Groebner.jl: A package for Gr\"obner bases computations in Julia

We introduce the Julia package Groebner.jl for computing Gr\"obner bases with the F4 algorithm. Groebner.jl is an efficient, lightweight, portable, thoroughly tested, and documented open-source software. The package works over integers modulo a prime and over the rationals and supports various monomial orderings. The implementation incorporates modern symbolic computation techniques and leverages the Julia type system and tooling, which allows Groebner.jl to be on par in performance with the leading computer algebra systems. Our package is freely available at https://github.com/sumiya11/Groebner.jl .Comment: 10 page

A new approach to identifying high-tech manufacturing SMEs with sustainable technological development : Empirical evidence

Industry 4.0 has already become part of the world's largest manufacturers and is beginning to influencing small and medium-sized enterprises (SMEs) through the supply chain. High-tech industries, such as pharmaceuticals, electronic equipment, aircraft manufacturing, etc., will be the first to face technological transformation. To this end, it becomes relevant to assess the sustainability of the technological development of SMEs as a factor of their successful digital transformation. This paper fills a gap in the study of such development as it pertains to Russian high-tech SMEs. Based on a critical literature review, we propose a new approach to assessing the sustainable technological development of these industries. The approach is distinguished by the use of a set of five indicators highlighted during the literature review, which can be quantified based on financial statements. The choice of variables is justified by their compliance with the specifics of industrial SMEs and KMO and Bartlett tests. We empirically tested the selected indicators using a sample of 7980 enterprises in two high-tech industries: Electrical and Electronic Equipment (EEE). We concluded that the larger the business, the higher the sustainability of its technological development. At the same time, SMEs have two key advantages in the implementation of technological development – a decrease in resource costs of production, flexibility in asset management and gross profit. The proposed approach allows us to identify promising high-tech SMEs for the transition to Industry 4.0 technologies. Our research will be useful both for private enterprises when searching for technologically promising contractors and for public authorities when analyzing and selecting enterprises for pilot digital transformation.© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

The Edinburgh human metabolic network reconstruction and its functional analysis

A better understanding of human metabolism and its relationship with diseases is an important task in human systems biology studies. In this paper, we present a high-quality human metabolic network manually reconstructed by integrating genome annotation information from different databases and metabolic reaction information from literature. The network contains nearly 3000 metabolic reactions, which were reorganized into about 70 human-specific metabolic pathways according to their functional relationships. By analysis of the functional connectivity of the metabolites in the network, the bow-tie structure, which was found previously by structure analysis, is reconfirmed. Furthermore, the distribution of the disease related genes in the network suggests that the IN (substrates) subset of the bow-tie structure has more flexibility than other parts

ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer.

The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa

RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC

CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ T follicular helper (Tfh) cells are the main subset regulating autoreactive B cells. Here we report a CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively modulated by Stat5. These CD8+ Tfh cells regulate the germinal center B cell response and control autoantibody production, as deficiency of Stat5 in CD8 T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and concomitant autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh, and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study thus highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance

Analysis of cross-correlations in electroencephalogram signals as an approach to proactive diagnosis of schizophrenia

We apply flicker-noise spectroscopy (FNS), a time series analysis method operating on structure functions and power spectrum estimates, to study the clinical electroencephalogram (EEG) signals recorded in children/adolescents (11 to 14 years of age) with diagnosed schizophrenia-spectrum symptoms at the National Center for Psychiatric Health (NCPH) of the Russian Academy of Medical Sciences. The EEG signals for these subjects were compared with the signals for a control sample of chronically depressed children/adolescents. The purpose of the study is to look for diagnostic signs of subjects' susceptibility to schizophrenia in the FNS parameters for specific electrodes and cross-correlations between the signals simultaneously measured at different points on the scalp. Our analysis of EEG signals from scalp-mounted electrodes at locations F3 and F4, which are symmetrically positioned in the left and right frontal areas of cerebral cortex, respectively, demonstrates an essential role of frequency-phase synchronization, a phenomenon representing specific correlations between the characteristic frequencies and phases of excitations in the brain. We introduce quantitative measures of frequency-phase synchronization and systematize the values of FNS parameters for the EEG data. The comparison of our results with the medical diagnoses for 84 subjects performed at NCPH makes it possible to group the EEG signals into 4 categories corresponding to different risk levels of subjects' susceptibility to schizophrenia. We suggest that the introduced quantitative characteristics and classification of cross-correlations may be used for the diagnosis of schizophrenia at the early stages of its development.Comment: 36 pages, 6 figures, 2 tables; to be published in "Physica A

Follow-Up After Hip and Knee Arthroplasty: a Review of the Literature and a Report on a Pilot Project at the Vreden National Medical Research Center of Traumatology and Orthopedics

Background. Today in our country, the follow-up of patients after arthroplasty is carried out in accordance with clinical guidelines, the wording of which is based on monographs from 2006, 2008, and 2014, in addition, clinical guidelines for follow-up do not take into account the results of treatment assessed by the patient himself. The purpose of this study was to examine existing systems and develop a proprietary follow-up system for patients after hip and knee arthroplasty. Results. A review of the literature revealed that follow-up of patients after arthroplasty is an unsolved problem, within which there is low coverage, reluctance or forgetfulness of the asymptomatic patient, the problem of accessibility of medical examinations, and an excessive financial burden on the health care system. Since 2022, fixed recommendations for follow-up after arthroplasty have been used in the clinical practice of our center in discharge epicrisis. Recommendations for the frequency of follow-up were formulated by experts based on a comprehensive review of the literature and their own experience. In the first three months, 221 hip and 235 knee evaluation questionnaires were collected through the proposed mechanism, with a progressive increase in the number of questionnaires based on weekly monitoring data. Conclusion. Unfortunately, the outpatient clinic system is not always able to provide qualitative monitoring of patients after arthroplasty due to various reasons, therefore, in our opinion, the implementation of the mechanism of remote monitoring of patients will allow detecting various complications at the stage of early diagnosis, which will contribute to prompt solution of these problems. The remote monitoring system is also an important source of scientific data