Realizability of the Lorentzian (n,1)-Simplex

In a previous article [JHEP 1111 (2011) 072; arXiv:1108.4965] we have developed a Lorentzian version of the Quantum Regge Calculus in which the significant differences between simplices in Lorentzian signature and Euclidean signature are crucial. In this article we extend a central result used in the previous article, regarding the realizability of Lorentzian triangles, to arbitrary dimension. This technical step will be crucial for developing the Lorentzian model in the case of most physical interest: 3+1 dimensions. We first state (and derive in an appendix) the realizability conditions on the edge-lengths of a Lorentzian n-simplex in total dimension n=d+1, where d is the number of space-like dimensions. We then show that in any dimension there is a certain type of simplex which has all of its time-like edge lengths completely unconstrained by any sort of triangle inequality. This result is the d+1 dimensional analogue of the 1+1 dimensional case of the Lorentzian triangle.Comment: V1: 15 pages, 2 figures. V2: Minor clarifications added to Introduction and Discussion sections. 1 reference updated. This version accepted for publication in JHEP. V3: minor updates and clarifications, this version closely corresponds to the version published in JHE

Group-based memory rehabilitation for people with multiple sclerosis: subgroup analysis of the ReMiND trial

Background/Aim: Memory problems are frequently reported in people with multiple sclerosis (MS). These can be debilitating and affect individuals and their families. This sub-group analysis focused on the effectiveness of memory rehabilitation in patients with MS. Methods: Data were extracted from a single blind randomised controlled trial, the ReMiND trial, which also included participants with traumatic brain injury and stroke. Participants were randomly allocated to compensation or restitution treatment programmes, or a self-help control. The programmes were manual-based and comprised two individual and ten group sessions. Outcome measures included assessments of memory, mood and activities of daily living. A total of 39 patients with MS participated in this study (ten males (26%), 29 females (74%); mean±SD age: 48.3±10.8 years). Results: Comparison of groups showed no significant effect of treatment on memory, but there were significant differences between compensation and restitution on self-report symptoms of emotional distress at both 5- (p=0.04) and 7-month (p=0.05) follow-up sessions. The compensation group showed less distress than the restitution group. Conclusions: Individuals with MS who received compensation memory rehabilitation reported significantly less emotional distress than those who received restitution. Further research is needed to explore why self-reported memory problems did not differ between groups

Accumulation of fibronectin in the heart after myocardial infarction: a putative stimulator of adhesion and proliferation of adipose-derived stem cells

Stem cell therapy is a promising treatment after myocardial infarction (MI). A major problem in stem cell therapy, however, is that only a small proportion of stem cells applied to the heart can survive and differentiate into cardiomyocytes. We hypothesized that fibronectin in the heart after MI might positively affect stem cell adhesion and proliferation at the site of injury. Therefore, we investigated the kinetics of attachment and proliferation of adipose-tissue-derived stem cells (ASC) on fibronectin and analysed the time frame and localization of fibronectin accumulation in the human heart after MI. ASCs were seeded onto fibronectin-coated and uncoated culture wells. The numbers of adhering ASC were quantified after various incubation periods (5-30 min) by using DNA quantification assays. The proliferation of ASC was quantified after culturing ASC for various periods (0-9 days) by using DNA assays. Fibronectin accumulation after MI was quantified by immunohistochemical staining of heart sections from 35 patients, after different infarction periods (0-14 days old). We found that ASC attachment and proliferation on fibronectin-coated culture wells was significantly higher than on uncoated wells. Fibronectin deposition was significantly increased from 12 h to 14 days post-infarction, both in the infarction area and in the border-zone, compared with the uninfarcted heart. Our results suggest that a positive effect of fibronectin on stem cells in the heart can only be achieved when stem cell therapy is applied at least 12 h after MI, when the accumulation of fibronectin occurs in the infarcted heart. © 2008 The Author(s)

SPARC 2017 retrospect & prospects : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2017 SPARC conference. This year we not only celebrate the work of our PGRs but also the 50th anniversary of Salford as a University, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 130 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to exploit this great opportunity to engage with researchers working in different subject areas to your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Simple and Efficient Transformation and Gene Editing of Marchantia polymorpha Spores

Marchantia polymorpha (Marchantia) has become a model species for liverwort studies, owing to its rapid growth in vitro, ease of propagation, simple genetics, small genome, haploid-dominant life cycle, and because it is amenable to genetic transformation. Efficient transformation provides a foundation for many molecular and genetic analyses. The protocol described here is a simple and robust procedure for transforming Marchantia for a variety of applications, including gene overexpression and CRISPR genome editing. This simplified Agrobacterium tumefaciens-mediated transformation protocol targets spores, using common Agrobacterium strains GV3101 or EHA105, and overcomes challenges experienced in other methods. Spores are sterilized and distributed over sterile filter papers, which effectively retain spores and regenerating spores (known as sporelings). This approach enables the sporelings to be transferred to different agar growth media at different stages of transformation. A critical feature is preculturing the spores with acetosyringone (AS) prior to co-cultivation with Agrobacterium. This treatment profoundly enhances the transformation rate, particularly for Agrobacterium strain GV3101. GV3101 is preferred for its rapid growth rate, simple transformation, and lack of a recombinase (recA), stabilizing plasmids. The protocol is suitable for transforming Marchantia with constructs for CRISPR gene editing. Editing efficiency can be increased by introducing a heat-shock treatment during the transformation procedure, which increases the proportion of plants with larger edited sectors, facilitating mutant identification and propagation. Constructs and strategies for both overexpression and multiplex genome editing with sgRNA arrays using new and existing vectors are described. Using this spore transformation protocol for CRISPR gene editing, we routinely achieve 60% to 70% mutation rates, significantly reducing the effort required to generate and isolate mutants for functional analyses.fals

Macrocyclic Peptide Probes for Immunomodulatory Protein CD59: Potent Modulators of Bacterial Toxin Activity and Antibody-Dependent Cytotoxicity

\ua9 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH. CD59 is an immunomodulatory cell surface receptor associated with human disease. Despite its importance in complement regulation and bacterial pathogenesis, CD59 remains a challenging therapeutic target. Research to date has focused on antibody or protein-based strategies. Here we present a new approach to target CD59 using macrocyclic peptides with low nanomolar affinity for CD59. Through X-ray crystallographic studies and structure-activity relationship (SAR) studies, we identify key interactions that are essential for binding and activity. We find that the macrocyclic peptide CP-06 adopts a beta-hairpin structure and binds CD59 through an intermolecular beta-sheet, mimicking protein–protein interactions of biologically relevant CD59 interaction partners. We create dimeric and lipidated macrocyclic peptide conjugates as enhanced cell-active CD59 inhibitors and show that these probes can be used to modulate both complement-mediated killing of human cells and lytic activity of bacterial virulence factors. Together, our data provide a starting point for future development of macrocyclic peptides to target CD59 activity in diverse cellular contexts

Interplay between liver and blood stages of Plasmodium infection dictates malaria severity via γδ T cells and IL-17-promoted stress erythropoiesis

© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both stages dictated mortality outcomes. This dichotomy relied on liver stage-dependent activation of Vγ4+ γδ T cells. Subsequent blood stage parasite loads dictated their cytokine profiles, where low parasite loads preferentially expanded IL-17-producing γδ T cells. IL-17 drove extra-medullary erythropoiesis and concomitant reticulocytosis, which protected mice from lethal experimental cerebral malaria (ECM). Adoptive transfer of erythroid precursors could rescue mice from ECM. Modeling of γδ T cell dynamics suggests that this protective mechanism may be key for the establishment of naturally acquired malaria immunity among frequently exposed individuals.We would like to acknowledge Freddy Frischknecht (Integrative Parasitology Center for Infectious Diseases, Heidelberg) for providing the Plasmodium berghei lisp2− parasite line, Immo Prinz (Hannover Medical School, Hannover) for providing genetically modified mouse lines, Ana Parreira (iMM-JLA, Portugal) and Geoff McFadden’s lab (School of BioSciences, University of Melbourne, Australia) for mosquito rearing and infection with Plasmodium parasites, Helena Pinheiro (iMM-JLA, Portugal) for assistance with graphical design, Inês Bento and Miguel Prudêncio for critically reviewing this manuscript, and the Flow Cytometry and Rodent Facilities teams (iMM-JLA, Portugal) for their assistance. Work at iMM-JLA was supported by Fundação para a Ciência e a Tecnologia. Portugal (PTDC/MED-IMU/28664/2017) and the “La caixa” Banking Foundation, Spain (HR17-00264-PoEMM) grants attributed to Â.F.C. and M.M.M., respectively. Work at the Department of Microbiology and Immunology, The University of Melbourne, Australia, was funded by the National Health and Medical Research Council, Australia (1113293, 1154457) and the Australian Research Council, Australia (CE140100011). Â.F.C., S.M., J.L.G., M.I.M., R.M.R., and K.S. were supported by Fundação para a Ciência e a Tecnologia, Portugal (DL57/2016/CP1451/CT0004, DL57/2016/CP1451/CT0010, PD/BD/139053/2018, PD/BD/135454/2017, PTDC/MAT-APL/31602/2017, and CEECIND/00697/2018, respectively), P.L. was supported by Conselho Nacional de Desenvolvimento Científico e Tenológico, Brazil (SN/CGEFO/CNPQ 201801/2015-9), and A.T.T. was supported in part by Alfred P. Sloan Foundation Fellowship (FG-2020-12949).info:eu-repo/semantics/publishedVersio

TECNOB: study design of a randomized controlled trial of a multidisciplinary telecare intervention for obese patients with type-2 diabetes

Obesity is one of the most important medical and public health problems of our time: it increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. METHODS/DESIGN: TECNOB (TEChnology for OBesity) is a comprehensive two-phase stepped down program enhanced by telemedicine for the long-term treatment of obese people with type 2 diabetes seeking intervention for weight loss. Its core features are the hospital-based intensive treatment (1-month), that consists of diet therapy, physical training and psychological counseling, and the continuity of care at home using new information and communication technologies (ICT) such as internet and mobile phones. The effectiveness of the TECNOB program compared with usual care (hospital-based treatment only) will be evaluated in a randomized controlled trial (RCT) with a 12-month follow-up. The primary outcome is weight in kilograms. Secondary outcome measures are energy expenditure measured using an electronic armband, glycated hemoglobin, binge eating, self-efficacy in eating and weight control, body satisfaction, healthy habit formation, disordered eating-related behaviors and cognitions, psychopathological symptoms and weight-related quality of life. Furthermore, the study will explore what behavioral and psychological variables are predictive of treatment success among those we have considered. DISCUSSION: The TECNOB study aims to inform the evidence-based knowledge of how telemedicine may enhance the effectiveness of clinical interventions for weight loss and related type-2 diabetes, and which type of obese patients may benefit the most from such interventions. Broadly, the study aims also to have a effect on the theoretical model behind the traditional health care service, in favor of a change towards a new "health care everywhere" approach

Dynamic Phenotypic Clustering in Noisy Ecosystems

In natural ecosystems, hundreds of species typically share the same environment and are connected by a dense network of interactions such as predation or competition for resources. Much is known about how fixed ecological niches can determine species abundances in such systems, but far less attention has been paid to patterns of abundances in randomly varying environments. Here, we study this question in a simple model of competition between many species in a patchy ecosystem with randomly fluctuating environmental conditions. Paradoxically, we find that introducing noise can actually induce ordered patterns of abundance-fluctuations, leading to a distinct periodic variation in the correlations between species as a function of the phenotypic distance between them; here, difference in growth rate. This is further accompanied by the formation of discrete, dynamic clusters of abundant species along this otherwise continuous phenotypic axis. These ordered patterns depend on the collective behavior of many species; they disappear when only individual or pairs of species are considered in isolation. We show that they arise from a balance between the tendency of shared environmental noise to synchronize species abundances and the tendency for competition among species to make them fluctuate out of step. Our results demonstrate that in highly interconnected ecosystems, noise can act as an ordering force, dynamically generating ecological patterns even in environments lacking explicit niches