bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Tetracycline Using Ultrasound-Assisted Dispersive Liquid–Liquid Microextraction Based on Solidification of Floating Organic Droplet Followed by HPLC–UV System
Authors: Rahimi Moghadam Mojtaba , Zargar Behrooz , Rastegarzadeh Saadat
Published: March 2021

Background

Tetracyclines (TCs) are a group of broad-spectrum antibiotics that may be used to control bacterial diseases in humans or are applied as feed additives to enhance growth in farm animals. TCs are released into the aquatic environment via different pathways. Many analytical methods combined with a preconcentration step have been introduced for the determination of TC in various environmental samples.

Objective

The objective this paper is developing reliable analytical methods for determination of TC trace in various environmental samples.

Method

In the present work, combined ultrasound-assisted and dispersive liquid–liquid microextraction according to the solidification of floating organic drop as a sample preconcentration procedure for determining TC hydrochloride HPLC in water and serum samples was used.

Results

A series of parameters, including the type and volume of disperser and extraction solvents, salt effect, extraction time, and pH of solution influencing the extraction efficiency of UA-DLLME-SFO was examined. Enrichment factors were in the range of 125–137 for TC hydrochloride under optimum conditions. The linear range was calculated from 0.005 to 3 mg/L and LOD at 0.002 mg/L. RSDs were in the range of 2.7 to 3.2 (n = 5). The UA-DLLME-SFO method used in water and serum samples revealed good extraction recoveries with RSD of 2.7–4.3%.

Conclusions

This method significantly decreased the organic solvent volume from 3 mL to 90 µL, also LOD and linear ranges were lower than or almost close to levels obtained in other research studies. In this procedure, an ultrasound bath enhanced the mixing and contact between the sample solution and the extraction solvent.
Online Advertising Suppresses Visual Competition during Planned Purchases
Authors: van der Lans Ralf , Pieters Rik , Wedel Michel
Published: March 2021

Online advertising can help consumers to implement their purchase intentions on shopping websites. This research tests the hypothesis that online advertising can speed-up product search by visually suppressing competing products rather than by enhancing the target product on websites that lack a systematic visual organization. First, a survey shows that searching for products on a shopping website after having clicked on an online ad is a common experience. Second, a lay-theory experiment shows that the majority of participants incorrectly predict that online ads do not affect product search, but if these ads do, product search would be independent of shopping website design. Third, three eye-tracking and two search-time experiments reveal that online ads with an image of the target product improved search speed by about 25%, for websites without a systematic visual organization of products. Improved search speed was primarily due to faster rejection of competing products because the ads helped to perceptually suppress their color features. These results provide new insights into online advertising effects, the fundamental search processes through which these accrue, and how ads can support consumers in making their planned purchases.
Why Ideal Epistemology?
Authors: Carr Jennifer Rose
Published: March 2021

Ideal epistemologists investigate the nature of pure epistemic rationality, abstracting away from human cognitive limitations. Non-ideal epistemologists investigate epistemic norms that are satisfiable by most humans, most of the time. Ideal epistemology faces a number of challenges, aimed at both its substantive commitments and its philosophical worth. This paper explains the relation between ideal and non-ideal epistemology, with the aim of justifying ideal epistemology. Its approach is meta-epistemological, focusing on the meaning and purpose of epistemic evaluations. I provide an account on which the fundamental difference between ideal and non-ideal epistemic evaluations is that only the non-ideal epistemic ‘ought’ implies any substantive ‘can’. I argue that only ideal epistemic evaluations are ‘normatively robust’: they are neither conventional nor seriously context-sensitive. Non-ideal epistemic evaluations are normatively non-robust, exhibiting both conventionality and serious context-sensitivity from an interesting variety of distinct sources. For this reason, non-ideal epistemic evaluations won’t characterize the fundamental nature of epistemic rationality. Non-ideal epistemic rationality depends, not merely on what’s epistemically valuable, but also on modally contingent epistemic conventions and contextually contingent constraints on epistemic options. If we want a normatively robust theory of epistemic rationality, ideal epistemology is the only game in town.
BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI
Authors: Hangel Gilbert , Cadrien Cornelius , Lazen Philipp , Sharma Sukrit , Furtner Julia , Lipka Alexandra , Heckova Eva , Hingerl Lukas , Motyka Stanislav , Gruber Stephan , Strasser Bernhard , Kiesel Barbara , Mischkulnig Mario , Preusser Matthias , Roetzer Thomas , Wöhrer Adelheid , Widhalm Georg , Rössler Karl , Trattnig Siegfried , Bogner Wolfgang
Published: March 2021

OBJECTIVES

Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard.

METHODS

We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status).

RESULTS

We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs.

DISCUSSION

Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.
BIMG-06. RESPONSE ASSESSMENT OF BEVACIZUMAB THERAPY FOR GLIOBLASTOMA BY USING MULTIPLE PET TRACERS
Authors: Miyake Keisuke , Ogawa Daisuke , Hatakeyama Tetsuhiro , Tamiya Takashi
Published: March 2021

OBJECTIVE

Use of the positron emission tomography (PET), such as 18F-fluorodeoxyglucose (FDG), 11C-Methionine (MET), 18F- Fluorothymidine (FLT), and 18F-Fluoromisonidazole (FMISO), is expected to lead the way for novel applications aimed at achieving efficient malignancy grading and treatment of gliomas. The aim of this study was to assess FDG, MET, FLT, and FMISO PET studies to evaluate the biological effects induced by bevacizumab (BEV) therapy in glioblastoma patients.

METHODS

Seventy-one patients with glioblastoma were treated biweekly with BEV from July 2013 to November 2020. FDG, MET, FLT, and FMISO PET scans were obtained at baseline and at follow-up (4 weeks after treatment onset). Measures of FDG, MET, FLT, and FMISO avidity were recorded; the measures were SUVmax, metabolic tumor volume (MTV; volume of tumor with SUV>42% of SUVmax), SUVmean (within the MTV), tumor-to-normal ratio (TNR), tumor-to blood ratio (TBR), and total lesion avidity (TLA; calculated as MTV x SUVmean). The prognostic analysis was performed in relation to the response assessment by multiple PET tracers using progression-free survival (PFS) and overall survival (OS).

RESULTS

Under the assessment of the Cox proportional hazard model, increased changes of FDG SUVmax, MET TLA at follow-up, FLT TLA at follow up, increased changes of FLT TLA, increased changes of FMISO TBR and FMISO MTV were significant prognostic factor of PFS. Increase changes of FDG TLA and FLT TLA and increased changes of FMISO TBR were significant prognostic factor of OS.

CONCLUSION

Increased changes in FLT TLA and FMISO-PET after BEV therapy may be a useful biomarker for predicting PFS and OS in glioblastoma.
DDRE-03. IDH1-MUTANT GBM CELLS ARE HIGHLY SENSITIVE TO COMBINATION OF KDM6A/B AND HDAC INHIBITORS
Authors: Kayabölen Alişan , Sahin Gizem Nur , Seker Fidan , Cingöz Ahmet , Isik Bekir , Acar Simge , Wakimoto Hiroaki , Cahill Daniel P , Solaroglu Ihsan , Cribbs Adam , Oppermann Udo , Bagci-Onder Tugba
Published: March 2021

Mutations in IDH1 and IDH2 genes are common in low grade gliomas and secondary GBM and are known to cause a distinct epigenetic landscape in these tumors. To interrogate the epigenetic vulnerabilities of IDH-mutant gliomas, we performed a chemical screen with inhibitors of chromatin modifiers and identified 5-azacytidine, Chaetocin, GSK-J4 and Belinostat as potent agents against primary IDH1-mutant cell lines. Testing the combinatorial efficacy of these agents, we demonstrated GSK-J4 and Belinostat combination as a very effective treatment for the IDH1-mutant glioma cells. Engineering established cell lines to ectopically express IDH1R132H, we showed that IDH1R132H cells adopted a different transcriptome with changes in stress-related pathways that were reversible with the mutant IDH1 inhibitor, GSK864. The combination of GSK-J4 and Belinostat was highly effective on IDH1R132H cells, but not on wt glioma cells or nonmalignant fibroblasts and astrocytes. The cell death induced by GSK-J4 and Belinostat combination involved the induction of cell cycle arrest and apoptosis. RNA sequencing analyses revealed activation of inflammatory and unfolded protein response pathways in IDH1-mutant cells upon treatment with GSK-J4 and Belinostat conferring increased stress to glioma cells. Specifically, GSK-J4 induced ATF4-mediated integrated stress response and Belinostat induced cell cycle arrest in primary IDH1-mutant glioma cells; which were accompanied by DDIT3/CHOP-dependent upregulation of apoptosis. Moreover, to dissect out the responsible target histone demethylase, we undertook genetic approach and demonstrated that CRISPR/Cas9 mediated ablation of both KDM6A and KDM6B genes phenocopied the effects of GSK-J4 in IDH1-mutant cells. Finally, GSK-J4 and Belinostat combination significantly decreased tumor growth and increased survival in an orthotopic model in mice. Together, these results suggest a potential combination epigenetic therapy against IDH1-mutant gliomas.
DDRE-24. TARGETING PURINE METABOLISM TO OVERCOME GLIOBLASTOMA THERAPY RESISTANCE
Authors: Zhou Weihua , Yao Yangyang , Scott Andrew , Wilder-Romans Kari , Dresser Joseph , Werner Christian , Sun Hanshi , Pratt Drew , Sajjakulnukit Peter , Zaho Shuang , Davis Mary , Nelson Barbara , Halbrook Christopher , Zhang Li , Gatto Francesco , Srinivasan Sudharsan , Jairath Neil , Correa Luis , Umemura Yoshie , Walker Angela , Kachman Maureen , Qi Nathan , Sarkaria Jann , Xiong Jianping , Morgan Meredith , Rehemtulla Alnawaz , Castro Maria , Lowenstein Pedro , Chandrasekaran Sriram , Lawrence Theodore , Lyssiotis Costas , Wahl Daniel
Published: March 2021

Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming radiation (RT) resistance. To discover genotype-independent mediators of RT resistance, we correlated RT resistance with the concentration of approximately 700 metabolites across 23 GBM cell lines. Purine metabolites, especially those containing the base guanine, were most correlated with RT resistance. Similarly, increased abundance of tumor purines was associated with decreased survival in GBM patients treated with RT. This relationship is causal. Purine supplementation protected RT-sensitive GBMs from RT and promoted the repair of RT-induced double strand DNA breaks (DSBs). In vitro and in vivo stable isotope tracing confirmed that GBM cell lines and orthotopic patient-derived xenografts primarily generated purines through the de novo synthetic pathway. RT treatment further increased de novo purine synthesis in GBM through signaling via the DNA damage response. Inhibition of de novo GTP synthesis with mycophenolic acid (MPA) sensitized multiple GBM cell lines and neurospheres to RT by slowing the repair of RT-induced DSBs. MPA-induced radiosensitization was GTP-dependent as it was rescued by nucleoside supplementation. Modulating pyrimidine metabolism affected neither RT resistance nor DSB repair, suggesting these GTP-specific effects are due to active signaling rather than its ability to act as a physical substrate for DNA repair and candidate signaling molecules have been identified. These results were recapitulated in vivo with mycophenolate mofetil (MMF), the orally bioavailable FDA-approved prodrug of MPA. MMF potentiated RT efficacy, reduced tumor guanylates and slowed the repair of RT-induced DSBs across multiple models. Because de novo purine synthesis is activated by many of the oncogenic alterations that drive GBM, its inhibition is a promising genotype-independent strategy to overcome GBM RT resistance. We have now begun a clinical trial to determine whether combining MMF and RT is safe and potentially efficacious in patients with GBM.
ETMM-08 METABOLIC REGULATION OF THE EPIGENOME DRIVES LETHAL INFANTILE EPENDYMOMA
Authors: Kumar Sachin , Michealraj Antony , Kim Leo , Rich Jeremy , Taylor Michael
Published: March 2021

Ependymomas are malignant glial tumours that occur throughout the central nervous system. Of the nine distinct molecular subgroups of ependymoma, Posterior Fossa A (PFA), is the most prevalent, occurring in the hindbrain of infants and young children. Lacking highly recurrent somatic mutations, PFAs are thought to be a largely epigenetically driven entity, defined by hypomethylation at the histone 3 lysine 27 residue. Previous transcriptional analysis of PFAs revealed an enrichment of hypoxia signaling genes. Thus, we hypothesized that hypoxic signaling, in combination with a unique metabolic milieu, drive PFA oncogenesis through epigenetic regulation. In this study, we identified that PFA cells control the availability of specific metabolites under hypoxic conditions, resulting in diminished H3K27 trimethylation and increased H3K27 acetylation in vitro and in vivo. Unique to PFA cells, transient exposure to ambient oxygen results in irreversible cellular toxicity. Furthermore, perturbation of key metabolic pathways is sufficient to inhibit growth of PFA primary cultures in vitro. PFA cells sequester s-adenosylmethionine while upregulating EZHIP, a polycomb repressive complex 2 (PRC2) inhibitor, resulting in decreased H3K27 trimethylation. Furthermore, hypoxia fine-tunes the abundance of alpha-ketoglutarate and acetyl-CoA to fuel demethylase and acetyltransferase activity. Paradoxically, a genome-wide CRISPR knockout screen identified the core components of PRC2 as uniquely essential in PFAs. Our findings suggest that PFAs thrive in a narrow “Goldilocks” zone, whereby they must maintain a unique epigenome and deviation to increased or decreased H3K27 trimethylation results in diminished cellular fitness. Previously, we showed that PFAs have a putative cell of origin arising in the first trimester of development. Using single-cell RNAseq and metabolomics, we demonstrate that PFAs resemble the natural metabolic-hypoxic milieu of normal development. Therefore, targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
FSMP-14. METABOLIC SYMBIOSIS IN GLIOBLASTOMA: LACTATE DEHYDROGENASES TAKE THE LEAD
Authors: Guyon Joris , Romero-Garmendia Irati , Bikfalvi Andreas , Daubon Thomas
Published: March 2021

Glioblastoma (GBM) is a common and devastating brain tumor, associated with a low median survival, despite standard therapeutic management. Among its major features, GBMs are highly angiogenic, infiltrative, and exhibit paradoxically an elevated glycolysis. Most of differentiated cells convert glucose into pyruvate that enters into the Krebs cycle to maximize energy production in the presence of oxygen. For cancer cells, glucose uptake and catabolism are increased regardless of oxygen level. However, tumor cell energy needs are important, mainly for rapid growth, which require a much faster production flow. Lactate dehydrogenase (LDH) are involved at this step. LDHA converts pyruvate into lactate, and generates NAD+ to maintain glycolysis. Thus, lactate is exported into the extracellular compartment inducing an acidification of the microenvironment. Moreover, LDHB, another LDH isoform, metabolizes lactate into pyruvate for generating energy in mitochondria. LDHB is generally expressed in oligodendrocytes or neurons, but also in GBM cells. Though LDHA has already been studied in many cancers including GBM, the simultaneous role of LDH enzymes have not yet been investigated in GBM development. Our results showed that hypoxia significantly increased LDHA expression and lactate production, but no changes were observed for LDHB. In presence of lactate, cell invasion was significantly increased. In vitro results showed that, under hypoxic condition, double sgLDHA/B cell growth and invasion was dramatically decreased in comparison to control cells, mainly caused by an increase in apoptosis. In vivo experiments showed that double impairment of LDHA and B significantly reduced tumor growth and cell invasion, and induces a massive increase in mouse survival. Considered for a long time as a metabolic waste, lactate is shown here to play a critical role in the tumor niche. This study highlighted GBM adaptability through the LDH isoforms and their involvement in GBM development.
FSMP-18. COMPREHENSIVE METABOLIC PROFILING OF HIGH MYC MEDULLOBLASTOMA REVEALS KEY DIFFERENCES BETWEEN IN VITRO AND IN VIVO GLUCOSE AND GLUTAMINE USAGE
Authors: Pham Khoa , Poore Brad , Hanaford Allison , Maxwell Micah J , Sweeney Heather , Parthasarathy Akhila , Alt Jesse , Rais Rana , Slusher Barbara S , Eberhart Charles G , Raabe Eric H
Published: March 2021

Reprograming of cellular metabolism is a hallmark of cancer. Altered metabolism can overcome unfavorable conditions, allowing cancer cells to proliferate and invade in different tumor microenvironments. Medulloblastoma is the most common malignant brain tumor of children. Genomic amplification of MYC is a hallmark of a subset of poor-prognosis medulloblastoma. However, the metabolism of high MYC amplified medulloblastoma subgroup remains underexplored. We performed comprehensive metabolic studies of human MYC-amplified medulloblastoma by comparing the metabolic profiles of tumor cells in different environments – in vitro, in flank xenografts and in orthotopic xenografts. Principal component analysis showed that the metabolic profiles of brain and flank high-MYC medulloblastoma tumors clustered closely together and separated away from normal brain and the high-MYC medulloblastoma cells in culture. Compared to normal brain, MYC-amplified medulloblastoma orthotopic brain tumor xenografts showed upregulation of nucleotide, amino acid and glutathione pathways. Glucose was the main carbon source for the nucleotide synthesis and the TCA cycle in vivo. The glutaminase ii pathway was the main pathway utilizing glutamine in MYC-amplified medulloblastoma. In brain and flank xenografts, glutathione was the most abundant upregulated metabolite. Glutamine derived glutathione was synthesized through glutamine transaminase K (GTK) enzyme in vivo. The glutamine analog 6-diazo-5-oxo-l-norleucine (DON) significantly inhibited glutathione, amino acid, and nucleotide synthesis. In conclusion, we found that MYC-amplified medulloblastoma relied on glutamine metabolism in synthesizing glutathione in vivo. Glutamine antagonists may have therapeutic applications in human patients.
FSMP-19. SEX DIFFERENCES IN REDOX REGULATION UNDERLIE GLUTAMINE DEPENDENCY IN MALE GLIOBLASTOMA
Authors: Sponagel Jasmin , Zhang Shanshan , Frankfater Cheryl , Jones Jill , Selmanovic Din , Chinnaiyan Prakash , Rubin Joshua B , Ippolito Joseph E
Published: March 2021

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. GBM occurs more commonly in males but female patients survive significantly longer. Understanding the molecular mechanisms underlying this clinical sex disparity could support novel treatment strategies to improve outcomes for GBM patients. In this regard, we found that male and female GBM patient tissues differ in their metabolite profiles and that male GBM exhibit a higher abundance of amino acid metabolites. We confirmed these findings in a murine model of GBM. Furthermore, we found that male GBM cells are more sensitive to amino acid deprivation. This male-specific dependency on amino acids is almost entirely driven by amino acids involved in reactive oxygen species (ROS) regulation and glutathione synthesis. We found that male GBM cells are more sensitive to depletion of glutathione, which resulted in a significant increase in ROS and cell death in male GBM cells. Moreover, assays of glutathione oxidation demonstrated that male GBM cells exist in a chronically oxidized state. GLS1 mediates the conversion from glutamine to glutamate, a crucial component of glutathione. We found that male GBM cells are more sensitive to GLS1 inhibition with the clinical inhibitor CB-839. This correlated with significantly increased ROS and glutathione levels as well as significantly decreased TCA cycle metabolites in male GBM. Lastly, we found that the TCA cycle metabolite α-ketoglutarate rescues the effects of CB-839 in male GBM cells. Together, these data suggest that (1) male and female GBM differ in their amino acid requirements, (2) male GBM are more dependent on glutathione to regulate ROS levels, and (3) male GBM increase glutathione synthesis at the expense of TCA cycle metabolites upon GLS1 inhibition, suggesting an increased susceptibility to drugs targeting the glutamate/glutathione axis in male GBM. Our data underline the importance of considering sex in metabolic targeting approaches.
Molecular design and application of luminescent materials composed of group 13 elements with an aggregation-induced emission property
Authors: Ito Shunichiro , Gon Masayuki , Tanaka Kazuo , Chujo Yoshiki
Published: March 2021

Complexation of π-conjugated ligands by metal or semimetal ions leads to the enhancement of the planarity and rigidity of π-conjugated systems. Boron, especially, has played a central role in the design of luminescent main-group complexes. However, these complexes still suffer the disadvantage of aggregation-caused quenching as well as typical organic fluorophores. It has recently been reported that some types of boron complexes exhibit the aggregation-induced emission (AIE) property. Moreover, AIE behavior from complexes and organometallic compounds composed of the other group 13 elements, such as aluminum and gallium, has emerged in this decade. These observations greatly encourage us to develop advanced functional materials based on the group 13 elements. Indeed, recent research has demonstrated that these classes of materials are potentially versatile scaffolds for constructing chromic luminophores, efficiently emissive π-conjugated polymers and so on. This review mainly describes AIE-active group 13 complexes with four-coordinate structures and their application as photo-functional materials. Proposed mechanisms of the origins of AIE behavior are briefly discussed.
Dual Microcatheter Technique for Coiling of Intracranial Aneurysms: 2-Dimensional Operative Video
Authors: Waqas Muhammad , Dossani Rimal H , Cappuzzo Justin M , Sonig Ashish , Becker Alexander B , Levy Elad I
Published: March 2021

Primary coiling of large intracranial aneurysms with complex morphology, such as multiple lobes and a wide neck, is challenging. In these aneurysms, achieving adequate intra-aneurysmal packing density while preventing coil herniation into the parent vessel may be difficult with traditional coiling technique. In the setting of acute aneurysm rupture, alternative treatment options such as stent-assisted coiling or flow diversion may not be feasible due to the need for dual antiplatelets. In this video, we demonstrate the use of a dual microcatheter technique to achieve adequate packing density within a wide-necked, bilobed saccular aneurysm. The patient presented with a ruptured posterior communicating artery aneurysm with Hunt and Hess grade 2 and Fisher grade 4 subarachnoid hemorrhage. A biaxial catheter system was used for primary coiling of the aneurysm. Two .017-inch microcatheters were strategically positioned in the aneurysm lobes. The first coil was deployed through the distal catheter, which created a basket for the second coil to be deployed through the proximal microcatheter. Subsequent simultaneously deployed coils were weaved into each other to form a stable coil mass that prevented coil herniation into the parent vessel. Complete obliteration of the aneurysm was achieved.

The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary.

Video. ©University at Buffalo Neurosurgery, Inc., January 2020. With permission.
Financial Stability, Systemic Risk, and Taxpayers’ Money—The Rationale for a Special Resolution Regime
Authors: Schillig Michael
Published: March 2021

Special resolution regimes are generally introduced with the objective of helping to ‘maintain financial stability, minimize systemic risk, protect consumers, limit moral hazard and promote market efficiency’. The recurring themes are financial stability, systemic risk, and taxpayers’ exposure to losses. This chapter explores whether and to what extent a special resolution regime for banks and financial institutions can contribute to the enhancement of financial (system) stability and can limit systemic risk. It seeks to clarify these concepts and discusses possible ex ante incentives that a (recovery and) resolution regime may provide for controlling systemic risk. Further, it focuses on ex post remedies for the curtailment of systemic risk, and considers the international and cross-border implications.
The International Dimension: Cross-border Groups
Authors: Schillig Michael
Published: March 2021

The difficulties associated with the supervision and failure resolution of cross-border financial groups were among the key issues that came into renewed focus as a result of the global financial crisis. The cross-border dimension affects the recovery and resolution process in its entirety from the initial planning phase right through to liquidation. The chapter summarizes the elements of cross-border group law mentioned in previous chapters. It looks briefly at the US framework and the changes introduced through the Dodd–Frank Act. It discusses international jurisdiction of authorities and courts, the applicable law that governs proceedings, and the recognition and effects of foreign proceedings, in particular, in accordance with Directive 2001/24/EC on the reorganization and winding up of credit institutions and investment firms and the UNCITRAL Model Law on Cross-Border Insolvency. It also analyses the new European framework for co-operation in the cross-border group resolution context.
Introduction to compensatory damages
Authors: Burrows Andrew
Published: March 2021

This chapter, by way of introduction to compensatory damages, looks at the different types of loss, the compensatory aims, and the theoretical underpinnings of compensation. It goes on to examine, albeit to reject, the thesis that the primary function of damages is not compensation but is rather to value the right infringed. It also examines the controversial view that a standard measure of damages is a non-compensatory cost of cure.
Nominal and contemptuous damages and declarations
Authors: Burrows Andrew
Published: March 2021

Many torts are actionable only on proof of damage. But torts actionable per se, as well as breach of contract, are actionable without proof of damage. One consequence is that even though the court is satisfied that the claimant has not suffered any damage, it is still entitled to damages for the defendant’s breach of contract or tort actionable per se. Such damages are termed nominal and they comprise a trivial sum of money, usually about £2–£10. Nominal damages are therefore in no sense compensatory and must be distinguished from a small sum of compensatory damages. Their function is merely to declare that the defendant has committed a wrong against the claimant and hence that the claimant’s rights have been infringed. Given that the remedy of a declaration is specifically designed to serve this purpose, nominal damages are superfluous and could happily be abolished. This is particularly so since what was previously an important practical consequence of an award of nominal damages has been removed by Devlin J’s decision in Anglo-Cyprian Trade Agencies v Paphos Wine Industries Ltd that a claimant awarded nominal damages should not necessarily be regarded as a successful claimant for the purposes of costs.
Defences to Infringement
Authors: Stone David
Published: March 2021

If infringement of a Community design (registered or unregistered) or a national (or Benelux) registered design has been established, there are only a few defences of which a defendant might avail itself.
Case Study—Apple v Samsung
Authors: Stone David
Published: March 2021

In June 2011, Californian technology company Apple commenced proceedings against Korean electronics company Samsung. The global dispute concerned a range of mobile phone and tablet designs (in addition to a number of patents owned by each side). The various decisions in the European Union provide a useful insight into the treatment of design disputes by various Community design courts, and some of the procedural, jurisdictional, and other matters that may arise.
Introduction
Authors: Riordan Jaani
Published: March 2021

Internet intermediaries are essential features of modern commerce, social and political life, and the dissemination of ideas. Some act as conduits through which our transmissions pass; others are custodians of our personal data and gatekeepers of the world’s knowledge. They supply the infrastructure and tools which make electronic communications possible. These services encompass a vast ecosystem of different entities: internet service providers, website operators, hosts, data centres, social networks, media platforms, search engines, app developers, marketplaces, app stores, and others—many of which are household names.
Blocking Injunctions
Authors: Riordan Jaani
Published: March 2021

A blocking injunction is an order requiring an internet intermediary to implement technical measures directed at preventing or disabling access to a specified internet location. The essential purpose of such an order is to restrict the ability of individuals located in a particular jurisdiction to access or download material the subject of the order using the respondent’s service. Although theoretically available against any service provider, blocking injunctions are most commonly sought against ISPs, who possess a comparatively high degree of control at the network layer and may operate systems that can drop or re-route packets based on criteria including the destination of a request. Blocking injunctions require the respondent to adopt these technical measures in an attempt to prevent others from using its service to infringe the applicant’s rights. Section 2 provides an overview of the most common technical measures employed by ISPs.
Trade Mark Law in Europe
Authors: Mühlendahl Alexander , Botis Dimitris , Maniatis Spyros , Wiseman Imogen
Published: March 2021

In light of the ever-growing and developing jurisprudence of the Court of Justice and the General Court, and forthcoming substantive and systemic changes to the law, there is a need for a fresh and practical approach to the procedure and case law of trade marks in Europe. Trade Mark Law in Europe is a comprehensive guide to European trade mark law following the jurisprudence of the Court of Justice of the European Union and the case law of the General Court. It provides a wide-ranging overview of the trade mark system, including detailed and critical discussion of forthcoming changes, as well as an in-depth look at the life of a trade mark up to enforcement. It considers the conditions for maintaining a registration, the protection and enforcement of trade marks, and the interface between trade mark law and other areas of practice. Finally, it offers detailed and insightful analysis of current developments, challenges, and opportunities. This is complemented by an international and comparative approach which selectively considers the contemporary jurisprudence of the Supreme Court of the United States and general US practice, as well as national jurisprudence in areas not yet covered by the CJEU. Written by highly-regarded authors with considerable expertise across a range of constituencies, Trade Marks in Europe is a timely and important study of this complex and challenging area of law.
Recognition of Insolvency Proceedings
Authors: Veder Michael , Oberhammer Paul
Published: March 2021

Article 19 is a key provision of the Insolvency Regulation. It sets out the fundamental principle of the immediate and automatic recognition of judgments opening insolvency proceedings.
International Jurisdiction
Authors: Bork Reinhard , Mangano Renato
Published: March 2021

This chapter examines the contents of Arts. 3-6 EIR in order to answer the following questions: which Member States have international jurisdiction; has the seized court a power and a duty to examine jurisdiction; might a creditor challenge this choice; does the jurisdiction of the seized court extend to so-called connected actions, i.e. to actions directly deriving from the insolvency proceeding and closely linked with it? For this purpose, the concept and rationale of the centre of a debtor’s main interests (COMI) is analysed, as well as the power and duty of the seized courts to examine jurisdiction. This chapter also focuses on the increasingly popular phenomenon of ‘forum shopping’, and on the theoretical and practical attempts to distinguish between forum shopping which is compliant with the acquis communautaire on the freedom of establishment across Europe and forum shopping which is fraudulent.
Recognition and Enforcement
Authors: Bork Reinhard , Mangano Renato
Published: March 2021

Automatic recognition of judgments rendered within the course of insolvency proceedings constitutes one of the fundamental principles of the EIR, as recognition is based on mutual trust and is crucial regarding maintenance of the universality of (main) insolvency proceedings. This chapter scrutinizes the mechanism through which recognition operates pursuant to the EIR. Recognition applies only to certain judgments handed down during insolvency proceedings; therefore, we must determine which types of judgment enjoy recognition pursuant to the EIR. Discussion then focuses on the impact of recognizing foreign judgments before exploring the public policy exception, this being the only ground upon which refusal of recognition may be based. As enforcement of judgments in foreign Member States may be necessary, the manner in which the EIR ensures the enforceability of judgments handed down during insolvency proceedings will also be observed.
Sweden
Authors: Häger Johan , Hanqvist Dan , Mahir Harem , Moskowicz Mattias
Published: March 2021

The material contained herein is intended as a general guide only. The information and opinions which it contains are not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
The Rule in Hastings-Bass, Mistake, and Rectification
Authors: Panico Paolo
Published: March 2021

Things may go wrong. A settlor may create a trust mistakenly believing that the arrangement will achieve certain results. Trustees may exercise their dispositive powers mistakenly believing to provide for the beneficiaries in a certain manner. Alternatively, trustees may exercise their powers failing to take into account relevant considerations they ought to have paid attention to, or taking into account irrelevant considerations they ought to have disregarded. Finally, the documents recording the relevant transactions, such as a trust instrument or an instrument of appointment, may contain words with a different meaning to what the parties intended.
Duty To Exercise Reasonable Care, Skill, and Diligence
Authors: Arnold Mark
Published: March 2021

The 2006 Act, s 174 thus codifies the director’s duty to exercise reasonable care, skill, and diligence. It reflects the current position at common law, which itself reflects the tests laid down in the context of wrongful trading, as set out in the Insolvency Act, s 214. Indeed, the wording of this section of the 2006 Act is substantially the same as that of the Insolvency Act, s 214(4).
European patent with unitary effect
Authors: Tilmann Winfried
Published: March 2021

A European patent granted with the same set of claims in respect of all the participating Member States shall benefit from unitary effect in the participating Member States provided that its unitary effect has been registered in the Register for unitary patent protection.
Administrative tasks in the framework of the European Patent Organisation
Authors: Tilmann Winfried
Published: March 2021

The EPUE Reg is a ‘special agreement’ within the meaning of Art 142(1) EPC (Recital 6; → Introduction to this Commentary, mn 125–34). The participating Member States, as a ‘group of Contracting States’ to the EPC, may therefore ‘give additional tasks’ to the EPO (Art 143(1) EPC). Art 9(1) EPUE Reg sets out which tasks these are and provides that they are to be given to the EPO. They have been given to the EPO by the Rules relating to Unitary Patent Protection (RUPR) (→ Annex following mn 45).
Level of renewal fees
Authors: Tilmann Winfried
Published: March 2021

National or, as set out above, collectively national renewal fees are to be paid by the patent proprietor after the EPUE has been granted. It is at that point in time that the EPO has finished its part (receiving the application and reviewing compliance with formal requirements; checking that fees have been received; checking of priority, search, publication, substantive review after examination application, decision). The costs arising from this activity are covered by fees, at least potentially. In the period leading up to the EPUE Reg, this repeatedly elicited critical remarks from those asking why the EPO, for a phase of relative inactivity, should now additionally be paid rising renewal fees. These remarks are all the more critical when it comes to the question of whether the countries of protection should have any claim at all to retaining part of the renewal fees.
Territorial scope of decisions
Authors: von Falck Andreas , Dorn Stephan
Published: March 2021

Decisions of the Court shall cover, in the case of a European patent, the territory of those Contracting Member States for which the European patent has effect.
Patent mediation and arbitration centre
Authors: Tochtermann Peter
Published: March 2021

As yet, mediation and arbitration as alternative dispute resolution procedures are rarely invoked in the context of patent disputes. Therefore these procedures do not play a significant role.
Article 87 Revision
Authors: Tilmann Winfried
Published: March 2021

Pursuant to para 1, the period after which the Administrative Committee carries out a consultation with the users of the patent system established by the UPCA is defined by the first sentence as follows: ‘Either seven years after entry into force of this Agreement or once 2000 infringement cases have been decided by the Court, whichever is the later point in time’.
Impartiality
Authors: Tochtermann Peter
Published: March 2021

Art 7 UPC Statute stipulates the impartiality of the judges of the UPC. It does not make a difference whether the provision refers to the impartiality of the judges or to their independence, as both concepts describe two sides of the same coin and are regularly used interchangeably. Whereas the term ‘independence’ has rather an objective notion in the sense of being free from any influence, the term ‘impartiality’ refers to the subjective mindset of the judge towards the dispute and the parties as well as their representatives.
President of the Court of Appeal
Authors: Tochtermann Peter
Published: March 2021

The President of the Court of Appeal is elected for a term of three years and may be re-elected twice, thus the maximum term of office is nine years. If the office of the President of the Court of Appeal falls vacant before the expiry of his term, a successor will be elected for the remainder of that term.
Presidium
Authors: Tochtermann Peter
Published: March 2021

The Presidium consists of the President of the Court of Appeal who is the President of the Presidium by law, the President of the Court of First Instance, two elected judges of the Court of Appeal, and three full-time judges of the Court of First Instance. The Registrar is also a member of the Presidium but is not entitled to vote. Decisions of the Presidium referred to in Arts 7, 8, 10, and 22 UPC Statute are to be taken without the participation of the Registrar.
Panels
Authors: Tochtermann Peter
Published: March 2021

The presiding judge of a panel (not to be confused with the presiding judge of a division) is to be appointed by the Presidium. In the absence of such decision, the most senior judge shall be the presiding judge (Rule 341(4) UPCARoP). The allocation of judges and the assignment of cases within a division to its panels are governed by the Rules of Procedure.
Authorization for expenditure
Authors: Tochtermann Peter
Published: March 2021

The expenditure in the budget is authorized for the duration of one accounting period by the adoption of the budget (Art 29 Draft Financial Regulations). After the budget has been adopted, the Registrar and the Presidium are authorized to enter into the financial commitments set out in the budget.
Accounting period
Authors: Tochtermann Peter
Published: March 2021

Art 29 UPC Statute defines the calendar year as the accounting period. The provision is repeated in Art 22(2) Draft Financial Regulations.
Fee for the Counterclaim for revocation
Authors: Plassmann Clemens
Published: March 2021

Rule 26 UPCARoP specifies in more detail for the Counterclaim for revocation the obligation of the parties to the proceedings, stipulated in Art 70 UPCA, to pay Court fees by imposing on the defendant and revocation counterclaimant the obligation to pay a fixed fee. The level of such fee is set in Rule 370.2 (Fee Scale Section III) at €20,000 (maximum: fee of the infringement action). Pursuant to Rule 371.1, the fee is to be paid by lodging the action (for derogations from this requirement, → Rule 371 UPCARoP) by transfer to one of the bank accounts of the UPC stating the party or his representative, the patent number, and the case reference. Pursuant to Rule 371.2, proof of payment is to be provided together with the Statement of claim.
Fee for the revocation action
Authors: Plassmann Clemens
Published: March 2021

The claimant shall pay the fee for the revocation action in accordance with Part 6. Rule 15.2 shall apply mutatis mutandis.
Rule 53: Fee for the Counterclaim for infringement
Authors: Plassmann Clemens
Published: March 2021

Rule 53 defines, for the infringement counterclaim, the obligation stated in Art 70 UPCA for the parties to pay Court fees. It does so in obliging the defendant and claimant of the infringement counterclaim to pay a fixed fee. The amount of that fee is determined by Rule 370.2(a) in the amount of €11,000. Pursuant to Rule 371.1, the fee must be paid before bringing the action (for exceptions from this requirement, → Rule 371 UPCARoP) by transmitting the amount to one of the bank accounts of the UPC indicating the paying party or its representative together with the number of the patent involved and the number of the case. Proof of payment must be provided together with the relevant pleading or application pursuant to Rule 371.2.
Rule 73: Closure of the written procedure subject to the possible exchange of further pleadings
Authors: Plassmann Clemens , Steininger Steffen
Published: March 2021

The Rule is self-explanatory. Refer to the commentaries on the Rules to which it refers.
Rule 77: Action for declaration of non-infringement and action for revocation
Authors: von Falck Andreas , Dorn Stephan
Published: March 2021

Rule 77 is based on the competence of the central division for actions for declaration of non-infringement (Art 32(1)(b) UPCA) and for revocation actions (Art 32(1)(d)) pursuant to Art 33(4). Both actions may be lodged together at the central division. The lis pendens rule of Art 33(2) subpara 1 does not prevent that combination. Actions for declaration of non-infringement (Art 32(1)(b)) and revocation actions (Art 32(1)(d)) are not mentioned in the blocking provision of Art 33(2) subpara 1.
Rule 88: Application to annul or alter a decision of the Office
Authors: Kuczera Markus
Published: March 2021

The reference to Art 7(2) UPCA and Annex II thereto means that the claimant has no choice whether the action is heard at the seat of the central division in Paris or by one of the two sections (in London and Munich). Actions against administrative decisions taken by the EPO in carrying out the tasks referred to in Art 9 EPUE Reg are not bundled at one location of the central division. In fact, they are allocated to one of the two sections or to the seat of the central division (which is treated below as a section). The question of which section of the division is competent depends on which of the sections A–H of the IPC of the WIPO the patent is assigned. The details are determined according to Rule 17.3 UPCARoP, of which lits a and c are applicable.
Rule 101: Role of the judge-rapporteur (Case management)
Authors: Tochtermann Peter
Published: March 2021

During the interim procedure, the judge-rapporteur shall make all necessary preparations for the oral hearing. He may in particular, where appropriate, and subject to the mandate of the panel, hold an interim conference with the parties which may be held on more than one occasion and may exercise the powers provided for in Rule 334.
Rule 117 Absence of both parties from the oral hearing
Authors: Tochtermann Peter
Published: March 2021

Pursuant to Art 52(3) UPCA, the parties may inform the Court that they give their consent for the Court to decide without an oral hearing being held. In that event, the Court will decide the case on the basis of the files.