Metodología del derecho privado comunitario: problemas y perspectivas en cuanto a la interpretación literal e histórica

[Resumen] El debate científico sobre la integración del Derecho privado europeo afecta actualmente también a las cuestiones metodológicas. Los métodos jurídicos difieren entre los diferentes Estados miembros. Esto entraña riesgos para la consecución del mercado interior. En particular, los rasgos tradicionales de la interpretación literal e histórica se ponen en entredicho en el seno de una Comunidad multilingüística que no es ni un Estado ni una organización internacional en el sentido tradicional. En teoría, todas las lenguas oficiales han de ser tenidas en cuenta en la interpretación del Derecho comunitario. Sin embargo, resulta imposible en la práctica cumplir esta regla – al menos a partir de la última ampliación. Por otro lado, el principio de igual trato de todas las lenguas oficiales exige que un tribunal que interprete el Derecho comunitario no pueda decidir con arreglo a la mayoría de las versiones lingüísticas. En cuanto a lo que concierne a las intenciones del legislador, hay acuerdo en que la concepción clásica de la interpretación histórica es de muy poca ayuda. Por el contrario, una concepción más amplia que cubra también el desarrollo general de los conceptos y las estructuras sistemáticas en las tradiciones nacionales y regionales del Derecho privado podría tornarse muy útil para una mejor creación del Derecho y un perfeccionamiento en las decisiones judiciales a un nivel europeo. Finalmente, el objeto y propósito del Derecho privado comunitario debe desempeñar un papel más importante en el proceso de interpretación. En definitiva, esta cuestión merece una mayor atención en el marco de la discusión científica.[Abstract] The scientific debate on the integration of European Private Law touches nowadays also methodological problems. Legal methods diverge in the different Member States. This entails risks for the finalization of the internal market. In particular, the traditional features of literal and historical interpretation are critical in a multi-linguistic Community that is neither state nor international organization in a traditional meaning. In theory, all official languages have to be taken into account when interpreting Community law. However, it has become impossible in practice to comply with this rule - at least after the last enlargement of the EU. On the other hand, the priciple of equal treatment of all official languages demands that a Court interpreting Community law may not decide according to the majority of linguistic versions. As far as the legislator’s intentions are concerned, it is agreed that the classical understanding of historical interpretation is of very little help. On the contrary, a broader understanding that covers also the general development of concepts and systematic structures in national or regional private law traditions could turn out to be very useful for better law-making and for the improvement of judicial decisions at the european level. In the end, object and purpose of EC Private Law have to play a major role in the process of interpretation. Definitely, this subject needs to be paid more attention to in the scientific discussion

Prognostic impact of <i>CEBPA </i>mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIP ms). (Figure presented.)</p

Prognostic impact of CEBPA mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms)

The Desensitized Channelrhodopsin-2 Photointermediate Contains 13-cis,15-syn retinal schiff base

Channelrhodopsin-2 (ChR2) is a light-gated cation channel and was used to lay the foundations of optogenetics. Its dark state X-ray structure has been determined in 2017 for the wild-type, which is the prototype for all other ChR variants. However, the mechanistic understanding of the channel function is still incomplete in terms of structural changes after photon absorption by the retinal chromophore and in the framework of functional models. Hence, detailed information needs to be collected on the dark state as well as on the different photointermediates. For ChR-2 detailed knowledge on the chromophore configuration in the different states is still missing and a consensus has not been achieved. Using DNP-enhanced solid-state MAS NMR spectroscopy on proteoliposome samples, we unambiguously determine the chromophore configuration in the desensitized state, and we show that this state occurs towards the end of the photocycle

Influence of electrostatic charges and solid-mass loading on particle dynamics in duct

The modulation of particle-laden flows through electrostatic forces is utilized in various industrial applications, for example powder coating and electrostatic precipitation. However, excessive charge accumulation also results in the formation of deposits on component surfaces and spark discharges which may lead to dust explosions. In order to elucidate the dynamics of charged particles, we performed large-eddy simulations of a fully-developed turbulent gas flow (Re = 10 000) through a generic squared-shaped duct. The flow was seeded by charged monodisperse particles. In our talk we will discuss the influence of the solid-mass loading and the electrostatic charges carried by the particles on the particle concentration over the duct’s cross section. Electrostatic charges of 0 pC, 0.125 pC and 0.25 pC were assigned to the particles whereas solid-gas mass loading ratios between 0.01 and 0.04 were considered. Based on our previous findings we expect an increase of each of these parameters to counteract the turbophoretic drift and smoothen the particle concentration profiles

Rapid prediction of multi-dimensional NMR data sets

We present a computational environment for Fast Analysis of multidimensional NMR DAta Sets (FANDAS) that allows assembling multidimensional data sets from a variety of input parameters and facilitates comparing and modifying such “in silico” data sets during the various stages of the NMR data analysis. The input parameters can vary from (partial) NMR assignments directly obtained from experiments to values retrieved from in silico prediction programs. The resulting predicted data sets enable a rapid evaluation of sample labeling in light of spectral resolution and structural content, using standard NMR software such as Sparky. In addition, direct comparison to experimental data sets can be used to validate NMR assignments, distinguish different molecular components, refine structural models or other parameters derived from NMR data. The method is demonstrated in the context of solid-state NMR data obtained for the cyclic nucleotide binding domain of a bacterial cyclic nucleotide-gated channel and on membrane-embedded sensory rhodopsin II. FANDAS is freely available as web portal under WeNMR (http://www.wenmr.eu/services/FANDAS)

Enlightening the photoactive site of channelrhodopsin-2 by DNP-enhanced solid-state NMR spectroscopy

Channelrhodopsin-2 from Chlamydomonas reinhardtii is a light-gated ion channel. Over recent years, this ion channel has attracted considerable interest because of its unparalleled role in optogenetic applications. However, despite considerable efforts, an understanding of how molecular events during the photocycle, including the retinal trans-cis isomerization and the deprotonation/reprotonation of the Schiff base, are coupled to the channel-opening mechanism remains elusive. To elucidate this question, changes of conformation and configuration of several photocycle and conducting/nonconducting states need to be determined at atomic resolution. Here, we show that such data can be obtained by solid-state NMR enhanced by dynamic nuclear polarization applied to 15N-labeled channelrhodopsin-2 carrying 14,15-13C2 retinal reconstituted into lipid bilayers. In its dark state, a pure all-trans retinal conformation with a stretched C14-C15 bond and a significant out-of-plane twist of the H-C14-C15-H dihedral angle could be observed. Using a combination of illumination, freezing, and thermal relaxation procedures, a number of intermediate states was generated and analyzed by DNP-enhanced solid-state NMR. Three distinct intermediates could be analyzed with high structural resolution: the early P5001 K-like state, the slowly decaying late intermediate P4804, and a third intermediate populated only under continuous illumination conditions. Our data provide novel insight into the photoactive site of channelrhodopsin-2 during the photocycle. They further show that DNP-enhanced solid-state NMR fills the gap for challenging membrane proteins between functional studies and X-ray–based structure analysis, which is required for resolving molecular mechanisms

Is there a benefit of ICD treatment in patients with persistent severely reduced systolic left ventricular function after TAVI?

Background In patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) and heart failure with severely reduced ejection fraction, prediction of postprocedural left ventricular ejection fraction (LVEF) improvement is challenging. Decision-making and timing for implantable cardioverter defibrillator (ICD) treatment are difficult and benefit is still unclear in this patient population. Objective Aims of the study were to analyse long-term overall mortality in TAVI-patients with a preprocedural LVEF <= 35% regarding LVEF improvement and effect of ICD therapy. Methods and results Retrospective analysis of a high-risk TAVI-population suffering from severe AS and heart failure with a LVEF <= 35%. Out of 1485 TAVI-patients treated at this center between January 2013 and April 2018, 120 patients revealed a preprocedural LVEF <= 35% and had sufficient follow-up. 36.7% (44/120) of the patients suffered from persistent reduced LVEF without a postprocedural increase above 35% within 1 year after TAVI or before death, respectively. Overall mortality was neither significantly reduced by LVEF recovery above 35% (p = 0.31) nor by additional ICD treatment in patients with persistent LVEF <= 35% (p = 0.33). Conclusion In high-risk TAVI-patients suffering from heart failure with LVEF <= 35%, LVEF improvement to more than 35% did not reduce overall mortality. Patients with postprocedural persistent LVEF reduction did not seem to benefit from ICD treatment. Effects of LVEF improvement and ICD treatment on mortality are masked by the competing risk of death from relevant comorbidities. [GRAPHICS]