The modified Yule-Walker method for multidimensional infinite-variance periodic autoregressive model of order 1

The time series with periodic behavior, such as the periodic autoregressive (PAR) models belonging to the class of the periodically correlated processes, are present in various real applications. In the literature, such processes were considered in different directions, especially with the Gaussian-distributed noise. However, in most of the applications, the assumption of the finite-variance distribution seems to be too simplified. Thus, one can consider the extensions of the classical PAR model where the non-Gaussian distribution is applied. In particular, the Gaussian distribution can be replaced by the infinite-variance distribution, e.g. by the $\alpha-$stable distribution. In this paper, we focus on the multidimensional $\alpha-$stable PAR time series models. For such models, we propose a new estimation method based on the Yule-Walker equations. However, since for the infinite-variance case the covariance does not exist, thus it is replaced by another measure, namely the covariation. In this paper we propose to apply two estimators of the covariation measure. The first one is based on moment representation (moment-based) while the second one - on the spectral measure representation (spectral-based). The validity of the new approaches are verified using the Monte Carlo simulations in different contexts, including the sample size and the index of stability of the noise. Moreover, we compare the moment-based covariation-based method with spectral-based covariation-based technique. Finally, the real data analysis is presented.Comment: 31 pages, 17 figure

GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway

Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis. GAME9 knockdown and overexpression in tomato and potato alters expression of SGAs and upstream mevalonate pathway genes including the cholesterol biosynthesis gene STEROL SIDE CHAIN REDUCTASE 2 (SSR2). Levels of SGAs, C24-alkylsterols and the upstream mevalonate and cholesterol pathways intermediates are modified in these plants. Delta(7)-STEROL-C5(6)-DESATURASE (C5-SD) in the hitherto unresolved cholesterol pathway is a direct target of GAME9. Transactivation and promoter-binding assays show that GAME9 exerts its activity either directly or cooperatively with the SlMYC2 transcription factor as in the case of the C5-SD gene promoter. Our findings provide insight into the regulation of SGA biosynthesis and means for manipulating these metabolites in crops

Newer Horizon of Mesenchymal Stem Cell-Based Therapy in the Management of SARS-CoV-2-Associated Mucormycosis: A Safe Hope for Future Medicine

SARS-CoV-2-infected patients are reported to show immunocompromised behavior that gives rise to a wide variety of complications due to impaired innate immune response, cytokine storm, and thrombo-inflammation. Prolonged use of steroids, diabetes mellitus, and diabetic ketoacidosis (DKA) are some of the factors responsible for the growth of Mucorales in such immunocompromised patients and, thus, can lead to a life-threatening condition referred to as mucormycosis. Therefore, an early diagnosis and cell-based management cosis is the need of the hour to help affected patients overcome this severe condition. In addition, extended exposure to antifungal drugs/therapeutics is found to initiate hormonal and neurological complications. More recently, mesenchymal stem cells (MSCs) have been used to exhibit immunomodulatory function and proven to be beneficial in a clinical cell-based regenerative approach. The immunomodulation ability of MSCs in mucormycosis patient boosts the immunity by the release of chemotactic proteins. MSC-based therapy in mucormycosis along with the combination of short-term antifungal drugs can be utilized as a prospective approach for mucormycosis treatment with promising outcomes. However, preclinical and in mucormyIn mucormycosis, the hyphae of clinical trials are needed to establish the precise mechanism of MSCs in mucormycosis treatment

Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Does HDIs level sustainable during 1999/2018 across cross-nations? An application of bootstrap quantile regression approach

Potential growth and overall economic development across nations since 1990s till 2018 is functioning as a 'wake-up' call for researchers and policy makers to process for investigation the phenomenon of HDI convergence globally via two framework: σ- and unconditional β- convergence. A proper investigation of such knowledge is of utmost important for regulators of economies, suggesting whether the difference in HDI level across natons has narrowed, including the period of global recession (2007/09). The empirical evidence is analyzed from different methods that act in a complementary way: i) bootstrap quantile regression approach in static panel framework, which allows the assumption of nonlinearities, especially for those groups that have shared a common path in terms of economic development while estimating the convergence results. ii) pooled OLS model, which seek to examine the soundness of the evaluated convergence results and confirmed the validity of our core applied model. All methods revealed strong evidences of unconditional β- convergence for all HDI groups, reflecting all classified HDI groups had potential to increase their tendency toward convergence. This is mainly driven by both the slower forward mobility with the less developed nations and faster backward mobility with the more developed nations. The σ- convergence estimates provides further insights and suggests that the formation and comprising of multiple convergence HDI clusters is a salient feature of reduction in inequality and dispersion across medium and lower nations

Congenital hyperinsulinism and Poland syndrome in association with 10p13–14 duplication

Poland syndrome (PS) is a rare congenital condition, affecting 1 in 30 000 live births worldwide, characterised by a unilateral absence of the sternal head of the pectoralis major and ipsilateral symbrachydactyly occasionally associated with abnormalities of musculoskeletal structures. A baby girl, born at 40 weeks’ gestation with birth weight of 3.33 kg (−0.55 SDS) had typical phenotypical features of PS. She had recurrent hypoglycaemic episodes early in life requiring high concentration of glucose and glucagon infusion. The diagnosis of congenital hyperinsulinism (CHI) was biochemically confirmed by inappropriately high plasma concentrations of insulin and C-peptide and low plasma free fatty acids and β-hydroxyl butyrate concentrations during hypoglycaemia. Sequencing of ABCC8, KCNJ11 and HNF4A did not show any pathogenic mutation. Microarray analysis revealed a novel duplication in the short arm of chromosome 10 at 10p13–14 region. This is the first reported case of CHI in association with PS and 10p duplication. We hypothesise that the HK1 located on the chromosome 10 encoding hexokinase-1 is possibly linked to the pathophysiology of CHI

Experimental and analytical evaluation of stress-strain behavior of basalt fibred concrete

The aim of this study is to determine the stress-strain behavior of basalt fibred concrete experimentally. Cylinders of standard size 150 x 300 mm are cast with with and without basalt fibres and tested in uni-axial compression under strain control as per IS: 516-1999 to understand the stress-strain behavior of basalt fibred concrete. After developing empirical equations for stress-strain curves of basalt fibred concrete, theoretical values of stresses are calculated at different values of strains in concrete based on the developed empirical equations as given above and theoretical stress-strain curves are plotted. These theoretical stress-strain curves are compared with experimental stress-strain curves and found that, theoretical stress-strain curves have shown good correlation with experimental stress-strain curves for all concrete mixes