Simplicial gauge theory on spacetime

We define a discrete gauge-invariant Yang-Mills-Higgs action on spacetime simplicial meshes. The formulation is a generalization of classical lattice gauge theory, and we prove consistency of the action in the sense of approximation theory. In addition, we perform numerical tests of convergence towards exact continuum results for several choices of gauge fields in pure gauge theory.Comment: 18 pages, 2 figure

Grazer diversity, functional redundancy, and productivity in seagrass beds: An experimental test

Concern over the accelerating loss of biodiversity has stimulated renewed interest in relationships among species richness, species composition, and the functional properties of ecosystems. Mechanistically, the degree of functional differentiation or complementarity among individual species determines the form of such relationships and is thus important to distinguishing among alternative hypotheses for the effects of diversity on ecosystem processes. Although a growing number of studies have reported relationships between plant diversity and ecosystem processes, few have explicitly addressed how functional diversity at higher trophic levels influences ecosystem processes. We used mesocosm experiments to test the impacts of three herbivorous crustacean species (Gammarus mucronatus, Idotea baltica, and Erichsonella attenuata) on plant biomass accumulation, relative dominance of plant functional groups, and herbivore secondary production in beds of eelgrass (Zostera marina), a dominant feature of naturally low-diversity estuaries throughout the northern hemisphere. By establishing treatments with all possible combinations of the three grazer species, we tested the degree of functional redundancy among grazers and their relative impacts on productivity. Grazer species composition strongly influenced eelgrass biomass accumulation and grazer secondary production, whereas none of the processes we studied was clearly related to grazer species richness over the narrow range (0–3 species) studied. In fact, all three measured ecosystem processes—epiphyte grazing, and eelgrass and grazer biomass accumulation— reached highest values in particular single-species treatments. Experimental deletions of individual species from the otherwise-intact assemblage confirmed that the three grazer species were functionally redundant in impacting epiphyte accumulation, whereas secondary production was sensitive to deletion of G. mucronatus, indicating its unique, nonredundant role in influencing this variable. In the field, seasonal abundance patterns differed markedly among the dominant grazer species, suggesting that complementary grazer phenologies may reduce total variance in grazing pressure on an annual basis. Our results show that even superficially similar grazer species can differ in both sign and magnitude of impacts on ecosystem processes and emphasize that one must be cautious in assuming redundancy when assigning species to functional groups

Creating tissue on chip constructs in microtitre plates for drug discovery

We report upon a novel coplanar dielectrophoresis (DEP) based cell patterning system for generating transferrable hepatic cell constructs, resembling a liver-lobule, in culture. The use of paper reinforced gel substrates provided sufficient strength to enable these constructs to be transfered into 96-well plates for long term functional studies, including in the future, drug development studies. Experimental results showed that hepatic cells formed DEP field-induced structures corresponding to an array of lobulemimetic patterns. Hepatic viability was observed over a period of 3 days by the use of a fluorescent cell staining technique, whilst the liver specific functionality of albumin secretion showed a significant enhancement due to the layer patterning of cell lines (HepG2/C3A), compared to 2D patterned cells and un-patterned control. This “build and transfer” concept could, in future, also be adapted for the layer-bylayer construction of organs-on-chip in microtitre formats

Development of microdialysis methodology for interstitial insulin measurement in rodents.

INTRODUCTION: Accurate assessment of muscle insulin sensitivity requires measurement of insulin concentration in interstitial fluid (ISF), but has proved difficult. We aimed to optimise measurement of ISF insulin concentrations in rat muscles in vivo using microdialysis. METHODS: Factorial experimental design experiments were performed in vitro to determine optimal conditions for insulin recovery with microdialysis probes. These conditions were tested in vivo, adjusted appropriately and used in lean and obese Zucker rats to compare ISF insulin concentrations basally and during hyperinsulinaemic-euglycaemic (HE) clamp. RESULTS: Optimal conditions in vivo were: a 100kDa microdialysis probe inserted in muscle, perfused with 1% BSA, 1.5mM glucose in 0.9% sodium chloride at 1μl/min. Samples were collected into siliconised glass microvials. As a reference for insulin, we established a protocol of inulin infusion, beginning at -80min and reaching equilibrium within 60min. HE clamp, beginning at 0min, increased ISF insulin concentration from 122±56 basally to 429±180pmol/l (P<0.05) in lean rats and from 643±165 to 1087±243pmol/l (P=0.07) in obese rats; ISF insulin concentrations were significantly higher throughout in obese rats. The difference between ISF and plasma insulin concentration (ISF:plasma ratio) was substantially higher in obese rats, but fell to similar values in obese and lean rats during HE clamp. DISCUSSION: Optimising insulin recovery with microdialysis allowed accurate measurement of basal ISF insulin in muscle of lean and obese Zucker rats and indicates insulin transport across capillaries is impaired in obese rats, basally and during hyperinsulinaemia

Competition law and policy and the food value chain

This On-Topic revisits the complex issues rising in the food sector and its value chain. Both the European Union and the US competition authorities have scrutinized relationships between food chain actors. The increasing market concentration raises new challenges for competition enforcement authorities dealing with the creation of new powerful actors at the distribution but also at the factor of production (input) levels. The concept of superior bargaining power has played a key role, sometimes criticised, in order to assess these relationships. The papers also discuss the critical intersection of competition law with public policy, with the aim to preserve sustainability, food safety and the stability of agricultural markets

Unique activities of two overlapping PAX6 retinal enhancers

Enhancers play a critical role in development by precisely modulating spatial, temporal, and cell type-specific gene expression. Sequence variants in enhancers have been implicated in diseases; however, establishing the functional consequences of these variants is challenging because of a lack of understanding of precise cell types and developmental stages where the enhancers are normally active. PAX6 is the master regulator of eye development, with a regulatory landscape containing multiple enhancers driving the expression in the eye. Whether these enhancers perform additive, redundant or distinct functions is unknown. Here, we describe the precise cell types and regulatory activity of two PAX6 retinal enhancers, HS5 and NRE. Using a unique combination of live imaging and single-cell RNA sequencing in dual enhancer-reporter zebrafish embryos, we uncover differences in the spatiotemporal activity of these enhancers. Our results show that although overlapping, these enhancers have distinct activities in different cell types and therefore likely nonredundant functions. This work demonstrates that unique cell type-specific activities can be uncovered for apparently similar enhancers when investigated at high resolution in vivo

Lewis Base Passivation Mediates Charge Transfer at Perovskite Heterojunctions

Understanding interfacial charge transfer processes such as trap-mediated recombination and injection into charge transport layers (CTLs) is crucial for the improvement of perovskite solar cells. Herein, we reveal that the chemical binding of charge transport layers to CH3NH3PbI3 defect sites is an integral part of the interfacial charge injection mechanism in both n-i-p and p-i-n architectures. Specifically, we use a mixture of optical and X-ray photoelectron spectroscopy to show that binding interactions occur via Lewis base interactions between electron-donating moieties on hole transport layers and the CH3NH3PbI3 surface. We then correlate the extent of binding with an improvement in the yield and longer lifetime of injected holes with transient absorption spectroscopy. Our results show that passivation-mediated charge transfer has been occurring undetected in some of the most common perovskite configurations and elucidate a key design rule for the chemical structure of next-generation CTLs

The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P &#60; 0.01), tumour length (P &#60; 0.0001), TNM stage (P&#60;0.0001), weight loss (P&#60;0.0001), dysphagia score (P&#60;0.001), performance status (P&#60;0.1) and treatment (P&#60;0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P&#60;0.0001), role functioning (P&#60;0.001), cognitive functioning (P&#60;0.01), social functioning (P&#60;0.0001), global quality of life (P&#60;0.0001), fatigue (P&#60;0.0001), nausea/vomiting (P&#60;0.01), pain (P&#60;0.001), dyspnoea (P&#60;0.0001), appetite loss (P&#60;0.0001) and constipation (P&#60;0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P&#60;0.0001), treatment (P&#60;0.001) and appetite loss (P&#60;0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

A powerful intervention: general practitioners' use of sickness certification in depression

&lt;b&gt;Background&lt;/b&gt; Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry