The curvature of the conical intersection seam: an approximate second-order analysis

We present a method for analyzing the curvature (second derivatives) of the conical intersection hyperline at an optimized critical point. Our method uses the projected Hessians of the degenerate states after elimination of the two branching space coordinates, and is equivalent to a frequency calculation on a single Born-Oppenheimer potential-energy surface. Based on the projected Hessians, we develop an equation for the energy as a function of a set of curvilinear coordinates where the degeneracy is preserved to second order (i.e., the conical intersection hyperline). The curvature of the potential-energy surface in these coordinates is the curvature of the conical intersection hyperline itself, and thus determines whether one has a minimum or saddle point on the hyperline. The equation used to classify optimized conical intersection points depends in a simple way on the first- and second-order degeneracy splittings calculated at these points. As an example, for fulvene, we show that the two optimized conical intersection points of C2v symmetry are saddle points on the intersection hyperline. Accordingly, there are further intersection points of lower energy, and one of C2 symmetry - presented here for the first time - is found to be the global minimum in the intersection space

Constant p53 pathway inactivation in a large series of soft tissue sarcomas with complex genetics.

Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers. We have performed an exhaustive analysis of TP53, p14, p15, and p16 status in a large series of 143 soft tissue sarcomas, rare tumors accounting for around 1% of all adult cancers, with complex genetics. For this purpose, we performed genomic studies, combining sequencing, copy number assessment, and expression analyses. TP53 mutations and deletions are more frequent in leiomyosarcomas than in undifferentiated pleomorphic sarcomas. Moreover, 50% of leiomyosarcomas present TP53 biallelic inactivation, whereas most undifferentiated pleomorphic sarcomas retain one wild-type TP53 allele (87.2%). The spectrum of mutations between these two groups of sarcomas is different, particularly with a higher rate of complex mutations in undifferentiated pleomorphic sarcomas. Most tumors without TP53 alteration exhibit a deletion of p14 and/or lack of mRNA expression, suggesting that p14 loss could be an alternative genotype for direct TP53 inactivation. Nevertheless, the fact that even in tumors altered for TP53, we could not detect p14 protein suggests that other p14 functions, independent of p53, could be implicated in sarcoma oncogenesis. In addition, both p15 and p16 are frequently codeleted or transcriptionally co-inhibited with p14, essentially in tumors with two wild-type TP53 alleles. Conversely, in TP53-altered tumors, p15 and p16 are well expressed, a feature not incompatible with an oncogenic process.

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 53 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 64 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 66 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 69 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 71 / Partie 2 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 58 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1