bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintaining Stable Macroeconomic Conditions
Authors: Jones Russell , Llewellyn John 
Published: October 2019

Executive SummaryThe UK economy faces more than usually uncertain times. Outside the European Union, and in an increasingly challenging global environment characterised by ageing populations, climate change, populism, protectionism, and more, the country needs to chart a new course. This may well require policymakers to consider unconventional approaches to monetary and fiscal policy and, at the very least argues for important modifications of the current policy regime, including the autonomous mandate of the Bank of England.At some point, there will be a major slowdown in economic activity. Yet the Bank of England has very little leeway to respond by cutting interest rates, and it has already adopted an armoury of unorthodox tools that may be decreasing in effectiveness. More radical monetary approaches would be likely to be politically controversial; and are not without risks. In these circumstances it would be a mistake to rely solely, or even largely, on monetary policy to maintain demand. It would be better to conduct monetary and fiscal policy in tandem, and for discretionary fiscal policy to be required to play a much more active role in demand management than hitherto. This would, for example, imply major extension of the automatic stabilisers and efforts better to calibrate discretionary initiatives with the business cycle.But given the long-term pressures on the public finances, more fundamental changes in the structure of spending and taxation are needed, along with a redrawing of fiscal rules and targets, under independent budgetary oversight. The current, historically low, share in GDP of public spending is itself unsustainable in light of the demand for services of an ageing population; plans should be made to raise it closer to the European average. In the most extreme circumstances it might become necessary to waive the fiscal rules entirely and for the Bank of England directly to underwrite fiscal stimulus in order to sustain aggregate demand. It would be wise for the authorities to consider the options in detail now, while the environment is still relatively stable.
Reorienting Foreign Policy
Authors: Greenstock Jeremy 
Published: October 2019

Executive SummaryAfter Brexit, the UK must show that it has a voice. It will need to re-earn international respect, and in particular establish the concept of a ‘global Britain’ on the basis of performance, not rhetoric. That means re-establishing a strong network of relationships around the world in support of its security and economic health, but also continuing to play a leading role in support of the international rules-based order. For example, it should make the most of its continuing status as a Permanent Member of the UN Security Council to act as a problem-solver and system-enhancer in the collective interest.An early, first-order priority will be establishing a new, mutually beneficial partnership with the European Union, which continues to form our economic and political neighbourhood. Reconstructing a modern relationship with the United States is not secondary to that, but cannot substitute for it and must be undertaken in recognition of the differing interests and instincts of the two sides. A further challenge is building the right relationship with China based on mutual interest in trade, peace, and international respect and on confronting expansionist or opportunistic practices. With Russia, too, it is possible to design a predictable set of behaviours on either side, and with both countries good communication channels will need to be maintained.Brexit gives the UK the scope to construct a more deliberate diplomatic approach to the rest of the English-speaking world than was explicitly possible as an EU member – notably in working with Canada, Australia and New Zealand to promote the international rules-based order. But this should be complemented by more effective outreach to non-English-speaking countries, notably in support of trade and investment opportunities with emerging nations. But with them as with all the UK's interlocutors, the need to earn its place, and to show that it realises that, will be vital.In defence and security, the UK will continue in its commitment to the strength of NATO as its essential alliance under US leadership, while also liaising carefully with EU Member States as they seek to improve their own capacities to contribute to European security. But it cannot simply rely on old institutional structures. It needs to lead, for example by playing a stronger role in the control of non-military forms of aggression, such as cyber warfare, economic sanctions, rivalry in space, and commercial espionage.A strategy for realising the UK's interests in the international arena will require the Prime Minister's constant attention, but also a specific mandate for a very senior minister to supervise the interlinked policy areas of foreign affairs, international development, and international trade within a single government department.
Updating Security and Defence Policy
Authors: Grant Mark Lyall 
Published: October 2019

Executive SummaryThreats to the security of the UK are evolving with the changing nature of conflict and balance of power in the world. They are multiple and fragmented, and domestic and online as well as overseas in nature: principally state-based threats such as posed by Russian activity; terrorism; cyber-attacks; and serious organised crime. To respond, the United Kingdom will need flexible capabilities aimed at fostering infrastructural and societal resilience as much as conventional defence. Above all, the UK needs to focus on maintaining, promoting, and defending the international rules-based order, as represented by the UN and NATO among other institutions.The UK possesses significant assets to these ends, including its continuing status as one of eight acknowledged nuclear powers – a status that it should not abandon unilaterally; permanent membership of the UN Security Council; membership of the ‘Five Eyes' intelligence community; and its internationally respected armed forces.But effort and resources are required to support these commitments, for example in helping to encourage other European states to spend more on defence; in contributing to UN peace-keeping operations or other collaborative overseas actions; and most of all in ensuring that army and navy manpower is rebuilt. Two per cent of GDP is no longer sufficient for the proper defence of the nation. Even allowing for the demands of other parts of government, the target for defence spending should be raised in the next review to 2.2 per cent.The principal focus will need to be on efficiency and redeployment of resources as the current equipment-heavy procurement cycle comes to an end. In particular, investment needs to continue to be rebalanced towards new capabilities such as drone technology, offensive and defensive cyber and intelligence manpower.But, to avoid any weakening of the country's security, priority should be given to negotiating a new agreement on security and intelligence cooperation with its European allies to replace the arrangements it had within the EU.
Redesigning Housing Policy
Authors: Barker Kate 
Published: October 2019

Executive SummaryDiscussion of the UK's housing crisis is of long date, and tends to focus on a simple story about a mismatch in housing supply and demand and the consequent need to build more homes. Yet the reality is more complex with multiple sub-plots including social housing, stress in the private rented sector, benefits, subsidies and ultimately taxation of home ownership.At the bottom of the market, the crisis is real and acute, as manifested in a sharp increase in homelessness and rough sleeping. The inescapable answer is to increase the depleted stock of social housing and widen eligibility criteria. An increase of 100,000 social units a year in England would help address this problem, as well as alleviate the financial squeeze on tenants of the private rented sector, whose number has grown sharply in the past 15 years in tandem with a steep rise in the housing benefit bill. Recent efforts to curb housing benefit have further increased distress, so it will be necessary to consider increasing benefits again alongside regulatory interventions with private landlords.In the home ownership market, recent government intervention has taken the form of the much-criticised Help-to-Buy Equity Loan scheme. This market policy to support new-build homes should be wound down and replaced by a scheme to endow all young people with a capital sum that they could use for second-hand homes as well. More generally, a more sophisticated approach to planning home-building is needed, both for assessing overall numbers and their regional distribution and in financing the supporting infrastructure.But none of these measures is a panacea for a housing crisis that is in large part a symptom of problems in the wider economy, such as low relative wages for young people, a lack of clarity about environmental issues, and failing places. A successful policy package to address the distorted structure of the housing market must also grasp the most difficult nettle of all – namely the way the tax benefits of owner-occupation incentivise overconsumption of housing and a widening wealth gap between renters and home owners, and between owners in different parts of the country. If we spend more to help those who struggle to afford decent housing, then it is only just to raise more taxation from those who benefit from restrictions on housing supply – whether through reform to council tax, a wider wealth tax or a limited form of Capital Gains Tax on principal residences.
National trends in coronary intensive care unit admissions, resource utilization, and outcomes
Authors: Woolridge Sarah , Alemayehu Wendimagegn , Kaul Padma , Fordyce Christopher B , Lawler Patrick R , Lemay Michel , Jentzer Jacob C , Goldfarb Michael , Wong Graham C , Armstrong Paul W , van Diepen Sean 
Published: October 2019

Background:
Emerging evidence suggests that coronary intensive care units are evolving into intensive care environments with an increasing burden of non-cardiovascular illness, but previous studies have been limited to older populations or single center experiences.

Methods:
Canadian national health-care data was used to identify all patients ≥18 years admitted to dedicated coronary intensive care units (2005–2015) and admissions were categorized as primary cardiac or non-cardiac. The outcomes of interest included longitudinal trends in admission diagnoses, critical care therapies, and all-cause in-hospital mortality.

Results:
Among the 373,992 patients admitted to a coronary intensive care unit, minimal changes in the proportion of patients admitted with a primary cardiac (88.2% to 86.9%; p&lt;0.001) and non-cardiac diagnoses (11.8% to 13.1%; p&lt;0.001) were observed. Among cardiac admissions, a temporal increase in the proportion of ST-segment elevation myocardial infarction (19.4% to 24.1%, p&lt;0.001), non-ST-segment elevation myocardial infarction (14.6% to 16.2%, p&lt;0.001), heart failure (7.3% to 8.4%, p&lt;0.001), shock (4.9% to 5.7%, p&lt;0.001), and decline in unstable angina (4.9% to 4.0%, p&lt;0.001) and stable coronary diseases (21.3% to 12.4%, p&lt;0.001) was observed. The proportion of patients requiring critical care therapies (57.8% to 63.5%, p&lt;0.001) including mechanical ventilation (9.6% to 13.1%, p&lt;0.001) increased. In-hospital mortality rates for patients with primary cardiac (4.9% to 4.4%; adjusted odds ratio 0.71, 95% confidence interval 0.63–0.79) and non-cardiac (17.8% to 16.1%; adjusted odds ratio 0.84, 0.73–0.97) declined; results were consistent when stratified by academic vs community hospital, and by the presence of on-site percutaneous coronary intervention.

Conclusion:
In a national dataset we observed a changing case-mix among patients admitted to a coronary intensive care unit, though the proportion of patients with a primary cardiac diagnosis remained stable. There was an increase in clinical acuity highlighted by critical care therapies, but in-hospital mortality rates for both primary cardiac and non-cardiac conditions declined across all hospitals. Our findings confirm the changing coronary intensive care unit case-mix and have implications for future coronary intensive care unit training and staffing.
Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma
Authors: Schmidts Andrea , Ormhøj Maria , Choi Bryan D. , Taylor Allison O. , Bouffard Amanda A. , Scarfò Irene , Larson Rebecca C. , Frigault Matthew J. , Gallagher Kathleen , Castano Ana P. , Riley Lauren S. , Cabral Maria L. , Boroughs Angela C. , Velasco Cárdenas Rubí M.-H. , Schamel Wolfgang , Zhou Jing , Mackay Sean , Tai Yu-Tzu , Anderson Kenneth C. , Maus Marcela V. 
Published: October 2019

Key PointsA trimeric extracellular moiety of APRIL has enhanced binding to BCMA and TACI compared with monomeric APRIL when incorporated into a CAR. T cells transduced with a trimeric APRIL-based CAR are a promising approach for the treatment of MM.
Predicting protein inter-residue contacts using composite likelihood maximization and deep learning
Authors: Zhang Haicang , Zhang Qi , Ju Fusong , Zhu Jianwei , Gao Yujuan , Xie Ziwei , Deng Minghua , Sun Shiwei , Zheng Wei-Mou , Bu Dongbo 
Published: October 2019

AbstractBackgroundAccurate prediction of inter-residue contacts of a protein is important to calculating its tertiary structure. Analysis of co-evolutionary events among residues has been proved effective in inferring inter-residue contacts. The Markov random field (MRF) technique, although being widely used for contact prediction, suffers from the following dilemma: the actual likelihood function of MRF is accurate but time-consuming to calculate; in contrast, approximations to the actual likelihood, say pseudo-likelihood, are efficient to calculate but inaccurate. Thus, how to achieve both accuracy and efficiency simultaneously remains a challenge.ResultsIn this study, we present such an approach (called clmDCA) for contact prediction. Unlike plmDCA using pseudo-likelihood, i.e., the product of conditional probability of individual residues, our approach uses composite-likelihood, i.e., the product of conditional probability of all residue pairs. Composite likelihood has been theoretically proved as a better approximation to the actual likelihood function than pseudo-likelihood. Meanwhile, composite likelihood is still efficient to maximize, thus ensuring the efficiency of clmDCA. We present comprehensive experiments on popular benchmark datasets, including PSICOV dataset and CASP-11 dataset, to show that:i) clmDCA alone outperforms the existing MRF-based approaches in prediction accuracy.ii) When equipped with deep learning technique for refinement, the prediction accuracy of clmDCA was further significantly improved, suggesting the suitability of clmDCA for subsequent refinement procedure. We further present a successful application of the predicted contacts to accurately build tertiary structures for proteins in the PSICOV dataset.ConclusionsComposite likelihood maximization algorithm can efficiently estimate the parameters of Markov Random Fields and can improve the prediction accuracy of protein inter-residue contacts.
Exploring effective approaches for haplotype block phasing
Authors: Al Bkhetan Ziad , Zobel Justin , Kowalczyk Adam , Verspoor Karin , Goudey Benjamin 
Published: October 2019

AbstractBackgroundKnowledge of phase, the specific allele sequence on each copy of homologous chromosomes, is increasingly recognized as critical for detecting certain classes of disease-associated mutations. One approach for detecting such mutations is through phased haplotype association analysis. While the accuracy of methods for phasing genotype data has been widely explored, there has been little attention given to phasing accuracy at haplotype block scale. Understanding the combined impact of the accuracy of phasing tool and the method used to determine haplotype blocks on the error rate within the determined blocks is essential to conduct accurate haplotype analyses.ResultsWe present a systematic study exploring the relationship between seven widely used phasing methods and two common methods for determining haplotype blocks. The evaluation focuses on the number of haplotype blocks that are incorrectly phased. Insights from these results are used to develop a haplotype estimator based on a consensus of three tools. The consensus estimator achieved the most accurate phasing in all applied tests. Individually, EAGLE2, BEAGLE and SHAPEIT2 alternate in being the best performing tool in different scenarios. Determining haplotype blocks based on linkage disequilibrium leads to more correctly phased blocks compared to a sliding window approach. We find that there is little difference between phasing sections of a genome (e.g. a gene) compared to phasing entire chromosomes. Finally, we show that the location of phasing error varies when the tools are applied to the same data several times, a finding that could be important for downstream analyses.ConclusionsThe choice of phasing and block determination algorithms and their interaction impacts the accuracy of phased haplotype blocks. This work provides guidance and evidence for the different design choices needed for analyses using haplotype blocks. The study highlights a number of issues that may have limited the replicability of previous haplotype analysis.
Comprehensive analysis of genetic and evolutionary features of the hepatitis E virus
Authors: Baha Sarra , Behloul Nouredine , Liu Zhenzhen , Wei Wenjuan , Shi Ruihua , Meng Jihong 
Published: October 2019

Abstract

Background
The hepatitis E virus (HEV) is the causative pathogen of hepatitis E, a global public health concern. HEV comprises 8 genotypes with a wide host range and geographic distribution. This study aims to determine the genetic factors influencing the molecular adaptive changes of HEV open reading frames (ORFs) and estimate the HEV origin and evolutionary history.

Results
Sequences of HEV strains isolated between 1982 and 2017 were retrieved and multiple analyses were performed to determine overall codon usage patterns, effects of natural selection and/or mutation pressure and host influence on the evolution of HEV ORFs. Besides, Bayesian Coalescent Markov Chain Monte Carlo (MCMC) Analysis was performed to estimate the spatial-temporal evolution of HEV. The results indicated an A/C nucleotide bias and ORF-dependent codon usage bias affected mainly by natural selection. The adaptation of HEV ORFs to their hosts was also ORF-dependent, with ORF1 and ORF2 sharing an almost similar adaptation profile to the different hosts. The discriminant analysis based on the adaptation index suggested that ORF1 and ORF3 could play a pivotal role in viral host tropism.

Conclusion
In this study, we estimate that the common ancestor of the modern HEV strains emerged ~ 6000 years ago, in the period following the domestication of pigs. Then, natural selection played the major role in the evolution of the codon usage of HEV ORFs. The significant adaptation of ORF1 of genotype 1 to humans, makes ORF1 an evolutionary indicator of HEV host speciation, and could explain the epidemic character of genotype 1 strains in humans.
Expression profiles of cell-wall related genes vary broadly between two common maize inbreds during stem development
Authors: Penning Bryan W. , Shiga Tânia M. , Klimek John F. , SanMiguel Philip J. , Shreve Jacob , Thimmapuram Jyothi , Sykes Robert W. , Davis Mark F. , McCann Maureen C. , Carpita Nicholas C. 
Published: October 2019

AbstractBackgroundThe cellular machinery for cell wall synthesis and metabolism is encoded by members of large multi-gene families. Maize is both a genetic model for grass species and a potential source of lignocellulosic biomass from crop residues. Genetic improvement of maize for its utility as a bioenergy feedstock depends on identification of the specific gene family members expressed during secondary wall development in stems.ResultsHigh-throughput sequencing of transcripts expressed in developing rind tissues of stem internodes provided a comprehensive inventory of cell wall-related genes in maize (Zea mays, cultivar B73). Of 1239 of these genes, 854 were expressed among the internodes at ≥95 reads per 20 M, and 693 of them at ≥500 reads per 20 M. Grasses have cell wall compositions distinct from non-commelinid species; only one-quarter of maize cell wall-related genes expressed in stems were putatively orthologous with those of the eudicot Arabidopsis. Using a slope-metric algorithm, five distinct patterns for sub-sets of co-expressed genes were defined across a time course of stem development. For the subset of genes associated with secondary wall formation, fifteen sequence motifs were found in promoter regions. The same members of gene families were often expressed in two maize inbreds, B73 and Mo17, but levels of gene expression between them varied, with 30% of all genes exhibiting at least a 5-fold difference at any stage. Although presence-absence and copy-number variation might account for much of these differences, fold-changes of expression of aCADaand aFLA11gene were attributed to polymorphisms in promoter response elements.ConclusionsLarge genetic variation in maize as a species precludes the extrapolation of cell wall-related gene expression networks even from one common inbred line to another. Elucidation of genotype-specific expression patterns and their regulatory controls will be needed for association panels of inbreds and landraces to fully exploit genetic variation in maize and other bioenergy grass species.
RETRACTED ARTICLE: TaWRKY40 transcription factor positively regulate the expression of TaGAPC1 to enhance drought tolerance
Authors: Zhang Lin , Xu Zhiyong , Ji Haikun , Zhou Ye , Yang Shushen 
Published: October 2019

Abstract
Backgrounds
Drought stress is one of the major factors that affects wheat yield. Glyceraldehyde-3-Phosphate dehydrogenase (GAPDH) is a multifunctional enzyme that plays the important role in abiotic stress and plant development. However, in wheat, limited information about drought-responsive GAPC genes has been reported, and the mechanism underlying the regulation of the GAPC protein is unknown.

Results
In this study, we evaluated the potential role of GAPC1 in drought stress in wheat and Arabidopsis. We found that the overexpression of TaGAPC1 could enhance the tolerance to drought stress in transgenic Arabidopsis. Yeast one-hybrid library screening and EMSA showed that TaWRKY40 acts as a direct regulator of the TaGAPC1 gene. A dual luciferase reporter assay indicated that TaWRKY40 improved the TaGAPC1 promoter activity. The results of qRT-PCR in wheat protoplast cells with instantaneous overexpression of TaWRKY40 indicated that the expression level of TaGAPC1 induced by abiotic stress was upregulated by TaWRKY40. Moreover, TaGAPC1 promoted H2O2 detoxification in response to drought.

Conclusion
These results demonstrate that the inducible transcription factor TaWRKY40 could activate the transcription of the TaGAPC1 gene, thereby increasing the tolerance of plants to drought stress.