Need Polynomial Systems Be Doubly-Exponential?

Polynomial Systems, or at least their algorithms, have the reputation of being doubly-exponential in the number of variables [Mayr and Mayer, 1982], [Davenport and Heintz, 1988]. Nevertheless, the Bezout bound tells us that that number of zeros of a zero-dimensional system is singly-exponential in the number of variables. How should this contradiction be reconciled? We first note that [Mayr and Ritscher, 2013] shows that the doubly exponential nature of Gr\"{o}bner bases is with respect to the dimension of the ideal, not the number of variables. This inspires us to consider what can be done for Cylindrical Algebraic Decomposition which produces a doubly-exponential number of polynomials of doubly-exponential degree. We review work from ISSAC 2015 which showed the number of polynomials could be restricted to doubly-exponential in the (complex) dimension using McCallum's theory of reduced projection in the presence of equational constraints. We then discuss preliminary results showing the same for the degree of those polynomials. The results are under primitivity assumptions whose importance we illustrate.Comment: Extended Abstract for ICMS 2016 Presentation. arXiv admin note: text overlap with arXiv:1605.0249

Recent advances in real geometric reasoning

In the 1930s Tarski showed that real quantifier elimination was possible, and in 1975 Collins gave a remotely practicable method, albeit with doubly-exponential complexity, which was later shown to be inherent. We discuss some of the recent major advances in Collins method: such as an alternative approach based on passing via the complexes, and advances which come closer to "solving the question asked" rather than "solving all problems to do with these polynomials"

Genetic dissection of heterosis using epistatic association mapping in a partial NCII mating design

Heterosis refers to the phenomenon in which an F1 hybrid exhibits enhanced growth or agronomic performance. However, previous theoretical studies on heterosis have been based on bi-parental segregating populations instead of F1 hybrids. To understand the genetic basis of heterosis, here we used a subset of F1 hybrids, named a partial North Carolina II design, to perform association mapping for dependent variables: original trait value, general combining ability (GCA), specific combining ability (SCA) and mid-parental heterosis (MPH). Our models jointly fitted all the additive, dominance and epistatic effects. The analyses resulted in several important findings: 1) Main components are additive and additive-by-additive effects for GCA and dominance-related effects for SCA and MPH, and additive-by-dominant effect for MPH was partly identified as additive effect; 2) the ranking of factors affecting heterosis was dominance > dominance-by-dominance > over-dominance > complete dominance; and 3) increasing the proportion of F1 hybrids in the population could significantly increase the power to detect dominance-related effects, and slightly reduce the power to detect additive and additive-by-additive effects. Analyses of cotton and rapeseed datasets showed that more additive-by-additive QTL were detected from GCA than from trait phenotype, and fewer QTL were from MPH than from other dependent variables

Untangling knowledge creation and knowledge integration in enterprise wikis

A central challenge organizations face is how to build, store, and maintain knowledge over time. Enterprise wikis are community-based knowledge systems situated in an organizational context. These systems have the potential to play an important role in managing knowledge within organizations, but the motivating factors that drive individuals to contribute their knowledge to these systems is not very well understood. We theorize that enterprise wiki initiatives require two separate and distinct types of knowledge-sharing behaviors to succeed: knowledge creation (KC) and knowledge integration (KI). We examine a Wiki initiative at a major German bank to untangle the motivating factors behind KC and KI. Our results suggest KC and KI are indeed two distinct behaviors, reconcile inconsistent findings from past studies on the role of motivational factors for knowledge sharing to establish shared electronic knowledge resources in organizations, and identify factors that can be leveraged to tilt behaviors in favor of KC or KI

Mucosal antibody responses following Vaxzevria vaccination

Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs). Here, we profiled paired mucosal (saliva, tears) and plasma antibodies from COVID-19 vaccinated only vaccinees (uninfected, vaccinated) and COVID-19 recovered vaccinees (COVID-19 recovered, vaccinated) who both received Vaxzevria vaccines. SARS-CoV-2 ancestral-specific IgG antibodies capable of engaging FcγR3a were significantly higher in the mucosal samples of COVID-19 recovered Vaxzevria vaccinees in comparison with vaccinated only vaccinees. However, when IgG and FcγR3a engaging antibodies were tested against a panel of SARS-CoV-2 VoCs, the responses were ancestral-centric with weaker recognition of Omicron strains observed. In contrast, salivary IgA, but not plasma IgA, from Vaxzevria vaccinees displayed broad cross-reactivity across all SARS-CoV-2 VoCs tested. Our data highlight that while intramuscular Vaxzevria vaccination can enhance mucosal antibodies responses in COVID-19 recovered vaccinees, restrictions by ancestral-centric bias may have implications for COVID-19 protection. However, highly cross-reactive mucosal IgA could be key in addressing these gaps in mucosal immunity and may be an important focus of future SARS-CoV-2 vaccine development

Chemerin Elicits Potent Constrictor Actions via Chemokine-Like Receptor 1 (CMKLR1), not G-Protein-Coupled Receptor 1 (GPR1), in Human and Rat Vasculature

BACKGROUND: Circulating levels of chemerin are significantly higher in hypertensive patients and positively correlate with blood pressure. Chemerin activates chemokine-like receptor 1 (CMKLR1 or ChemR23) and is proposed to activate the "orphan" G-protein-coupled receptor 1 (GPR1), which has been linked with hypertension. Our aim was to localize chemerin, CMKLR1, and GPR1 in the human vasculature and determine whether 1 or both of these receptors mediate vasoconstriction. METHODS AND RESULTS: Using immunohistochemistry and molecular biology in conduit arteries and veins and resistance vessels, we localized chemerin to endothelium, smooth muscle, and adventitia and found that CMKLR1 and GPR1 were widely expressed in smooth muscle. C9 (chemerin149-157) contracted human saphenous vein (pD2=7.30±0.31) and resistance arteries (pD2=7.05±0.54) and increased blood pressure in rats by 9.1±1.0 mm Hg at 200 nmol. Crucially, these in vitro and in vivo vascular actions were blocked by CCX832, which we confirmed to be highly selective for CMKLR1 over GPR1. C9 inhibited cAMP accumulation in human aortic smooth muscle cells and preconstricted rat aorta, consistent with the observed vasoconstrictor action. Downstream signaling was explored further and, compared to chemerin, C9 showed a bias factor=≈5000 for the Gi protein pathway, suggesting that CMKLR1 exhibits biased agonism. CONCLUSIONS: Our data suggest that chemerin acts at CMKLR1, but not GPR1, to increase blood pressure. Chemerin has an established detrimental role in metabolic syndrome, and these direct vascular actions may contribute to hypertension, an additional risk factor for cardiovascular disease. This study provides proof of principle for the therapeutic potential of selective CMKLR1 antagonists.This work was supported by the British Heart Foundation (FS/12/64/30001 [to AJK], FS/14/59/31282 [to CR], and PG/09/050/27734); Wellcome Trust (100780/Z/12/Z [to LY], 101844 [to CWT], 107715/Z/15/Z [to APD and JJM], and 096822/Z/11/Z [to APD and PY]); the Raymond and Beverley Sackler Fellowship (to LY), and the Medical Research Council (MRC MC_PC_14116; to APD) and by the Pulmonary Hypertension Association and the Cambridge Biomedical Research Centre. Biomedical Resources (grant 099156/Z/12/Z)

Preexisting immunity restricts mucosal antibody recognition of SARS-CoV-2 and Fc profiles during breakthrough infections

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19–recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19–recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19–uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2–specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2–specific antibody responses and has implications for long-term protection from COVID-19

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Anticipatory nausea in cyclical vomiting

BACKGROUND: Cyclical Vomiting Syndrome (CVS) is characterised by discrete, unexplained episodes of intense nausea and vomiting, and mainly affects children and adolescents. Comprehending Cyclical Vomiting Syndrome requires awareness of the severity of nausea experienced by patients. As a subjective symptom, nausea is easily overlooked, yet is the most distressing symptom for patients and causes many behavioural changes during attacks. CASE PRESENTATION: This first-hand account of one patient's experience of Cyclical Vomiting Syndrome shows how severe nausea contributed to the development of anticipatory nausea and vomiting (ANV), a conditioned response frequently observed in chemotherapy patients. This conditioning apparently worsened the course of the patient's disease. Anticipatory nausea and vomiting has not previously been recognised in Cyclical Vomiting Syndrome, however predictors of its occurrence in oncology patients indicate that it could complicate many cases. CONCLUSION: We suggest a model whereby untreated severe and prolonged nausea provokes anxiety about further cyclical vomiting attacks. This anxiety facilitates conditioning, thus increasing the range of triggers in a self-perpetuating manner. Effective management of the nausea-anxiety feedback loop can reduce the likelihood of anticipatory nausea and vomiting developing in other patients