230 research outputs found
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
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
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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
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
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
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Performance and Operation of the CMS Electromagnetic Calorimeter
The operation and general performance of the CMS electromagnetic calorimeter
using cosmic-ray muons are described. These muons were recorded after the
closure of the CMS detector in late 2008. The calorimeter is made of lead
tungstate crystals and the overall status of the 75848 channels corresponding
to the barrel and endcap detectors is reported. The stability of crucial
operational parameters, such as high voltage, temperature and electronic noise,
is summarised and the performance of the light monitoring system is presented
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