The Effect of Nb, Ta, and Ti on the Oxidation of a New Polycrystalline Ni-Based Superalloy.

The effect of variations in Nb, Ta, and Ti concentrations in exchange for Al on the oxidation resistance of a new polycrystalline Ni-based superalloy (C19) was studied in air at 800 °C for up to 1000 h. An external scale of Ti-doped Cr2O3 and a sub-scale of discontinuous Al2O3 intrusions formed on the surface of all the studied alloys. Contrary to other reports, increasing the Nb concentration improved the oxidation performance and may have promoted the formation of a CrTaO4 layer, thereby reducing oxygen ingress. The addition of Ta also significantly improved oxidation resistance and reduced the depth of the Al2O3 intrusions. Increasing the Ti concentration did not significantly affect the oxidation performance, potentially due to the relatively low Ti concentrations investigated. Several of the studied alloys with modified Ta and Ti concentrations showed regions of continuous Al2O3 scale formation, suggesting that the compositions are in a transition regime between Cr2O3-forming and Al2O3-forming behaviour. The findings suggested that part of the Ti content in C19 could potentially be replaced with Nb, Ta and/or other elements to further enhance oxidation resistance and other desirable properties. Overall, the insights gained could serve as a guide to optimise the composition of C19 and similar alloys for enhanced oxidation resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10218-7.

Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.

We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.

Evaluating Wagner Oxidation Criteria for Protective Al2O3 Scale Formation in Ni-Based Superalloys.

An assessment is made of the Wagner transition criteria for predicting the formation of a continuous Al2O3 scale in Ni-based superalloys. Predictions are compared with data from an experimental Ni-based superalloy as well as commercial superalloys for which published data are available. The methodology was generally successful in predicting the transition temperature of the commercial superalloys but underpredicted the transition temperature of the experimental superalloy by approximately 50-100 °C. The difference in the transition temperature of the experimental superalloy to form a continuous Al2O3 scale is primarily attributed to a complex oxide subscale that increased the internal volume fraction of oxide and led to reduced oxygen ingress. The sensitivity and limitations of the methodology are discussed, and recommendations are made to refine the methodology to facilitate the interpretation of oxidation behaviour in polycrystalline Ni-based superalloys. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10163-5.

Efficacy of clonidine in 24 patients with acute mania.

The authors treated 24 newly hospitalized patients suffering from acute mania with 450-900 micrograms/day of clonidine, an alpha 2-adrenergic agonist, for 2 weeks. A marked decrease in manic symptoms was observed after 5 and 13 days of treatment in about half of the patients. Early response seemed to predict the final result. Patients with a family history of affective disorder and patients who had had a good response to neuroleptics during a previous manic episode tended not to respond to clonidine. At the doses given, the patients' tolerance to clonidine was excellent: sedation was markedly lower than it is with neuroleptic treatment.

Production of antigen-specific human antibodies from mice engineered with human heavy and light chain YACs.

Our paper describes the introduction of large fragments of both the human heavy and light chain Ig genes into the mouse germline to create a mouse strain capable of producing a broad repertoire of antigen-specific, fully human antibodies. The human immunoglobulin gene sequences were functional in the context of the mouse machinery for antibody recombination and expression, either in the presence or absence of functional endogenous genes. This was demonstrated by their ability to undergo diverse rearrangement, to be expressed at significant levels, and to exclude expression of mouse immunoglobulins irrespective of their copy number or site of integration. The decrease in susceptibility to influence by adjacent genomic sequences may reflect the greater size, variable gene content, or structural integrity of the human Ig YACs and/or the presence of unidentified but important regulatory elements needed for optimal expression of the human immunoglobulin genes and their correct regulation. Our results show that mouse B cells coexpressing human heavy and kappa chains, upon immunization, can produce antigen-specific, fully human antibodies. Furthermore, the human heavy and kappa chain YACs induced differentiation and maturation of the growth-arrested B-cell lineage in mice with inactivated endogenous Ig genes, leading to the production of a diverse repertoire of fully human antibodies at levels approaching those in normal serum. These results suggest the potential value of these mice as a source of fully human antibodies for human therapy. Furthermore, it is expected that such mice would lack immunological tolerance to and thus readily yield antibodies to human proteins, which may constitute an important class of targets for monoclonal antibody therapy. Our findings suggest that the introduction of even larger portions of the human heavy and light chain loci, which should be achievable with the ES cell-yeast spheroplast fusion technology described, will result in strains of mice ultimately capable of recapitulating the full antibody repertoire characteristic of the human humoral response to infection and immunization. The present and future mouse strains may prove to be valuable tools for studying the molecular mechanisms and regulatory sequences influencing the programmed assembly and expression of human antibodies in the normal immune response, as well as the abnormal response characteristic of autoimmune disease and other disorders. The strategy we have described for the introduction of large segments of the human genome into mice in conjunction with the inactivation of the corresponding mouse loci may also have broad applicability to the investigation of other complex or uncharacterized loci.

[Toward a new approach to mania]. / Pour une nouvelle approche de la manie.

After giving a brief summary of the classical psychiatry contribution (taken down a medical pattern of psychiatry diseases) to the knowledge of manic-depressing disorder, the problem of clinical-biological connection to which this classical psychiatry is still confronted is underlined. As a possible answer to this problem, a new approach to mania is possible in a dimensional perspective of the mental disease taking into account the connection model as well as the pathological characteristics within the clinical chart. The notion of integrated behaviour will supply to notion of syndrome (in which all symptoms are equivalents). So, a behaviour dimension, well defined from a clinical analysis connected with a factorial analysis, is proposed as a specific maniac size and as a compartmental aim to the treatments. A dividing of mental pathology in terms of behaviour anomalies should allow a better link between the clinical and the biological.

Evaluating the impact of library services on the quality and cost of medical care.

Recent federal regulations have minimized the role of the hospital library in contributing to the quality of medical care and in lowering hospital costs. We trace the events that have led to these assumptions and discuss the complex problem of evaluating the impact of library services. Current research on the value and effectiveness of information is outlined.

Analysis of the structural integrity of YACs comprising human immunoglobulin genes in yeast and in embryonic stem cells.

With the goal of creating a strain of mice capable of producing human antibodies, we are cloning and reconstructing the human immunoglobulin germline repertoire in yeast artificial chromosomes (YACs). We describe the identification of YACs containing variable and constant region sequences from the human heavy chain (IgH) and kappa light chain (IgK) loci and the characterization of their integrity in yeast and in mouse embryonic stem (ES) cells. The IgH locus-derived YAC contains five variable (VH) genes, the major diversity (D) gene cluster, the joining (JH) genes, the intronic enhancer (EH), and the constant region genes, mu (C mu) and delta (C delta). Two IgK locus-derived YACs each contain three variable (V kappa) genes, the joining (J kappa) region, the intronic enhancer (E kappa), the constant gene (C kappa), and the kappa deleting element (kde). The IgH YAC was unstable in yeast, generating a variety of deletion derivatives, whereas both IgK YACs were stable. YACs encoding heavy chain and kappa light chain, retrofitted with the mammalian selectable marker, hypoxanthine phosphoribosyltransferase (HPRT), were each introduced into HPRT-deficient mouse ES cells. Analysis of YAC integrity in ES cell lines revealed that the majority of DNA inserts were integrated in substantially intact form.