Liquidity-Driven Risks to Large Valued Payments

During particularly stressed financial or macroeconomic circumstances, banks’ access to liquidity can become severely restricted. The recent financial crisis demonstrated this phenomenon all too plainly, when, in a climate of fear and uncertainty, both the interbank and international money markets ceased to function in a meaningful manner. Liquidity shortages can potentially create problems for a bank’s ability to meet its outward intraday payments obligations on the TARGET2 real-time gross settlement system. Such a situation not only has negative implications for the respective bank but could also produce contagion effects for the TARGET2 system as a whole. In order to provide increased clarity regarding liquidity driven risks to large value payment systems, the Central Bank of Ireland has developed a ‘liquidity buffer’ indicator for the domestic credit institutions. The initial focus of this project centred primarily upon the development of an ‘early warning’ system, capable of identifying TARGET2 liquidity issues as they occurred in real time. However, during the development of such a platform, the analysis has also presented a means from which it is possible to derive a proxy for the level of risk banks detect in their environment. The analysis undertaken reveals that the Reserve Requirement (RR) plays an important role in how banks formulate their liquidity management strategies throughout the maintenance period. In times of increased uncertainty banks appear willing to hold excess liquidity, at a greater expense, in order to be guaranteed access to liquidity towards the latter half of the maintenance period. In a similar fashion, during a period of stability or relative certainty, banks do not choose to maintain excess liquidity on the TARGET2 platform, implying a degree of increased confidence in accessing liquidity when they require it later in the maintenance period. In this sense we can, to some degree, infer the degree of risk a bank perceives to be present in its immediate environment, by examining the respective institutions’ liquidity management strategy over the maintenance period. In a broader fashion, the indicator also serves as a tool from which the Central Bank of Ireland can monitor banks’ liquidity position with increased precision.

Community, rurality, and older people: critically comparing older people's experiences across different rural communities

Recent years have witnessed renewed academic interest in community as both an organizing concept and empirical case study. While previous work on community was largely limited to descriptive accounts of people's interactions in particular places, recent research has provided broader and more critical understandings of community by making connections between social imaginaries and social actions. This paper contributes to this work by applying a multilayered critical theory approach to the study of community. Starting from a general position that views community as a set of cognitively stabilized ideas and expectations, this approach compares discourses at different social levels of community in terms of how they unfold over time. The paper then applies this approach to experiences of community amongst older people in three rural places in England and Wales. Drawing on materials from interviews with older people and stakeholders, the paper explores the extent to which institutional discourses of community include different points of view and interpersonal discourses draw on reflective discourses. The empirical study highlights how community represents both a social system and a space in which individuals learn to live with others in the context of common practices and rule systems. It is also clear from the study that civil society and state actors need to develop new ideas, resources and practices to transform ageing from a demographic descriptor of rural places to an essential component of a shifting rural community discourse

Public contracts as accountability mechanisms: assuring quality in public healthcare in England and Wales

Contracting in the public sector is designed to enhance the accountability of service providers to their funders. The idea is that quality is improved by the use of service specifications, monitoring of performance and imposition of contractual sanctions. Socio-legal and economic theories of contract indicate that it will be difficult to make and enforce contracts to achieve this. The results of a study of National Health Services contracting in England and Wales are reported. We conclude that contracts alone are not sufficient to improve accountability – collibration of various regulatory measures (including more hierarchical mechanisms such as performance targets) is required

TGLI1 transcription factor mediates breast cancer brain metastasis via activating metastasis-initiating cancer stem cells and astrocytes in the tumor microenvironment

Mechanisms for breast cancer metastasis remain unclear. Whether truncated glioma-associated oncogene homolog 1 (TGLI1), a transcription factor known to promote angiogenesis, migration and invasion, plays any role in metastasis of any tumor type has never been investigated. In this study, results of two mouse models of breast cancer metastasis showed that ectopic expression of TGLI1, but not GLI1, promoted preferential metastasis to the brain. Conversely, selective TGLI1 knockdown using antisense oligonucleotides led to decreased breast cancer brain metastasis (BCBM) in vivo. Immunohistochemical staining showed that TGLI1, but not GLI1, was increased in lymph node metastases compared to matched primary tumors, and that TGLI1 was expressed at higher levels in BCBM specimens compared to primary tumors. TGLI1 activation is associated with a shortened time to develop BCBM and enriched in HER2-enriched and triple-negative breast cancers. Radioresistant BCBM cell lines and specimens expressed higher levels of TGLI1, but not GLI1, than radiosensitive counterparts. Since cancer stem cells (CSCs) are radioresistant and metastasis-initiating cells, we examined TGLI1 for its involvement in breast CSCs and found TGLI1 to transcriptionally activate stemness genes CD44, Nanog, Sox2, and OCT4 leading to CSC renewal, and TGLI1 outcompetes with GLI1 for binding to target promoters. We next examined whether astrocyte-priming underlies TGLI1-mediated brain tropism and found that TGLI1-positive CSCs strongly activated and interacted with astrocytes in vitro and in vivo. These findings demonstrate, for the first time, that TGLI1 mediates breast cancer metastasis to the brain, in part, through promoting metastasis-initiating CSCs and activating astrocytes in BCBM microenvironment

Development of an efficient glucosinolate extraction method

Background: Glucosinolates, anionic sulfur rich secondary metabolites, have been extensively studied because of their occurrence in the agriculturally important brassicaceae and their impact on human and animal health. There is also increasing interest in the biofumigant properties of toxic glucosinolate hydrolysis products as a method to control agricultural pests. Evaluating biofumigation potential requires rapid and accurate quantification of glucosinolates, but current commonly used methods of extraction prior to analysis involve a number of time consuming and hazardous steps; this study aimed to develop an improved method for glucosinolate extraction. Results: Three methods previously used to extract glucosinolates from brassicaceae tissues, namely extraction in cold methanol, extraction in boiling methanol, and extraction in boiling water were compared across tissue type (root, stem leaf ) and four brassicaceae species (B. juncea, S. alba, R. sativus, and E. sativa). Cold methanol extraction was shown to perform as well or better than all other tested methods for extraction of glucosinolates with the exception of glucoraphasatin in R. sativus shoots. It was also demonstrated that lyophilisation methods, routinely used during extraction to allow tissue disruption, can reduce final glucosinolate concentrations and that extracting from frozen wet tissue samples in cold 80% methanol is more effective. Conclusions: We present a simplified method for extracting glucosinolates from plant tissues which does not require the use of a freeze drier or boiling methanol, and is therefore less hazardous, and more time and cost effective. The presented method has been shown to have comparable or improved glucosinolate extraction efficiency relative to the commonly used ISO method for major glucosinolates in the Brassicaceae species studied: sinigrin and gluconasturtiin in B. juncea; sinalbin, glucotropaeolin, and gluconasturtiin in S. alba; glucoraphenin and glucoraphasatin in R. sativus; and glucosatavin, glucoerucin and glucoraphanin in E. sativa

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in γ-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance

Increasing water-use efficiency directly through genetic manipulation of stomatal density

Improvement in crop water-use efficiency (WUE) is a critical priority for regions facing increased drought or diminished groundwater resources. Despite new tools for the manipulation of stomatal development, the engineering of plants with high WUE remains a challenge. We used Arabidopsis epidermal patterning factor (EPF) mutants exhibiting altered stomatal density to test whether WUE could be improved directly by manipulation of the genes controlling stomatal density. Specifically, we tested whether constitutive overexpression of EPF2 reduced stomatal density and maximum stomatal conductance (gw(max)) sufficiently to increase WUE. We found that a reduction in gw(max) via reduced stomatal density in EPF2-overexpressing plants (EPF2OE) increased both instantaneous and long-term WUE without altering significantly the photosynthetic capacity. Conversely, plants lacking both EPF1 and EPF2 expression (epf1epf2) exhibited higher stomatal density, higher gw(max) and lower instantaneous WUE, as well as lower (but not significantly so) long-term WUE. Targeted genetic modification of stomatal conductance, such as in EPF2OE, is a viable approach for the engineering of higher WUE in crops, particularly in future high-carbon-dioxide (CO2) atmospheres

Using Numbas As a Revision Tool For Mathematics Students

Summary of Teaching Context For the continuous assessment element of my courses, I use Moodle quizzes but to help students revise and practise the mathematical methodologies I have created Numbas quizzes. Overview of the Strategy ‘Numbas’ is a free to use online assessment system developed by mathematicians at Newcastle University. In Moodle the “calculated question” allows you to generate a bank of questions testing the same methodology by inserting variables within the question design. This allows for randomised questions being offered to the students. The only drawback is that it can only accept a single response for each question. Numbas allows you to design questions using variables within the question text but can also allow for several questions/answers to be posed within the one question. The answers can be numerical or algebraic. Furthermore, it allows you to code in the general solution to the problem using variables which automatically change as the numbers change with each randomly generated version. This allows students to compare their worked solution to the “model solution” and pinpoint where they are going wrong. In this way it becomes a teaching and learning tool

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine