bluuebunny/crossref_metadata_2025_split huggingface dataset:
Certainty
Authors: Andrews Neil 
Published: October 2021

Abstract
A requirement in English law is that an agreement must have sufficient commercial certainty. The extensive case law is examined closely, with instances being cited of numerous cases where the courts have either concluded that the certainty requirement has been satisfied, or that the transaction is void for lack of fundamental clarity. An agreement to agree is not valid, nor an agreement to negotiate reasonably or in good faith. These restrictions are examined closely. An interesting exception has emerged, requiring a party to adhere to an undertaking to negotiate in an amicable and constructive way as a preliminary to commencing arbitration.
Intent to Create Legal Relations
Authors: Andrews Neil 
Published: October 2021

Abstract
The intent to create legal relations doctrine operates as a safety-net principle, supplementing the requirement of consideration. These two doctrines operate in tandem in English law. The chapter examines case law applications of the following two presumptions. (1) An agreement between spouses is presumed not to be legally enforceable, unless the marriage has already become seriously fractured. The same presumption probably extends to other close family relations. Pre-nuptial agreements are enforceable. (2) Conversely, commercial agreements are presumed to be legally enforceable. But a series of sales does not constitute a long-term supply agreement. And a ‘letter of comfort’, not intended to be a guarantee, lacks an intent to create legal relations.
Unconscionability
Authors: Andrews Neil 
Published: October 2021

Abstract
‘Unconscionability’ is a narrow equitable doctrine which protects a vulnerable party against reprehensible exploitation of his position of weakness. The doctrine of unconscionability comprises four factors: (i) the vulnerable party’s special or serious disadvantage; (ii) actual or constructive fraud, that is, conscious and reprehensible exploitation; (iii) highly disadvantageous terms; and (iv) lack of independent advice.
Illegality
Authors: Andrews Neil 
Published: October 2021

Abstract
This chapter examines the various heads of illegality, such as agreements contrary to statute or agreements to defraud the tax authorities. Neither party can sue on a contract if the contract is expressly or by necessary implication prohibited by statute or the common purpose was to commit a crime or other civil wrong. Nor can a claimant sue on a contract if the claimant became aware that the contract would involve illegally and then participated in, or was implicated in, that wrongdoing (it is otherwise if claimant was ignorant of, and not implicated in, the defendant’s decision to perform it in an illegal fashion, or the claimant was guilty of only incidental illegality during performance). The court must refuse to give effect to a transaction if its illegal nature emerges during the course of the case. In Patel v Mirza (2016) the Supreme Court radically tilted the law in favour of the restitution of money or property transferred under an illegal contract, unless there is a compelling contrary argument of legal policy.
Good Faith
Authors: Andrews Neil 
Published: October 2021

Abstract
There is some judicial interest in recognizing a principle of good faith performance in English contract law (the topic was introduced at [2.69]). The idea is gaining, or at least might gain, momentum. But the traditional view, to which the appellate courts in England and Wales have remained loyal, is that there is no general doctrine that contracts must be performed in good faith. In other words, there is no general implied term that a contract must be performed in good faith.
Specific Performance and Other Equitable Remedies
Authors: Andrews Neil 
Published: October 2021

Abstract
The equitable remedy of specific performance to compel performance is a mandatory final injunction. This remedy takes the back-seat in English law when compared with the Common Law money remedies of debt and damages. But specific performance is the default remedy in the context of contracts for the transfer of interests in land or shares in a private company. Injunctions are primarily ordered when the contractual breach involves the commission of something which the wrongdoer has promised not to do (a ‘negative undertaking’).
The Electronic Bill of Exchange and Its Use in International Trade
Authors: Geva Benjamin 
Published: October 2021

Abstract
This chapter explores the ‘electronification’ of bills of exchange in connection with their use as credit and payment instruments in international trade. The chapter observes that the infinite number of international trade participants spread throughout the globe at different stages of technological development militates against the feasibility of a common, universal, and worldwide technological platform for handling electronic bills of exchange. Instead, particularly by reference to the extensive experience in the US in relation to the ‘electronification’ of cheques, the chapter proposes that a robust and flexible legal frameworkbe implanted in the Bills of Exchange Act, and used as agreed, to cover electronic presentment of bills of exchange and the exchange and negotiation of substitute bills, bills images, and electronic bills.
Digitalisation of Shipping and Insurance Documents
Authors: Goldby Miriam 
Published: October 2021

Abstract
The inefficiencies inherent in processing pieces of paper manually down a cross-border chain of sales have prompted the international trade community to attempt to replace bills of lading with digital alternatives. These efforts have been ongoing for thirty years, but the recent availability of new technologies, particularly distributed-ledger technology (‘DLT’), which can be used in combination with ‘smart contracts’, the internet of things (‘IoT’) and machine-learning, has given these efforts a new impetus. Digitalisation holds many promises, including the creation of a context wherein new and cheaper financing options may be developed that do not involve manual checking of large volumes of paper documents. However, doing away with the paper-based documents of title creates uncertainties in terms of the bank’s position as secured creditor. Similarly, while cargo insurance certificates have been issued over electronic platforms for many years now, their transfer by endorsement is still effected by printing the certificate out and endorsing the paper-based certificate. In order for the benefits of digitalisation to be reaped in full, cargo insurance certificates also need to be fully digitalised, which would in turn raise questions as to the bank’s position as assured under the insurance contract. This chapter will examine the options available for making the bank’s position more certain. These options include legislative intervention and the development of contractual frameworks governed by English law.
Will Blockchain Transform Trade Finance?
Authors: Winn Jane K 
Published: October 2021

Abstract
The administration of cross-border trade remains dominated by complex, old-fashioned, hybrid human-computer-paper systems long after disruptive innovations have transformed commerce in many other domains. Interest in blockchain is driven by the desire to cut through the ‘Gordian knot’ of complex, fragmented, anachronistic legacy trade-finance systems now in use. Blockchain advocates believe it is superior to the legacy database technologies currently in use in all important transaction-processing systems and designed to work within hierarchically networked computer systems controlled by large organisations. These advocates appear unaware, however, of the wide range of practical functions performed by different elements of existing trade finance systems, and are thus proposing alternatives that cannot perform all the functions of the systems they propose to replace. This kind of mismatch between real-world business requirements and the theoretical advantages of blockchain alternatives goes a long way to explain the failure of any blockchain projects to achieve widespread success in the market. Incremental efforts to transform trade finance in light of actual stakeholder requirements are both less vulnerable to speculative bubbles and more likely to meet the actual requirements of the many, diverse participants in global trade-finance systems today.
Islamic Trade Law and the Smart Contract Revolution
Authors: Ercanbrack Jonathan 
Published: October 2021

Abstract
The history of Islam is inextricably connected to a celebrated history of trade and commerce which distinguishes it amongst monotheistic faiths. The modern incarnation of Islamic trade finance, however, bears only rudimentary similarity to the trade practices of old. Modern Islamic trade finance is devised to replicate conventional trade practices so that the barter-like immediacy of the Islamic contract of sale has been replaced with promissory attributes (wa’d). Yet Islamic law (sharia) has shown itself to be fully capable of adapting to modern trade practices so long as its major principles remain intact. The introduction of blockchain and smart contracts for Islamic trade finance does not change this basic calculus and yet these technologies promise to revolutionise Islamic trade practices in a way that compels the industry to operate in closer keeping with its commercial principles. Paradoxically, these technologies require substantive changes in the way in which Islamic trade finance is practiced, helping the industry to overcome its attachment to legal artifice (hiyal). Using comparative law methodology, this chapter briefly examines a short history of trade and commerce in the Islamic tradition, followed by the development of modern Islamic finance. It addresses the principles of Islamic commercial law as the basis for understanding the murabaha contract for trade finance, followed by an analysis of the legal and sharia-related issues that English courts have dealt with in the practice of Islamic trade finance. Finally, the chapter considers the transformative capacity of blockchain and smart contracts for Islamic trade finance, highlighting prominent legal and sharia-related issues that compel the industry to transform its trade practices markedly.
Appointment of a Provisional Liquidator
Authors: French Derek 
Published: October 2021

Abstract
The chapter discusses various aspects of appointing a provisional liquidator. A provisional liquidator of a company may be appointed by the court under the Insolvency Act 1986 (IA 1986), s 135 at any time after the making of an application for a bank insolvency order. Provisional liquidators are independent persons operating under the direction of the court for a purpose that is one entirely of preservation during an interim period. He/she will take charge of the company’s affairs, maintain the status quo and prevent prejudice either to those supporting the winding-up petition or to those against it, pending the court’s decision on the petition. He/she terminates the powers of its directors as effectively as does the making of a winding-up order. The appointment terminates the actual authority of all the company’s agents, but the authority of an agent is not terminated until the agent has notice of the appointment of the provisional liquidator.
Petitions by Creditors
Authors: French Derek 
Published: October 2021

Abstract
Creditors may petition concurrently for the winding up of a partnership and the winding up or bankruptcy of a member or former member of the partnership. It must state how the petitioner came to be a creditor, merely describing the petitioner as ‘creditor’ is not sufficient. A creditor of a private company may apply under the Companies Act 2006, s 758, if the company has contravened the prohibition on public offers by private companies. If a company fails to comply with a statutory demand within 21 days, it will be deemed to be unable to pay its debts, and the claimant may present a winding-up petition. The Court of Appeal held that there should be no order as to costs up to the time the petition was served, but the company should pay the petitioner’s costs thereafter. The onus is on the company to show why it should not be ordered to pay the petitioner’s costs.
Petitions by Contributories
Authors: French Derek 
Published: October 2021

Abstract
Only an insolvent partnership can be wound up on a member’s petition under IPO 1994, but, in practice, almost all contributories’ petitions to wind up registered companies relate to solvent companies. A winding-up petition should not be used as a means of putting pressure on a company to meet the petitioner’s demands in relation to allotment of shares. If the partnership has eight or more members, any member may petition under article 9. If the partnership has fewer than eight members, by IA 1986, s 221A(2) inserted by IPO 1994, Petitions can be presented under article 10 for the winding up of a partnership and the winding up or bankruptcy of every one of its members only by a member of the partnership and only if all the members consent to orders being made against them. Any person liable to contribute to the assets of a registered company in the event of its being wound up is one of the company’s contributories.
Linear response theory and damped modes of stellar clusters
Authors: Fouvry Jean-Baptiste , Prunet Simon 
Published: October 2021

Abstract
Because all stars contribute to its gravitational potential, stellar clusters amplify perturbations collectively. In the limit of small fluctuations, this is described through linear response theory, via the so-called response matrix. While the evaluation of this matrix is somewhat straightforward for unstable modes (i.e. with a positive growth rate), it requires a careful analytic continuation for damped modes (i.e. with a negative growth rate). We present a generic method to perform such a calculation in spherically symmetric stellar clusters. When applied to an isotropic isochrone cluster, we recover the presence of a low-frequency weakly damped ℓ = 1 mode. We finally use a set of direct N-body simulations to test explicitly this prediction through the statistics of the correlated random walk undergone by a cluster’s density centre.
Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures
Authors: Snary Anya , Grundy Richard , Layfield Rob , Rahman Ruman , Haque Farhana 
Published: October 2021

Abstract

Aims
Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome (cell membrane proteins) signature.

Method
We therefore analysed the cell surface proteomics of pHGG and DIPG, in order to identify novel targets for therapy. We have at first isolated the cell membrane fractions from a range of patient cells carrying different histone 3 mutations (G34R, G34V), relative to wild type histone 3. A comparative quantitative mass-spectrometry analyses of these cell surface membrane fractions is then performed.

Results
The results obtained to date demonstrated unique differential cell membrane expression patterns which correlated to specific mutation type. For example, increased expression of Ras-related proteins Rab-3, Rab-3D is detected only in histone H3.3-G34R mutated cell line in comparison.

Conclusion
Identification and analyses of these unique cell membrane proteins’ association with specific in H3.3 mutation in pHGG, will help to identify precise mutation specific therapeutic targets, benefiting the patients to receive therapy based on tumour’s molecular signature.
Excessive new origin firing underlies selective glioma stem cell cytotoxicity induced by replication stress response inhibition
Authors: Clough Emily , Strathdee Karen , Carruthers Ross 
Published: October 2021

Abstract

Aims
Glioblastoma (GBM) is a treatment refractory cancer of extreme unmet need which exhibits treatment resistance due to a subpopulation of GBM cancer stem cells which have constitutive DNA damage response activation driven by elevated replication stress (RS). RS response inhibition is potently cytotoxic to GSC, however mechanistic understanding will be key to biomarker discovery and successful clinical translation.
We investigated response to combined ATR and PARP inhibition (CAiPi) to gain mechanistic insight and inform biomarker development.

Method
A panel of patient-derived GBM cell lines were cultured as stem enriched (GSCs) or stem depleted (bulk), to characterise response to combined ATR inhibition (VE821 5μM) and PARP inhibition (Olaparib 1μM), by CellTiter-Glo viability assay.
Mechanistic investigations included immunofluorescence of 53BP1 nuclear bodies and DNA fibre analysis. Studies into the importance of PARP trapping included another PARPi Veliparib (1μM), and investigations into inhibition of origin firing used the CDK inhibitor Roscovitine.

Results
Responses to CAiPi in a panel of primary paired GBM GSCs vs differentiated progeny were heterogenous. CAiPi is selectively GSC cytotoxic in a subpopulation of tumours. DNA fibre analysis identified increased new origin firing with PARPi, which was correlated with increased PARP trapping. Inhibition of origin firing by exposure to roscovitine rescued the CAiPi cytotoxic phenotype, suggesting origin firing has an important role in selective GSC cytotoxicity.
A population of treatment-sensitive GSCs with increased numbers of 53BP1 nuclear bodies in G1 phase with CAiPi were identified, indicative of under-replication of DNA in S phase.

Conclusion
Selective GSC cytotoxicity is induced by CAiPi via dysregulation of replication, by both DNA under-replication resulting in DNA lesions, and the novel finding of increased new origin firing in GSC due to PARPi.
Characteristics of glioblastoma long-term survivors
Authors: Ali Tamara , Olubajo Farouk , Rathi Nitika , Pal Piyali , Jenkinson Michael , Brodbelt Andrew 
Published: October 2021

Abstract

Aims
Glioblastoma (GBM) is the commonest and most aggressive primary malignant brain tumour in adults. A small number of patients survive for &gt;5 years and are referred to as long-term survivors (LTS). This study aimed to quantify and characterise GBM LTS in a single large UK centre.

Method
A retrospective observational cohort study was performed. Patients diagnosed with GBM in a single UK centre between 2000–2011 (inclusive) who survived &gt;5 years from diagnosis were included. Histopathological samples were re-examined as per the WHO 2016 classification criteria and tested for molecular biomarkers including MGMT promoter methylation, IDH1/2 mutations, 1p19q codeletion and ATRX. Demographic, imaging, treatment and outcome data were collected.

Results
1130 patients diagnosed with GBM were identified, 30 of whom survived for &gt;5 years. Twenty-three were re-confirmed as GBM histologically and seven were reclassified as anaplastic oligodendroglioma or anaplastic astroctyoma. Median overall survival for this cohort was 6.2 years. We report a 2% 5-year survival, and a 0.7% 7-year survival. LTS-associated factors were younger age (&lt;65 years old), frontal unilateral tumours, maximal management (surgery and chemoradiotherapy), good post-operative performance status (WHO &lt;2), MGMT promoter methylation and IDH1/2 mutation.

Conclusion
A small subset of GBM patients survive for &gt;5 years. Most still succumb to the disease, implying 5-year survival is not indicative of a cure. On applying current molecular markers, a quarter of previously diagnosed glioblastoma in this LTS population were revised to be WHO grade III gliomas.
Glioblastoma cytotoxicity conferred through dual disruption of endolysosomal homeostasis by Vacquinol-1
Authors: Kwak Dongoh , Hammarström Lars G J , Haraldsson Martin , Ernfors Patrik 
Published: October 2021

Abstract

Background
Increased membrane trafficking is observed in numerous cancer types, including glioblastoma. Targeting the oncogenic driven acquired alterations in membrane trafficking by synthetic cationic amphiphilic small molecules has recently been shown to induce death of glioblastoma cells, although the molecular targets are unknown.

Methods
The mechanism of action of the cationic amphiphilic drug Vacquinol-1 (Vacq1)-induced cytotoxicity was investigated using cell biology, biochemistry, functional experiments, chemical biology, unbiased antibody-based post-translation modification profiling, and mass spectrometry-based chemical proteomic analysis on patient-derived glioblastoma cells.

Results
Vacq1 induced two types of abnormal endolysosomal vesicles, enlarged vacuoles and acidic vesicle organelles (AVOs). Mechanistically, enlarged vacuoles were formed by the impairment of lysosome reformation through the direct interaction and inhibition of calmodulin (CaM) by Vacq1, while AVO formation was induced by Vacq1 accumulation and acidification in the endosomal compartments through its activation of the v-ATPase. As a consequence of v-ATPase activation, cellular ATP consumption markedly increased, causing cellular energy shortage and cytotoxicity. This effect of Vacq1 was exacerbated by its inhibitory effects on calmodulin, causing lysosomal depletion and a failure of acidic vesicle organelle clearance.

Conclusion
Our study identifies the targets of Vacq1 and the mechanisms underlying its selective cytotoxicity in glioblastoma cells. The dual function of Vacq1 sets in motion a glioblastoma-specific vicious cycle of ATP consumption resulting in cellular energy crisis and cell death.
Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence
Authors: Brooks Skylar J , Katz Eliot S , Stamoulis Catherine 
Published: October 2021

AbstractSleep is critical for cognitive health, especially during complex developmental periods such as adolescence. However, its effects on maturating brain networks that support cognitive function are only partially understood. We investigated the impact of shorter duration and reduced quality sleep, common stressors during development, on functional network properties in early adolescence—a period of significant neural maturation, using resting-state functional magnetic resonance imaging from 5566 children (median age = 120.0 months; 52.1% females) in the Adolescent Brain Cognitive Development cohort. Decreased sleep duration, increased sleep latency, frequent waking up at night, and sleep-disordered breathing symptoms were associated with lower topological efficiency, flexibility, and robustness of visual, sensorimotor, attention, fronto-parietal control, default-mode and/or limbic networks, and with aberrant changes in the thalamus, basal ganglia, hippocampus, and cerebellum (P &lt; 0.05). These widespread effects, many of which were body mass index-independent, suggest that unhealthy sleep in early adolescence may impair neural information processing and integration across incompletely developed networks, potentially leading to deficits in their cognitive correlates, including attention, reward, emotion processing and regulation, memory, and executive control. Shorter sleep duration, frequent snoring, difficulty waking up, and daytime sleepiness had additional detrimental network effects in nonwhite participants, indicating racial disparities in the influence of sleep metrics.