La théologie universitaire et l’intelligence du devenir humain : En réaction à Jean-Marie Sevrin

Des difficultés financières conduisent certaines universités à remettre en question leur investissement en théologie. Mais par-delà ces difficultés, la théologie fait face à une grave crise de légitimité épistémologique, le prestige de la rationalité scientifique et technique tendant à disqualifier toute forme de pensée qui ne s’inscrit pas dans ses paramètres. Il n’y a d’avenir pour la théologie à l’université que dans la mesure où elle parviendra à montrer que la foi s’inscrit dans une rationalité intégrale , et que sa prise en compte est essentielle à l’intelligence du devenir humain.Certain universities cite financial difficulties as a reason for eliminating teaching and research in the field of theology. Beyond questions of dollars and cents, however, theology faces a serious crisis of epistemological legitimacy, since scientific and technical rationality tends to disqualify any mode of thinking that strays beyond its borders. The future of theology as an academic discipline is thus tied to its ability to demonstrate that faith constitutes an example of integral rationality, and that its study is essential to an understanding of the future of humanity

L’Évangile au risque des cultures : La réponse chrétienne

Dans la foulée de l’oeuvre du théologien français Claude Geffré, cet article réfléchit au rapport entre l’Évangile et les cultures. L’Évangile apparaît comme un « au-delà intérieur » à la culture ; ceci n’est possible que parce que la culture est ouverte, par sa dynamique même, à une « transcendance sans nom » (Fernand Dumont). Le rapport entre les deux est envisagé comme une dialectique se résolvant dans la « réponse chrétienne », c’est-à-dire dans les diverses manières dont les croyants, individuellement et collectivement, interprètent en paroles et actes la Parole entendue.In the footsteps of the French theologian Claude Geffré, this article reflects upon the relationship between the Gospel and cultures. The Gospel is both beyond and within culture ; this is only possible because culture is inherently open to an “anonymous transcendence” (Fernand Dumont). The relationship appears as a dialectic resolving itself in “Christian response”, that is, in the different ways believers, individually and collectively, interpret in words and deeds the Word they perceive

From Earth to Orbit: An assessment of transportation options

The report assesses the requirements, benefits, technological feasibility, and roles of Earth-to-Orbit transportation systems and options that could be developed in support of future national space programs. Transportation requirements, including those for Mission-to-Planet Earth, Space Station Freedom assembly and operation, human exploration of space, space science missions, and other major civil space missions are examined. These requirements are compared with existing, planned, and potential launch capabilities, including expendable launch vehicles (ELV's), the Space Shuttle, the National Launch System (NLS), and new launch options. In addition, the report examines propulsion systems in the context of various launch vehicles. These include the Advanced Solid Rocket Motor (ASRM), the Redesigned Solid Rocket Motor (RSRM), the Solid Rocket Motor Upgrade (SRMU), the Space Shuttle Main Engine (SSME), the Space Transportation Main Engine (STME), existing expendable launch vehicle engines, and liquid-oxygen/hydrocarbon engines. Consideration is given to systems that have been proposed to accomplish the national interests in relatively cost effective ways, with the recognition that safety and reliability contribute to cost-effectiveness. Related resources, including technology, propulsion test facilities, and manufacturing capabilities are also discussed

Evolution in the Disks and Bulges of Group Galaxies since z=0.4

We present quantitative morphology measurements of a sample of optically selected group galaxies at 0.3 < z < 0.55 using the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) and the GIM2D surface brightness--fitting software package. The group sample is derived from the Canadian Network for Observational Cosmology Field Redshift survey (CNOC2) and follow-up Magellan spectroscopy. We compare these measurements to a similarly selected group sample from the Millennium Galaxy Catalogue (MGC) at 0.05 < z < 0.12. We find that, at both epochs, the group and field fractional bulge luminosity (B/T) distributions differ significantly, with the dominant difference being a deficit of disk--dominated (B/T < 0.2) galaxies in the group samples. At fixed luminosity, z=0.4 groups have ~ 5.5 +/- 2 % fewer disk--dominated galaxies than the field, while by z=0.1 this difference has increased to ~ 19 +/- 6 %. Despite the morphological evolution we see no evidence that the group environment is actively perturbing or otherwise affecting the entire existing disk population. At both redshifts, the disks of group galaxies have similar scaling relations and show similar median asymmetries as the disks of field galaxies. We do find evidence that the fraction of highly asymmetric, bulge--dominated galaxies is 6 +/- 3 % higher in groups than in the field, suggesting there may be enhanced merging in group environments. We replicate our group samples at z=0.4 and z=0 using the semi-analytic galaxy catalogues of Bower et al (2006). This model accurately reproduces the B/T distributions of the group and field at z=0.1. However, the model does not reproduce our finding that the deficit of disks in groups has increased significantly since z=0.4.Comment: Accepted for publication in MNRAS. 20 pages, 17 figure

Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes

Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic ‘host’ gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters

Targeted Drug Delivery by Gemtuzumab Ozogamicin: Mechanism-Based Mathematical Model for Treatment Strategy Improvement and Therapy Individualization

Gemtuzumab ozogamicin (GO) is a chemotherapy-conjugated anti-CD33 monoclonal antibody effective in some patients with acute myeloid leukemia (AML). The optimal treatment schedule and optimal timing of GO administration relative to other agents remains unknown. Conventional pharmacokinetic analysis has been of limited insight for the schedule optimization. We developed a mechanism-based mathematical model and employed it to analyze the time-course of free and GO-bound CD33 molecules on the lekemic blasts in individual AML patients treated with GO. We calculated expected intravascular drug exposure (I-AUC) as a surrogate marker for the response to the drug. A high CD33 production rate and low drug efflux were the most important determinants of high I-AUC, characterizing patients with favorable pharmacokinetic profile and, hence, improved response. I-AUC was insensitive to other studied parameters within biologically relevant ranges, including internalization rate and dissociation constant. Our computations suggested that even moderate blast burden reduction prior to drug administration enables lowering of GO doses without significantly compromising intracellular drug exposure. These findings indicate that GO may optimally be used after cyto-reductive chemotherapy, rather than before, or concomitantly with it, and that GO efficacy can be maintained by dose reduction to 6 mg/m2 and a dosing interval of 7 days. Model predictions are validated by comparison with the results of EORTC-GIMEMA AML19 clinical trial, where two different GO schedules were administered. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinic

Mendelian gene identification through mouse embryo viability screening.

BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property. METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project. RESULTS: We found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts. CONCLUSIONS: Information on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases