bluuebunny/crossref_metadata_2025 huggingface dataset:
A Conserved Mitochondrial Chaperone-Protease Complex Involved in Protein Homeostasis
Authors: Serricchio Mauro , Bütikofer Peter
Published: November 2021

Mitochondria are essential organelles involved in cellular energy production. The inner mitochondrial membrane protein stomatin-like protein 2 (SLP-2) is a member of the SPFH (stomatin, prohibitin, flotilin, and HflK/C) superfamily and binds to the mitochondrial glycerophospholipid cardiolipin, forming cardiolipin-enriched membrane domains to promote the assembly and/or stabilization of protein complexes involved in oxidative phosphorylation. In addition, human SLP-2 anchors a mitochondrial processing complex required for proteolytic regulation of proteins involved in mitochondrial dynamics and quality control. We now show that deletion of the gene encoding theTrypanosoma bruceihomolog TbSlp2 has no effect on respiratory protein complex stability and mitochondrial functions under normal culture conditions and is dispensable for growth ofT. bruceiparasites. In addition, we demonstrate that TbSlp2 binds to the metalloprotease TbYme1 and together they form a large mitochondrial protein complex. The two proteins negatively regulate each other’s expression levels by accelerating protein turnover. Furthermore, we show that TbYme1 plays a role in heat-stress resistance, as TbYme1 knock-out parasites displayed mitochondrial fragmentation and loss of viability when cultured at elevated temperatures. Unbiased interaction studies uncovered putative TbYme1 substrates, some of which were differentially affected by the absence of TbYme1. Our results support emerging evidence for the presence of mitochondrial quality control pathways in this ancient eukaryote.
Identification and Validation of TYMS as a Potential Biomarker for Risk of Metastasis Development in Hepatocellular Carcinoma
Authors: Li Shuai , Zhao Jingyuan , Lv Linlin , Dong Deshi
Published: November 2021

Metastasis is the major cause of hepatocellular carcinoma (HCC) mortality. Unfortunately, there are few reports on effective biomarkers for HCC metastasis. This study aimed to discover potential key genes of HCC, which could provide new insights for HCC metastasis. GEO (Gene Expression Omnibus) microarray and TCGA (The Cancer Genome Atlas) datasets were integrated to screen for candidate genes involved in HCC metastasis. Differentially expressed genes (DEGs) were screened, and then we performed enrichment analysis of Gene Ontology (GO), together with Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 10 hub genes by cytoHubba. Four genes were associated with survival, their prognostic value was verified by prognostic signature analysis. Thymidylate synthase (TYMS) gene was identified as significant HCC metastasis-associated genes after mRNA expression validation and IHC analysis. TYMS silencing in HCC cells remarkedly inhibited growth and invasion. Finally, we found TYMS silencing dramatically decrease DNA synthesis and extracellular matrix (ECM) degradation, resulting in the inhibition of HCC metastasis, indicating TYMS had close associations with HCC development. These findings provided new insights into HCC metastasis and identified candidate gene prognosis signatures for HCC metastasis.
Antioxidant Potential and Inhibition of Mitochondrial Permeability Transition Pore by Myricetin Reduces Aluminium Phosphide-Induced Cytotoxicity and Mitochondrial Impairments
Authors: Salimi Ahmad , Jamali Zhaleh , Shabani Mohammad
Published: November 2021

Oxidative stress and mitochondrial dysfunction are involved in the mechanisms of cardiac toxicity induced by aluminum phosphide (AlP). AlP-induced cardiotoxicity leads to cardiomyocyte death, cardiomyopathy, cardiac dysfunction, and eventually severe heart failure and death. Importantly, protecting cardiomyocytes from death resulting from AlP is vital for improving survival. It has been reported that flavonoids such as myricetin (Myr) act as modifiers of mitochondrial function and prevent mitochondrial damage resulting from many insults and subsequent cell dysfunction. In this study, the ameliorative effect of Myr, as an important antioxidant and mitochondrial protective agent, was investigated in cardiomyocytes and mitochondria isolated from rat heart against AlP-induced toxicity, oxidative stress, and mitochondrial dysfunction. Treatment of AlP (20 μg/ml) significantly increased cytotoxicity; reduced glutathione (GSH) depletion, cellular reactive oxygen species (ROS) formation, malondialdehyde (MDA) level, ATP depletion, caspase-3 activation, mitochondrial membrane potential (ΔΨm) collapse, and lysosomal dysfunction; and decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in intact cardiomyocytes. Also, treatment of AlP (20 μg/ml) significantly increased mitochondrial dysfunction and swelling in isolated mitochondria. Myr (80 µM) appeared to ameliorate AlP-induced cytotoxicity in isolated cardiomyocytes; significantly lessened the AlP-stimulated intracellular ROS and MDA production and depletion of GSH; and increased the activities of SOD, CAT, and GSH-Px. Furthermore, Myr (40 and 80 µM) lowered AlP-induced lysosomal/mitochondrial dysfunction, ATP depletion, and caspase-3 activation. In the light of these findings, we concluded that Myr through antioxidant potential and inhibition of mitochondrial permeability transition (MPT) pore exerted an ameliorative role in AlP-induced toxicity in isolated cardiomyocytes and mitochondria, and it would be valuable to examine its in vivo effects.
In silico Identification of Disrupted Myocardial Calcium Homeostasis as Proarrhythmic Trigger in Arrhythmogenic Cardiomyopathy
Authors: Lyon Aurore , van Opbergen Chantal J. M. , Delmar Mario , Heijman Jordi , van Veen Toon A. B.
Published: November 2021

Background: Patients with arrhythmogenic cardiomyopathy may suffer from lethal ventricular arrhythmias. Arrhythmogenic cardiomyopathy is predominantly triggered by mutations in plakophilin-2, a key component of cell-to-cell adhesion and calcium cycling regulation in cardiomyocytes. Calcium dysregulation due to plakophilin-2 mutations may lead to arrhythmias but the underlying pro-arrhythmic mechanisms remain unclear.

Aim: To unravel the mechanisms by which calcium-handling abnormalities in plakophilin-2 loss-of-function may contribute to proarrhythmic events in arrhythmogenic cardiomyopathy.

Methods: We adapted a computer model of mouse ventricular electrophysiology using recent experimental calcium-handling data from plakophilin-2 conditional knock-out (PKP2-cKO) mice. We simulated individual effects of beta-adrenergic stimulation, modifications in connexin43-mediated calcium entry, sodium-calcium exchanger (NCX) activity and ryanodine-receptor 2 (RyR2) calcium affinity on cellular electrophysiology and occurrence of arrhythmogenic events (delayed-afterdepolarizations). A population-of-models approach was used to investigate the generalizability of our findings. Finally, we assessed the potential translation of proposed mechanisms to humans, using a human ventricular cardiomyocyte computational model.

Results: The model robustly reproduced the experimental calcium-handling changes in PKP2-cKO cardiomyocytes: an increased calcium transient amplitude (562 vs. 383 nM), increased diastolic calcium (120 vs. 91 nM), reduced L-type calcium current (15.0 vs. 21.4 pA/pF) and an increased free SR calcium (0.69 vs. 0.50 mM). Under beta-adrenergic stimulation, PKP2-cKO models from the population of models (n = 61) showed a higher susceptibility to delayed-afterdepolarizations compared to control (41 vs. 3.3%). Increased connexin43-mediated calcium entry further elevated the number of delayed-afterdepolarizations (78.7%, 2.5-fold increase in background calcium influx). Elevated diastolic cleft calcium appeared responsible for the increased RyR2-mediated calcium leak, promoting delayed-afterdepolarizations occurrence. A reduction in RyR2 calcium affinity prevented delayed-afterdepolarizations in PKP2-cKO models (24.6 vs. 41%). An additional increase in INCX strongly reduced delayed-afterdepolarizations occurrence, by lowering diastolic cleft calcium levels. The human model showed similar outcomes, suggesting a potential translational value of these findings.

Conclusion: Beta-adrenergic stimulation and connexin43-mediated calcium entry upon loss of plakophilin-2 function contribute to generation of delayed-afterdepolarizations. RyR2 and NCX dysregulation play a key role in modulating these proarrhythmic events. This work provides insights into potential future antiarrhythmic strategies in arrhythmogenic cardiomyopathy due to plakophilin-2 loss-of-function.
The Swedish Version of the Multidimensional Inventory for Religious/Spiritual Well-Being: First Results From Swedish Students
Authors: Wenzl Magdalena , Fuchshuber Jürgen , Podolin-Danner Nikita , Silani Giorgia , Unterrainer Human-Friedrich
Published: November 2021

Background: Studies investigating the relationship between religiosity/spirituality and mental health have suggested both positive and negative associations, highlighting the importance of multifaceted assessment of these rather broad constructs. The present study aims at contributing to this field of research by providing a validated Swedish version of the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB-S) and further examining how this instrument relates to Big Five personality factors, Sense of Coherence (SOC), and religiosity.

Methods: Data were collected from a total of 1,011 Swedish students (747 females; age range 18–40) via completion of an online survey, including a new Swedish Version of the MI-RSWB-S, the Ten Item Personality Inventory (TIPI), the Sense of Coherence Scale (SOC-13), and the Centrality of Religiosity Scale (CRS-5).

Results: Results revealed adequate estimates of internal consistency and substantial evidence for the postulated six-dimensional structure. However, confirmatory factor analysis yielded poor fit indices, resulting in the development and validation of a revised measure of Religious/Spiritual Well-Being (RSWB), comprising the subscales General Religiosity and Connectedness. Most of the MI-RSWB-S dimensions were positively correlated with the personality domains Extraversion, Openness to Experience, Conscientiousness, and Agreeableness and negatively related to Neuroticism. SOC was positively linked to Hope Immanent, Forgiveness, Hope Transcendent, and Experiences of Sense of Meaning, whereas CRS exhibited positive correlations with all MI-RSWB-S subscales except Hope Transcendent.

Conclusion: The findings of the current study support the validity and reliability of the Swedish adoption of the MI-RSWB and confirm previously reported associations with the Big Five personality traits, SOC, and CRS. More in general, our results underline the putative substantial link between RSWB dimensions and mental health. Further research especially in clinical surroundings as well as by employing more representative samples is now warranted.
Impact of Storage Conditions on Equine Fecal Inoculum for Estimating In Vitro Digestibility
Authors: O’Donnell Delaney , Sukovaty Lacy , Webb Gary
Published: November 2021

This study evaluated the effect of storage conditions of equine fecal material on the viability of microbial inoculum used for in vitro equine digestibility trials. Pooled fecal material from three mature Quarter Horse geldings was stored at 39 °C anaerobically for 15 min (control), while aerobic samples were stored at 22 °C for 6 h (SC1), 3 °C for 6 h (SC2), and −18 °C for 24 h (SC3). Following storage, the feces were utilized to prepare microbial inoculum for the digestion of six different forages using the Daisy II Incubator. After incubation, DM, NDF, and ADF compositions were determined and used to calculate DMD, NDFD, and ADFD. Analysis using the OLS regression model for differences in DMD, NDFD, and ADFD across the storage conditions found significant interactions between the forage sample and the storage condition (p < 0.05). The results between the control and SC1, SC2, and SC3 were not different (p < 0.8). Fecal material stored aerobically for six hours at 22 °C provided similar digestibility estimates compared to the control, while DMD decreased by 3.86% in SC2 and by 4.08% in SC3.
Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated
Authors: Tatalović Nikola , Vidonja Uzelac Teodora , Oreščanin Dušić Zorana , Nikolić-Kokić Aleksandra , Bresjanac Mara , Blagojević Duško
Published: November 2021

Ibogaine effects are mediated by cellular receptors, ATP depletion followed by ROS production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since the role of KATP channels and β-adrenoceptors in ROS cellular circuit was established here we explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e., 28.8 μmol/L) was applied to isolated rat uterus (spontaneous and Ca2+-stimulated) and contractility and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and frequency of spontaneous active uteri immediately after addition that was prevented by propranolol (β1 and β2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor; only frequency) pre-treatment. In Ca2+-stimulated uteri, ibogaine decreased both amplitude and frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering, while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in SOD1 and an increase in CAT activity after 2 h. In Ca2+-stimulated uterus, there was also a decrease of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β-adrenergic receptors and KATP channels mediated.
A New Separation Methodology for the Maritime Sector Emissions over the Mediterranean and Black Sea Regions
Authors: Pseftogkas Andreas , Koukouli Maria-Elissavet , Skoulidou Ioanna , Balis Dimitrios , Meleti Charikleia , Stavrakou Trissevgeni , Falco Luigi , van Geffen Jos , Eskes Henk , Segers Arjo , Manders Astrid
Published: November 2021

The aim of this paper is to apply a new lane separation methodology for the maritime sector emissions attributed to the different vessel types and marine traffic loads in the Mediterranean and the Black Sea defined via the European Marine and Observation Data network (EMODnet), developed in 2016. This methodology is implemented for the first time on the Copernicus Atmospheric Monitoring Service Global Shipping (CAMS-GLOB-SHIP v2.1) nitrogen oxides (NOX) emissions inventory, on the Sentinel-5 Precursor Tropospheric Monitoring Instrument (TROPOMI) nitrogen dioxide (NO2) tropospheric vertical column densities, and on the LOTOS-EUROS (Long Term Ozone Simulation—European Operational Smog) CTM (chemical transport model) simulations. By applying this new EMODnet-based lane separation method to the CAMS-GLOB-SHIP v2.1 emission inventory, we find that cargo and tanker vessels account for approximately 80% of the total emissions in the Mediterranean, followed by fishing, passenger, and other vessel emissions with contributions of 8%, 7%, and 5%, respectively. Tropospheric NO2 vertical column densities sensed by TROPOMI for 2019 and simulated by the LOTOS-EUROS CTM have been successfully attributed to the major vessel activities in the Mediterranean; the mean annual NO2 load of the observations and the simulations reported for the entire maritime EMODnet-reported fleet of the Mediterranean is in satisfactory agreement, 1.26 ± 0.56 × 1015 molecules cm−2 and 0.98 ± 0.41 × 1015 molecules cm−2, respectively. The spatial correlation of the annual maritime NO2 loads of all vessel types between observation and simulation ranges between 0.93 and 0.98. On a seasonal basis, both observations and simulations show a common variability. The wintertime comparisons are in excellent agreement for the highest emitting sector, cargo vessels, with the observations reporting a mean load of 0.98 ± 0.54 and the simulations of 0.81 ± 0.45 × 1015 molecules cm−2 and correlation of 0.88. Similarly, the passenger sector reports 0.45 ± 0.49 and 0.39 ± 0.45 × 1015 molecules cm−2 respectively, with correlation of 0.95. In summertime, the simulations report a higher decrease in modelled tropospheric columns than the observations, however, still resulting in a high correlation between 0.85 and 0.94 for all sectors. These encouraging findings will permit us to proceed with creating a top-down inventory for NOx shipping emissions using S5P/TROPOMI satellite observations and a data assimilation technique based on the LOTOS-EUROS chemical transport model.
Regional Emissions Analysis of Light-Duty Battery Electric Vehicles
Authors: Burnham Andrew , Lu Zifeng , Wang Michael , Elgowainy Amgad
Published: November 2021

Light-duty battery electric vehicles (BEVs) can reduce both greenhouse gas (GHG) and criteria air pollutant (CAPs) emissions, when compared to gasoline vehicles. However, research has found that while today’s BEVs typically reduce GHGs, they can increase certain CAPs, though with significant regional variability based on the electric grid mix. In addition, the environmental performance of electric and gasoline vehicles is not static, as key factors driving emissions have undergone significant changes recently and are expected to continue to evolve. In this study, we perform a cradle-to-grave life cycle analysis using state-level generation mix and vehicle operation emission data. We generated state-level emission factors using a projection from 2020 to 2050 for three light-duty vehicle types. We found that BEVs currently provide GHG benefits in nearly every state, with the median state’s benefit being between approximately 50% to 60% lower than gasoline counterparts. However, gasoline vehicles currently have lower total NOx, urban NOx, total PM2.5, and urban PM2.5 in 33%; 15%; 70%; and 10% of states, respectively. BEV emissions will decrease in 2050 due to a cleaner grid, but the relative benefits when compared to gasoline vehicles do not change significantly, as gasoline vehicles are also improving over this time.
Dopamine in Health and Disease
Authors: Ekker Marc
Published: November 2021

The neurotransmitter dopamine (DA) is generally associated with Parkinson’s disease (PD) [...]
Role of Oxidative Stress in Heart Failure: Insights from Gene Transfer Studies
Authors: De Geest Bart , Mishra Mudit
Published: November 2021

Under physiological circumstances, there is an exquisite balance between reactive oxygen species (ROS) production and ROS degradation, resulting in low steady-state ROS levels. ROS participate in normal cellular function and in cellular homeostasis. Oxidative stress is the state of a transient or a persistent increase of steady-state ROS levels leading to disturbed signaling pathways and oxidative modification of cellular constituents. It is a key pathophysiological player in pathological hypertrophy, pathological remodeling, and the development and progression of heart failure. The heart is the metabolically most active organ and is characterized by the highest content of mitochondria of any tissue. Mitochondria are the main source of ROS in the myocardium. The causal role of oxidative stress in heart failure is highlighted by gene transfer studies of three primary antioxidant enzymes, thioredoxin, and heme oxygenase-1, and is further supported by gene therapy studies directed at correcting oxidative stress linked to metabolic risk factors. Moreover, gene transfer studies have demonstrated that redox-sensitive microRNAs constitute potential therapeutic targets for the treatment of heart failure. In conclusion, gene therapy studies have provided strong corroborative evidence for a key role of oxidative stress in pathological remodeling and in the development of heart failure.
Versatile Role of Prokineticins and Prokineticin Receptors in Neuroinflammation
Authors: Lattanzi Roberta , Miele Rossella
Published: November 2021

Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction. PKR2 is mainly overexpressed in neurons, whereas PKR1 and PK2 are mainly overexpressed in astrocytes. Once PK2 is released in inflamed tissue, it is involved in both innate and adaptive responses: it triggers macrophage recruitment, production of pro-inflammatory cytokines, and reduction of anti-inflammatory cytokines. Moreover, it modulates the function of T cells through the activation of PKR1 and directs them towards a pro-inflammatory Th1 phenotype. Since the prokineticin system appears to be upregulated following a series of pathological insults leading to neuroinflammation, we will focus here on the involvement of PK2 and PKRs in those pathologies that have a strong underlying inflammatory component, such as: inflammatory and neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, obesity, diabetes, and gastrointestinal inflammation.
Structural and Computational Study of the GroEL–Prion Protein Complex
Authors: Mamchur Aleksandra A. , Moiseenko Andrei V. , Panina Irina S. , Yaroshevich Igor A. , Kudryavtseva Sofia S. , Pichkur Evgeny B. , Sokolova Olga S. , Muronetz Vladimir I. , Stanishneva-Konovalova Tatiana B.
Published: November 2021

The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrPC, could lead to pathogenic transformation of the latter to the aggregation-prone PrPSc form. Here, the molecular basis of the interactions in the GroEL–PrP complex is studied with cryo-EM and molecular dynamics approaches. The obtained cryo-EM structure shows PrP to be bound to several subunits of GroEL at the level of their apical domains. According to MD simulations, the disordered N-domain of PrP forms much more intermolecular contacts with GroEL. Upon binding to the GroEL, the N-domain of PrP begins to form short helices, while the C-domain of PrP exhibits a tendency to unfold its α2-helix. In the absence of the nucleotides in the system, these processes are manifested at the hundred nanoseconds to microsecond timescale.
Mechanical Stretching-Induced Traumatic Brain Injury Is Mediated by the Formation of GSK-3β-Tau Complex to Impair Insulin Signaling Transduction
Authors: Cheng Pei-Wen , Wu Yi-Chung , Wong Tzyy-Yue , Sun Gwo-Ching , Tseng Ching-Jiunn
Published: November 2021

Traumatic brain injury confers a significant and growing public health burden. It is a major environmental risk factor for dementia. Nonetheless, the mechanism by which primary mechanical injury leads to neurodegeneration and an increased risk of dementia-related diseases is unclear. Thus, we aimed to investigate the effect of stretching on SH-SY5Y neuroblastoma cells that proliferate in vitro. These cells retain the dopamine-β-hydroxylase activity, thus being suitable for neuromechanistic studies. SH-SY5Y cells were cultured on stretchable membranes. The culture conditions contained two groups, namely non-stretched (control) and stretched. They were subjected to cyclic stretching (6 and 24 h) and 25% elongation at 1 Hz. Following stretching at 25% and 1 Hz for 6 h, the mechanical injury changed the mitochondrial membrane potential and triggered oxidative DNA damage at 24 h. Stretching decreased the level of brain-derived neurotrophic factors and increased amyloid-β, thus indicating neuronal stress. Moreover, the mechanical injury downregulated the insulin pathway and upregulated glycogen synthase kinase 3β (GSK-3β)S9/p-Tau protein levels, which caused a neuronal injury. Following 6 and 24 h of stretching, GSK-3βS9 was directly bound to p-TauS396. In contrast, the neuronal injury was improved using GSK-3β inhibitor TWS119, which downregulated amyloid-β/p-Taus396 phosphorylation by enhancing ERK1/2T202/Y204 and AktS473 phosphorylation. Our findings imply that the neurons were under stress and that the inactivation of the GSK3β could alleviate this defect.
Linearity of Age at Cancer Onset Worldwide: 25-Year Population-Based Cancer Registry Study
Authors: Bidoli Ettore , Lamaj Elda , Angelin Tiziana , Forgiarini Ornella , De Santis Emilia , Serraino Diego
Published: November 2021

Background The linear association between median age at cancer onset and median age of the underlying population has been described only for breast cancer. We quantified the shape and strength of such association for 20 cancer types using data from all population-based cancer registries (CRs) worldwide. Methods The patients’ median age at cancer onset and of the underlying population were extracted from all CRs listed in volumes VI (1983–1987 years) and XI (2008–2012 years) of Cancer Incidence in Five Continents. The association was assessed at cross-sectional level by linear regression models and longitudinally considering only the long-standing CRs active throughout the study period (i.e., 25-year span). Results During 2008–2012, each one-year increase in median population ageing was associated in men with a nearly half year increase of median age at onset of all cancers, but skin; and a 2/3 year increase in women. Variance explained by linear model was around 60%. In long-standing CRs a decrease in median age at cancer onset was observed for prostate and cervical cancers throughout the 25-year span. Conclusions Population ageing reflected 60% of the median age at cancer onset. Misinterpretation of peaks of cancer incidence in specific age groups may be avoided by examining population pyramids.
Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer
Authors: Vito Alyssa , El-Sayes Nader , Salem Omar , Wan Yonghong , Mossman Karen L.
Published: November 2021

The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing.
Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era
Authors: Porpaczy Edit , Wohlfarth Philipp , Königsbrügge Oliver , Rabitsch Werner , Skrabs Cathrin , Staber Philipp , Worel Nina , Müllauer Leonhard , Simonitsch-Klupp Ingrid , Kornauth Christoph , Rohrbeck Johannes , Jaeger Ulrich , Schiefer Ana-Iris
Published: November 2021

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.
An Overview of Natural Polymers as Reinforcing Agents for 3D Printing
Authors: Sabbatini Beatrice , Cambriani Alessandra , Cespi Marco , Palmieri Giovanni Filippo , Perinelli Diego Romano , Bonacucina Giulia
Published: November 2021

Three-dimensional (3D) printing, or additive manufacturing, is a group of innovative technologies that are increasingly employed for the production of 3D objects in different fields, including pharmaceutics, engineering, agri-food and medicines. The most processed materials by 3D printing techniques (e.g., fused deposition modelling, FDM; selective laser sintering, SLS; stereolithography, SLA) are polymeric materials since they offer chemical resistance, are low cost and have easy processability. However, one main drawback of using these materials alone (e.g., polylactic acid, PLA) in the manufacturing process is related to the poor mechanical and tensile properties of the final product. To overcome these limitations, fillers can be added to the polymeric matrix during the manufacturing to act as reinforcing agents. These include inorganic or organic materials such as glass, carbon fibers, silicon, ceramic or metals. One emerging approach is the employment of natural polymers (polysaccharides and proteins) as reinforcing agents, which are extracted from plants or obtained from biomasses or agricultural/industrial wastes. The advantages of using these natural materials as fillers for 3D printing are related to their availability together with the possibility of producing printed specimens with a smaller environmental impact and higher biodegradability. Therefore, they represent a “green option” for 3D printing processing, and many studies have been published in the last year to evaluate their ability to improve the mechanical properties of 3D printed objects. The present review provides an overview of the recent literature regarding natural polymers as reinforcing agents for 3D printing.
Intelligent Real-Time Deep System for Robust Objects Tracking in Low-Light Driving Scenario
Authors: Rundo Francesco
Published: November 2021

The detection of moving objects, animals, or pedestrians, as well as static objects such as road signs, is one of the fundamental tasks for assisted or self-driving vehicles. This accomplishment becomes even more difficult in low light conditions such as driving at night or inside road tunnels. Since the objects found in the driving scene represent a significant collision risk, the aim of this scientific contribution is to propose an innovative pipeline that allows real time low-light driving salient objects tracking. Using a combination of the time-transient non-linear cellular networks and deep architectures with self-attention, the proposed solution will be able to perform a real-time enhancement of the low-light driving scenario frames. The downstream deep network will learn from the frames thus improved in terms of brightness in order to identify and segment salient objects by bounding-box based approach. The proposed algorithm is ongoing to be ported over a hybrid architecture consisting of a an embedded system with SPC5x Chorus MCU integrated with an automotive-grade system based on STA1295 MCU core. The performances (accuracy of about 90% and correlation coefficient of about 0.49) obtained in the experimental validation phase confirmed the effectiveness of the proposed method.
Influence of Selected Factors on the Duration and Energy Efficiency of Autoclave Steaming Regimes of Non-Frozen Prisms for Veneer Production
Authors: Deliiski Nencho , Dzurenda Ladislav , Angelski Dimitar , Tumbarkova Natalia
Published: November 2021

This paper puts forward a methodology for calculating the duration and energy efficiency of regimes for autoclave steaming of wooden prisms for veneer production at limited heat power of the steam generator, depending on the dimensions of the prism’s cross section, wood moisture content, and loading level of the autoclave. The methodology is based on the use of two personal mathematical models: the 2D non-linear model of the temperature distribution in non-frozen wooden prisms subjected to steaming and subsequent conditioning in an air medium, and the model of the non-stationary heat balance of autoclaves for steaming wood materials. Using the suggested methodology, the calculation and research into the duration and energy efficiency of regimes for heating of beech prisms have been carried out. The variables used were an initial temperature of 0 °C, cross-section dimensions 0.3 × 0.3 m, 0.4 × 0.4 m, and 0.5 × 0.5 m, moisture content of 0.4, 0.6, and 0.8 kg·kg−1, during their steaming in an autoclave with a diameter of 2.4 m, length of 9.0 m and loading level of 40, 50, and 60% at a limited heat power of the steam generator, equal to 500 kW. It has been determined that the duration of the autoclave steaming regimes, at a loading level of 50% being most often used in the practice beech prisms with moisture of 0.6 kg·kg−1, does not exceed 9 h, 13 h, and 20 h for prisms with cross-section 0.3 × 0.3 m, 0.4 × 0.4 m, and 0.5 × 0.5 m, respectively. This duration is less than half of the corresponding duration of the steaming regimes at atmospheric pressure. The energy needed for warming up such prisms themselves does not exceed 60, 65, and 69 kWh·m−3, respectively, and the energy consumption of the whole autoclave then is equal to about 90, 99, and 105 kWh·m−3, respectively. The energy efficiency of the autoclave steaming regimes changes between 62.2% and 68.8% for the studied ranges of the influencing factors and it turns out to be more than 2–3 times larger in comparison with the efficiency of the steaming at atmospheric pressure. The methodology can be used for various calculations with ANSYS and to create the software for systems used for computing and model-based automatic realization of energy-efficient regimes for autoclave steaming of different wood materials from various species. This could be useful in developing similar methodologies in different areas of thermal treatment at increased pressure of various capillary-porous materials of plant or technical origin.
Experimental Study on the Insulation Layer Thickness of a Novel Ice Coring Device in Loose Sandstone-Type Uranium Deposits
Authors: Huang Chaoyang , Peng Jianming , Li Yanliang , Lian Moke , Guo Chao , Luo Yongjiang , Bo Kun
Published: November 2021

The target strata of sandstone-type uranium deposits are usually located in the fragile and loose strata, which makes it difficult to obtain core samples; consequently, a novel ice coring device for loose sandstone-type uranium deposits is proposed to solve this problem. Experiments proved that the artificial sample can replace the natural sample, and the coring method has high reliability. Ensuring the allegro formation of an ice valve with a given cold source is critical for this coring system, and reducing the loss of cold energy with help of insulation layer is one of the methods to speed up the formation of ice valve. Since the diameter of the drill tool is limited by its working scenario, the thickness of insulation layer is limited to ensure the size of core. Therefore, this paper conducted laboratory experiments of the insulation layer with different thicknesses to study the effect of the insulation layer on the formation of the sand–ice valve. Results show that the insulation layer can reduce the loss of cold energy during the freezing process and significantly affect the formation time of the sand–ice valve. When the thickness of the aerogel insulation layer is 2 mm, the freezing time is 44% shorter than that without insulation layer. According to the tests, the novel ice coring device is expected to solve the coring problem in loose sandstone-type uranium deposits.
Development of a Fast Thermal Model for Calculating the Temperature of the Interior PMSM
Authors: Chen Qixu , Wu Dechen , Li Guoli , Cao Wenping , Qian Zhe , Wang Qunjing
Published: November 2021

A 40 kW–4000 rpm interior permanent magnet synchronous machine (IPMSM) applied to an electric vehicle (EV) is introduced as the study object in this paper. The main work of this paper is theoretical derivation and validation of the first-order and multi-order transient lumped-parameter thermal network (LPTN) for the development of a fast thermal model. Based on the first-order LPTN built, the study finds that the heat transfer coefficient of fluid and thickness of the air gap layer are the main influencing factors for the final temperature and time of reaching the steady state. The larger the heat transfer coefficient of fluid is, the lower the steady node temperature is. The smaller the air layer thickness is, the lower the steady node temperature is. The multi-order LPTN theory is further deduced based on the extension of the first-order LPTN. For the constant load and rectangular periodic load, transient node temperatures of the IPMSM are obtained by modeling and solving the first order inhomogeneous differential equations. Temperature rise curves and efficiency maps of the IPMSM under load conditions are realized on a dynamometer platform. The FLUKE infrared-thermal imager and the thermocouple PTC100 are used to validate the mentioned method. The experiment shows that the LPTN of the IPMSM can accurately predict the node temperature.
Utilization of Renewable Energy Sources in Road Transport in EU Countries—TOPSIS Results
Authors: Kisielińska Joanna , Roman Monika , Pietrzak Piotr , Roman Michał , Łukasiewicz Katarzyna , Kacperska Elżbieta
Published: November 2021

The primary aim of this study was to assess and compare EU countries in terms of the use of renewable energy sources in road transport. The following research tasks were undertaken to realize this aim: (1) a review of the literature concerning the negative externalities in road transport, the concept of sustainable development, and legal regulations referring to the utilization of renewable energy sources; (2) presentation of changes in energy consumption (both traditional and renewable) in road transport in EU countries in the years 2008–2019; and (3) identification of leaders among the EU countries in terms of consumption of renewable energy sources in road transport. The aim and tasks were realized using the literature review and TOPSIS method as well as descriptive, tabular, and graphic methods. The analysis was conducted for 28 EU countries according to the status for 2019. The period of 2008–2019 was investigated. Sources of materials included literature on the subject and Eurostat data. Although renewable energy sources accounted for as little as 6% of total energy consumption in road transport in EU countries in 2019, this is a significant topical issue. It results from the direction in which changes need to be implemented in terms of energy generation in this area of human activity. It turned out that blended biodiesel and blended biogasoline were the most commonly used fuels originating from renewable sources. The application of the TOPSIS method resulted in the identification of five groups of EU member countries, which differed in terms of the degree of utilization of renewable energy sources in road transport. Luxemburg, Sweden, and Austria were leaders in this respect. In turn, Malta, Estonia, and Croatia were characterized by very low consumption of renewable energy. The greatest progress in the utilization of renewable energy sources in road transport was recorded in Sweden, Finland, and Bulgaria (changes in the relative closeness to the ideal solution from 0.15 to 0.27), while the greatest reduction in relation to other countries was observed in Austria, Germany, and Lithuania (changes from −0.35 to −0.22).
Methods of Condition Monitoring and Fault Detection for Electrical Machines
Authors: Kudelina Karolina , Asad Bilal , Vaimann Toomas , Rassõlkin Anton , Kallaste Ants , Khang Huynh Van
Published: November 2021

Nowadays, electrical machines and drive systems are playing an essential role in different applications. Eventually, various failures occur in long-term continuous operation. Due to the increased influence of such devices on industry, industrial branches, as well as ordinary human life, condition monitoring and timely fault diagnostics have gained a reasonable importance. In this review article, there are studied different diagnostic techniques that can be used for algorithms’ training and realization of predictive maintenance. Benefits and drawbacks of intelligent diagnostic techniques are highlighted. The most widespread faults of electrical machines are discussed as well as techniques for parameters’ monitoring are introduced.
FEC Additive for Improved SEI Film and Electrochemical Performance of the Lithium Primary Battery
Authors: Zhou Xuan , Li Ping , Tang Zhihao , Liu Jialu , Zhang Shaowei , Zhou Yingke , Tian Xiaohui
Published: November 2021

The solid electrolyte interphase (SEI) film plays a significant role in the capacity and storage performance of lithium primary batteries. The electrolyte additives are essential in controlling the morphology, composition and structure of the SEI film. Herein, fluoroethylene carbonate (FEC) is chosen as the additive, its effects on the lithium primary battery performance are investigated, and the relevant formation mechanism of SEI film is analyzed. By comparing the electrochemical performance of the Li/AlF3 primary batteries and the microstructure of the Li anode surface under different conditions, the evolution model of the SEI film is established. The FEC additive can decrease the electrolyte decomposition and protect the lithium metal anode effectively. When an optimal 5% FEC is added, the discharge specific capacity of the Li/AlF3 primary battery is 212.8 mAh g−1, and the discharge specific capacities are respectively 205.7 and 122.3 mAh g−1 after storage for 7 days at room temperature and 55 °C. Compared to primary electrolytes, the charge transfer resistance of the Li/AlF3 batteries with FEC additive decreases, indicating that FEC is a promising electrolyte additive to effectively improve the SEI film, increase discharge-specific capacities and promote charge transfer of the lithium primary batteries.
Development of Comfort and Safety Performance of Passenger Seats in Large City Buses
Authors: Kernytskyy Ivan , Yakovenko Yevheniia , Horbay Orest , Ryviuk Maryana , Humenyuk Ruslan , Sholudko Yaroslav , Voichyshyn Yurii , Mazur Łukasz , Osiński Piotr , Rusakov Konstantin , Koda Eugeniusz
Published: November 2021

A bus seat needs to be designed ergonomically for better seating comfort. The present study is intended to develop a cost-effective ergonomic bus seat design based on seat comfort and safety demands. As part of the proposed seat design procedure, seating comfort analysis, identifying preferred design features, and developing a seat design are included. An analysis of the bus seat back and seat pan profiles was conducted. Based on the results of the comfort analysis, the authors identified the preferred design features of bus seats during the design identification process. An improved bus seat prototype was developed based on selected design features in the design development stage. Seating comfort analyses were used to compare the achieved seat with the reference seat. The seat design developed in the present study may be applicable for various types of bus public transport.
Comprehensive Review on Electricity Market Price and Load Forecasting Based on Wind Energy
Authors: Acaroğlu Hakan , García Márquez Fausto Pedro
Published: November 2021

Forecasting the electricity price and load has been a critical area of concern for researchers over the last two decades. There has been a significant economic impact on producers and consumers. Various techniques and methods of forecasting have been developed. The motivation of this paper is to present a comprehensive review on electricity market price and load forecasting, while observing the scientific approaches and techniques based on wind energy. As a methodology, this review follows the historical and structural development of electricity markets, price, and load forecasting methods, and recent trends in wind energy generation, transmission, and consumption. As wind power prediction depends on wind speed, precipitation, temperature, etc., this may have some inauspicious effects on the market operations. The improvements of the forecasting methods in this market are necessary and attract market participants as well as decision makers. To this end, this research shows the main variables of developing electricity markets through wind energy. Findings are discussed and compared with each other via quantitative and qualitative analysis. The results reveal that the complexity of forecasting electricity markets’ price and load depends on the increasing number of employed variables as input for better accuracy, and the trend in methodologies varies between the economic and engineering approach. Findings are specifically gathered and summarized based on researches in the conclusions.
Full-Scale Field Experimental Investigation on the Intended Irregularity of CWR Track in Vertical Plane
Authors: Bednarek Włodzimierz Andrzej
Published: November 2021

The purpose of the following paper is to present the author’s experimental field investigations of a jointless railway track subjected to a generated imperfection and analysis of track response to applied static loads. An optical measurement system, Pontos, was used for the static and dynamic analysis of the track’s deflections in 3D. The investigations allow us to recommend a direct application of this system for the non-contact measurement, visualization and analysis of simulated defects in the jointless track, as presented by the author. It is stated that simulation of an effect called the hanging sleeper, a short irregularity in the railway track with the initial parameters provided (a gap and a length of irregularity), is possible. The proposed method, based on the measurement in the loaded track (a static load from the locomotive wheels), allows for a description of the effect of the changing track support condition. Moreover, it also proves its usefulness for the analysis of the changes in deflection and stress values and the force transferred from the rail on the railway sleeper and for the assumed shape of defects simulating the short irregularities arising in the operated railway track. The arising irregularity in the track affects driving comfort and the safety of travellers.