Particular concerns with regard to the Rotterdam Rules

Resumen: A medida que el proceso de fi rma de las Reglas de Rotterdam va tomando cuerpo, también cobran fuerza las voces discordantes. Este artículo o manifi esto recoge la opinión crítica colectiva de un grupo de nueve destacados especialistas en Derecho marítimo de distintas partes del mundo, pertenecientes a los sectores académico y profesional. El artículo analiza con brevedad y precisión los rasgos más destacados de las Reglas de Rotterdam, particularmente aquéllos que, a juicio de los firmantes, meritan mayor debate y crítica. La conclusión a la que llegan los miembros de este grupo de juristas es que las Reglas de Rotterdam no vienen sino a añadir más complejidad a la actual regulación internacional del transporte marítimo y multimodal. El artículo finaliza con una propuesta de alternativas que permitan aprovechar lo mejor de la regulación vigente y abrir las puertas a una actualización y complementación de dicha regulación. Palabras clave: Reglas, Rotterdam, Crítica, Alternativas. Abstract: As the Rotterdam Rules signature process gains momentum, strong dissenting opinions are also starting to be heard. This article or manifesto sums up the collective critical voice of nine worldwide leading shipping lawyers and professors. It provides a short and precise analysis of the Rotterdam Rules main features from the point of view of those issues which the authors fi nd unworthy of praise. And their conclusion is that the Rotterdam Rules simply just add up more complexity to the present shipping and multimodal international regulation. The article closes with a quest for alternatives aimed to get the best of what we already have and opens the gate to proposals based on the updating and complementation of the regulation in force today. Key words: Rules, Rotterdam, Critical, Alternatives

A Blue Print for a Worldwide Multimodal Regime

Resumen: En el nº 2 de 2010 de CDT se publicó un manifiesto del llamado “Grupo de los 9” titulado “Particular concerns with regard to the Rotterdam Rules” en el que estos destacados profesores y juristas expresaban sus dudas acerca de este nuevo instrumento internacional. Este Grupo ofrece ahora un nuevo manifiesto que supone un paso adelante en el que se indica que a pesar de la innegable necesidad de poner al día las Reglas de La Haya-Visby, y de las aportaciones efectuadas en tal sentido por las Reglas de Rótterdam, las perspectivas de éxito de estas últimas se ven ensombrecidas por su pretensión de extenderse más allá de lo que en puridad debía ser su objeto, el transporte marítimo, para convertirse en el texto de referencia para el transporte multimodal que cuente con una fase marítima. Lejos de contribuir a un verdadero y efectivo régimen unificado de la multimodalidad, plantea nuevas dudas a la hora de determinar qué régimen, de entro los existentes para cada tipo de transporte, debe ser de aplicación en cada caso. Mientras tanto, parece que para conseguir los objetivos referidos al transporte marítimo de las Reglas de Rótterdam habría bastado con la introducción de Protocolos a las Reglas de La Haya-Visby, dejando que lo concerniente al transporte multimodal continuara por la senda establecida a tal efecto por el CMR, cuyo sistema quizás debiera traspasar las fronteras europeas con el impulso de las diferentes instituciones internacionales. Palabras clave: Reglas de Rotterdam, transporte multimodal, transporte marítimo, Reglas de La Haya-Visby, CMR.  Abstract: In the issue n. 2 of 2010 of CDT it was published a manifesto of the so-called “Group of the 9” under the title of “Particular concerns with regard to the Rotterdam Rules” where these renowned scholars and attorneys expressed their doubts about this new international legal instrument. The Group offers now a new manifesto providing a step further whereby they indicate that notwithstanding the undeniable necessity to update the Hague-Visby Rules and the contributions carried out in this direction by the Rotterdam Rules, success expectations of the latter rules are hindered because of the aim to expand the scope of application beyond their object in strict sense, namely maritime transport, so as to become the text of reference as for every multimodal transport that includes a sea leg. Far from contributing to a real and effective multimodal unified regime, new doubts arise when determining which regime, of all those for each type of transport, shall apply in each case. In any event, it seems that in order to reach the objectives appointed to by the Rotterdam Rules, introducing Protocols to the Hague-Visby Rules would have been good enough, whereas all that related to multimodal transport continues by the CMR established paths, a system which should trespass European borders with the help of different international institutions. Key words: Rotterdam Rules, multimodal transport, maritime transport, Hague-Visby Rules, CMR

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Microbiomes of Thalassia testudinum throughout the Atlantic Ocean, Caribbean Sea, and Gulf of Mexico are influenced by site and region while maintaining a core microbiome

Plant microbiomes are known to serve several important functions for their host, and it is therefore important to understand their composition as well as the factors that may influence these microbial communities. The microbiome of Thalassia testudinum has only recently been explored, and studies to-date have primarily focused on characterizing the microbiome of plants in a single region. Here, we present the first characterization of the composition of the microbial communities of T. testudinum across a wide geographical range spanning three distinct regions with varying physicochemical conditions. We collected samples of leaves, roots, sediment, and water from six sites throughout the Atlantic Ocean, Caribbean Sea, and the Gulf of Mexico. We then analyzed these samples using 16S rRNA amplicon sequencing. We found that site and region can influence the microbial communities of T. testudinum, while maintaining a plant-associated core microbiome. A comprehensive comparison of available microbial community data from T. testudinum studies determined a core microbiome composed of 14 ASVs that consisted mostly of the family Rhodobacteraceae. The most abundant genera in the microbial communities included organisms with possible plant-beneficial functions, like plant-growth promoting taxa, disease suppressing taxa, and nitrogen fixers

Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk

Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characterized tumor suppressors, p16INK4a, p15INK4b, and ARF, the SNPs most strongly associated with ASVD are ∼120 kb from the nearest coding gene within a long non-coding RNA (ncRNA) known as ANRIL (CDKN2BAS). While individuals homozygous for the atherosclerotic risk allele show decreased expression of ANRIL and the coding INK4/ARF transcripts, the mechanism by which such distant genetic variants influence INK4/ARF expression is unknown. Here, using rapid amplification of cDNA ends (RACE) and analysis of next-generation RNA sequencing datasets, we determined the structure and abundance of multiple ANRIL species. Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles. Surprisingly, RACE also identified transcripts containing non-colinear ANRIL exonic sequences, whose expression also correlated with genotype and INK4/ARF expression. These non-polyadenylated RNAs resisted RNAse R digestion and could be PCR amplified using outward-facing primers, suggesting they represent circular RNA structures that could arise from by-products of mRNA splicing. Next-generation DNA sequencing and splice prediction algorithms identified polymorphisms within the ASVD risk interval that may regulate ANRIL splicing and circular ANRIL (cANRIL) production. These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure

Analytical methods for inferring functional effects of single base pair substitutions in human cancers

Cancer is a genetic disease that results from a variety of genomic alterations. Identification of some of these causal genetic events has enabled the development of targeted therapeutics and spurred efforts to discover the key genes that drive cancer formation. Rapidly improving sequencing and genotyping technology continues to generate increasingly large datasets that require analytical methods to identify functional alterations that deserve additional investigation. This review examines statistical and computational approaches for the identification of functional changes among sets of single-nucleotide substitutions. Frequency-based methods identify the most highly mutated genes in large-scale cancer sequencing efforts while bioinformatics approaches are effective for independent evaluation of both non-synonymous mutations and polymorphisms. We also review current knowledge and tools that can be utilized for analysis of alterations in non-protein-coding genomic sequence