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Abstract Background Diabetes is associated with a prothrombotic state that contributes to cardiovascular (CV) events in type 2 diabetes (T2DM). Activated factor VII (FVIIa)– antithrombin (AT) complexes are indicative of tissue factor (TF) exposure and have been associated with thromboembolic risk in coronary artery disease. To our knowledge there have been no reports on FVIIa-AT complexes in T2DM, therefore we assessed factors that determine FVIIa-AT complexes in this disease and the impact of higher complexes on a prothrombotic state. Methods In 108 T2DM patients (mean age 63.8 years, 52.8% men, median HbA1c of 6.9 [interquartile range 6.1–8.2] %) and 83 age- and sex-matched non-diabetic subjects, we measured FVIIa-AT complexes. Metabolic control of T2DM involved fasting glucose, glycated hemoglobin (HbA1c), albumin/creatinine ratio (ACR), and lipid levels. To characterize a prothrombotic state, we determined thrombin generation parameters, fibrinolysis markers, and plasma fibrin clot properties. Results FVII-AT complexes in T2DM patients were similar to controls (73.6 [59.4–91.7] vs. 79.6 [59.2–97.1]pM, respectively, p = 0.30). The T2DM patients with FVIIa-AT in the top vs. the bottom quartile had a larger prevalence of active smoking and insulin use, along with higher fasting glucose (+ 36.4%), HbA1c (+ 27.4%), ACR (+ 72.8%), total cholesterol (+ 34.5%), and LDL-cholesterol (+ 80%). FVIIa-AT complexes showed no associations with in vitro thrombin generation potential, plasma fibrin clot properties, or fibrinolysis variables. On multivariable analysis HbA1c, ACR, and total cholesterol remained independently associated with FVIIa-AT complexes in T2DM. Conclusions This is the first study to show that in T2DM higher FVIIa-AT complexes are associated with markers of dyslipidemia and glycemia control, indicating that TF-induced coagulation activation could be suppressed by achieving treatment targets. Graphical abstract

Artykuł przedstawia postrzeganie ustroju Republiki Weneckiej przez polskich podróżników na przełomie XVIII i XIX w. W relacjach z podróży peregrynanci opisywali poszczególne organy władzy, często porównując je z ich odpowiednikami na ziemiach polskich, bądź wyrażali chęć wprowadzenia podobnych rozwiązań w Rzeczypospolitej Obojga Narodów. Opisywano także zachowania szlachty oraz doszukiwano się przyczyn słabnącej potęgi miasta i upadku Republiki Weneckiej, co także wielokrotnie nawiązywało do sytuacji w ojczyźnie pamiętnikarzy.

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.

Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values. Oral iAs administration accelerates neonatal intestinal maturation, an event that is directly associated with UGT1A1 induction. As a reactive oxygen species producer, oral iAs treatment activated the Keap-Nrf2 pathway in the intestinal tract and liver. When Nrf2-deficient hUGT1 mice (hUGT1/Nrf2-/-) were treated with iAs, it was shown that activated Nrf2 contributed significantly toward intestinal maturation and UGT1A1 induction. However, hepatic UGT1A1 was not induced upon iAs exposure. We previously demonstrated that the nuclear receptor PXR represses liver UGT1A1 in neonatal hUGT1 mice. When PXR was deleted in hUGT1 mice (hUGT1/Pxr-/-), derepression of UGT1A1 was evident in both liver and intestinal tissue in neonates. Furthermore, when neonatal hUGT1/Pxr-/- mice were treated with iAs, UGT1A1 was superinduced in both tissues, confirming PXR release derepressed key regulatory elements on the gene that could be activated by iAs exposure. With iAs capable of generating reactive oxygen species in both liver and intestinal tissue, we conclude that PXR deficiency in neonatal hUGT1/Pxr-/- mice allows greater access of activated transcriptional modifiers such as Nrf2 leading to superinduction of UGT1A1.

Abstract Objectives Emergency department (ED) visits resulting from suicidal thoughts and behaviors have increased at alarming rates among youth in the United States in recent years. Understanding trends among specific racial, ethnic, gender, and/or age subgroups can provide the foundation for tailored solutions for those with the greatest need for support. Methods Using data from the Florida State Emergency Department Database from 2016 to 2021, we calculated annual rates of ED suicide‐related diagnoses per 1000 young people aged 8‒21 years. We explored annual trends by age and intersectional race/ethnicity and sex subgroups. Additionally, we examined subgroup‐specific stratified percent changes from 2016 to 2019 and 2016 to 2021. Results Among 8‒12‐year olds, the highest rates of suicide‐related ED encounters occurred among Black males and females and this trend was steady over time. Among 13‒21‐year‐old patients, Black and White females displayed the highest rates of suicide‐related ED encounters across 2016‒2021, and all subgroups experienced a slight decline in 2020 and 2021. Rates generally increased between 2016 and 2019, with the largest percent increase (10.6%) occurring among Black females aged 18‒21 years, whereas there was a trend of decreased rates among most subgroups between 2019 and 2021. Conclusions Across all years and age groups, Black females showed consistently higher rates of suicide‐related ED encounters than almost any other subgroup, supporting previous research that Black adolescent females may be disproportionately suffering from the mental health crisis faced by young people. Furthermore, preteen Black males need additional mental health support, as do adolescent and young adult White females.

Dissemination of food-borne L. monocytogenes in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-ΔC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-ΔC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes.

Abstract We present a novel problem, called MetaEC, which aims to infer gene-species assignments in a collection of partially leaf-labeled gene trees labels by minimizing the size of duplication episode clustering (EC). This problem is particularly relevant in metagenomics, where incomplete data often poses a challenge in the accurate reconstruction of gene histories. To solve MetaEC, we propose a polynomial time dynamic programming (DP) formulation that verifies the existence of a set of duplication episodes from a predefined set of episode candidates. In addition, we design a method to infer distributions of gene-species mappings. We then demonstrate how to use DP to design an algorithm that solves MetaEC. Although the algorithm is exponential in the worst case, we introduce a heuristic modification of the algorithm that provides a solution with the knowledge that it is exact. To evaluate our method, we perform two computational experiments on simulated and empirical data containing whole genome duplication events, showing that our algorithm is able to accurately infer the corresponding events.

Abstract Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily oscillations in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.

This article analyses and evaluates the model used by the Jastrzebie Coal Company in Poland to forecast the values of continuous deformations of land surfaces caused by underground mining. Particular attention is paid to the values of terrain inclinations, which cause significant deflections of buildings located in mining areas affected by exploitation. The inclination forecasts were made using Bialek’s model, with the values of its parameters determined in situ and after completion of the exploitation of a longwall. The obtained results were compared with the values of the terrain inclinations calculated from the results of geodetic measurements carried out at observation points located near the buildings and discontinuous linear deformations (i.e., the ground steps). The conducted research shows that the correlations between the absolute values of the practical inclinations and the values of the theoretical inclinations were rather weak, as the values of their correlation coefficients did not exceed 0.24. The tested model underestimated 45.5% of the values of the inclinations observed in situ by an average of −53.5%. The model values of the inclinations for the remaining observed inclinations (54.5%) were overestimated by an average of 461.9%. The largest anomalies were obtained in the case of inclination values from points located near the ground steps. The effectiveness of predicting inclination values with a commonly used model is strongly reduced when discontinuous linear deformations appear. Nonetheless, it reflects well the mining area categories.

Abstract Background Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation. Methods In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2–10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months. Results Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46–26.87, p

ABSTRACTLamins A/C are nuclear intermediate filament proteins that are involved in diverse cellular mechanical and biochemical functions. Here, we report that recognition of Lamins A/C by a commonly used antibody (JOL-2) that binds the Lamin A/C Ig-fold and other antibodies targeting similar epitopes is highly dependent on cell density, even though Lamin A/Clevels do not change. We propose that the effect is caused by partial unfolding or masking of the C’E and/or EF loops of the Ig-fold in response to cell spreading. Surprisingly, JOL-2 antibody labeling was insensitive to disruption of cytoskeletal filaments or the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Furthermore, neither nuclear stiffness nor nucleo-cytoskeletal force transmission changed with cell density. These findings are important for the interpretation of immunofluorescence data for Lamin A/C and also raise the intriguing prospect that the conformational changes may play a role in Lamin A/C mediated cellular function.

MicroRNAs (miRNA) are involved in the process of carcinogenesis, including the development of endometrial cancer (EC). This study aimed to investigate the association between the expression of three miRNAs (miR-21-5p, miR-205-5p, and miR-222-3p) in endometrial cancer tissues. In addition, the stability of expression of SNORD48 and U6, which were initially planned to be used as reference miRNAs for normalization, was investigated. Endometrial tissue was obtained from 111 patients with EC during hysterectomy and from 19 patients undergoing surgery for uterine fibroids or pelvic organ prolapse as a control group without neoplastic changes. Our study was based on calculations made with a digital PCR method (Qiagen, Hilden, Germany) to measure the absolute expression. In the endometrial cancer tissue, miR-205-5p was upregulated, while miR-222-3p and SNORD48 were downregulated compared to the control group. We detected statistically significant correlation of miR-205-5p, U6, and SNORD48 expression with different histological grades; the expression of miR-205-5p increases with the histopathological grade advancement (intraepithelial neoplasia- EIN = 1590, G1 = 3367.2, G2 = 8067 and G3 = 20,360), while U6 and SNORD expression decreases from EIN to G2 and increases again in the G3 grade (U6: EIN = 19,032, G1 = 16,482.4, G2 = 13,642.4, G3 = 133,008; SNORD48: EIN = 97,088, G1 = 59,520, G2 = 43,544, G3 = 227,200). Our study suggests that upregulation of miR-205-5p and downregulation of miR-222-3p and SNORD48 may influence development of endometrial cancer. Moreover, miR-205-5p, U6, and SNORD48 expression changes may be associated with progression of endometrial cancer. The results also indicate that SNORD48 and U6, commonly used as internal references, may influence endometrial cancer development and progression; therefore, they should not be used as references. However, it is important to note that further research is required to understand their role in endometrial cancer.

Background & aimsColonic stem cells are essential for producing the mucosal lining, which in turn protects stem cells from insult by luminal factors. Discovery of genetic and biochemical events that control stem cell proliferation and differentiation can be leveraged to decipher the causal factors of ulcerative colitis and aid the development of more effective therapy.MethodsWe performed in vivo and in vitro studies from control (nuclear receptor corepressor 1 [NCoR1F/F]) and intestinal epithelial cell-specific NCoR1-deficient mice (NCoR1ΔIEC). Mice were challenged with dextran sodium sulfate to induce experimental ulcerative colitis, followed by colitis examination, barrier permeability analysis, cell proliferation immunostaining assays, and RNA sequencing analysis. By using crypt cultures, the organoid-forming efficiency, cell proliferation, apoptosis, and histone acetylation were analyzed after butyrate and/or tumor necrosis factor α treatments.ResultsNCoR1ΔIEC mice showed a dramatic increase in disease severity in this colitis model, with suppression of proliferative cells at the crypt base as an early event and a concomitant increase in barrier permeability. Genome expression patterns showed an important role for NCoR1 in colonic stem cell proliferation and secretory cell differentiation. Colonic organoids cultured from NCoR1ΔIEC mice were more sensitive to butyrate-induced cell growth inhibition and apoptosis, which were exaggerated further by tumor necrosis factor α co-treatment, which was accompanied by increased histone acetylation.ConclusionsNCoR1 regulates colonic stem cell proliferation and secretory cell differentiation. When NCoR1 is disrupted, barrier protection is weakened, allowing luminal products such as butyrate to penetrate and synergistically damage the colonic crypt cells. Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153.

Environmental toxicants such as heavy metals from contaminated water or soil and isothiocyanates (ITC) from dietary sources act as pro-oxidants by directly generating reactive oxygen species (ROS) or through depleting cellular antioxidants such as glutathione. Toxicants can alter drug metabolism, and it was reported that CYP2B10 and UGT1A1 are induced by phenethyl isothiocyanate (PEITC) through the constitutive androstane receptor (CAR). The possibility that nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of the antioxidant response, could coactivate CAR was investigated in neonatal hUGT1/Nrf2 -/- mice. Neonatal mice were treated with PEITC or cadmium (Cd2+) by oral gavage for 2 days. Both PEITC and Cd2+ induced UGT1A1 RNA and protein in intestinal tissues in both hUGT1/Nrf2 +/- and hUGT1/Nrf2 -/- neonates, indicating NRF2-independent regulation of UGT1A1. Increases in CYP2B10 RNA in intestinal tissues were observed following PEITC or Cd2+ exposure. Activation of intestinal CAR by Cd2+ exposure was directly assessed by nuclear fractionation and Western blot analyses at 0.5, 1, 2, and 4 hours after treatment in hUGT1 neonates and after 48 hours in hUGT1/Nrf2 +/- and hUGT1/Nrf2 -/- neonates. CAR localized to the nucleus independently of NRF2 48 hours after exposure. Substantial CAR localization to the nucleus occurred at the 2- and 4-hour time points, coinciding with a decrease in phosphorylation of cytoplasmic extracellular signal-regulated kinases 1 and 2 and a nuclear increase in P38/p-P38 content. This suggests that a novel oxidative stress-MAPK-CAR axis exists with phenotypic consequences. SIGNIFICANCE STATEMENT: Pro-oxidant toxicants can alter drug metabolism through activation of CAR, independent of the NRF2-KEAP1 signaling pathway. Changes in proteins associated with drug metabolism and linked to increases in intestinal maturation are mediated through an oxidative stress-MAPK-CAR axis.

Pathogens have developed intricate strategies to overcome the host’s innate immune responses. In this paper we use live-cell microscopy with a single bacterium resolution to follow in real time interactions between the food-borne pathogen L. monocytogenes and host macrophages, a key event controlling the infection in vivo. We demonstrate that infection results in heterogeneous outcomes, with only a subset of bacteria able to establish a replicative invasion of macrophages. The fate of individual bacteria in the same host cell was independent from the host cell and non-cooperative, being independent from co-infecting bacteria. A higher multiplicity of infection resulted in a reduced probability of replication of the overall bacterial population. By use of internalisation assays and conditional probabilities to mathematically describe the two-stage invasion process, we demonstrate that the higher MOI compromises the ability of macrophages to phagocytose bacteria. We found that the rate of phagocytosis is mediated via the secreted Listeriolysin toxin (LLO), while the probability of replication of intracellular bacteria remained constant. Using strains expressing fluorescent reporters to follow transcription of either the LLO-encoding hly or actA genes, we show that replicative bacteria exhibited higher PrfA regulon expression in comparison to those bacteria that did not replicate, however elevated PrfA expression per se was not sufficient to increase the probability of replication. Overall, this demonstrates a new role for the population-level, but not single cell, PrfA-mediated activity to regulate outcomes of host pathogen interactions.

Transcription of almost all mammalian genes occurs in stochastic bursts, however the fundamental control mechanisms that allow appropriate single-cell responses remain unresolved. Here we utilise single cell genomics data and stochastic models of transcription to perform global analysis of the toll-like receptor (TLR)-induced gene expression variability. Based on analysis of more than 2000 TLR-response genes across multiple experimental conditions we demonstrate that the single-cell, gene-by-gene expression variability can be empirically described by a linear function of the population mean. We show that response heterogeneity of individual genes can be characterised by the slope of the mean-variance line, which captures how cells respond to stimulus and provides insight into evolutionary differences between species. We further demonstrate that linear relationships theoretically determine the underlying transcriptional bursting kinetics, revealing different regulatory modes of TLR response heterogeneity. Stochastic modelling of temporal scRNA-seq count distributions demonstrates that increased response variability is associated with larger and more frequent transcriptional bursts, which emerge via increased complexity of transcriptional regulatory networks between genes and different species. Overall, we provide a methodology relying on inference of empirical mean-variance relationships from single cell data and new insights into control of innate immune response variability.

During the more than 3 years of the “Quality” program at JSW S.A., a geological database has been built from scratch, collecting data from all exploratory boreholes, roadway profiling and the results of chemical analyses in one place – placing particular emphasis on parameters affecting the quality of coke. Working with digital databases requires new competencies for geologists – the ability to efficiently obtain information ready for further processing. As intended, the geological model became the basis for forecasting the quantity and quality of mined coal used in coke production. In the course of the work, a discrepancy became apparent between the geological interpretation of the structure of the deposit – as understood by the assumptions of the geological documentation, and the technological conditions of mining. The article presents resulting changes in the approach to modeling lithology and quality parameters. In addition, examples of the application of the geological database and the geological model in the daily work of the geological department are presented.

Background: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. Methods: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. Results: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 μg/L vs. 1176.42 μg/L, p < 0.001; Zn: 707.05 μg/L vs. 901.67 μg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). Conclusion: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

In this paper, the design issue of effective damping of electromechanical swings in a medium voltage network with distributed generation by the use of a PSS2A type power system stabiliser is described. This stabiliser was installed in the generating unit with the highest rated power. Time constants of correction blocks, as well as the main gain, were determined by analyzing a single-machine system, generating unit – infinite bus. The time constants were calculated on the basis of the frequency-phase transfer functions both of the electromagnetic moment to the voltage regulator reference voltage and of the generator voltage to the voltage regulator reference voltage, under the assumption of an infinite and real value of the generating unit inertia time constant for various initial generator loads. The main stabiliser gain was calculated by analyzing the position, on the complex plane, of eigenvalues of the state matrix of the single-machine system, linearised around a steady operating point, at the changed value of this gain.

In the paper, the application of multi-criteria optimization of the parameters of PSS3B system stabilizers to damping electromechanical swings in an extended power system (PS) is presented. The calculations of the power system stabilizer (PSS) parameters were divided into two stages. In the first stage, single-machine systems, generating unit – infinite bus, of generating units critical for the angular stability of the PS were analyzed. Time constants and preliminary values of the PSS gains were calculated. In the second stage, the main one, the main gains on which the effectiveness of operation of PSSs depends the most were calculated by multi-criteria optimization of the extended PS. The calculations were carried out in several variants: for two-dimensional objective functions and the six-dimensional objective function. In multi-criteria optimization, the solution is not one set of PSS parameters, but a set of sets of these parameters, i.e. a set of compromises that were determined for each analyzed case. Additionally, for the six-dimensional compromise set, projections of this set on the planes connected with the quantities of individual generating units and the boundary of these projections on these planes were determined. A genetic algorithm adapted to multi-criteria issues was used to minimize the multivariate objective function. Sample calculations were made for the model of the National (Polish) Power System taking into account 57 selected generating units operating in high and extra high voltage networks (220 and 400 kV). The presented calculations show that the applied multi-criteria optimization of the PSS3B stabilizer parameters allows effectively damping electromechanical swings withoutworsening the voltagewaveforms of generating units in the extended PS.

Cells respond to inflammatory stimuli such as cytokines by activation of the nuclear factor-κB (NF-κB) signalling pathway, resulting in oscillatory translocation of the transcription factor p65 between nucleus and cytoplasm in some cell types. We investigate the relationship between p65 and inhibitor-κB⍺ (IκBα) protein levels and dynamic properties of the system, and how this interaction impacts on the expression of key inflammatory genes. Using bacterial artificial chromosomes, we developed new cell models of IκB⍺-eGFP protein overexpression in a pseudo-native genomic context. We find that cells with high levels of the negative regulator IκBα remain responsive to inflammatory stimuli and maintain dynamics for both p65 and IκBα. In contrast, canonical target gene expression is dramatically reduced by overexpression of IκBα, but can be partially rescued by overexpression of p65. Treatment with leptomycin B to promote nuclear accumulation of IκB⍺ also suppresses canonical target gene expression, suggesting a mechanism in which nuclear IκB⍺ accumulation prevents productive p65 interaction with promoter binding sites. This causes reduced target promoter binding and gene transcription, which we validate by chromatin immunoprecipitation and in primary cells. Overall, we show how inflammatory gene transcription is modulated by the expression levels of both IκB⍺ and p65. This results in an anti-inflammatory effect on transcription, demonstrating a broad mechanism to modulate the strength of inflammatory response.

This article analyses and evaluates the model used by the Jastrzebie Coal Company in Poland to forecast the values of continuous deformations of land surfaces caused by underground mining. Particular attention is paid to the values of terrain inclinations, which cause significant deflections of buildings located in mining areas affected by exploitation. The inclination forecasts were made using Bialek's model, with the values of its parameters determined in situ and after completion of the exploitation of a longwall. The obtained results were compared with the values of the terrain inclinations calculated from the results of geodetic measurements carried out at observation points located near the buildings and discontinuous linear deformations (i.e., the ground steps). The conducted research shows that the correlations between the absolute values of the practical inclinations and the values of the theoretical inclinations were rather weak, as the values of their correlation coefficients did not exceed 0.24. The tested model underestimated 45.5% of the values of the inclinations observed in situ by an average of −53.5%. The model values of the inclinations for the remaining observed inclinations (54.5%) were overestimated by an average of 461.9%. The largest anomalies were obtained in the case of inclination values from points located near the ground steps. The effectiveness of predicting inclination values with a commonly used model is strongly reduced when discontinuous linear deformations appear. Nonetheless, it reflects well the mining area categories. [ABSTRACT FROM AUTHOR]

Automation of transportation will play a crucial role in the future when people driving vehicles will be replaced by autonomous systems. Currently, the positioning systems are not used alone but are combined in order to create cooperative positioning systems. The ultra-wideband (UWB) system is an excellent alternative to the global positioning system (GPS) in a limited area but has some drawbacks. Despite many advantages of various object positioning systems, none is free from the problem of object displacement during measurement (data acquisition), which affects positioning accuracy. In addition, temporarily missing data from the absolute positioning system can lead to dangerous situations. Moreover, data pre-processing is unavoidable and takes some time, affecting additionally the object’s displacement in relation to its previous position and its starting point of the new positioning process. So, the prediction of the position of an object is necessary to minimize the time when the position is unknown or out of date, especially when the object is moving at high speed and the position update rate is low. This article proposes using the long short-term memory (LSTM) artificial neural network to predict objects’ positions based on historical data from the UWB system and inertial navigation. The proposed solution creates a reliable positioning system that predicts 10 positions of low and high-speed moving objects with an error below 10 cm. Position prediction allows detection of possible collisions—the intersection of the trajectories of moving objects.