bluuebunny/crossref_metadata_2025_split huggingface dataset:
E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells
Authors: Lee Hyun-Wook , Park Sung-Hyun , Weng Mao-wen , Wang Hsiang-Tsui , Huang William C. , Lepor Herbert , Wu Xue-Ru , Chen Lung-Chi , Tang Moon-shong 
Published: January 2018

Significance
E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indicate that nicotine nitrosation occurs in the lung, bladder, and heart, and that its products are further metabolized into DNA damaging agents. We propose that ECS, through damaging DNA and inhibiting DNA repair, might contribute to human lung and bladder cancer as well as to heart disease, although further studies are required to substantiate this proposal.
Holo-lipocalin-2–derived siderophores increase mitochondrial ROS and impair oxidative phosphorylation in rat cardiomyocytes
Authors: Song Erfei , Ramos Sofhia V. , Huang Xiaojing , Liu Ying , Botta Amy , Sung Hye Kyoung , Turnbull Patrick C. , Wheeler Michael B. , Berger Thorsten , Wilson Derek J. , Perry Christopher G. R. , Mak Tak W. , Sweeney Gary 
Published: January 2018

Significance
Metabolic dysfunction associated with decreased mitochondrial oxidative capacity is a major underlying cause of heart failure. Our study sheds new light on the potential role of bacteria-derived or endogenous siderophores as direct regulators of cardiomyocyte mitochondrial function. Furthermore, we demonstrate that lipocalin-2, a key feature of the innate immune response, facilitates the transport of siderophore–iron complexes into cells. This mechanism may have important physiological implications because elevated lipocalin-2 levels correlate positively with heart failure in humans, and mice lacking lipocalin-2 are protected from stress-induced mitochondrial dysfunction and heart failure.
Comparison of Nostocean hormogonium induction and its motility on solid plates between agar and gellan gum at varying gel matrix concentrations
Authors: Nishizuka Hiroaki , Hashidoko Yasuyuki 
Published: January 2018

Abstract
To establish a sensitive bioassay for Nostocean hormogonium induction, we compared the effectiveness of the morpho-differentiation induction on two gelled plates, agar and gellan gum, for anacardic acid C15:1-Δ8 decyl ester (1) (100 nmol/disc). On BG-110 (nitrogen-free) medium-based 0.6 and 0.8% agar plates, Nostoc sp. strain Yaku-1 isolated from a coralloid root of Cycas revoluta in Yakushima Island showed clear morpho-differentiation from filamentous aggregates into hormogonia, and the induced hormogonia dispersed within 24 h; however, similar hormogonium formation was not observed at agar concentrations of 1.0% or higher. Conversely, hormogonium induction was considerably more pronounced on gellan gum plates than those on agar plates through concentrations ranging from 0.6 to 1.6% even after 12 h of incubation, particularly active on the 0.8–1.0% gellan gum plates. Thus, gellan gum plates can achieve clear results within 12 h and are thus highly useful for primary screening for hormogonium-inducing factors (HIFs).
Co-complex protein membership evaluation using Maximum Entropy on GO ontology and InterPro annotation
Authors: Armean Irina M , Lilley Kathryn S , Trotter Matthew W B , Pilkington Nicholas C V , Holden Sean B 
Published: January 2018

Abstract

Motivation
Protein–protein interactions (PPI) play a crucial role in our understanding of protein function and biological processes. The standardization and recording of experimental findings is increasingly stored in ontologies, with the Gene Ontology (GO) being one of the most successful projects. Several PPI evaluation algorithms have been based on the application of probabilistic frameworks or machine learning algorithms to GO properties. Here, we introduce a new training set design and machine learning based approach that combines dependent heterogeneous protein annotations from the entire ontology to evaluate putative co-complex protein interactions determined by empirical studies.

Results
PPI annotations are built combinatorically using corresponding GO terms and InterPro annotation. We use a S.cerevisiae high-confidence complex dataset as a positive training set. A series of classifiers based on Maximum Entropy and support vector machines (SVMs), each with a composite counterpart algorithm, are trained on a series of training sets. These achieve a high performance area under the ROC curve of ≤0.97, outperforming go2ppi—a previously established prediction tool for protein-protein interactions (PPI) based on Gene Ontology (GO) annotations.

Availability and implementation
https://github.com/ima23/maxent-ppi

Supplementary information
Supplementary data are available at Bioinformatics online.
Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer’s disease
Authors: Manczak Maria , Kandimalla Ramesh , Yin Xiangling , Reddy P Hemachandra 
Published: January 2018

Abstract
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris water maze tests, immunoblotting and immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2 and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express Swedish mutation. Mitochondrial function was assessed by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. Morris water maze and rotarod tests revealed that hippocampal learning and memory and motor learning and coordination were impaired in APP mice relative to wild-type (WT) mice. Increased levels of mitochondrial fission proteins, Drp1 and Fis1 and decreased levels of fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 and TFAM), autophagy (ATG5 and LC3BI, LC3BII), mitophagy (PINK1 and TERT), synaptic (synaptophysin and PSD95) and dendritic (MAP2) proteins were found in 12-month-old APP mice relative to age-matched non-transgenic WT mice. Golgi-cox staining analysis revealed that dendritic spines are significantly reduced. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in APP mice. These findings suggest that hippocampal accumulation of mutant APP and Aβ is responsible for abnormal mitochondrial dynamics and defective biogenesis, reduced MAP2, autophagy, mitophagy and synaptic proteins and reduced dendritic spines and hippocampal-based learning and memory impairments, and mitochondrial structural and functional changes in 12-month-old APP mice.
Mainstreaming Marine Biological Diversity Conservation in the Law of the Sea
Authors: Harrison James 
Published: January 2018

Abstract
Chapter 3 considers how the conservation of marine biological diversity has emerged as a major concept that has influenced the development of the international legal framework for the protection of the marine environment. Whilst the United Nations Convention on the Law of the Sea (UNCLOS) only obliquely refers to the importance of protecting marine ecosystems, biodiversity has come to play a much greater role in the modern law of the sea, particularly since the conclusion of the Convention Biological Diversity (CBD). The chapter analyses the structure and content of this Convention and related global biodiversity treaties and how they apply to marine areas. It also considers how the conservation of marine biodiversity has emerged as a central objective of many regional seas treaties and the roles that these instruments have played in offering protection to endangered or threatened marine species and promoting the global objective of increasing the number and scope of marine protected areas.
Land-Based Sources of Marine Pollution
Authors: Harrison James 
Published: January 2018

Abstract
Chapter 4 addresses the major international instruments that have been adopted to address land-based sources of marine pollution. This category includes industrial, agricultural, and urban discharges, which are amongst the most serious causes of marine environmental degradation, as well as some of the most difficult to regulate. The chapter begins by reviewing the relevant provisions of the United Nations Convention on the Law of the Sea (UNCLOS) and how they apply to land-based activities. It then explores the range of other instruments that have been negotiated on the topic. At the global level, the analysis covers the Global Programme of Action, the POPs Convention, and the Mercury Convention. The most detailed regulations are seen at the regional level, and, therefore, the chapter explains the manner in which regional institutions have developed and overseen a variety of rules and standards to address this threat. The interaction of these different levels is also taken into account, using a case study of marine litter.
Addressing the Marine Environmental Impacts of Climate Change and Ocean Acidification
Authors: Harrison James 
Published: January 2018

Abstract
Chapter 9 addresses the impacts of climate change and ocean acidification on the marine environment and the extent to which international law has reacted to this emerging threat to the ecological integrity of the oceans. These issues are particularly challenging to regulate because of their wide-ranging causes and effects. This chapter, therefore, takes into account both how the global legal regime relating to climate change, including the United Nations Framework Convention on Climate Change and the Paris Agreement, has taken into account the oceans, as well as how sectoral treaties dealing with specific maritime activities have addressed climate change and ocean acidification within their normative framework. In this latter respect, the chapter focuses on the global regulation of carbon emissions from shipping and the way in which the international community has responded to proposed carbon sequestration activities at sea, including sub-seabed storage and geo-engineering.
The Role of International Law in Saving the Oceans and Future Challenges for the Legal Framework
Authors: Harrison James 
Published: January 2018

Abstract
Chapter 11 is the concluding chapter of this book and it provides an overview of the current state of the legal framework for the protection of the marine environment. It describes the multifaceted and multilayered nature of regulation in this field and sketches the key interrelationships that take place between different treaty regimes. It also draws general conclusions about how key general principles have been applied across different sectors and what law-making procedures have been used in order to ensure the evolution of the legal framework. Finally, the chapter offers reflections on the key challenges that remain for the international community in tackling threats to the marine environment and potential strategies that may be available for States to meet these challenges.
The Investment Treaty Regime in Context
Authors: Bonnitcha Jonathan , Skovgaard Poulsen Lauge N , Waibel Michael 
Published: January 2018

Abstract
This chapter charts the rise of the global network of more than 3000 investment treaties and of investment treaty arbitration. Investors have used investment treaties to ask for compensation for a very wide range of government conduct. The chapter surveys the investment treaty regime and the investment regime complex. The regime consists of three main components: (i) investment treaties; (ii) the set of treaties, rules, and institutions governing investment treaty arbitration; and (iii) the decisions of arbitral tribunals applying and interpreting investment treaties. The growing role of investment treaty arbitration has made it highly controversial in both developed and developing countries, and has transformed the investment treaty regime from an obscure field of international law to a central part of the investment regime complex.
Investment Treaty Arbitration
Authors: Bonnitcha Jonathan , Skovgaard Poulsen Lauge N , Waibel Michael 
Published: January 2018

Abstract
This chapter provides an overview of investment treaty arbitration, where a host state’s consent to investor–state arbitration is contained in an investment treaty. The first section explains the basic features of investment treaty arbitration, and compares it to other dispute resolution processes—such as domestic and international courts, investor–state arbitration based on contracts, as well as state-to-state arbitration. The second section describes different institutions and arbitral rules for investment treaty arbitrations. It outlines the phases of investment treaty arbitrations and the core features of the arbitration process, such as the choice of remedies. The third section deals with issues that arise following the conclusion of an investment treaty arbitration—notably, the review, enforcement, and compliance with arbitral awards. The fourth section evaluates two potential alternatives to investment treaty arbitration—alternative dispute resolution (ADR) and litigation in domestic courts.
Standards of Investment Protection
Authors: Bonnitcha Jonathan , Skovgaard Poulsen Lauge N , Waibel Michael 
Published: January 2018

Abstract
This chapter introduces the substantive obligations in investment treaties. Most offer a common core of six substantive protections to foreign investors. The chapter first considers the two ‘relative’ standards of protection—most-favoured nation treatment and national treatment. It then turns to four ‘absolute’ standards of protection: expropriation, fair and equitable treatment, umbrella clauses, and free transfer of funds. The third section examines carve-outs that remove certain state measures from the scope of application of investment treaties, defences that can justify or excuse breaches of investment treaty protections, and the standard of review that tribunals apply when examining host state conduct. The fourth and final section discusses the calculation of compensation or damages if host states have breached investment treaties.
Politics of Investment Treaties in Developed Countries
Authors: Bonnitcha Jonathan , Skovgaard Poulsen Lauge N , Waibel Michael 
Published: January 2018

Abstract
This chapter focuses on the main factors driving investment treaty policy-making in developed countries. This can only be done based on an understanding of the changing socio-economic environment for foreign investments, and the chapter therefore provides significant historical context to the law and economics of the investment treaty regime. The chapter evaluates four potential explanations for why and how developed countries adopted investment treaties. These are: (i) the promotion of business interests; (ii) de-politicizing investment disputes; (iii) building customary international law; and (iv) using investment treaties for diplomatic and symbolic reasons. The chapter concludes by examining recent developments. These include the rise of investment treaty arbitration against developed country states themselves, which has prompted unprecedented political debate about investment treaties.
Legitimacy and Governance Challenges
Authors: Bonnitcha Jonathan , Skovgaard Poulsen Lauge N , Waibel Michael 
Published: January 2018

Abstract
The rapid growth of investment treaty arbitrations in often sensitive policy areas has focused public attention on the investment treaty regime. This chapter draws together several strands of the book to focus on two central debates about legitimacy and governance challenges facing the investment treaty regime. The first section considers the impact of investment treaties on national governance. It assesses criticisms that investment treaties unduly fetter democratic decision-making and discourage states from regulating in the public interest. The second section examines the legitimacy of investment treaty arbitration—the regime feature that has come under the closest scrutiny over the last decade. It assesses debates about transparency and consistency in investment treaty arbitration, its impact on the broader investment regime complex, the selection, identity, and alleged biases of arbitrators, as well as the lack of investor obligations.
Principles and Policies
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter provides an outline of the principles and policies of construction. It also summarises the main topics to be discussed in this volume; such as the evolution of the principles of construction, interpretation, leading decisions, and so on. Ascertaining the meaning and effect of the language of contracts and other documents, the chapter shows, constitutes a central concern of private law and is of great significance to commercial and financial transactions. Construction generally involves identifying in a document a rule for future cooperative behaviour from the language of the instrument, and then applying that rule to subsequent facts or situations. As such, issues concerning construction represent an unavoidable source of potential dispute.
Comparative and Theoretical Perspectives
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter first considers civil law jurisdictions and various international legal instruments and their approach to the construction of contracts. In particular, the chapter focuses on the objective/subjective debate and the admissible evidence. It then looks at the international restatements of contract law, which are committed to a subjective theory of contract, such as is found in civil law countries. Next, the chapter considers a more theoretical perspective in the topic of contractual interpretation, and introduces the relevant literature to that effect. Such wider perspectives have been a source of recent developments—and may continue to be the source of future developments—in this field.
The Objective Principle of Construction
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter presents an objective approach to the enforcement of contracts. This approach is based on the reasonable expectation of the community in general, and individual contractors in particular, that promisors will perform in accordance with their undertakings. The justifiable reliance of the recipients of promises on the apparent meaning of the words used thus requires protection. This in turn favours an objective approach, which concentrates on the question of how the promisor manifested its intentions. The issue is not what the promisor meant to say or write, but what the promisor said or wrote. English law is firmly committed to this particular approach.
Presumptions
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter discusses statutory and common law presumptions. It first considers two statutory presumptions: the Law of Property Act 1925 and the Interpretation Act 1978. The chapter then shifts the analysis to several common law presumptions. First, it discusses the presumption that a contracting party cannot take advantage of its own wrong. Next, the chapter turns to the presumption that clear words are required to exclude or modify remedies that arise by operation of law. Finally, this chapter discusses further types of common law presumptions: the presumption of legality, the presumption against impossibility, the presumption of technical legal usage in documents drafted by lawyers, and the presumption in favour of one-stop dispute-resolution.
Technical and Legal Language
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter describes the use of language in interpretation. In traditional accounts, primary effect was given to the ‘plain’ or ‘ordinary’ meaning of words. However, where appropriate—in order to reflect the intentions of the parties—regard would be paid to a specialist or technical meaning of particular words. Legal meanings in particular may be significant in documents intended to have legal effect. Accordingly the chapter shows that context can always override technical meaning, and substitute a conventional or other meaning. However, this chapter mainly focuses on the approaches used for legal language; scientific, technical, and specialist language; and foreign languages.
Exemption Clauses and Unfair Contract Terms
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter focuses on exemption clauses. Particular attention is placed on the detailed rules of construction still applicable to exemption clauses. Moreover, the chapter considers the statutory interventions in this field in the shape of the Unfair Contract Terms Act 1977 and Part 2 of the Consumer Rights Act 2015 (superseding the Unfair Terms in Consumer Contracts Regulations 1999). Since these statutory interventions there has been a marked tendency to construe exemption clauses in commercial agreements in a more realistic way. This is especially prevalent where the parties are of relatively equal bargaining power and where the clause is perceived as giving effect to a sensible allocation of risk.
Change of Circumstances and ‘ Force Majeure ’ Clauses
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter looks at regimes for change of circumstances and other future events which have an impact on performance. These are universally known as force majeure provisions. Such clauses opt out of the narrow and uncertain scope of the common law doctrine of frustration. They avoid the common law rule that any element of choice or election as to which contracts to perform is incompatible with frustration. The parties can design their own remedial scheme, including suspension of performance (if appropriate) as well as complete relief from the obligation to perform. Furthermore, they can make appropriate adjustments to the parties' liabilities and circumvent the arcane regime of the Law Reform (Frustrated Contracts) Act 1943.
Payment, Agreed Damages, and Acceleration Clauses
Authors: McMeel Gerard 
Published: January 2018

Abstract
This chapter discusses payment, liquidated damages, minimum payment, and accelerated payment clauses. It first gives a brief introduction to payment clauses and their construction, before turning to liquidated damages clauses. For the latter, the chapter introduces the clause with a set of propositions delivered during the Dunlop Pneumatic Tyre Co Ltd v New Garage and Motor Co Ltd case. Next, the chapter turns to minimum payment clauses. These clauses are a feature of many hire-purchase arrangements and are subject to the new legitimate interest test. Acceleration clauses, meanwhile, are particularly common in asset finance arrangements and commercial lending. Such clauses often work in tandem with express termination clauses, and appear to have become more common in the wake of the restrictive common law approach to damages resulting from the exercise of an express termination provision.