Introduction: Institutionalisation beyond the nation state: new paradigms? Transatlantic relations: data, privacy and trade law

The chapter explores how we should understand the development of institutionalisation beyond the Nation State. It focuses largely but not exclusively upon a possibly ‘hard case’ of global governance, EU-US relations, long understood to be a non-institutionalised space, in light of recent legal and political developments in trade and data law How should we reflect upon ‘progress’ as a narrative beyond the Nation State? What is the place of bottom-up led process? The lexicon and framework of institutionalisation is argued to be both important and a valuable one worthy of being developed out of the shadows of many disciplines. Institutionalisation may be the antithesis of the desired political outcome and simultaneously also the panacea for all harms. Contrariwise, it is a highly provocative lexicon in its own right for its capacity to provoke questions of sovereignty and sensitivity towards embedded institutionalised frameworks. Transatlantic relations provide a vivid multi-disciplinary example of the relationship between institutionalisation and private power and quest for new forms of institutionalisation across a range of subjects. Exploring ‘de-institutionalisation’ may not capture adequately developments taking place between the EU and US in trade and data privacy. A broader context of extreme volatility in the global legal order is arguably also difficult to capture and pin down as to its specific temporal or conceptual elements. Strong internationalised institutionalisation appears to constitute the outcome of the ‘trade’ case study whereas weak localised institutionalisation appears to constitute the outcome of the ‘data’ case study. Nonetheless, they both represent important evolving concepts of power, rights and authority beyond the State

Biobank Oversight and Sanctions Under the General Data Protection Regulation

This contribution offers an insight into the function and problems of the oversight and sanctions mechanisms outlined in the General Data Protection Regulation as they relate to the biobanking context. These mechanisms might be considered as meta-mechanisms—mechanisms relating to, but not consisting of, substantive legal principles—functioning in tandem to ensure biobank compliance with data protection principles. Each of the mechanisms outlines, on paper at least, comprehensive and impressive compliance architecture—both expanding on their capacity in relation to Directive 95/46. Accordingly, each mechanism looks likely to have a significant and lasting impact on biobanks and biobanking. Despite this comprehensiveness, however, the mechanisms are not immune from critique. Problems appear regarding the standard of protection provided for research subject rights, regarding the disproportionate impact on legitimate interests tied up with the biobanking process—particularly genomic research interests—and regarding their practical implementability in biobanking

The EU as a Good Global Actor

This paper outlines an exploratory workshop at City Law School, City, University of London funded by HEIF/ ‘EUTIP’ Marie Skłodowska-Curie Innovative Training Network (ITN) on understanding of the EU as a Good Global Actor.1 The EU has as its mission to be a good global governance actor yet is continuously challenged in the world. As a global actor, the EU is both a weak and strong actor in a divergent range of global governance areas. It is not comparable to study the EU as a global trade actor for example to its efforts in human rights, data, cyber or the environment. EU international relations constitutes arguably a booming field of law where the EU appears often to be a victim of its own success. The range of the subjects and objects of EU law continues to expand and the EU is arguably increasingly a victim of its own success, increasingly taking decisions with impacts on third countries or parties, subjecting more entities to sanctions regimes, being bound to consult more entities and have more third countries, parties and entities such as lobbyists interested in the directions of EU law. The assessment of the EU as a global actor includes broad checks on normative action ex ante and ex post facto- yet it is no less harsh. Ex ante metrics of EU global action include court-centred ones such as an opinion from the CJEU on legality of an international agreement, often precluded in most constitutional systems on account of its conflict with pacta sunt servanda. The contours of the principle of the autonomy of EU law have the capacity to put more stringent parameters on EU institutionalised evolutions as to international engagement. How can we assess the EU as a global actor given these realities? The aim of the event was to explore informally the nexus between trade and security, trade and economics and trade and human rights as a future research agenda with input from a variety of scholars It reflected upon four major themes: 1) The EU’s Contribution to the Democratisation of Global Governance 2) Deeper Trade Agreements and New Normative Foundations 3) The EU as a Global Actor in Trade and Fundamental Rights 4) EU’s Trade in the Era of Global Data Flows

Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors $\textit{in vivo}$. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.This study was funded by DFG collaborative research grant SFB958 (projects A09 to K.P. and G.R.L., A01 to V.H. and Z02 to J.S.). Additional support was provided by a senior ERC grant (grant number 294678 to G.R.L.) and by the NeuroCure Cluster of Excellence (to V.H., G.R.L. and J.F.A.P.). K.P. was supported by a Cecile-Vogt Fellowship (MDC). S.P. was supported by a Marie Curie Fellowship from the European Union (grant number 253663 Touch in situ). C.P. received a Ph.D. fellowship from the University of Cagliari. J.F.A.P. was funded by a European Research Council (ERC) starting grant (ERC-2010-StG-260590), the DFG (FOR 1341, FOR 2143), the Berlin Institute of Health (BIH) and the European Union (FP7, 3x3Dimaging 323945). R.K. was supported by an ERC Advanced Investigator grant (294293-PAIN PLASTICITY). D.H. was funded by the Berlin Institute of Health (BIH). E.St.J.S., L.E. and M.M. were supported by an Alexander von Humboldt Fellowship

Genome-Wide DNA Methylation Profiling in Early Stage I Lung Adenocarcinoma Reveals Predictive Aberrant Methylation in the Promoter Region of the Long Noncoding RNA PLUT: An Exploratory Study

Introduction: Surgical procedure is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable number of patients experience recurrence within the first 2 years after complete resection. Suitable prognostic biomarkers that identify patients at high risk of recurrence (who may probably benefit from adjuvant treatment) are still not available. This study aimed at identifying methylation markers for early recurrence that may become important tools for the development of new treatment modalities. Methods: Genome-wide DNA methylation profiling was performed on 30 stage I lung adenocarcinomas, comparing 14 patients with early metastatic recurrence with 16 patients with a long-term relapse-free survival period using methylated-CpG-immunoprecipitation followed by high-throughput next-generation sequencing. The differentially methylated regions between the two subgroups were validated for their prognostic value in two independent cohorts using the MassCLEAVE assay, a high-resolution quantitative methylation analysis. Results: Unsupervised clustering of patients in the discovery cohort on the basis of differentially methylated regions identified patients with shorter relapse-free survival (hazard ratio: 2.23; 95% confidence interval: 0.66-7.53; p = 0.03). In two validation cohorts, promoter hypermethylation of the long noncoding RNA PLUT was significantly associated with shorter relapse-free survival (hazard ratio: 0.54; 95% confidence interval: 0.31-0.93; p < 0.026) and could be reported as an independent prognostic factor in the multivariate Cox regression analysis. Conclusions: Promoter hypermethylation of the long noncoding RNA PLUT is predictive in patients with early stage I adenocarcinoma at high risk for early recurrence. Further studies are needed to validate its role in carcinogenesis and its use as a biomarker to facilitate patient selection and risk stratification

Dimensions of a Projection Column and Architecture of VPM and POm Axons in Rat Vibrissal Cortex

This is the first article in a series of 3 studies that investigate the anatomical determinants of thalamocortical (TC) input to excitatory neurons in a cortical column of rat primary somatosensory cortex (S1). S1 receives 2 major types of TC inputs, lemiscal and paralemniscal. Lemiscal axons arise from the ventral posteromedial nucleus (VPM) of the thalamus, whereas paralemniscal fibers originate in the posteromedial nucleus (POm). While these 2 TC projections are largely complementary in L4, overlap in other cortical layers is still a matter of debate. VPM and POm axons were specifically labeled in the same rat by virus-mediated expression of different fluorescent proteins. We show that columnar and septal projection patterns are maintained throughout most of the cortical depth with a lower degree of separation in infragranular layers, where TC axons form bands along rows. Finally, we present anatomical dimensions of “TC projection domains” for a standard column in S1

Sharing health-related data:A privacy test?

Greater sharing of potentially sensitive data raises important ethical, legal and social issues (ELSI), which risk hindering and even preventing useful data sharing if not properly addressed. One such important issue is respecting the privacy-related interests of individuals whose data are used in genomic research and clinical care. As part of the Global Alliance for Genomics and Health (GA4GH), we examined the ELSI status of health-related data that are typically considered ‘sensitive’ in international policy and data protection laws. We propose that ‘tiered protection’ of such data could be implemented in contexts such as that of the GA4GH Beacon Project to facilitate responsible data sharing. To this end, we discuss a Data Sharing Privacy Test developed to distinguish degrees of sensitivity within categories of data recognised as ‘sensitive’. Based on this, we propose guidance for determining the level of protection when sharing genomic and health-related data for the Beacon Project and in other international data sharing initiatives

Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.</p> <p>Methods</p> <p>We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.</p> <p>Conclusions</p> <p>Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.</p

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA