bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterising Modal Behaviour of a Cantilever Beam at Different Heating Rates for Isothermal Conditions
Authors: Kamei Khangamlung , Khan Muhammad A. , Khan Kamran A.
Published: May 2021

The effect of temperature on structural response is a concern in engineering applications. The literature has highlighted that applied temperature loads change the system vibration behaviour. However, there is limited information available about temperature impacting the dynamic response. This paper investigated the heating rates effects on modal parameters for both with crack and without crack conditions in a cantilever beam. A beam subjected to three heating rates was considered: 2, 5, and 8 °C/min. The first one was assumed as a slow heating rate while the others were assumed as moderate and high, respectively. This controlled rate of heating was achieved by using a proportional-integral-derivative (PID) temperature controller. The results showed that heating at different rates has little impact on modal parameters. While this effect is minimal at lower temperatures and more evident at higher temperatures. The results of temperature ramped at 2, 5, and 8 °C/min were compared with the numerical and analytical results only for all the isothermal conditions. It was observed that the beam natural frequency and its modal amplitude decrease with the increase in temperatures and crack depths. Therefore, it is concluded that the rate of heating can make a slight impact on the dynamics response of any mechanical system.
Independent Component Analysis Applied on Pulsed Thermographic Data for Carbon Fiber Reinforced Plastic Inspection: A Comparative Study
Authors: Fleuret Julien R. , Ebrahimi Samira , Ibarra-Castanedo Clemente , Maldague Xavier P. V.
Published: May 2021

Dimensional reduction methods have significantly improved the simplification of Pulsed Thermography (PT) data while improving the accuracy of the results. Such approaches reduce the quantity of data to analyze and improve the contrast of the main defects in the samples contributed to their popularity. Many works have been proposed in the literature mainly based on improving the Principal Component Thermography (PCT). Recently the Independent Component Analysis (ICA) has been a topic of attention. Many different approaches have been proposed in the literature to solve the ICA. In this paper, we investigated several recent ICA methods and evaluated their influence on PT data compared with the state-of-the-art methods. We conducted our evaluation on reference CFRP samples with known defects. We found that ICA outperform PCT for small and deep defects. For other defects ICA results are often not far from the results obtained by PCT. However, the frequency of acquisition and the ICA methods have a great influence on the results.
Interior Sound Quality Prediction of Pure Electric Vehicles Based on Transfer Path Synthesis
Authors: Qian Kun , Hou Zhichao , Liang Jie , Liu Ruixue , Sun Dengke
Published: May 2021

The interior sound quality (SQ) of pure electric vehicles (PEVs) has become an important consideration for users purchasing vehicles. At present, it is insufficient to take the sound pressure level as the interior acoustics design index of PEVs. Transfer path analysis (TPA) and transfer path synthesis (TPS) that take the SQ of interior noise as the improvement target remains in the preliminary exploration stage. In this paper, objective psychoacoustic parameters of SQ were taken as evaluation indexes of interior PEV noise. A virtual interior SQ synthesis model was designed on the basis of TPA and TPS, which combines experimentation and simulation. The SQ synthesis model demonstrates each noise component contribution in a PEV by new SQ separation technology. First, the interior noise transfer path and noise source of the PEV were determined in a synthesis analysis method of the interior PEV noise. Second, on the basis of the composition mechanism of interior noise and the basic principle of TPA, the excitation signal and transfer function of each interior noise path in the PEV were tested. On the basis of TPS, the interior SQ synthesis model of PEV was then established. Finally, the accuracy of the prediction model was verified in simulation and experimental comparison studies on the psychoacoustic objective parameters of SQ. The SQ objective parameter value of each transfer path was quantified by using contribution analysis. The results are expected to improve the comfort of the interior acoustic environment and enhance the competitiveness of vehicle products. They also provide an effective reference and new ideas for the development of interior SQ in PEVs.
Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication
Authors: Lichtenauer Michael , Jirak Peter , Paar Vera , Sipos Brigitte , Kopp Kristen , Berezin Alexander E.
Published: May 2021

Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.
Performance-Based Ranking of Existing Road Bridges
Authors: Mandić Ivanković Ana , Skokandić Dominik , Kušter Marić Marija , Srbić Mladen
Published: May 2021

Bridge condition assessment in most European countries is based on visual inspection in combination with damage assessment of bridge components. For adequate bridge management, the assessment needs to be further developed to move from the bridge component level to the system functionality level and finally to the priority ranking level for repairs in the network. Although visual inspection provides only qualitative insights into bridge condition and cannot predict load-carrying capacity, it is still very often the only way to collect data on existing bridges and can provide very important information for evaluating structural safety, traffic safety, durability, and overall bridge condition. Therefore, this paper presents a unique procedure that establishes a relationship between a country-specific bridge condition assessment procedure based on visual inspection and the systematization of key bridge performance indicators developed within the European integrated management approach at three complementary and interrelated levels—component, system, and network levels. The assessment procedure for existing bridges initiates with damage assessment based on visual inspection of bridge components and runs through weighting at component, system, and network levels to the six most important key performance indicators (KPIs) for road bridges, which are organized as graphical and numerical inputs for ranking priority maintenance. These are bridge condition assessment, structural safety, traffic safety, durability indicator, availability, and the importance of the bridge in the network. The procedure is validated on a case study set of five real bridges, using the decision-making process as an example for the small sample size. The case study bridges differ in cross-section, type, and span (which vary from 9.5 to 72 m). The bridges were built between 1958 and 2001 and are located either on state or municipal roads in Croatia. The results, in terms of condition classification and priorities of future interventions within the representative group of bridges, justify the application of the described assessment procedure. Additional digitization efforts could easily implement the described assessment approach at the infrastructure network level.
Inspection System for Vehicle Headlight Defects Based on Convolutional Neural Network
Authors: Moon Chang-Bae , Lee Jong-Yeol , Kim Dong-Seong , Kim Byeong-Man
Published: May 2021

This paper proposes a method to detect the defects in the region of interest (ROI) based on a convolutional neural network (CNN) after alignment (position and rotation calibration) of a manufacturer’s headlights to determine whether the vehicle headlights are defective. The results were compared with an existing method for distinguishing defects among the previously proposed methods. One hundred original headlight images were acquired for each of the two vehicle types for the purpose of this experiment, and 20,000 high quality images and 20,000 defective images were obtained by applying the position and rotation transformation to the original images. It was found that the method proposed in this paper demonstrated a performance improvement of more than 0.1569 (15.69% on average) as compared to the existing method.
Person Identification by Footstep Sound Using Convolutional Neural Networks
Authors: Algermissen Stephan , Hörnlein Max
Published: May 2021

Human gait is very individual and it may serve as biometric to identify people in camera recordings. Comparable results can be achieved while using the acoustic signature of human footstep sounds. This acoustic solution offers the opportunity of less installation space and the use of cost-efficient microphones when compared to visual system. In this paper, a method for person identification based on footstep sounds is proposed. First, step sounds are isolated from microphone recordings and separated into 500 ms samples. The samples are transformed with a sliding window into mel-frequency cepstral coefficients (MFCC). The result is represented as an image that serves as input to a convolutional neural network (CNN). The dataset for training and validating the CNN is recorded with five subjects in the acoustic lab of DLR. These experiments identify a total number of 1125 steps. The validation of the CNN reveals a minimum F1-score of 0.94 for all five classes and an accuracy of 0.98. The Grad-CAM method is applied to visualize the background of its decision in order to verify the functionality of the proposed CNN. Subsequently, two challenges for practical implementations, noise and different footwear, are discussed using experimental data.
Annual and Seasonal Precipitation and Their Extremes over the Tibetan Plateau and Its Surroundings in 1963–2015
Authors: Ding Jin , Cuo Lan , Zhang Yongxin , Zhang Cunjie , Liang Liqiao , Liu Zhe
Published: May 2021

Based on daily precipitation data from 115 climate stations, seasonal and annual precipitation and their extremes over the Tibetan Plateau and its surroundings (TPS) in 1963–2015 are investigated. There exists a clear southeast-northwest gradient in precipitation and extreme daily precipitation but an opposite pattern for the consecutive dry days (CDDs). The wet southeast is trending dry while the dry center and northwest are trending wet in 1963–2015. Correspondingly, there is a drying tendency over the wet basins in the southeast and a wetting tendency over the dry and semi-dry basins in the center and northwest in summer, which will affect the water resources in the corresponding areas. The increase (decrease) in precipitation tends to correspond to the increase (decrease) in maximum daily precipitation but the decrease (increase) in CDDs. Extreme precipitation events with 20-year, 50-year, 100-year, and 200-year recurrence occurred frequently in the past decades especially in the 1980s. The greatest extreme precipitation events tend to occur after the late 1990s and in the southeastern TPS. The ERA5 reanalysis and climate system indices reveal that (1) decreased moisture transports to the southeast in summer due to the weakening of the summer monsoons and the East Asian westerly jet; (2) increased moisture transports to the center in winter due to the strengthening of the winter westerly jet and north Atlantic oscillation; and (3) decreased instability over the southeast thus suppressing precipitation and increased instability over the northwest thus promoting precipitation. All these are conducive to the drying trends in the southeast and the wetting trends in the center.
Flooding Risk Assessment and Analysis Based on GIS and the TFN-AHP Method: A Case Study of Chongqing, China
Authors: Cai Shunyao , Fan Jiamin , Yang Wei
Published: May 2021

Flood risk assessment and mapping is required for management and mitigation of flood in mountain cities. However, the specific characteristics of population, society, economy, environment, transportation and other disaster-bearing bodies in various regions of mountain cities are significantly different, which increases the uncertainty of risk assessment index weight and risk assessment accuracy. To overcome these problems, the triangular fuzzy number-based analytical hierarchy process (TFN-AHP) was employed to determine the weights of eleven indexes influencing flooding. Further, the geographic information system (GIS) spatial statistics technique was introduced to investigate global regional risk pattern, as well as to identify local risk hot spots. Experiments were conducted using open data of Chongqing, China. From the results, it was observed that the TFN-AHP has a higher efficiency in flood risk assessment on mountain cities than the AHP method. The dynamically changing risk pattern and risk hot spots were explored, and the results are generally consistent with seasonal characteristics of precipitation. Lastly, sensitivity analysis of assessment factors’ weights was conducted. The comparative consequences indicate that TFN-AHP can better assess the flooding risk and can be successfully applied to urban development policy.
A Review of High-Gain Free-Electron Laser Theory
Authors: Piovella Nicola , Volpe Luca
Published: May 2021

High-gain free-electron lasers, conceived in the 1980s, are nowadays the only bright sources of coherent X-ray radiation available. In this article, we review the theory developed by R. Bonifacio and coworkers, who have been some of the first scientists envisaging its operation as a single-pass amplifier starting from incoherent undulator radiation, in the so called self-amplified spontaneous emission (SASE) regime. We review the FEL theory, discussing how the FEL parameters emerge from it, which are fundamental for describing, designing and understanding all FEL experiments in the high-gain, single-pass operation.
Canine Angiostrongylus vasorum-Induced Early Innate Immune Reactions Based on NETs Formation and Canine Vascular Endothelial Cell Activation In Vitro
Authors: Grob Daniela , Conejeros Iván , López-Osorio Sara , Velásquez Zahady D. , Segeritz Lisa , Gärtner Ulrich , Schaper Roland , Hermosilla Carlos , Taubert Anja
Published: May 2021

Due to its localization in the canine blood stream, Angiostrongylus vasorum is exposed to circulating polymorphonuclear neutrophils (PMN) and the endothelial cells of vessels. NETs release of canine PMN exposed to A. vasorum infective stages (third stage larvae, L3) and early pro-inflammatory immune reactions of primary canine aortic endothelial cells (CAEC) stimulated with A. vasorum L3-derived soluble antigens (AvAg) were analyzed. Expression profiles of the pro-inflammatory adhesion molecules ICAM-1, VCAM-1, P-selectin and E-selectin were analyzed in AvAg-stimulated CAEC. Immunofluorescence analyses demonstrated that motile A. vasorum L3 triggered different NETs phenotypes, with spread NETs (sprNETs) as the most abundant. Scanning electron microscopy confirmed that the co-culture of canine PMN with A. vasorum L3 resulted in significant larval entanglement. Distinct inter-donor variations of P-selectin, E-selectin, ICAM-1 and VCAM-1 gene transcription and protein expression were observed in CAEC isolates which might contribute to the high individual variability of pathological findings in severe canine angiostrongylosis. Even though canine NETs did not result in larval killing, the entanglement of L3 might facilitate further leukocyte attraction to their surface. Since NETs have already been documented as involved in both thrombosis and endothelium damage events, we speculate that A. vasorum-triggered NETs might play a critical role in disease outcome in vivo.
Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss
Authors: Biemann Ronald , Buß Enrico , Benndorf Dirk , Lehmann Theresa , Schallert Kay , Püttker Sebastian , Reichl Udo , Isermann Berend , Schneider Jochen G. , Saake Gunter , Heyer Robert
Published: May 2021

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (−13.7%), improved insulin sensitivity (HOMA-IR, −46.1%), and reduced levels of circulating hsCRP (−39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.
Spontaneous Non-Sustained Ventricular Tachycardia and Premature Ventricular Contractions and Their Prognostic Relevance in Patients with Cancer in Routine Care
Authors: Albrecht Annemarie , Porthun Jan , Eucker Jan , Coats Andrew , von Haehling Stephan , Pezzutto Antonio , Karakas Mahir , Riess Hanno , Keller Ulrich , Landmesser Ulf , Haverkamp Wilhelm , Anker Stefan , Anker Markus
Published: May 2021

Aims: It is largely unknown whether cancer patients seen in routine care show ventricular arrhythmias in 24 h electrocardiograms (ECGs), and whether when they are detected they carry prognostic relevance. Methods and Results: We included 261 consecutive cancer patients that were referred to the department of cardiology for 24 h ECG examination and 35 healthy controls of similar age and sex in the analysis. To reduce selection bias, cancer patients with known left ventricular ejection fraction <45% were not included in the analysis. Non–sustained ventricular tachycardia (NSVT) episodes of either ≥3 and ≥4 beats duration were more frequent in cancer patients than controls (17% vs. 0%, p = 0.0008; 10% vs. 0%, p = 0.016). Premature ventricular contractions (PVCs)/24 h were not more frequent in cancer patients compared to controls (median (IQR), 26 (2–360) vs. 9 (1–43), p = 0.06; ≥20 PVCs 53% vs. 37%, p = 0.07). During follow-up, (up to 7.2 years, median 15 months) of the cancer patients, 158 (61%) died (1-/3-/5-year mortality rates: 45% [95%CI 39–51%], 66% [95%CI 59–73%], 73% [95%CI 64–82%]). Both non-sustained ventricular tachycardia of ≥4 beats and ≥20 PVCs/24 h independently predicted mortality in univariate and multivariate survival analyses, adjusted for all other univariate predictors of mortality as well as relevant clinical factors, including cancer stage and type, performance status (ECOG), prior potentially cardiotoxic anti-cancer drug therapy, coronary artery disease, potassium concentration, and haemoglobin (multivariate adjusted hazard ratios: NSVT ≥4 beats [HR 1.76, p = 0.022], ≥20 PVCs/24 h [HR 1.63, p < 0.0064]). Conclusions: NSVT ≥4 beats and ≥20 PVCs/day seen in routine 24 h ECGs of patients with cancer carry prognostic relevance.
Clinical Predictors of Early Trial Discontinuation for Patients Participating in Phase I Clinical Trials in Oncology
Authors: Douma Joeri A. J. , Buffart Laurien M. , Sedhom Ramy , Labots Mariette , Menke-van der Houven van Oordt Willemien C. , Skardhamar Mikkjal , De Felice Anthony , Lee Esther , Dharmaraj Divya , Azad Nilofer S. , Carducci Michael A. , Verheul Henk M. W.
Published: May 2021

Despite stringent eligibility criteria for trial participation, early discontinuation often occurs in phase I trials. To better identify patients unlikely to benefit from phase I trials, we investigated predictors for early trial discontinuation. Data from 415 patients with solid tumors who participated in 66 trials were pooled for the current analysis. Early trial discontinuation was defined as (i) trial discontinuation within 28 days after start of treatment or (ii) discontinuation before administration of the first dosage in eligible patients. Multilevel logistic regression analyses were conducted to identify predictors for early trial discontinuation. Eighty-two participants (20%) demonstrated early trial discontinuation. Baseline sodium level below the lower limit of normal (OR = 2.95, 95%CI = 1.27–6.84), elevated alkaline phosphatase level > 2.5 times the upper limit of normal (OR = 2.72, 95%CI = 1.49–4.99), performance score ≥ 1 (OR = 2.07, 95%CI = 1.03–4.19) and opioid use (OR = 1.82, 95%CI = 1.07–3.08) were independent predictors for early trial discontinuation. Almost 50% of the patients with hyponatremia and all four patients in whom all four predictors were present together discontinued the trial early. Hyponatremia, elevated alkaline phosphatase level, performance score ≥ 1 and opioid use were identified as significant predictors for early trial discontinuation. Hyponatremia was the strongest predictor and deserves consideration for inclusion in eligibility criteria for future trials.
High Temperature Drives Topoisomerase Mediated Chromosomal Break Repair Pathway Choice
Authors: Ashour Mohamed E. , Allam Walaa , Elsayed Waheba , Atteya Reham , Elserafy Menattallah , Magdeldin Sameh , Hassan Mohamed K. , El-Khamisy Sherif F.
Published: May 2021

Cancer-causing mutations often arise from inappropriate DNA repair, yet acute exposure to DNA damage is widely used to treat cancer. The challenge remains in how to specifically induce excessive DNA damage in cancer cells while minimizing the undesirable effects of genomic instability in noncancerous cells. One approach is the acute exposure to hyperthermia, which suppresses DNA repair and synergizes with radiotherapy and chemotherapy. An exception, however, is the protective effect of hyperthermia on topoisomerase targeting therapeutics. The molecular explanation for this conundrum remains unclear. Here, we show that hyperthermia suppresses the level of topoisomerase mediated single- and double-strand breaks induced by exposure to topoisomerase poisons. We further uncover that, hyperthermia suppresses hallmarks of genomic instability induced by topoisomerase targeting therapeutics by inhibiting nuclease activities, thereby channeling repair to error-free pathways driven by tyrosyl-DNA phosphodiesterases. These findings provide an explanation for the protective effect of hyperthermia from topoisomerase-induced DNA damage and may help to explain the inverse relationship between cancer incidence and temperature. They also pave the way for the use of controlled heat as a therapeutic adjunct to topoisomerase targeting therapeutics.
Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia
Authors: Sági Judit C. , Gézsi András , Egyed Bálint , Jakab Zsuzsanna , Benedek Noémi , Attarbaschi Andishe , Köhrer Stefan , Sipek Jakub , Winkowska Lucie , Zaliova Marketa , Anastasopoulou Stavroula , Wolthers Benjamin Ole , Ranta Susanna , Szalai Csaba , Kovács Gábor T. , Semsei Ágnes F. , Erdélyi Dániel J.
Published: May 2021

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.
Survival Following Relapse in Children with Acute Myeloid Leukemia: A Report from AML-BFM and COG
Authors: Rasche Mareike , Zimmermann Martin , Steidel Emma , Alonzo Todd , Aplenc Richard , Bourquin Jean-Pierre , Boztug Heidrun , Cooper Todd , Gamis Alan , Gerbing Robert , Janotova Iveta , Klusmann Jan-Henning , Lehrnbecher Thomas , Mühlegger Nora , Neuhoff Nils , Niktoreh Naghmeh , Sramkova Lucie , Stary Jan , Waack Katharina , Walter Christiane , Creutzig Ursula , Dworzak Michael , Kaspers Gertjan , Kolb Edward , Reinhardt Dirk
Published: May 2021

Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, p = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies.
Enhanced Antitumor Effect of Trastuzumab and Duligotuzumab or Ipatasertib Combination in HER-2 Positive Gastric Cancer Cells
Authors: Laterza Maria Maddalena , Ciaramella Vincenza , Facchini Bianca Arianna , Franzese Elisena , Liguori Carmela , De Falco Stefano , Coppola Paola , Pompella Luca , Tirino Giuseppe , Berretta Massimiliano , Montella Liliana , Facchini Gaetano , Ciardiello Fortunato , de Vita Ferdinando
Published: May 2021

The anti-HER2 monoclonal antibody trastuzumab is a key drug for the treatment of HER2-positive gastric cancer (GC); however, its activity is often limited by the onset of resistance and mechanisms of resistance are still poorly understood. Several targeted agents showed synergistic activity by concomitant use with trastuzumab in vitro and are under clinical investigation. The aim of this study was to assess the antitumor activity of duligotuzumab, an anti HER3/EGFR antibody or ipatasertib, an AKT inhibitor, combined with trastuzumab in a panel of HER2-positive human gastric cancer cells (GCC), and the efficacy of such combinations in HER2-resistant cells. We have assessed the efficacy of duligotuzumab or ipatasertib and trastuzumab in combination, analyzing proliferation, migration and apoptosis and downstream intracellular signaling in vitro on human HER2-positive GCC (NCI-N87, OE33, OE19) and in negative HER2 GCC (MKN28). We observed a reduction of proliferation, migration and apoptotic rate in HER2-positive OE33, OE19 and N87 cell lines with the combination of duligotuzumab or ipatasertib plus trastuzumab. In particular, in OE33 and OE19 cell lines, the same combined treatment inhibited the activation of proteins downstream of HER2, HER3, AKT and MAPK pathways. Targeting both HER2 and HER3, or HER2 and AKT, results in an improved antitumor effect on HER2-positive GCC.
The Isocyanurate-Carbamate-Bridged Hybrid Mesoporous Organosilica: An Exceptional Anchor for Pd Nanoparticles and a Unique Catalyst for Nitroaromatics Reduction
Authors: Zebardasti Ali , Dekamin Mohammad , Doustkhah Esmail
Published: May 2021

Hybridisation of mesoporous organosilicas (MO) to reinforce the surface capability in adsorption and stabilisation of noble metal nanoparticles is of great attention in generating/supporting noble metal within their matrices and transforming them into efficient heterogeneous catalysts. Here, we used a unique hybrid of organic-inorganic mesoporous silica in which pore profile pattern was similar to the well-known mesoporous silica, SBA-15 for catalysis. This hybrid mesoporous organosilica was further engaged as a support in the synthesis and stabilisation of Pd nanoparticles on its surface, and then, the obtained Pd-supported MO was employed as a heterogeneous green catalyst in the conversion of aqueous p-nitrophenol (PNP) to p-aminophenol (PAP) at room temperature with efficient recyclability.
Photoelectrochemical Water Oxidation by Cobalt Cytochrome C Integrated-ATO Photoanode
Authors: Casadevall Carla , Zhang Haojie , Chen Shaojiang , Sommer Dayn J. , Seo Dong-Kyun , Ghirlanda Giovanna
Published: May 2021

Here, we report the immobilization of Co-protoporphyrin IX (Co-PPIX) substituted cytochrome c (Co-cyt c) on Antimony-doped Tin Oxide (ATO) as a catalyst for photoelectrochemical oxidation of water. Under visible light irradiation (λ > 450 nm), the ATO-Co-cyt c photoanode displays ~6-fold enhancement in photocurrent density relative to ATO-Co-PPIX at 0.25 V vs. RHE at pH 5.0. The light-induced water oxidation activity of the system was demonstrated by detecting evolved stoichiometric oxygen by gas chromatography, and incident photon to current efficiency was measured as 4.1% at 450 nm. The faradaic efficiency for the generated oxygen was 97%, with a 671 turnover number (TON) for oxygen. The current density had a slow decay over the course of 6 h of constant irradiation and applied potential, which exhibits the robustness of catalyst-ATO interaction.
The Role of GH/IGF Axis in Dento-Alveolar Complex from Development to Aging and Therapeutics: A Narrative Review
Authors: Koffi Kouassi Armel , Doublier Sophie , Ricort Jean-Marc , Babajko Sylvie , Nassif Ali , Isaac Juliane
Published: May 2021

The GH/IGF axis is a major regulator of bone formation and resorption and is essential to the achievement of normal skeleton growth and homeostasis. Beyond its key role in bone physiology, the GH/IGF axis has also major pleiotropic endocrine and autocrine/paracrine effects on mineralized tissues throughout life. This article aims to review the literature on GH, IGFs, IGF binding proteins, and their respective receptors in dental tissues, both epithelium (enamel) and mesenchyme (dentin, pulp, and tooth-supporting periodontium). The present review re-examines and refines the expression of the elements of the GH/IGF axis in oral tissues and their in vivo and in vitro mechanisms of action in different mineralizing cell types of the dento-alveolar complex including ameloblasts, odontoblasts, pulp cells, cementoblasts, periodontal ligament cells, and jaw osteoblasts focusing on cell-specific activities. Together, these data emphasize the determinant role of the GH/IGF axis in physiological and pathological development, morphometry, and aging of the teeth, the periodontium, and oral bones in humans, rodents, and other vertebrates. These advancements in oral biology have elicited an enormous interest among investigators to translate the fundamental discoveries on the GH/IGF axis into innovative strategies for targeted oral tissue therapies with local treatments, associated or not with materials, for orthodontics and the repair and regeneration of the dento-alveolar complex and oral bones.
Immunoproteasome Activity and Content Determine Hematopoietic Cell Sensitivity to ONX-0914 and to the Infection of Cells with Lentiviruses
Authors: Vagapova Elmira , Burov Alexander , Spasskaya Daria , Lebedev Timofey , Astakhova Tatiana , Spirin Pavel , Prassolov Vladimir , Karpov Vadim , Morozov Alexey
Published: May 2021

Proteasomes are intracellular structures responsible for protein degradation. The 20S proteasome is a core catalytic element of the proteasome assembly. Variations of catalytic subunits generate different forms of 20S proteasomes including immunoproteasomes (iPs), which are present mostly in the immune cells. Certain cells of the immune system are primary targets of retroviruses. It has been shown that several viral proteins directly affect proteasome functionality, while inhibition of proteasome activity with broad specificity proteasome inhibitors stimulates viral transduction. Here we specifically addressed the role of the immunoproteasomes during early stages of viral transduction and investigated the effects of specific immunoproteasome inhibition and activation prior to infection using a panel of cell lines. Inhibition of iPs in hematopoietic cells with immunoproteasome-specific inhibitor ONX-0914 resulted in increased infection by VSV-G pseudotyped lentiviruses. Moreover, a tendency for increased infection of cloned cells with endogenously decreased proteasome activity was revealed. Conversely, activation of iPs by IFN-γ markedly reduced the viral infectivity, which was rescued upon simultaneous immunoproteasome inhibition. Our results indicate that immunoproteasome activity might be determinative for the cellular antiretroviral resistance at least for the cells with high iP content. Finally, therapeutic application of immunoproteasome inhibitors might promote retroviral infection of cells in vivo.
Group Contribution Revisited: The Enthalpy of Formation of Organic Compounds with “Chemical Accuracy”
Authors: Meier Robert J.
Published: May 2021

Group contribution (GC) methods to predict thermochemical properties are of eminent importance to process design. Compared to previous works, we present an improved group contribution parametrization for the heat of formation of organic molecules exhibiting chemical accuracy, i.e., a maximum 1 kcal/mol (4.2 kJ/mol) difference between the experiment and model, while, at the same time, minimizing the number of parameters. The latter is extremely important as too many parameters lead to overfitting and, therewith, to more or less serious incorrect predictions for molecules that were not within the data set used for parametrization. Moreover, it was found to be important to explicitly account for common chemical knowledge, e.g., geminal effects or ring strain. The group-related parameters were determined step-wise: first, alkanes only, and then only one additional group in the next class of molecules. This ensures unique and optimal parameter values for each chemical group. All data will be made available, enabling other researchers to extend the set to other classes of molecules.
Bonding SiCp/Al Composites via Laser-Induced Exothermic Reactions
Authors: Wang Yifeng , Feng Guangjie , Wei Yan , Hu Bingxu , Deng Dean
Published: May 2021

In this paper, the SiCp/Al composites were bonded via laser-induced exothermic reactions of a Ni–Al–Zr interlayer. The Ni–Al–Zr interlayer was designed based on its exothermic property and chemical compatibility with the SiCp/Al composites. The influences of the interlayer composition and bonding pressure on the joint microstructure and shear strength were investigated. Results indicated that high exothermic reactions occurred in the Ni–Al–Zr interlayer and realized the reliable bonding with the SiCp/Al composites. The interlayer products were the eutectic structure of NiAl+Ni2AlZr+Ni3Al5Zr2. NiAl3 and Ni2Al3 reaction layers were formed at the bonding interfaces. The interlayer composition and the bonding pressure determined the morphology and distribution of the voids and the reaction layers, thus controlling the joint shear strength. When the SiCp/Al composites were bonded using the interlayer with the Zr content of 15 wt.% under the bonding pressure of 3 MPa, the joint shear strength reached the maximum of 24 MPa.
Estimation of Ferroelectric Material Properties and Phase-Shifter Design Key Parameters Influence on Its Figure of Merit for Optimization of Development Process
Authors: Gagarin Alexander , Platonov Roman , Legkova Tatiana , Altynnikov Andrey
Published: May 2021

A model of the estimation of the ferroelectric-based phase-shifter figure of merit concerning the material properties and phase-shifter design parameters is presented. The influence of ferroelectric material tunability and losses on phase-shifter characteristics are analyzed. Two approaches to phase-shifter design (transmission line and band-pass filter) are considered. The review of the published results on the ferroelectric phase-shifter design was performed to approve the method proposed. Recommendations to optimize the phase-shifter development process are suggested on the basis of the elaborated model and analysis performed.
On the Use of Stable Hydrogen Isotope Measurements (δ2H) to Discern Trophic Level in Avian Terrestrial Food Webs
Authors: van Wijk Rien E. , Barshep Yahkat , Hobson Keith A.
Published: May 2021

The measurement of stable hydrogen isotope ratios (δ2H) in animal tissues is a popular means of inferring spatial origins and migratory connections. However, the use of this isotope to infer diet and potentially trophic position remains poorly understood, especially in non-aquatic terrestrial ecosystems. In many animal communities, tissue δ15N values are strongly associated with trophic position. Correlations between tissue δ2H and δ15N are expected, then, if δ2H is affected by trophic enrichment of 2H. In addition, within sites, we would expect higher tissue δ2H values in insectivorous species compared to granivores or nectarivores. We tested these hypotheses for two resident avian communities in Nigeria consisting of 30 species representing a range of dietary guilds (granivores, frugivores, nectarivores, omnivores, insectivores) by comparing feather δ2H, δ15N and δ13C values. We found considerable isotopic overlap among all guilds except granivores, with no clear pattern of enrichment in 2H with trophic position. However, at one of our sites (open scrubland), feather δ2H was positively correlated with feather δ15N (R2 = 0.30) compared to a closed canopy forest site (R2 = 0.09). Our results indicate weak evidence for predictable trophic enrichment in 2H in terrestrial environments and indicate that controlled studies are now required to definitively elucidate the behavior of H isotopes in terrestrial food webs.
Towards a Microwave Imaging System for Continuous Monitoring of Liver Tumor Ablation: Design and In Silico Validation of an Experimental Setup
Authors: Wang Mengchu , Scapaticci Rosa , Cavagnaro Marta , Crocco Lorenzo
Published: May 2021

Liver cancer is one of the most common liver malignancies worldwide. Thermal ablation has been recognized as a promising method for its treatment, with a significant impact on clinical practice. However, the treatment’s effectiveness is heavily dependent on the experience of the clinician and would improve if paired with an image-guidance device for treatment monitoring. Conventional imaging modalities, such as computed tomography, ultrasound, and magnetic resonance imaging, show some disadvantages, motivating interest in alternative technologies. In this framework, microwave imaging was recently proposed as a potential candidate, being capable of implementing real-time monitoring by means of low-cost and portable devices. In this work, the in silico assessment of a microwave imaging device specifically designed for liver ablation monitoring is presented. To this end, an imaging experiment involving eight Vivaldi antennas in an array configuration and a practically realizable liver phantom mimicking the evolving treatment was simulated. In particular, since the actual phantom will be realized by 3D printing technology, the effect of the plastic shells containing tissues mimicking materials was investigated and discussed. The outcomes of this study confirm that the presence of printing materials does not impair the significance of the experiments and that the designed device is capable of providing 3D images of the ablated region conveying information on its extent and evolution. Moreover, the observed results suggest possible improvements to the system, paving the way for the next stage in which the device will be implemented and experimentally assessed in the same conditions as those simulated in this study.
Long-Term Data Traffic Forecasting for Network Dimensioning in LTE with Short Time Series
Authors: Gijón Carolina , Toril Matías , Luna-Ramírez Salvador , Marí-Altozano María Luisa , Ruiz-Avilés José María
Published: May 2021

Network dimensioning is a critical task in current mobile networks, as any failure in this process leads to degraded user experience or unnecessary upgrades of network resources. For this purpose, radio planning tools often predict monthly busy-hour data traffic to detect capacity bottlenecks in advance. Supervised Learning (SL) arises as a promising solution to improve predictions obtained with legacy approaches. Previous works have shown that deep learning outperforms classical time series analysis when predicting data traffic in cellular networks in the short term (seconds/minutes) and medium term (hours/days) from long historical data series. However, long-term forecasting (several months horizon) performed in radio planning tools relies on short and noisy time series, thus requiring a separate analysis. In this work, we present the first study comparing SL and time series analysis approaches to predict monthly busy-hour data traffic on a cell basis in a live LTE network. To this end, an extensive dataset is collected, comprising data traffic per cell for a whole country during 30 months. The considered methods include Random Forest, different Neural Networks, Support Vector Regression, Seasonal Auto Regressive Integrated Moving Average and Additive Holt–Winters. Results show that SL models outperform time series approaches, while reducing data storage capacity requirements. More importantly, unlike in short-term and medium-term traffic forecasting, non-deep SL approaches are competitive with deep learning while being more computationally efficient.
Input Impedance Analysis of Wearable Antenna and Experimental Study with Real Human Subjects: Differences between Individual Users
Authors: Muramatsu Dairoku , Sasaki Ken
Published: May 2021

In human body communication (HBC) systems, radio-frequency signals are excited in the human body through a wearable antenna comprised of electrodes that are in contact with the surface of the body. The input impedance characteristics of these antennas are important design parameters for increasing transmission efficiency and reducing signal reflection, similar to other wireless circuits. In this study, we discuss variations of input impedance characteristics of a wearable antenna prototype caused by differences among real human subjects. A realistic human arm model is used for simulations, and the analytical results obtained are compared to measured data obtained from real human subjects, in a range from 1 to 100 MHz. The simulations of input impedance characteristics from antennas worn on the wrists of male and female models with dry and wet skin conditions show that the impedance variation between genders is small. The moisture condition of the skin has little influence on frequencies exceeding several MHz. Measurements with a proto-type wearable antenna and 22 real human subjects reveal that HBC is robust against the variations of individual users from the viewpoint of the voltage standing wave ratio. Moreover, a simplified rectangular prism model is proposed to analyze the thickness of body tissues. Comparisons of measured input impedances indicate that individual differences in impedance are mainly due to differences in the thickness of skin and fat layers. The model also enables us to design the antenna prototype without multiple subject experiments.
Evaluating the Pollution Risk of Soil Due to Natural Drainage of Orange Peel: First Results
Authors: Andiloro Serafina , Calabrò Paolo Salvatore , Folino Adele , Zema Demetrio Antonio , Zimbone Santo Marcello
Published: May 2021

Orange peel (OP), the main residue of the citrus industry, is usually used for animal feeding and soil fertilisation if more advanced options are lacking. In areas with warm and dry climatic conditions, OP is land-spread for solar-drying on the fields, the leachate produced is a potential pollution factor for soil especially due to the release of organic matter; heavy rainfalls could even aggravate the hazard. Since literature does not report any quantitative evaluation of this risk, this study presents three OP drainage tests in lysimeters, where OP was left releasing leachate on a soil layer. A first test was carried out on raw OP naturally draining, while, in a second and a third test, a rainfall of 100 mm was applied on already drained and solar-dried OP, respectively. After drainage, raw OP reduced its initial volume by about 90% and the leachate production accounted only for about 20% of the initial volume. The simulated rainfall produced even lower volumes of leachate (2–3% of the initial biomass volume), in spite of the high rainfall volume and long drainage time after its application. The COD concentration in the leachate from the raw OP was significantly higher than those produced after simulated rainfall. However, the COD amount released to the soil was negligible. The lysimetric tests showed that the release of leachate occurs mainly during the first phase of drainage and that rainfall is absorbed and does not produce significant leaching. Overall, the risk of soil pollution due to the natural drainage of OP is negligible, due to both limited amounts of leachate and organic loading.