Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity.

Natural and lymphokine activated killer cells (NK and LAK) are believed to play an important role in the control of tumour progression and metastasis. Their specific receptors on tumours cells are still unknown. Several studies suggest that these cells recognise and eliminate abnormal cells with deleted or reduced expression of MHC class I molecules. Previous reports suggest that interferons (IFN), by increasing MHC class I expression on target cells, induce resistance to killing by NK cells. We investigated the role of MHC molecule expression by two human breast cancer cell lines T47D and ZR75-1 in their susceptibility to NK and LAK cells. These two cell lines spontaneously express low levels of HLA class I antigens but no HLA class II molecules. After IFN-gamma treatment they both overexpressed MHC class I and de novo expressed class II molecules as detected by flow cytometry, quantified by a radioimmunoassay and analysed by two-dimensional gel electrophoresis. Opposed to untreated cells these IFN-gamma treated cells were resistant to NK and LAK lysis. Furthermore, preincubation of IFN-gamma treated breast cancer cells with F(ab')2 fragments of monoclonal antibodies to HLA class I and HLA class II molecules was unable to restore lysis. In contrast, several complete monoclonal antibodies including anti-HLA class I and HLA class II induced the lysis of target cells whether or not they had been treated by IFN-gamma. The therapeutic use of monoclonal antibodies directed against antigens expressed on tumour cells (ADCC) in conjunction with interferon therapy should be discussed in lymphokine-based strategies for treatment of cancer patients

AST/ALT ratio is not an index of liver fibrosis in chronic hepatitis C when aminotransferase activities are determinate according to the international recommendations.

OBJECTIVE: The aspartate aminotransferase activity (AST)/alanine aminotransferase activity (ALT) ratio is used as liver fibrosis index whereas the reported data are conflicting. In chronic hepatitis C (CHC), reported diagnostic accuracies range from none to good for significant fibrosis and to excellent for cirrhosis. Assuming that AST/ALT increases are mainly due to vitamin B6 defects since pyridoxal phosphate (PLP), active form of B6, acts as coenzyme in transamination reactions, we evaluated the diagnostic accuracy of the AST/ALT ratio using standardized methods for AST and ALT activities, with PLP addition as recommended, in a prospective multicenter cohort of CHC patients. METHODS: ALT and AST activities were measured using the recommended IFCC methods with addition of pyridoxal 5\u27-phosphate. We evaluated the AST/ALT ratio for the diagnosis of liver fibrosis or cirrhosis in a cohort of CHC patients included in a multicenter prospective study. A liver biopsy was performed in each patient and reviewed by two independent pathologists in order to determine the fibrosis stage according to Metavir classification which was the reference standard. RESULTS: AST/ALT ratio significantly increased with histological stage of liver fibrosis and there was a significant correlation between Metavir fibrosis stage and AST/ALT ratio (r=0.129, P<0.0035). The ROC curve analyses showed that the AST/ALT ratio does not discriminate significant fibrosis (F≥2) (AUROC=0.531) and had only very poor diagnostic accuracies for severe fibrosis (F≥3) (AUROC=0.584) or cirrhosis (F4) (AUROC=0.626). CONCLUSION: AST/ALT ratio is not a good and discriminative index of liver fibrosis in CHC when aminotransferase activities are determinate according to the international recommendations

Neutron-proton interaction in rare-earth nuclei: Role of tensor force

We investigate the role of the tensor force in the description of doubly odd deformed nuclei within the framework of the particle-rotor model. We study the rare-earth nuclei 174Lu, 180Ta, 182Ta, and 188Re using a finite-range interaction, with and without tensor terms. Attention is focused on the lowest K=0 and K=1 bands, where the effects of the residual neutron-proton interaction are particularly evident. Comparison of the calculated results with experimental data evidences the importance of the tensor-force effects.Comment: 8 pages, 5 figures, to be published on Physical Review

Les débats entre État, Église catholique et Églises réformées autour de l’édit de tolérance de 1787

Un siècle après l’édit de Fontainebleau de 1685 qui révoque l’édit de Nantes, et à la suite de nombreux débats, Louis XVI accorde en novembre 1787 aux non-catholiques du royaume, protestants et juifs, un édit que l’on appelle couramment l’édit de tolérance ou l’édit de Breteuil, du nom du secrétaire d’État qui a participé à sa rédaction. Ce texte ne donne en aucune façon une quelconque liberté de culte aux non-catholiques, mais uniquement un état civil. En effet, désormais, ils peuvent faire enregistrer les naissances, mariages et décès de leurs communautés, réhabiliter les unions illégales contractées avant l’édit et faire légitimer les enfants nés de ces unions auprès d’un juge ou d’un curé, ce dernier n’ayant aucun rôle religieux mais devenant seulement un officier d’état civil . Depuis la fin du XVIIe siècle, les protestants français, car ce sont principalement eux qui sont concernés par cette loi, refusent la plupart du temps de faire célébrer leur union par un curé, se contentant de la signature d’un contrat notarié et de la bénédiction éventuelle d’un pasteur du Désert, comme ils renoncent également à faire baptiser les enfants nés de ces unions et à demander une sépulture au curé dans le cimetière catholique ; ces comportements, variables selon les provinces, se trouvent confortées par le synode national du Désert de 1744 qui exhorte les réformés à n’accepter aucune compromission avec la confession adverse . Ainsi, tout au long du siècle des Lumières, une partie de la population française vit sans état civil. Ce ne sont pas les mesures répressives prises contre les réformés, que ce soit les nombreuses lois, les enfermements, les enlèvements d’enfants, les procès contre les cadavres ou les campagnes de rebaptisations des enfants réformés, sur le modèle des dragonnades des années 1680, qui changent la situation . À partir du milieu du XVIIIe siècle un débat tripartite s’instaure entre l’État, les Églises réformées et l’Église catholique, chacun avec ses propositions, avant même l’affaire Calas  qui éclate en 1761, et les négociations aboutissent à un accord en 1787 entre l’État et les Églises réformées, contre l’avis de l’Église catholique. L’objectif de cette communication est d’une part d’essayer de comprendre l’évolution de la position de l’État à l’égard des protestants, alors que les persécutions sont nombreuses jusqu’au début des années 1760, mais aussi d’étudier les arguments des trois partenaires pour obtenir une solution en s’intéressant à des écrits publiés durant cette période , principalement des pamphlets et des mémoires. Je m’appuierai pour comprendre les trois points de vue sur un texte publié anonymement en 1788 et intitulé Conférence entre le frère Pancrace, Capucin, le docteur Hoth-Man, ministre protestant, & M. Robino, avocat au Parlement de Paris

Roles of triaxiality and residual interaction in signature inversions of A~130 odd-odd nuclei

Rotational bands with (neutron h_11/2)^1 (proton h_11/2)^1 configurations are studied using a particle-rotor model in which a proton and a neutron quasiparticles interacting through a zero-range force are coupled with a triaxial rotor. It is shown for 124Cs that one can reproduce the signature dependence of energy and B(M1)/B(E2) ratio best when one takes into account gamma-deformations with irrotational-flow moment of inertia in addition to the proton-neutron interaction proposed by Semmes and Ragnarsson. Including both effects, a systematic calculation of signature splittings is performed for Cs, La isotopes and N=75 isotones to be compared with experiments. Discussions are also done on the deficiencies of the cranking model concerning its applicability to signature inversion phenomena in odd-odd nuclei.Comment: 19 pages of LaTex, (11 figures not included, hard copy available upon request), UT-Komaba 93-1

The Molonglo Reference Catalog 1-Jy radio source survey IV. Optical spectroscopy of a complete quasar sample

Optical spectroscopic data are presented here for quasars from the Molonglo Quasar Sample (MQS), which forms part of a complete survey of 1-Jy radio sources from the Molonglo Reference Catalogue. The combination of low-frequency selection and complete identifications means that the MQS is relatively free from the orientation biases which affect most other quasar samples. To date, the sample includes 105 quasars and 6 BL Lac objects, 106 of which have now been confirmed spectroscopically. This paper presents a homogenous set of low-resolution optical spectra for 79 MQS quasars, the majority of which have been obtained at the Anglo-Australian Telescope. Full observational details are given and redshifts, continuum and emission-line data tabulated for all confirmed quasars.Comment: 40 pages, ApJS in pres

CDG: an online server proposing biologically closest disease-causing genes and pathologies and its application to primary immunodeficiency

Summary: In analyses of exome data, candidate gene selection can be challenging in the absence of variants in known disease-causing genes. We calculated the putative biologically closest known disease-causing genes for 13,005 human genes not currently reported to be disease-causing. We used these data to construct the Closest Disease-Causing Genes (CDG) server, which can be used to infer the closest associated disease-causing genes and phenotypes for lists of candidate genes. This resource will be a considerable asset for ascertaining the poten-tial relevance of lists of genes to specific diseases of interest

Active Galactic Nuclei under the scrutiny of CTA

Active Galactic Nuclei (hereafter AGN) produce powerful outflows which offer excellent conditions for efficient particle acceleration in internal and external shocks, turbulence, and magnetic reconnection events. The jets as well as particle accelerating regions close to the supermassive black holes (hereafter SMBH) at the intersection of plasma inflows and outflows, can produce readily detectable very high energy gamma-ray emission. As of now, more than 45 AGN including 41 blazars and 4 radiogalaxies have been detected by the present ground-based gamma-ray telescopes, which represents more than one third of the cosmic sources detected so far in the VHE gamma-ray regime. The future Cherenkov Telescope Array (CTA) should boost the sample of AGN detected in the VHE range by about one order of magnitude, shedding new light on AGN population studies, and AGN classification and unification schemes. CTA will be a unique tool to scrutinize the extreme high-energy tail of accelerated particles in SMBH environments, to revisit the central engines and their associated relativistic jets, and to study the particle acceleration and emission mechanisms, particularly exploring the missing link between accretion physics, SMBH magnetospheres and jet formation. Monitoring of distant AGN will be an extremely rewarding observing program which will inform us about the inner workings and evolution of AGN. Furthermore these AGN are bright beacons of gamma-rays which will allow us to constrain the extragalactic infrared and optical backgrounds as well as the intergalactic magnetic field, and will enable tests of quantum gravity and other "exotic" phenomena.Comment: 28 pages, 23 figure