Renormalization Group and Universality

It is argued that universality is severely limited for models with multiple fixed points. As a demonstration the renormalization group equations are presented for the potential and the wave function renormalization constants in the $O(N)$ scalar field theory. Our equations are superior compared with the usual approach which retains only the contributions that are non-vanishing in the ultraviolet regime. We find an indication for the existence of relevant operators at the infrared fixed point, contrary to common expectations. This result makes the sufficiency of using only renormalizable coupling constants in parametrizing the long distance phenomena questionable.Comment: 32pp in plain tex; revised version to appear in PR

Statement by Eric Mehnert and Rhonda Decontie collected by Rachel George on December 5, 2014

This is the author accepted manuscript. The final version is available from the Society for Neuroscience via the DOI in this recordFertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons co-expressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modelling and in-vivo optogenetics we reveal for the first time how this neural construct initiates and sustains the appropriate ultradian frequency essential for reproduction. Prompted by mathematical modelling, we show experimentally using female estrous mice that robust pulsatile release of luteinizing hormone, a proxy for GnRH, emerges abruptly as we increase the basal activity of the neuronal network using continuous low frequency optogenetic stimulation. Further increase in basal activity markedly increases pulse frequency and eventually leads to pulse termination. Additional model predictions that pulsatile dynamics emerge from non-linear positive and negative feedback interactions mediated through neurokinin-B and dynorphin signaling respectively are confirmed neuropharmacologically. Our results shed light on the long-elusive GnRH pulse generator offering new horizons for reproductive health and wellbeing.SIGNIFICANCE STATEMENTThe gonadotropin-releasing hormone (GnRH) pulse generator controls the pulsatile secretion of the gonadotropic hormones LH and FSH and is critical for fertility. The hypothalamic arcuate kisspeptin neurons are thought to represent the GnRH pulse generator, since their oscillatory activity is coincident with LH pulses in the blood; a proxy for GnRH pulses. However, the mechanisms underlying GnRH pulse generation remain elusive. We developed a mathematical model of the kisspeptin neuronal network and confirmed its predictions experimentally, showing how LH secretion is frequency-modulated as we increase the basal activity of the arcuate kisspeptin neurons in-vivo using continuous optogenetic stimulation. Our model provides a quantitative framework for understanding the reproductive neuroendocrine system and opens new horizons for fertility regulation.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC)Biotechnology and Biological Sciences Research Council (BBSRC

The fidelity of dynamic signaling by noisy biomolecular networks

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Cells live in changing, dynamic environments. To understand cellular decision-making, we must therefore understand how fluctuating inputs are processed by noisy biomolecular networks. Here we present a general methodology for analyzing the fidelity with which different statistics of a fluctuating input are represented, or encoded, in the output of a signaling system over time. We identify two orthogonal sources of error that corrupt perfect representation of the signal: dynamical error, which occurs when the network responds on average to other features of the input trajectory as well as to the signal of interest, and mechanistic error, which occurs because biochemical reactions comprising the signaling mechanism are stochastic. Trade-offs between these two errors can determine the system's fidelity. By developing mathematical approaches to derive dynamics conditional on input trajectories we can show, for example, that increased biochemical noise (mechanistic error) can improve fidelity and that both negative and positive feedback degrade fidelity, for standard models of genetic autoregulation. For a group of cells, the fidelity of the collective output exceeds that of an individual cell and negative feedback then typically becomes beneficial. We can also predict the dynamic signal for which a given system has highest fidelity and, conversely, how to modify the network design to maximize fidelity for a given dynamic signal. Our approach is general, has applications to both systems and synthetic biology, and will help underpin studies of cellular behavior in natural, dynamic environments.We acknowledge support from a Medical Research Council and Engineering and Physical Sciences Council funded Fellowship in Biomedical Informatics (CGB) and a Scottish Universities Life Sciences Alliance chair in Systems Biology (PSS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Lectures on the functional renormalization group method

These introductory notes are about functional renormalization group equations and some of their applications. It is emphasised that the applicability of this method extends well beyond critical systems, it actually provides us a general purpose algorithm to solve strongly coupled quantum field theories. The renormalization group equation of F. Wegner and A. Houghton is shown to resum the loop-expansion. Another version, due to J. Polchinski, is obtained by the method of collective coordinates and can be used for the resummation of the perturbation series. The genuinely non-perturbative evolution equation is obtained in a manner reminiscent of the Schwinger-Dyson equations. Two variants of this scheme are presented where the scale which determines the order of the successive elimination of the modes is extracted from external and internal spaces. The renormalization of composite operators is discussed briefly as an alternative way to arrive at the renormalization group equation. The scaling laws and fixed points are considered from local and global points of view. Instability induced renormalization and new scaling laws are shown to occur in the symmetry broken phase of the scalar theory. The flattening of the effective potential of a compact variable is demonstrated in case of the sine-Gordon model. Finally, a manifestly gauge invariant evolution equation is given for QED.Comment: 47 pages, 11 figures, final versio

Exact Renormalization Group Equations. An Introductory Review

We critically review the use of the exact renormalization group equations (ERGE) in the framework of the scalar theory. We lay emphasis on the existence of different versions of the ERGE and on an approximation method to solve it: the derivative expansion. The leading order of this expansion appears as an excellent textbook example to underline the nonperturbative features of the Wilson renormalization group theory. We limit ourselves to the consideration of the scalar field (this is why it is an introductory review) but the reader will find (at the end of the review) a set of references to existing studies on more complex systems.Comment: Final version to appear in Phys. Rep.; Many references added, section 4.2 added, minor corrections. 65 pages, 6 fig

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study

BACKGROUND: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. METHODS: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. FINDINGS: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). INTERPRETATION: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council

Oral health of adults with intellectual disabilities: A systematic review

Background: There have been several past reports that adults with intellectual disabilities experience poor oral health (tooth loss, periodontal health and untreated dental caries). Loss of a functional dentition has serious consequences, including problems with chewing, swallowing, nutrition, speech, temporomandibular joint osteoarthritis and pain and systemic health conditions. Poor oral health is largely preventable through proactive oral care support. In recent years, social care provision for adults has changed, with deinstitutionalisation and home‐based personalised care now being the typical provision in high income countries. Hence, oral health inequalities might be reducing. However, there is limited recent evidence‐synthesis on the topic. We aimed to address this. Method: PROSPERO registration number: CRD42018089880. We conducted a preferred reporting items for systematic reviews and meta‐analyses systematic review of publications since 2008. Four databases were searched with a clear search strategy, strict inclusion criteria for selection of papers, double scoring (two raters), systematic data extraction and quality appraisal of included papers. Results: A total of 33/3958 retrieved articles were included, of which 14 were drawn from dental service users and 10 from Special Olympic athletes, therefore not necessarily being representative of the wider population with intellectual disabilities. Despite this limitation, adults with intellectual disabilities were still shown to experience poor oral health. High levels of poor oral hygiene and gingivitis were found, with many also affected by periodontitis and untreated dental decay. There is clear unmet need relating to both periodontal (gum) and tooth health, leading to tooth loss. Conclusions: Despite reports in the past of poor oral health amongst adults with intellectual disabilities, and despite it being preventable, there remains a high burden of poor oral health. This highlights the need to raise awareness, and for polices on effective daily oral care, and appropriate service provision. The importance of oral health and its possible negative sequelae needs to be elevated amongst carers and professionals

Dental erosive wear and salivary flow rate in physically active young adults

Background Little attention has been directed towards identifying the relationship between physical exercise, dental erosive wear and salivary secretion. The study aimed i) to describe the prevalence and severity of dental erosive wear among a group of physically active young adults, ii) to describe the patterns of dietary consumption and lifestyle among these individuals and iii) to study possible effect of exercise on salivary flow rate. Methods Young members (age range 18-32 years) of a fitness-centre were invited to participate in the study. Inclusion criteria were healthy young adults training hard at least twice a week. A non-exercising comparison group was selected from an ongoing study among 18-year-olds. Two hundred and twenty participants accepted an intraoral examination and completed a questionnaire. Seventy of the exercising participants provided saliva samples. The examination was performed at the fitness-centre or at a dental clinic (comparison group), using tested erosive wear system (VEDE). Saliva sampling (unstimulated and stimulated) was performed before and after exercise. Occlusal surfaces of the first molars in both jaws and the labial and palatal surfaces of the upper incisors and canines were selected as index teeth. Results Dental erosive wear was registered in 64% of the exercising participants, more often in the older age group, and in 20% of the comparison group. Enamel lesions were most observed in the upper central incisors (33%); dentine lesions in lower first molar (27%). One fourth of the participants had erosive wear into dentine, significantly more in males than in females (p = 0.047). More participants with erosive wear had decreased salivary flow during exercise compared with the non-erosion group (p < 0.01). The stimulated salivary flow rate was in the lower rage (≤ 1 ml/min) among more than one third of the participants, and more erosive lesions were registered than in subjects with higher flow rates (p < 0.01). Conclusion The study showed that a high proportion of physically active young adults have erosive lesions and indicate that hard exercise and decreased stimulated salivary flow rate may be associated with such wear

A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia

\ua9 The Author(s) 2024.Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease