Dead Again: The Latest Demise of the Confrontation Clause

In Crawford v. Washington, the Supreme Court abandoned its Roberts “reliability” approach to the right of confrontation. The Court conceded that the Roberts decision had killed the Confrontation Clause by: (1) impermissibly tying the right of confrontation to the rule against hearsay; (2) inappropriately allowing pretrial determinations of reliability to replace actual cross-examination at trial; (3) relying too heavily on malleable, multi-factor balancing tests; and (4) completely failing to constrain judicial discretion. Since Crawford, however, the Court has decided Davis v. Washington and Michigan v. Bryant. Unfortunately, in the course of deciding those cases the Court has once again killed the Confrontation Clause. More specifically, the Court has developed yet another framework that incorporates every single one of Roberts’s flaws, including its failure to constrain judicial discretion. This Essay exposes the underlying reasons for the Court’s failure, offers a solution to the problem, and provides suggestions for the Court when deciding future cases that involve the constitutional rights of criminal defendants

Law Review Publishing: Thoughts on Mass Submissions, Expedited Review, and Potential Reform

The current law review publishing system—in particular, mass submissions and expedited review—works well for prestige-driven professors; however, it places a tremendous burden on the editors of journals lower in the hierarchy. This problem is exacerbated by several professorial tactics including, most significantly, submitting articles to journals from which the professor would never accept an offer—not even when he or she fails to receive a “better” offer through the expedite process. This Essay discusses a potential fix: the eight-hour offer window. If a journal were to adopt a formal policy of holding its publication offers open for only eight hours, professors would, in theory, be unable to use the offer in the expedite process. Therefore, professors would not submit their articles to this journal unless and until they were serious about publishing in it. Unfortunately, what is good in theory does not always work in practice. This Essay discusses how professors would modify their existing tactics—tactics which currently include misrepresenting the terms of an offer in the expedite process—in order to defeat this attempted reform. The Essay also explores specific ways that a journal could overcome these tactics and implement meaningful reform despite the professoriate’s desire to protect the status quo

Targeting of polycombs to DNA in EMT

We here describe the conceptual advance provided by the study by Battistelli and coworkers (PMID: 27452518), that shed light on a molecular mechanism of Polycomb targeting in the biological process known as Epithelial-to-Mesenchymal Transition (EMT). In this paper, different working hypotheses of how EZH2 gets to its genomic targets have been reconciled and a new paradigm of function for a lncRNA is highlighted. The interest may also arise from the clarification of the role of a lncRNA as a new molecular player in EMT regulation. This evidence holds promise for the development of novel therapeutic targets in carcinoma progression

A new ‘inquisition'? Police reform, urban transparency and house numbering in eighteenth-century Geneva

As an administrative tool of police reform, the introduction of house numbering in eighteenth-century Geneva was the result of a broad desire for urban transparency that resulted in the production of a new ‘regime of visibility'. This article examines how the logic of ‘number' transformed the way in which urban space was conceived, organized and governed. As a political technology, the spatial practice of house numbering enabled governmental officials to divide, count, identify and classify urban populations in order to regulate the spaces of circulation in the modern city. Although the city's house-numbering system is taken for granted by most of the town-dwellers today, the current study illustrates how these police techniques encountered considerable resistance when they were initially imposed during the latter half of the eighteenth centur

Notes sur les bases et les effectifs militaires états-uniens à l'étranger

URL des Documents de travail : http://ces.univ-paris1.fr/cesdp/cesdp2013.htmlDocuments de travail du Centre d'Economie de la Sorbonne 2013.28 - ISSN : 1955-611XThis paper, mainly methodological, aims at providing an estimation of the number of U.S. military bases and personnel worldwide. The first part proposes a periodization of the spread of U.S. military bases. The second part exposes the official statistical data disseminated by the US Department of Defense. The third part analyzes in a critical way the main limitations of these data, and suggests some revisions. The fourth and last part gives a brief outline on networks of military bases on the northern countries which are strategic allies of the United States.Cet article, dont l'approche est essentiellement méthodologique, a pour objectif de fournir une estimation du nombre de bases et d'effectifs militaires actuellement déployés par les États-Unis dans le monde. La première partie propose une périodisation de l'expansion des installations de bases militaires états-uniennes. La deuxième partie expose, en synthèse, les données statistiques officielles mises à la disposition du public par l'US Department of Defense. La troisième partie analyse, de manière critique, les principales limites de ces mêmes données, et suggère quelques corrections. La quatrième partie complète le propos par une brève étude des réseaux de bases militaires des pays du Nord alliés stratégiques des États-Unis

YAP integrates the regulatory Snail/HNF4α circuitry controlling epithelial/hepatocyte differentiation

Yes-associated protein (YAP) is a transcriptional co-factor involved in many cell processes, including development, proliferation, stemness, differentiation, and tumorigenesis. It has been described as a sensor of mechanical and biochemical stimuli that enables cells to integrate environmental signals. Although in the liver the correlation between extracellular matrix elasticity (greatly increased in the most of chronic hepatic diseases), differentiation/functional state of parenchymal cells and subcellular localization/activation of YAP has been previously reported, its role as regulator of the hepatocyte differentiation remains to be clarified. The aim of this study was to evaluate the role of YAP in the regulation of epithelial/hepatocyte differentiation and to clarify how a transducer of general stimuli can integrate tissue-specific molecular mechanisms determining specific cell outcomes. By means of YAP silencing and overexpression we demonstrated that YAP has a functional role in the repression of epithelial/hepatocyte differentiation by inversely modulating the expression of Snail (master regulator of the epithelial-to-mesenchymal transition and liver stemness) and HNF4α (master regulator of hepatocyte differentiation) at transcriptional level, through the direct occupancy of their promoters. Furthermore, we found that Snail, in turn, is able to positively control YAP expression influencing protein level and subcellular localization and that HNF4α stably represses YAP transcription in differentiated hepatocytes both in cell culture and in adult liver. Overall, our data indicate YAP as a new member of the HNF4/Snail epistatic molecular circuitry previously demonstrated to control liver cell state. In this model, the dynamic balance between three main transcriptional regulators, that are able to control reciprocally their expression/activity, is responsible for the induction/maintenance of different liver cell differentiation states and its modulation could be the aim of therapeutic protocols for several chronic liver diseases

La construcción de sentido como estrategia política : Jóvenes, disputa cultural y revolución bolivariana

En este trabajo indagamos las características de la constitución del poder popular en Venezuela haciendo hincapié en el papel de los colectivos juveniles urbanos. Seguimos principalmente a Ociel López y su lectura crítica de Alberto Melucci para reflexionar sobre el trabajo de un grupo de colectivos culturales con jóvenes de clases populares de la urbe caraqueña, rastreando su incidencia en la conformación de la identidad sujeto joven popular, elemento clave en el contexto de cambio político que vive la Venezuela de la Revolución Bolivariana. Nos enfocamos en analizar los sentidos sumergidos articulados por estos jóvenes en su conformación como actores y la incidencia de su irrupción a través de los colectivos culturales en el espacio público. Damos cuenta de las tensiones políticas que han suscitado producto de las disputas llevadas a cabo en sus intentos de redefinición de lo cultural hegemónico. De esta forma pretendemos dilucidar los siguientes interrogantes: ¿Que incidencia ha tenido la juventud de los sectores populares urbanos en el proceso político venezolano?, ¿En qué consisten las redefiniciones dadas en el ámbito simbólico? ¿Qué rol cumplen estas en el presente escenario de cambio social?Mesa 27: El problema de las generaciones. Estudios sociológicos sobre edades y generacionales.Facultad de Humanidades y Ciencias de la Educació

Convergence of Wnt signalling on the HNF4a-driven transcription in controlling liver zonation

BACKGROUND & AIMS: In each hepatocyte, the specific repertoire of gene expression is influenced by its exact location along the portocentrovenular axis of the hepatic lobule and provides a reason for the liver functions compartmentalization defined "metabolic zonation." So far, few molecular players controlling genetic programs of periportal (PP) and perivenular (PV) hepatocytes have been identified; the elucidation of zonation mechanisms remains a challenge for experimental hepatology. Recently, a key role in induction and maintenance of the hepatocyte heterogeneity has been ascribed to Wnt/beta-catenin pathway. We sought to clarify how this wide-ranging stimulus integrates with hepatocyte specificity. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) allowed the transcriptional profiling of hepatocytes derived from in vitro differentiation of liver stem cells. The GSK3beta inhibitor 6-bromoindirubin-3'-oxime (BIO) was used for beta-catenin stabilization. Co-immunoprecipitations were used to study biochemical protein interactions while ChIP assays allowed the in vivo inspection of PV and PP genes regulatory regions. RESULTS: We found that spontaneous differentiation of liver stem cells gives rise to PP hepatocytes that, after Wnt pathway activation, switch into PV hepatocytes. Next, we showed that the Wnt downstream player LEF1 interacts with the liver-enriched transcriptional factor HNF4alpha. Finally, we unveiled that the BIO induced activation of PV genes correlates with LEF1 binding to both its own and HNF4alpha consensus, and the repression of PP genes correlates with HNF4alpha displacement from its own consensus. CONCLUSION: Our data show a direct and hitherto unknown convergence of the canonical Wnt signaling on the HNF4alpha-driven transcription providing evidences of a mechanism controlling liver zonated gene expression

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260