bluuebunny/crossref_metadata_2025 huggingface dataset:
cMapper: gene-centric connectivity mapper for EBI-RDF platform
Authors: Shoaib Muhammad , Ansari Adnan Ahmad , Ahn Sung-Min
Published: September 2016

Motivation

In this era of biological big data, data integration has become a common task and a challenge for biologists. The Resource Description Framework (RDF) was developed to enable interoperability of heterogeneous datasets. The EBI-RDF platform enables an efficient data integration of six independent biological databases using RDF technologies and shared ontologies. However, to take advantage of this platform, biologists need to be familiar with RDF technologies and SPARQL query language. To overcome this practical limitation of the EBI-RDF platform, we developed cMapper, a web-based tool that enables biologists to search the EBI-RDF databases in a gene-centric manner without a thorough knowledge of RDF and SPARQL.

Results

cMapper allows biologists to search data entities in the EBI-RDF platform that are connected to genes or small molecules of interest in multiple biological contexts. The input to cMapper consists of a set of genes or small molecules, and the output are data entities in six independent EBI-RDF databases connected with the given genes or small molecules in the user's query. cMapper provides output to users in the form of a graph in which nodes represent data entities and the edges represent connections between data entities and inputted set of genes or small molecules. Furthermore, users can apply filters based on database, taxonomy, organ and pathways in order to focus on a core connectivity graph of their interest. Data entities from multiple databases are differentiated based on background colors. cMapper also enables users to investigate shared connections between genes or small molecules of interest. Users can view the output graph on a web browser or download it in either GraphML or JSON formats.

Availability and Implementation

cMapper is available as a web application with an integrated MySQL database. The web application was developed using Java and deployed on Tomcat server. We developed the user interface using HTML5, JQuery and the Cytoscape Graph API. cMapper can be accessed at http://cmapper.ewostech.net. Readers can download the development manual from the website http://cmapper.ewostech.net/docs/cMapperDocumentation.pdf. Source Code is available at https://github.com/muhammadshoaib/cmapper.

Supplementary information

Supplementary data are available at Bioinformatics online.
Detecting subnetwork-level dynamic correlations
Authors: Yan Yan , Qiu Shangzhao , Jin Zhuxuan , Gong Sihong , Bai Yun , Lu Jianwei , Yu Tianwei
Published: September 2016

Motivation

The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them.

Results

Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method’s ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups.

Availability and Implementation

The R package is available at https://cran.r-project.org/web/packages/LANDD.

Supplementary information

Supplementary data are available at Bioinformatics online.
Systemic Age-Associated DNA Hypermethylation of ELOVL2 Gene:
In Vivo and In Vitro Evidences of a Cell Replication Process
Authors: Bacalini Maria Giulia , Deelen Joris , Pirazzini Chiara , De Cecco Marco , Giuliani Cristina , Lanzarini Catia , Ravaioli Francesco , Marasco Elena , van Heemst Diana , Suchiman H. Eka D. , Slieker Roderick , Giampieri Enrico , Recchioni Rina , Mercheselli Fiorella , Salvioli Stefano , Vitale Giovanni , Olivieri Fabiola , Spijkerman Annemieke M. W. , Dollé Martijn E. T. , Sedivy John M. , Castellani Gastone , Franceschi Claudio , Slagboom Pieternella E. , Garagnani Paolo
Published: September 2016

Epigenetic remodeling is one of the major features of the aging process. We recently demonstrated that DNA methylation of ELOVL2 and FHL2 CpG islands is highly correlated with age in whole blood. Here we investigated several aspects of age-associated hypermethylation of ELOVL2 and FHL2. We showed that ELOVL2 methylation is significantly different in primary dermal fibroblast cultures from donors of different ages. Using epigenomic data from public resources, we demonstrated that most of the tissues show ELOVL2 and FHL2 hypermethylation with age. Interestingly, ELOVL2 hypermethylation was not found in tissues with very low replication rate. We demonstrated that ELOVL2 hypermethylation is associated with in vitro cell replication rather than with senescence. We confirmed intra-individual hypermethylation of ELOVL2 and FHL2 in longitudinally assessed participants from the Doetinchem Cohort Study. Finally we showed that, although the methylation of the two loci is not associated with longevity/mortality in the Leiden Longevity Study, ELOVL2 methylation is associated with cytomegalovirus status in nonagenarians, which could be informative of a higher number of replication events in a fraction of whole-blood cells. Collectively, these results indicate that ELOVL2 methylation is a marker of cell divisions occurring during human aging.
1. Introduction
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This introductory chapter begins with an overview of conveyancing, which is the process by which legal title to property is transferred. It then discusses the conveyancing of registered land; defensive lawyering and the conveyancing process; conveyancing and information technology; and the future of conveyancing.
2. Taking instructions and other initial matters
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter begins with a look at the process of initial interviews with clients. At the start of any transaction it is important to establish a good working relationship with the client. The first interview marks the perfect time to do this, for it gives practitioners the opportunity to instil confidence in the client of their abilities as a conveyancer. The chapter then deals with estate agents; client care and advice on costs; advice on co-ownership; advice on finance; advice on survey; Law Society Conveyancing Protocol; professional conduct; and considerations for acting for either seller or buyer.
3. The draft contract
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter considers various issues relating to drafting a contract. These include preparatory steps by seller’s practitioner; formation of the contract; contents of the contract; sales of part; and special considerations.
4. Pre-contract searches and enquiries, Town and Country Planning
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter considers pre-contract searches, enquiries, and town and country planning. It explains the why, what, and when of pre-contract searches and enquiries; the National Land Information Service; effects of the Law Society Conveyancing Protocol; commercial property enquiries; planning and conveyancing; changes of use; enforcement notices and stop notices; and building regulations.
5. Deduction and investigation of title
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

Deducing title is the process by which the seller demonstrates to the buyer that the seller owns the land and can convey it. Conversely, the process of investigating title is the means by which the buyer ensures that the seller does own the land, and can convey. This chapter discusses when these procedures are carried out and then considers in detail the methods for deducing and investigating title in both registered and unregistered land.
6. Preparing for and implementing exchange of contracts
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter first considers matters that must be attended to before an exchange of contracts when acting for the buyer and when acting for the seller. It then discusses implementing the exchange of contracts; actions taken after exchange; and death or insolvency of contracting parties between exchange and completion.
9. Post-completion procedures: delays and remedies
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter considers two areas that provide practitioners with some of the more challenging parts of the conveyancing process: first, post-completion procedures; and, second, dealing with delays and seeking appropriate remedies. Practitioners must deal with time limits, with ‘what if’ scenarios, and with the mechanics of stamping and registration. In particular, delays affecting conveyancing contracts, and the consequential remedies available, are a fertile source for conflict between conveyancing practitioners.
12. Commercial conveyancing
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter focuses on commercial conveyancing, which involves the granting and renewal of business (or commercial) leases as well as the buying and selling of properties that are let to business occupants. It first considers revenue matters then turns to the key commercial area that most conveyancers will encounter in practice, the review of the contents of a commercial lease. The final section is devoted to the particular requirements a practitioner must bear in mind when acting for a client who is selling or buying a tenanted property. It also considers the Standard Commercial Property Conditions (SCPC) being commercial specific standard contractual terms.
13. Business tenancies and the Landlord and Tenant Act 1954, Part II
Authors: Abbey Professor Robert M. , Richards Mark B.
Published: September 2016

This chapter considers the provisions of the Landlord and Tenant Act 1954, Part II, which regulates the ways in which business tenancies may be terminated and gives statutory protection to business tenants. Topics discussed include agreements to which the 1954 Act applies; requirement for ‘tenancy’ tenancies excluded from statutory protection; requirement for ‘occupation’ methods of termination under the 1954 Act; Section 40 notices; rules for service of notices; interim rent applications; landlord’s statutory grounds of opposition; tenant’s right to compensation for failure to obtain a new tenancy; and court order for new tenancy.
4. Overriding objective and human rights
Authors: Sime Stuart
Published: September 2016

This chapter discusses the sources of procedural law, the general principles relevant to civil procedure established by the overriding objective, the European Convention on Human Rights, and some rules on how the courts approach construing the Civil Procedure Rules 1998 (CPR). The CPR and practice directions (PDs) are the procedural rules governing civil proceedings. The most important rule is the ‘overriding objective’ of dealing with claims justly and at proportionate cost. The most important Convention rights in civil litigation are the right to a fair trial, the right to respect for private and family life, and the right to freedom of expression.
7. Renewal of process
Authors: Sime Stuart
Published: September 2016

After proceedings commence by issuing a claim form or other originating process, they must be brought to the attention of the defendants or respondents by service. Generally, originating process remains valid for the purpose of service for a period of four months. Service of proceedings marks a watershed in the litigation process. It is at this point that the defendant is put on formal notice that legal proceedings have been brought, and the time limit on service of proceedings is one which is relaxed with extreme caution. This chapter discusses periods of validity; power to renew; claims in respect of cargo carried by sea; multiple defendants; effect of stay; procedure on seeking an extension; and challenging an order granting an extension.
10. Alternative dispute resolution
Authors: Sime Stuart
Published: September 2016

Alternative dispute resolution (ADR), particularly mediation, plays a key role in reducing the costs of civil disputes by fomenting the early settlement of cases. This chapter discusses ADR processes; advantages or disadvantages of ADR and litigation; the cost of ADR; reference to ADR; and court involvement in ADR. Adjudicative ADR results in the third party neutral deciding the dispute or difference between the parties. Non-adjudicative ADR processes involve moving the parties towards reaching a compromise agreement between themselves. Rules of court require parties to consider using ADR. Sanctions may be imposed on parties who act unreasonably.
16. Costs management
Authors: Sime Stuart
Published: September 2016

Costs management refers to the procedures used by the courts to manage the steps to be taken in civil proceedings while also managing the costs to be incurred by the parties in taking those steps to ensure that litigation is conducted at proportionate cost. This chapter discusses the elements of costs management; cases governed by costs management; costs management orders; costs budgets and case management; judicial control of costs budgets; and impact on costs orders.
25. Interim payments
Authors: Sime Stuart
Published: September 2016

This chapter discusses the rules on interim payments. An order for interim payment is an order for payment of a sum of money by a defendant on account of any damages, debt, or other sum which the court may hold the defendant liable to pay. Such orders are likely to be made in claims where it appears that the claimant will achieve at least some success, and where it would be unjust to delay, until after the trial, payment of the money to which the claimant appears to be entitled. The amount ordered must not exceed a reasonable proportion of the likely final award taking into account any counterclaim and contributory negligence.
29. Multi-track
Authors: Sime Stuart
Published: September 2016

The multi-track deals with a vast range of cases, from simple contractual disputes involving little more than £25,000, to complex commercial cases involving difficult issues of fact and law with values of several million pounds, to cases where perhaps no money is at stake but which raise points of real public importance. Cases on the multi-track will generally be dealt with either in the Royal Courts of Justice or other civil trial centre. This chapter discusses agreed directions; case management conferences; fixing the date for trial; pre-trial checklists; listing hearings; pre-trial review; directions given at other hearings; and variation of case management timetable.
31. Disclosure
Authors: Sime Stuart
Published: September 2016

The Civil Procedure Rules 1998 (CPR) require the parties to give advance notice to their opponents of all the material documentation in their control. This is done in two stages. At the first stage the parties send each other lists of documents, a process called ‘disclosure’. The second stage is ‘inspection’, which is the process by which the other side can request copies of documents appearing in the list of documents, typically with photocopies being provided by the disclosing party. This chapter discusses these processes. It covers lawyers’ and clients’ responsibilities; the stage when disclosure takes place; disclosure orders; standard disclosure; menu option disclosure; duty to search; list of documents; privilege; inspection; orders in support of disclosure; documents referred to in statements of case, etc.; admission of authenticity; and collateral use.
34. Admissions and documentary evidence
Authors: Sime Stuart
Published: September 2016

This chapter discusses the rules relating to the proof of admissions and documents at trial. It covers the nature of admissions; pre-action admissions of liability; permission to withdraw an admission; notice to admit facts; and proving documents.
39. Trial
Authors: Sime Stuart
Published: September 2016

This chapter discusses the issues that need to be addressed in the period leading up to a trial. These include contacting witnesses to ensure their availability; obtaining witness summonses where appropriate; briefing trial counsel; agreeing and compiling trial bundles; and counsel preparing speeches, examination-in-chief, and cross-examination of witnesses.
40. References to the Court of Justice of the European Union
Authors: Sime Stuart
Published: September 2016

An English court faced with a question of EU law may sometimes decide it itself, or may refer it to the Court of Justice of the European Union (CJEU) in Luxembourg for a preliminary ruling. If a reference is made, the English proceedings will be stayed pending the ruling of the CJEU. Once it is made, the ruling is binding on the English court, but it is only a preliminary ruling, in that the English court is left to apply the ruling to the facts of the case and to give judgment. This chapter discusses the questions which may be referred to the CJEU; mandatory references; discretionary references; procedures in England; procedure in the CJEU; and costs of the parties in seeking a ruling from the CJEU.
41. Judgments and orders
Authors: Sime Stuart
Published: September 2016

This chapter discusses the rules on judgments and orders. Although there is likely to be a delay between judgment being pronounced and the judgment being sealed and served, r 40.7(1) of the Civil Procedure Rules 1998 (CPR) provides that judgment in fact takes effect from the day it was given. After a judgment or order has been pronounced by the court, the next step is to have it drawn up. This chapter discusses settlements; orders made at hearings; form of judgments and orders; general rules relating to drawing up orders and judgments; and register of judgments.
47. Qualified one-way costs shifting
Authors: Sime Stuart
Published: September 2016

Qualified one-way costs shifting (QOCS) provides costs protection to claimants in personal injuries claims. If the claimant wins, the defendant should be ordered to pay the claimant’s costs in the usual way. However, if the claimant loses, under QOCS while the claimant remains liable to pay its own lawyers’ costs, and may be ordered to pay the successful defendant’s costs, the claimant will be protected against actually having to pay those costs to the defendant. This chapter discusses cases where QOCS applies; the effects of QOCS; and loss of QOCS protection.
2. Promotion of the company
Authors: Roach Lee
Published: September 2016

EachConcentraterevision guide is packed with essential information, key cases, revision tips, exam Q&As, and more.Concentratesshow you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the legal position of persons in the process of incorporating a company (known as ‘promoters’), and the legal relationship that exists between them and the unformed company and with any third parties who contract with the promoters or the company prior to it being incorporated. A promoter cannot make a secret profit out of the company’s promotion and will usually be personally liable on a contract entered into on behalf of a company if that company had not been incorporated at the time the contract was entered into.
3. Incorporation
Authors: Roach Lee
Published: September 2016

EachConcentraterevision guide is packed with essential information, key cases, revision tips, exam Q&As, and more.Concentratesshow you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the process of incorporation and the advantages and disadvantages of conducting business through a company. The three principal methods by which a company can be incorporated are: incorporation by Act of Parliament, incorporation by Royal Charter, and incorporation by registration. The advantages of incorporation include perpetual succession, asset ownership, and the ability to commence legal proceedings. The disadvantages of incorporation include increased formality, regulation, and publicity; and civil liability.
4. The constitution of the company
Authors: Roach Lee
Published: September 2016

EachConcentraterevision guide is packed with essential information, key cases, revision tips, exam Q&As, and more.Concentratesshow you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the company constitution. A company’s constitution consists primarily of the articles of association, and agreements and resolutions affecting the company’s constitution. The constitution forms a statutory contract between the company and its members, and between the members themselves, but only those provisions relating to membership rights will constitute terms of the statutory contract. A company can alter its articles by passing a special resolution, although statute and the common law restrict a company’s ability to alter its articles.
7. Corporate governance
Authors: Roach Lee
Published: September 2016

EachConcentraterevision guide is packed with essential information, key cases, revision tips, exam Q&As, and more.Concentratesshow you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses corporate governance in the UK, beginning with a discussion of the development of the UK’s corporate governance system. The chapter then discusses the effectiveness of the ‘comply or explain’ approach. It then discusses a number of key corporate governance mechanisms, namely institutional investors, non-executive directors, and directors’ remuneration.
9. Members’ remedies
Authors: Roach Lee
Published: September 2016

EachConcentraterevision guide is packed with essential information, key cases, revision tips, exam Q&As, and more.Concentratesshow you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the three principal remedies provided by law to members of a company: the derivative claim under Pt 11 of the Companies Act 2006 (CA 2006); the unfair prejudice remedy under Pt 30 of the CA 2006; and the petition for winding up the company under s 122 of the Insolvency Act 1986 (IA 1986).
2. An Introduction to the Law of Criminal Evidence and Advocacy
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

Both prosecutors and defence lawyers must have a good understanding of the rules of criminal evidence and be able to apply the rules in a highly practical way to the issues in a case. This chapter provides a brief introduction to the main evidential rules which are considered further in later chapters. In particular, it addresses the following: the purpose of rules of evidence; the core concepts of relevance, admissibility, and weight; and the different types of evidence.
5. The Right to Silence at the Police Station
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

This chapter explains the substantive law governing a defendant’s silence at the police station under ss. 34, 36, and 37 Criminal Justice and Public Order Act (CJPOA) 1994. It covers the risks associated with s. 34 CJPOA 1994; drawing inferences from a failure to account under ss. 36 and 37 CJPOA 1994; and the practical aspects associated with remaining silent.
8. The Decision to Prosecute and the Prosecution’s Duties of Disclosure of Evidence
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

This chapter first explains the role of the Crown Prosecution Service (CPS) and the factors that are taken into account when deciding to charge a suspect or to divert him from prosecution. It then examines the important obligations which are placed upon the CPS both at common law and under statute to serve pre-trial disclosure of evidence upon the defendant.
12. Prosecuting Summary Offences
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

A summary trial will be held where a defendant pleads not guilty to a summary-only offence or pleads not guilty to an either-way offence where the magistrates’ court has accepted jurisdiction to try the offence at the allocation hearing and the defendant has consented to summary trial. This chapter deals with the steps in preparing for a summary trial. It considers pleading guilty by post; the circumstances in which a defendant can be summarily tried in her absence; the rules governing the drafting of a written charge/information; the pre-trial disclosure of evidence in a summary case; case management; the steps when preparing for summary trial; and the procedure at a summary trial on a not guilty plea.
13. Crown Court Proceedings Pre-Trial
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

This chapter deals with pre-trial practices and procedures of indictable-only offences. It covers sending indictable-only cases to the Crown Court under s. 51 Crime and Disorder Act 1998 (CDA 1998); preparing for the preliminary hearing in the Crown Court; preparing for trial on indictment; pre-trial disclosure issues and defence statements; instructing counsel; and pre-trial hearings including the Plea and Case Management Hearing (PCMH).
18. Hearsay Evidence
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

Hearsay evidence in criminal cases most often arises in two situations: if a witness testifies about facts of which he has no personal knowledge because the facts were communicated to the witness by another person who is not in court; and where a witness’ written statement is put before the court because the witness is unable to attend court to give oral evidence. This chapter discusses the general rule of hearsay evidence; identifying hearsay evidence; statutory exceptions to the hearsay rule; hearsay evidence under the Criminal Justice Act (CJA) 2003; hearsay admissible under the preserved common law rules; procedure for admitting hearsay evidence; and hearsay evidence and the European Convention on Human Rights (ECHR) 1950.
21. Sentencing Procedure and the General Principles of Sentencing
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

This chapter explains the procedure on passing sentence and the general principles that govern a court’s decision when passing sentence. It discusses the role of the Crow Prosecution Service (CPS) on sentence; the procedure on sentencing; hierarchy of sentences; sentencing aims; the basis of sentencing under the Criminal Justice Act 2003; Sentencing Council for England and Wales; sentencing guidelines in the Crown Court; how the defence solicitor assesses the seriousness of an offence; Magistrates’ Court Sentencing Guidelines (MCSGs); personal offender mitigation; discount for timely guilty pleas; the Crown Court’s sentencing powers; victim impact statements; and taking other offences into consideration.
26. Sentencing Young Offenders
Authors: Hannibal Martin , Mountford Lisa
Published: September 2016

This chapter considers the range of disposals available where a young offender admits the offence(s) or a finding of guilt is recorded against him. It discusses the principles which guide the sentencing of youths; the youth court’s sentencing powers; the adult magistrates’ court sentencing powers; the Crown Court’s sentencing powers; and sentencing a ‘dangerous’ young offender.
Article 102 TFEU
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

Article 102 only applies to undertakings in a dominant position. Thus, whether or not an undertaking holds a ‘dominant position’ is of central importance to Article 102. This chapter discusses the definition of a dominant position in the case law of the Court and its relation to the concept of substantial market power, including the Commission’s treatment of it in the Guidance Paper. It explains how a dominant position is established. The chapter therefore deals with the definition of the relevant market for the purposes of Article 102, including issues of demand and supply substitution, the cellophane fallacy, and aftermarkets; the role of market share in establishing dominance; and barriers to entry and other factors indicating dominance; and dominant positions in the new economy.
Horizontal Cooperation Agreements
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter discusses EU competition policy towards horizontal cooperation agreements. It covers joint ventures; the contents of the 2010 Guidelines; the general approach to horizontal cooperation agreements in the Guidelines; information agreements; research and development agreements, including the block emption, Regulation 1217/2010; production agreements, including the block exemption on specialisation agreements, Regulation 1218/2010 ; purchasing agreements; commercialisation agreements; standardisation agreements; and agreements in particular sectors, such as the joint buying or selling of media rights to sports events.
Licensing Agreements and other Agreements Involving Intellectual Property Rights
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter examines some of the different types of intellectual property rights (IPRs) before outlining the relationship between intellectual property and both EU competition law and the EU free movement rules. It focuses, however, on IP licensing agreements and their treatment under Article 101. The chapter is organized as follows. Section 3 traces the development of EU competition policy to IP licensing agreements. Sections 4 and 5 examine the current Technology Transfer Block Exemption, Regulation 316/2014 (TTBER) and the Guidelines in detail. Sections 6, 7, and 8 deal with trade mark licences, trade mark delimitation agreements, and copyright (other than software) licences not covered by the TTBER and Guidelines. Section 9 outlines issues arising in cases involving IPRs under Article 102, while Section 10 concludes.
Private Enforcement
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter focuses on the private civil enforcement of EU antitrust rules through claims made by private litigants in the national courts and tribunals of the individual Member States. The discussions cover the principle of direct effect and national procedural autonomy; why there has been relatively little antitrust litigation in the EU; the relationship between public and private enforcement; the Commission's policy towards private enforcement, the initiatives it has taken to encourage private litigation, particularly the 2014 Damages Directive, and mechanisms for cooperation between the Commission and national courts; and the obligations of national courts when dealing with cases that raise the issue of whether a contract in violation of Article 101 or Article 102 is enforceable and whether, and if so when, damages and injunctions should be available to remedy such violations.
Surviving Phases: Introducing Multistate Survival Models
Authors: Metzger Shawna K. , Jones Benjamin T.
Published: September 2016

Many political processes consist of a series of theoretically meaningful transitions across discrete phases that occur through time. Yet political scientists are often theoretically interested in studying not just individual transitions between phases, but also the duration that subjects spend within phases, as well as the effect of covariates on subjects’ trajectories through the process's multiple phases. We introduce the multistate survival model to political scientists, which is capable of modeling precisely this type of situation. The model is appealing because of its ability to accommodate multiple forms of causal complexity that unfold over time. In particular, we highlight three attractive features of multistate models: transition-specific baseline hazards, transition-specific covariate effects, and the ability to estimate transition probabilities. We provide two applications to illustrate these features.
Title: Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal
Authors: Gao Yu-Rong , Ma Yuncong , Zhang Qingguang , Winder Aaron T. , Liang Zhifeng , Antinori Lilith , Drew Patrick J. , Zhang Nanyin
Published: September 2016

Functional magnetic resonance imaging (fMRI) has allowed the noninvasive study of task-based and resting-state brain dynamics in humans by inferring neural activity from blood-oxygenation-level dependent (BOLD) signal changes. An accurate interpretation of the hemodynamic changes that underlie fMRI signals depends on the understanding of the quantitative relationship between changes in neural activity and changes in cerebral blood flow, oxygenation and volume. While there has been extensive study of neurovascular coupling in anesthetized animal models, anesthesia causes large disruptions of brain metabolism, neural responsiveness and cardiovascular function. Here, we review work showing that neurovascular coupling and brain circuit function in the awake animal are profoundly different from those in the anesthetized state. We argue that the time is right to study neurovascular coupling and brain circuit function in the awake animal to bridge the physiological mechanisms that underlie animal and human neuroimaging signals, and to interpret them in light of underlying neural mechanisms. Lastly, we discuss recent experimental innovations that have enabled the study of neurovascular coupling and brain-wide circuit function in un-anesthetized and behaving animal models.
Traumatic brain injury causes retention of long introns in metabolic genes via regulation of intronic Histone 3 lysine 36 methylation levels in the sub-acute phase of injury
Authors: Sen Arko , Qu Wen , Nuga Oluwademi Okikiolu , Liu Jenney , Burl Rayanne , Gurdziel Katherine , Pique-Regi Roger , Hüttemann Maik , Ruden Douglas. M.
Published: September 2016

Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. This may lead to cognitive dysfunctions, depression, and even increased susceptibility to life threatening diseases, such as epilepsy and Alzheimer’s Disease. To investigate the underlying genetic and molecular basis of TBI, Wasserman and colleagues developed an inexpensive and reproducible model for simulating TBI inDrosophila melanogaster(Fruit Fly). Using a modified version of this high impact trauma (HIT) device, we subjected w1118fruit flies to mild closed head trauma. To determine the transcriptomic changes that contribute to survival post TBI, we collected fly heads from the survivors at 2 time points; 4 hours and 24 hours’ post-trauma. Mild TBI had limited impact on the steady state RNA levels but showed large perturbations in alternative splicing (AS) 24 hours’ post-trauma. Classification of these AS changes showed selective retention (RI) of long introns (>81bps), with a mean size of ~3000bps. Some of these RI genes also showed a significant reduction in transcript abundance and were specifically enriched in genes involved in mitochondrial metabolism. The RI are enriched in ACACACA motifs known to bind to Smooth (SM), an hnRNPL class of splicing factor. Mutating SM (sm4/Df) resulted in reversal of RI observed 24 hours’ post-trauma, and in some cases, elimination of basal levels of RI in long introns. This observation suggests that SM is critical regulator of RI and that this process is enhanced by TBI. Interestingly, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) for histone 3 lysine 36 trimethylation (H3K36me3) revealed increased levels of this histone modification in retained introns post-trauma. Consistent with this observation, mutations in lysine specific demethylase 4A (KDM4A), which de-methylate H3K36me3, increased RI in many of the same long introns affected by TBI. Additionally, higher H3K36me3 levels are observed around intronic SM-binding motifs post-trauma, suggesting interaction between H3K36me3 and SM binding to intronic splicing suppressor sites might be responsible for increasing RI of metabolic genes as a novel mechanism to improve survival after TBI.
Multidimensional stimulus-response correlation reveals supramodal neural responses to naturalistic stimuli
Authors: Dmochowski Jacek P. , Ki Jason , DeGuzman Paul , Sajda Paul , Parra Lucas C.
Published: September 2016

In neuroscience, stimulus-response relationships have traditionally been analyzed using either encoding or decoding models. Here we combined both techniques by decomposing neural activity into multiple components, each representing a portion of the stimulus. We tested this hybrid approach on encephalographic responses to auditory and audiovisual narratives identically experienced across subjects, as well as uniquely experienced video game play. The highest stimulus-response correlations (SRC) were detected for dynamic visual features. During narratives both auditory and visual SRC were modulated by attention and tracked correlations between subjects. During video game play, SRC was modulated by task difficulty and attentional state. Importantly, the strongest component extracted for visual and auditory features had nearly identical spatial distributions, suggesting that the predominant encephalographic response to naturalistic stimuli is supramodal. The variety of novel findings demonstrates the utility of measuring multidimensional stimulus-response correlations.
RIblast: An ultrafast RNA-RNA interaction prediction system for comprehensive lncRNA interaction analysis
Authors: Fukunaga Tsukasa , Hamada Michiaki
Published: September 2016

Long non-coding RNAs (lncRNAs) play important roles in various biological processes. Although more than 58,000 human lncRNA genes have been discovered, most known lncRNAs are still poorly characterised. One approach to understanding the functions of lncRNAs is the detection of the interacting RNA target of each lncRNA. Because experimental detection of comprehensive lncRNA-RNA interactions are difficult, computational prediction of lncRNA-RNA interactions is an indispensable technique. However, the high computational costs of existing RNA-RNA interaction prediction tools prevents their application to large-scale lncRNA datasets. Here, we present “RIblast”, an ultrafast RNA-RNA interaction prediction method based on the seed-and-extension approach. RIblast discovers seed regions using suffix arrays and subsequently extends seed regions based on an RNA secondary structure energy model. Computational experiments indicate that RIblast achieves a level of prediction accuracy similar to those of existing programs, but at speeds over 64 times faster than existing programs.
Reproductive biology of threeZiziphusspecies (Rhamnaceae)
Authors: Kulkarni M.
Published: September 2016

The reproductive biology of threeZiziphusspecies:Z. jujube,Z. mauritianaandZ. spina-christi, with respect to seasonal growth stages, floral biology, pollen performance, fruit set and seed viability were compared. To elucidate the reasons for variations in reproductive success we also estimated the ploidy levels among the genotypes of these tree species. Four genotypes ofZ. mauritianaandZ. jujubeeach, and two natural selections ofZ. spina-christiwere grown in the Negev highlands at the Sde Boqer experimental plot. Field observations were conducted to determine seasonal growth stages and floral biology; laboratory studies included florescent microscopy, differential interference contrast microscopy,in vitropollen germination and histological techniques. Seasonal growth stages were similar inZ. spina-christiandZ. mauritianabut distinct inZ. jujube, which was the earliest species. Flower opening stages were similar in all species and genotypes. Anthesis timing was genotype specific and did not depend on species. Anthesis types were subdivided into early and late morning as well as afternoon. We found a wide range of values for the number of flowers per inflorescence between species and genotypes, but all genotypes set one fruit per inflorescence with the exception ofZ. jujubegenotype Tamar, which set two fruit per inflorescence. Significant variation in fruit weight was observed between species as well as genotypes. Fruit ofZ. mauritianaandZ jujubeweighed between 9 to 37 g while fruit weight ofZ. spina-christiwas between 0.5 to 0.7 g. Flowers of all species and genotypes had two ovules but viable seed set per fruit differed dramatically between species under open pollination. Viable seed set was about 18% forZ. mauritianaandZ jujube, whileZ. spina-christi, had the highest viable seed set at about 84%. Histological analysis revealed post fertilization embryo abortion which may be responsible for the relatively low reproductive success inZ. mauritianaandZ. jujube. The results obtained in this study provide an important basis for selecting elite complementary genotypes toward the optimization ofZiziphusfruit production in semi-arid regions.
Stomatal and physiological response of contrastingZ. mauritiana(Lamk.) clones to water stress
Authors: Kulkarni M.
Published: September 2016

Water stress is one of the major limitations to fruit production worldwide. Identifying suitable indicators, screening techniques and quantifiable traits would facilitate the genetic improvement process for water stress tolerance. In the present study, we evaluated the ability of physiological parameters (Transpiration, E;Fv/Fm; leaf water potential, ψleaf; leaf temperature, LT; and, leaf relative water content, RWC) to distinguish between contrastingZ. mauritianaclones subjected to a 30-d drought cycle. Four field-grown clones Seb and Gola (tetraploid) and Q 29 and B 5/4 (diploid) were studied. By 30 d after the onset of water stress treatment, the E,Fv/Fm, ψleafand RWC of drought-stressed plants had declined significantly in all genotypes compared to values of well-watered treatments. However, the reductions were more severe in leaves of diploid clones. Under drought stress, the Seb and Gola, maintained higher E (31.5%),Fv/Fm (6.28%), ψleaf; (11.2%), and RWC (9.3 %) than Q 29 and B 5/4 clones. In general, LT of drought-stressed plants was higher (~4°C) than that of well-watered plants but the relative increase was greater among later than former ones. Under maximum drought stress, LT of Seb and Gola clones was on average 3.0°C lower than that of Q 29 and B 5/4. Former clones yielded 20% more than later ones, mainly reason being (14.8%) less fruit drop as an effect of water stress. The results indicate that presented parameters can be reliable in screening for water stress tolerance ability, withFv/Fm, ψleaf, RWC and LT having the added advantage of being easily and quickly assessed.
Cocrystals of 1,4-diethynylbenzene with 1,3-diacetylbenzene and benzene-1,4-dicarbaldehyde exhibiting strong nonconventional alkyne–carbonyl C—H...O hydrogen bonds between the components
Authors: Bosch Eric
Published: September 2016

Weak interactions between organic molecules are important in solid-state structures where the sum of the weaker interactions support the overall three-dimensional crystal structure. Thesp-C—H...N hydrogen-bonding interaction is strong enough to promote the deliberate cocrystallization of a series of diynes with a series of dipyridines. It is also possible that a similar series of cocrystals could be formed between molecules containing a terminal alkyne and molecules which contain carbonyl O atoms as the potential hydrogen-bond acceptor. I now report the crystal structure of two cocrystals that support this hypothesis. The 1:1 cocrystal of 1,4-diethynylbenzene with 1,3-diacetylbenzene, C10H6·C10H10O2, (1), and the 1:1 cocrystal of 1,4-diethynylbenzene with benzene-1,4-dicarbaldehyde, C10H6·C8H6O2, (2), are presented. In both cocrystals, a strong nonconventional ethynyl–carbonylsp-C—H...O hydrogen bond is observed between the components. In cocrystal (1), the C—H...O hydrogen-bond angle is 171.8 (16)° and the H...O and C...O hydrogen-bond distances are 2.200 (19) and 3.139 (2) Å, respectively. In cocrystal (2), the C—H...O hydrogen-bond angle is 172.5 (16)° and the H...O and C...O hydrogen-bond distances are 2.25 (2) and 3.203 (2) Å, respectively.
Phylogeography and pigment type diversity of Synechococcus cyanobacteria in surface waters of the northwestern pacific ocean
Authors: Xia Xiaomin , Partensky Frédéric , Garczarek Laurence , Suzuki Koji , Guo Cui , Yan Cheung Shun , Liu Hongbin
Published: September 2016

The widespread unicellular cyanobacteria Synechococcus are major contributors to global marine primary production. Here, we report their abundance, phylogenetic diversity (as assessed using the RNA polymerase gamma subunit gene rpoC1) and pigment diversity (as indirectly assessed using the laterally transferred cpeBA genes, encoding phycoerythrin‐I) in surface waters of the northwestern Pacific Ocean, sampled over nine distinct cruises (2008–2015). Abundance of Synechococcus was low in the subarctic ocean and South China Sea, intermediate in the western subtropical Pacific Ocean, and the highest in the Japan and East China seas. Clades I and II were by far the most abundant Synechococcus lineages, the former dominating in temperate cold waters and the latter in (sub)tropical waters. Clades III and VI were also fairly abundant in warm waters, but with a narrower distribution than clade II. One type of chromatic acclimater (3dA) largely dominated the Synechococcus communities in the subarctic ocean, while another (3dB) and/or cells with a fixed high phycourobilin to phycoerythrobilin ratio (pigment type 3c) predominated at mid and low latitudes. Altogether, our results suggest that the variety of pigment content found in most Synechococcus clades considerably extends the niches that they can colonize and therefore the whole genus habitat.