS Cells , Chlorocebus aethiops , Consanguinity , Cytotoxicity, Immunologic , DNA Mutational Analysis , Dimerization , Female , Genes, Recessive , Genotype , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/pathology , Male , Molecular Sequence Data , Mutation , Pedigree , Protein Subunits , Recombinant Fusion Proteins/immunology , Recurrence , Roma/genetics , Spain , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/pathology , TransfectionABSTRACT
We report a novel HLA-B*41 allele (HLA-B*4106) initially detected by an unusual sequence-specific oligonucleotide (SSO) hybridization pattern and identified by sequence-based HLA typing. Molecular cloning and sequencing determined that the new HLA-B allele was identical to the HLA-B*4101 in exon 2 and 3 except for a single nucleotide substitution in the exon 3 changing codon 204 from Glu to Gln (GAG-->CAG). In addition, intron 2 was identical to the published HLA-B*4104 intron 2, except for the base 509 (C-->G).
Subject(s)
HLA-B Antigens/analysis , HLA-B Antigens/genetics , Histocompatibility Testing/methods , Alleles , Base Sequence , Fetal Blood , Humans , Molecular Sequence Data , Nucleic Acid Hybridization , Polymorphism, Single Nucleotide , Sequence Alignment , Sequence Analysis, DNAABSTRACT
We previously described autoantibodies against a UGA serine tRNA-protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec antibodies was highly specific for type-1 autoimmune hepatitis, as 47.5% of patients were positive compared with none of the control subjects. To characterize the antigenic protein(s), we immunoscreened a human cDNA library with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone 19 encodes a protein with a predicted molecular mass of 48.8 kD. Clone 13 is a shorter cDNA, almost identical to clone 19, which encodes a 35.9-kD protein. Expression of both cDNAs was accomplished in Escherichia coli as His-tagged recombinant proteins. Antibodies eluted from both purified recombinant proteins were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract, demonstrating their cross-reactivity with the mammalian antigenic complex. Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec.
Subject(s)
Autoantibodies/immunology , Autoantigens/genetics , Autoimmune Diseases/immunology , DNA, Complementary/genetics , Hepatitis, Autoimmune/immunology , RNA, Messenger/genetics , RNA, Transfer, Amino Acyl/metabolism , Adolescent , Adult , Aged , Amino Acid Sequence , Antibody Specificity , Autoantigens/immunology , Base Sequence , Blotting, Western , DNA, Complementary/isolation & purification , Genes , Genes, Suppressor , HeLa Cells/chemistry , Humans , Liver/immunology , Liver Diseases/immunology , Macromolecular Substances , Middle Aged , Molecular Sequence Data , Pancreas/immunology , Recombinant Fusion Proteins/immunology , Sensitivity and SpecificityABSTRACT
Mice injected at birth with semiallogeneic spleen cells develop a host-versus-graft disease (HVGD) characterized by the polyclonal activation of donor B cells by alloreactive host CD4+ T cells, the production of autoantibodies (autoAb) and the development of an inmmunocomplex-mediated glomerulonephritis. It has been demonstrated that the recognition of MHC class II, but not class I or non MHC, alloantigens triggers the development of the autoimmune syndrome (AIS). The finding of different expression patterns of Ia molecules in different mouse strains, and a closed restriction of some immune responses to particular H-2 haplotypes, prompted us to analyze whether variations in the expressed MHC class II molecules modify the HVGD. First, newborn BALB/c mice received spleen cells from F1 hybrid mice obtained by mating BALB/c mice with several mouse strains differing in the H-2 haplotype. Second, spleen cells from different F1 mice were neonatally injected in mice of both parental strains. All groups of BALB/c mice injected with different combinations of F1 mice showed an HVGD with a very similar serological course. However, in some instances, duration was different when comparing both parental strains injected with spleen cells from the mutual F1 hybrids. These results suggest that host MHC, but not donor MHC haplotype may modulate the AIS associated with the induction of neonatal tolerance.
Subject(s)
H-2 Antigens/immunology , Host vs Graft Reaction/immunology , Immune Tolerance , Isoantigens/immunology , Animals , Animals, Newborn , Autoimmune Diseases , Haplotypes , Mice , Mice, Inbred Strains , Spleen/cytology , Spleen/immunologyABSTRACT
Autoantibodies to aminoacyl-tRNA synthetases are highly associated with myositis and detection is important in clinical diagnosis; however, current methods of screening limit its clinical utility. In the present study, alanyl-tRNA synthetase (PL-12) recombinant protein was obtained by immunological screening of a HeLa expression library and used in an ELISA with 22 anti-PL-12 sera, 200 autoimmune sera negative for PL-12 and 100 healthy individual sera. Sensitivity of the method was 95% (21/22) and specificity 100%. Mapping of the immunoreactive region was carried out using three anti-PL-12 sera and different recombinant protein-derived peptides. Results show that the same conformational epitope located within amino acids 730-951 of the PL-12 antigen outside the catalytic region was recognized by the three anti-PL-12 sera tested. We conclude that ELISA using recombinant protein is an effective and useful method for routine screening for anti-PL-12 autoantibodies.
Subject(s)
Alanine-tRNA Ligase/immunology , Autoantibodies/analysis , Enzyme-Linked Immunosorbent Assay/methods , Alanine-tRNA Ligase/genetics , Autoantibodies/immunology , Autoantigens/genetics , Autoantigens/immunology , Cloning, Molecular , Epitope Mapping , Epitopes, B-Lymphocyte/immunology , HeLa Cells , Humans , Recombinant Proteins/genetics , Recombinant Proteins/immunologyABSTRACT
We identified three patients (two of them relatives) with RA and signs of scleroderma whose sera contained a high titre of IgG class antibodies against the nucleoli and the nucleoplasm of cells of different mammalian origins. Sera from these patients uniformly immunoprecipitated four polypeptides, from a 35S-methionine-labelled HeLa cell extract, whose mol. wts were 120, 105, 95 and 42 kD. Of these, the 95-kD protein was highly phosphorylated. By immunoblotting, these sera reacted with 105-, 95- and 42-kD proteins and affinity-purified antibodies from these, demonstrating that 105- and 95-kD proteins shared cross-reactive epitopes. Moreover, affinity-purified antibodies from each of these proteins immunoprecipitated the whole complex. Localization studies using immunoelectron microscopy and in vivo actinomycin-D-treated cells demonstrated that the 105-, 95- and 42-kD proteins were present in the granular component of the nucleolus and the nucleoplasm. In addition, the 105- and 95-kD were present in free polyribosomes as well as ribosomes attached to endoplasmic reticulum. Pulse/chase experiments strongly suggested that the complex was accomplished shortly after a 10-min pulse. It was preferentially present in the nucleus after a 2 h chase and in both nucleus and cytoplasm after a 5 h chase. We conclude that a protein complex with a main nucleolar distribution is a new autoantigen (p105-p42) recognized by autoantibodies present in the serum of a subgroup of patients with RA and scleroderma signs. These antibodies could be useful as diagnostic markers and as tools for further studies involving the biology of the nucleolus.