bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration of Camera and Flash LiDAR System with a Triangular Pyramid Target
Authors: Bu Zean , Sun Changku , Wang Peng , Dong Hang
Published: January 2021

Calibration between multiple sensors is a fundamental procedure for data fusion. To address the problems of large errors and tedious operation, we present a novel method to conduct the calibration between light detection and ranging (LiDAR) and camera. We invent a calibration target, which is an arbitrary triangular pyramid with three chessboard patterns on its three planes. The target contains both 3D information and 2D information, which can be utilized to obtain intrinsic parameters of the camera and extrinsic parameters of the system. In the proposed method, the world coordinate system is established through the triangular pyramid. We extract the equations of triangular pyramid planes to find the relative transformation between two sensors. One capture of camera and LiDAR is sufficient for calibration, and errors are reduced by minimizing the distance between points and planes. Furthermore, the accuracy can be increased by more captures. We carried out experiments on simulated data with varying degrees of noise and numbers of frames. Finally, the calibration results were verified by real data through incremental validation and analyzing the root mean square error (RMSE), demonstrating that our calibration method is robust and provides state-of-the-art performance.
Nonlinear Dynamic Response of a Precast Concrete Building to Sudden Column Removal
Authors: Ravasini Simone , Belletti Beatrice , Brunesi Emanuele , Nascimbene Roberto , Parisi Fulvio
Published: January 2021

Robustness of reinforced concrete (RC) structures is an ongoing challenging research topic in the engineering community. During an extreme event, the loss of vertical load-bearing elements can activate large-deformation resisting mechanisms such as membrane and catenary actions in beams and floor slabs of cast-in-situ RC buildings to resist gravity loads. However, few studies have been conducted for precast concrete (PC) buildings, especially focused on the capacity of such structures to withstand column loss scenarios, which mainly relies on connection strength. Additional resistance resource and alternate load paths could be reached via tying systems. In this paper, the progressive collapse resistance of a PC frame building is analyzed by means of nonlinear dynamic finite element analyses focusing on the fundamental roles played by beam-to-column connection strength and tying reinforcement. A simplified modelling approach is illustrated in order to investigate the response of such a structural typology to a number of sudden column-removal scenarios. The relative simplicity of the modelling technique is considered useful for engineering practice, providing new input for further research in this field.
Adaptive Aggregated Attention Network for Pulmonary Nodule Classification
Authors: Xia Kai , Chi Jianning , Gao Yuan , Jiang Yang , Wu Chengdong
Published: January 2021

Lung cancer has one of the highest cancer mortality rates in the world and threatens people’s health. Timely and accurate diagnosis can greatly reduce the number of deaths. Therefore, an accurate diagnosis system is extremely important. The existing methods have achieved significant performances on lung cancer diagnosis, but they are insufficient in fine-grained representations. In this paper, we propose a novel attentive method to differentiate malignant and benign pulmonary nodules. Firstly, the residual attention network (RAN) and squeeze-and-excitation network (SEN) were utilized to extract spatial and contextual features. Secondly, a novel multi-scale attention network (MSAN) was proposed to capture multi-scale attention features automatically, and the MSAN integrated the advantages of the spatial attention mechanism and contextual attention mechanism, which are very important for capturing the salient features of nodules. Finally, the gradient boosting machine (GBM) algorithm was used to differentiate malignant and benign nodules. We conducted a series of experiments on the Lung Image Database Consortium image collection (LIDC-IDRI) database, achieving an accuracy of 91.9%, a sensitivity of 91.3%, a false positive rate of 8.0%, and an F1-score of 91.0%. The experimental results demonstrate that our proposed method outperforms the state-of-the-art methods with respect to accuracy, false positive rate, and F1-Score.
A Review on Recent Advancements of Graphene and Graphene-Related Materials in Biological Applications
Authors: Catania Federica , Marras Elena , Giorcelli Mauro , Jagdale Pravin , Lavagna Luca , Tagliaferro Alberto , Bartoli Mattia
Published: January 2021

Graphene is the most outstanding material among the new nanostructured carbonaceous species discovered and produced. Graphene’s astonishing properties (i.e., electronic conductivity, mechanical robustness, large surface area) have led to a deep change in the material science field. In this review, after a brief overview of the main characteristics of graphene and related materials, we present an extensive overview of the most recent achievements in biological uses of graphene and related materials.
Iterative Learning for K-Approval Votes in Crowdsourcing Systems
Authors: Kim Joonyoung , Lee Donghyeon , Jung Kyomin
Published: January 2021

Crowdsourcing systems have emerged as cornerstones to collect large amounts of qualified data in various human-powered problems with a relatively low budget. In eliciting the wisdom of crowds, many web-based crowdsourcing platforms have encouraged workers to select top-K alternatives rather than just one choice, which is called “K-approval voting”. This kind of setting has the advantage of inducing workers to make fewer mistakes when they respond to target tasks. However, there is not much work on inferring the correct answer from crowd-sourced data via a K-approval voting. In this paper, we propose a novel and efficient iterative algorithm to infer correct answers for a K-approval voting, which can be directly applied to real-world crowdsourcing systems. We analyze the average performance of our algorithm, and prove the theoretical error bound that decays exponentially in terms of the quality of workers and the number of queries. Through extensive experiments including the mixed case with various types of tasks, we show that our algorithm outperforms Expectation and Maximization (EM) and existing baseline algorithms.
Impact of Bimodal Particle Size Distribution Ratio of Functional Calcium Carbonate Filler on Thermal and Flowability Properties of Polyamide 12
Authors: Ippolito Fabio , Hübner Gunter , Claypole Tim , Gane Patrick
Published: January 2021

In previous investigations, it was shown that the melting, as well as crystallization behavior of polyamide 12, could be manipulated by adjusting the particle size distribution of calcium carbonate as a functional filler. It was demonstrated that the melt properties of this compound show a significant dependency on the filler volume-based particle size. As finer and narrower the calcium carbonate particles in the polymer matrix become, the less influence the filler has on the melting properties, influencing the melt flow less significantly than the same surface amount of broad size distribution coarse calcium carbonate filler particles. However, due to increased nucleation, the crystallization behavior on cooling showed a markedly more rapid onset in the case of fine sub-micrometer filler particle size. To control further and optimize the thermal response properties of a filling compound for improved properties in additive manufacturing processing through selective laser sintering, the possibility to combine precisely defined particle size distributions has been studied, thereby combining the benefits of each particle size range within the chosen material size distribution contributes to the matrix. The melt flow at 190 °C, the melting speed, melting and crystallization point as well as crystallization time at 170 °C were analyzed. The thermal and flow properties of a polyamide 12 matrix can potentially be optimized with a combination of a precise amount of coarse and fine calcium carbonate filler. The improvements were exemplified using a twin-screw extruder for compounding, indicating the potential for optimizing functionally filled polymer in additive manufacturing.
Object-Level Semantic Map Construction for Dynamic Scenes
Authors: Kang Xujie , Li Jing , Fan Xiangtao , Jian Hongdeng , Xu Chen
Published: January 2021

Visual simultaneous localization and mapping (SLAM) is challenging in dynamic environments as moving objects can impair camera pose tracking and mapping. This paper introduces a method for robust dense bject-level SLAM in dynamic environments that takes a live stream of RGB-D frame data as input, detects moving objects, and segments the scene into different objects while simultaneously tracking and reconstructing their 3D structures. This approach provides a new method of dynamic object detection, which integrates prior knowledge of the object model database constructed, object-oriented 3D tracking against the camera pose, and the association between the instance segmentation results on the current frame data and an object database to find dynamic objects in the current frame. By leveraging the 3D static model for frame-to-model alignment, as well as dynamic object culling, the camera motion estimation reduced the overall drift. According to the camera pose accuracy and instance segmentation results, an object-level semantic map representation was constructed for the world map. The experimental results obtained using the TUM RGB-D dataset, which compares the proposed method to the related state-of-the-art approaches, demonstrating that our method achieves similar performance in static scenes and improved accuracy and robustness in dynamic scenes.
Enhancement of Multi-Target Tracking Performance via Image Restoration and Face Embedding in Dynamic Environments
Authors: Kim Ji Seong , Chang Doo Soo , Choi Yong Suk
Published: January 2021

In this paper, we propose several methods to improve the performance of multiple object tracking (MOT), especially for humans, in dynamic environments such as robots and autonomous vehicles. The first method is to restore and re-detect unreliable results to improve the detection. The second is to restore noisy regions in the image before the tracking association to improve the identification. To implement the image restoration function used in these two methods, an image inference model based on SRGAN (super-resolution generative adversarial networks) is used. Finally, the third method includes an association method using face features to reduce failures in the tracking association. Three distance measurements are designed so that this method can be applied to various environments. In order to validate the effectiveness of our proposed methods, we select two baseline trackers for comparative experiments and construct a robotic environment that interacts with real people and provides services. Experimental results demonstrate that the proposed methods efficiently overcome dynamic situations and show favorable performance in general situations.
Research on Segmentation and Classification of Heart Sound Signals Based on Deep Learning
Authors: He Yi , Li Wuyou , Zhang Wangqi , Zhang Sheng , Pi Xitian , Liu Hongying
Published: January 2021

The heart sound signal is one of the signals that reflect the health of the heart. Research on the heart sound signal contributes to the early diagnosis and prevention of cardiovascular diseases. As a commonly used deep learning network, convolutional neural network (CNN) has been widely used in images. In this paper, the method of analyzing heart sound through using CNN has been studied. Firstly, the original data set was preprocessed, and then the heart sounds were segmented on U-net, based on the deep CNN. Finally, the classification of heart sounds was completed through CNN. The data from 2016 PhysioNet/CinC Challenge was utilized for algorithm validation, and the following results were obtained. When the heart sound segmented, the overall accuracy rate was 0.991, the accuracy of the first heart sound was 0.991, the accuracy of the systolic period was 0.996, the accuracy of the second heart sound was 0.996, and the accuracy of the diastolic period was 0.997, and the average accuracy rate was 0.995; While in classification, the accuracy was 0.964, the sensitivity was 0.781, and the specificity was 0.873. These results show that deep learning based on CNN shows good performance in the segmentation and classification of the heart sound signal.
Future Projections and Uncertainty Assessment of Precipitation Extremes in the Korean Peninsula from the CMIP6 Ensemble with a Statistical Framework
Authors: Shin Yonggwan , Shin Yire , Hong Juyoung , Kim Maeng-Ki , Byun Young-Hwa , Boo Kyung-On , Chung Il-Ung , Park Doo-Sun R. , Park Jeong-Soo
Published: January 2021

Scientists occasionally predict projected changes in extreme climate using multi-model ensemble methods that combine predictions from individual simulation models. To predict future changes in precipitation extremes in the Korean peninsula, we examined the observed data and 21 models of the Coupled Model Inter-Comparison Project Phase 6 (CMIP6) over East Asia. We applied generalized extreme value distribution (GEVD) to a series of annual maximum daily precipitation (AMP1) data. Multivariate bias-corrected simulation data under three shared socioeconomic pathway (SSP) scenarios—namely, SSP2-4.5, SSP3-7.0, and SSP5-8.5—were used. We employed a model weighting method that accounts for both performance and independence (PI-weighting). In calculating the PI-weights, two shape parameters should be determined, but usually, a perfect model test method requires a considerable amount of computing time. To address this problem, we suggest simple ways for selecting two shape parameters based on the chi-square statistic and entropy. Variance decomposition was applied to quantify the uncertainty of projecting the future AMP1. Return levels spanning over 20 and 50 years, as well as the return periods relative to the reference years (1973–2010), were estimated for three overlapping periods in the future, namely, period 1 (2021–2050), period 2 (2046–2075), and period 3 (2071–2100). From these analyses, we estimated that the relative increases in the observations for the spatial median 20-year return level will be approximately 18.4% in the SSP2-4.5, 25.9% in the SSP3-7.0, and 41.7% in the SSP5-8.5 scenarios, respectively, by the end of the 21st century. We predict that severe rainfall will be more prominent in the southern and central parts of the Korean peninsula.
Zebrafish Models of Photoreceptor Dysfunction and Degeneration
Authors: Noel Nicole C. L. , MacDonald Ian M. , Allison W. Ted
Published: January 2021

Zebrafish are an instrumental system for the generation of photoreceptor degeneration models, which can be utilized to determine underlying causes of photoreceptor dysfunction and death, and for the analysis of potential therapeutic compounds, as well as the characterization of regenerative responses. We review the wealth of information from existing zebrafish models of photoreceptor disease, specifically as they relate to currently accepted taxonomic classes of human rod and cone disease. We also highlight that rich, detailed information can be derived from studying photoreceptor development, structure, and function, including behavioural assessments and in vivo imaging of zebrafish. Zebrafish models are available for a diversity of photoreceptor diseases, including cone dystrophies, which are challenging to recapitulate in nocturnal mammalian systems. Newly discovered models of photoreceptor disease and drusenoid deposit formation may not only provide important insights into pathogenesis of disease, but also potential therapeutic approaches. Zebrafish have already shown their use in providing pre-clinical data prior to testing genetic therapies in clinical trials, such as antisense oligonucleotide therapy for Usher syndrome.
Isolation, Identification, and Bioinformatic Analysis of Antibacterial Proteins and Peptides from Immunized Hemolymph of Red Palm Weevil Rhynchophorus ferrugineus
Authors: Knutelski Stanisław , Awad Mona , Łukasz Natalia , Bukowski Michał , Śmiałek Justyna , Suder Piotr , Dubin Grzegorz , Mak Paweł
Published: January 2021

Red palm weevil (Rhynchophorus ferrugineus Olivier, 1791, Coleoptera: Curculionidae) is a destructive pest of palms, rapidly extending its native geographical range and causing large economic losses worldwide. The present work describes isolation, identification, and bioinformatic analysis of antibacterial proteins and peptides from the immunized hemolymph of this beetle. In total, 17 different bactericidal or bacteriostatic compounds were isolated via a series of high-pressure liquid chromatography steps, and their partial amino acid sequences were determined by N-terminal sequencing or by mass spectrometry. The bioinformatic analysis of the results facilitated identification and description of corresponding nucleotide coding sequences for each peptide and protein, based on the recently published R. ferrugineus transcriptome database. The identified compounds are represented by several well-known bactericidal factors: two peptides similar to defensins, one cecropin-A1-like peptide, and one attacin-B-like protein. Interestingly, we have also identified some unexpected compounds comprising five isoforms of pheromone-binding proteins as well as seven isoforms of odorant-binding proteins. The particular role of these factors in insect response to bacterial infection needs further investigation.
GADD45β Regulates Hepatic Gluconeogenesis via Modulating the Protein Stability of FoxO1
Authors: Kim Hyunmi , Lee Da Som , An Tae Hyeon , Park Tae-Jun , Lee Eun-Woo , Han Baek Soo , Kim Won Kon , Lee Chul-Ho , Lee Sang Chul , Oh Kyoung-Jin , Bae Kwang-Hee
Published: January 2021

Increased hepatic gluconeogenesis is one of the main contributors to the development of type 2 diabetes. Recently, it has been reported that growth arrest and DNA damage-inducible 45 beta (GADD45β) is induced under both fasting and high-fat diet (HFD) conditions that stimulate hepatic gluconeogenesis. Here, this study aimed to establish the molecular mechanisms underlying the novel role of GADD45β in hepatic gluconeogenesis. Both whole-body knockout (KO) mice and adenovirus-mediated knockdown (KD) mice of GADD45β exhibited decreased hepatic gluconeogenic gene expression concomitant with reduced blood glucose levels under fasting and HFD conditions, but showed a more pronounced effect in GADD45β KD mice. Further, in primary hepatocytes, GADD45β KD reduced glucose output, whereas GADD45β overexpression increased it. Mechanistically, GADD45β did not affect Akt-mediated forkhead box protein O1 (FoxO1) phosphorylation and forskolin-induced cAMP response element-binding protein (CREB) phosphorylation. Rather it increased FoxO1 transcriptional activity via enhanced protein stability of FoxO1. Further, GADD45β colocalized and physically interacted with FoxO1. Additionally, GADD45β deficiency potentiated insulin-mediated suppression of hepatic gluconeogenic genes, and it were impeded by the restoration of GADD45β expression. Our finding demonstrates GADD45β as a novel and essential regulator of hepatic gluconeogenesis. It will provide a deeper understanding of the FoxO1-mediated gluconeogenesis.
Splenectomy Prior to Experimental Induction of Autoimmune Hepatitis Promotes More Severe Hepatic Inflammation, Production of IL-17 and Apoptosis
Authors: Buitrago-Molina Laura Elisa , Dywicki Janine , Noyan Fatih , Trippler Martin , Pietrek Julia , Schlue Jerome , Manns Michael P. , Wedemeyer Heiner , Jaeckel Elmar , Hardtke-Wolenski Matthias
Published: January 2021

Autoimmune hepatitis (AIH) is detected at a late stage in the course of the disease. Therefore, induction and etiology are largely unclear. It is controversial if the induction of autoimmunity occurs in the liver or in the spleen. In our experimental murine AIH model, the induction of autoimmunity did not occur in the spleen. Instead, a protective role of the spleen could be more likely. Therefore, we splenectomized mice followed by induction of experimental murine AIH. Splenectomized mice presented more severe portal inflammation. Furthermore, these mice had more IL-17, IL-23 receptor (IL-23R) and caspase 3 (casp3) and a decreased amount of erythropoietin in serum, while intrahepatic T cell compartments were unaffected. These results indicate that the spleen is not necessary for induction of AIH, and splenectomy disrupts the ability to immune regulate the intensity of hepatic inflammation, production of IL-17 and apoptosis.
Does Platelet-Rich Fibrin Enhance the Early Angiogenetic Potential of Different Bone Substitute Materials? An In Vitro and In Vivo Analysis
Authors: Blatt Sebastian , Thiem Daniel G. E. , Pabst Andreas , Al-Nawas Bilal , Kämmerer Peer W.
Published: January 2021

The impaired angiogenic potential of bone substitute materials (BSMs) may limit regenerative processes. Therefore, changes in the angiogenetic properties of different BSMs in combination with platelet-rich fibrin (PRF) in comparison to PRF alone, as well as to native BSMs, were analyzed in vitro and in vivo to evaluate possible clinical application. In vitro, four BSMs of different origins (allogeneic, alloplastic, and xenogeneic) were biofunctionalized with PRF and compared to PRF in terms of platelet interaction and growth factor release (vascular endothelial growth factor (VEGF), tissue growth factor ß (TGFß) and platelet-derived growth factor (PDGF)) after 15 min. To visualize initial cell–cell interactions, SEM was performed. In vivo, all BSMs (±PRF) were analyzed after 24 h for new-formed vessels using a chorioallantoic membrane (CAM) assay. Especially for alloplastic BSMs, the addition of PRF led to a significant consumption of platelets (p = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: p < 0.013). SEM showed the close spatial relation of each BSM and PRF. In vivo, PRF had a significant positive pro-angiogenic influence in combination with alloplastic (p = 0.007) and xenogeneic materials (p = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased (p = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: p = 0.046; alloplastic: p = 0.046; and xenogeneic: p = 0.050). An early enhancement of angiogenetic properties was demonstrated when combining BSMs with PRF in vitro and led to upregulated vessel formation in vivo. Thus, the use of BSMs in combination with PRF may trigger bony regeneration in clinical approaches.
Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?
Authors: Bell Simon M. , Barnes Katy , De Marco Matteo , Shaw Pamela J. , Ferraiuolo Laura , Blackburn Daniel J. , Venneri Annalena , Mortiboys Heather
Published: January 2021

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use.
Molecular Characterization of Ovarian Yolk Sac Tumor (OYST)
Authors: Hodroj Khalil , Stevovic Aleksandra , Attignon Valery , Ferraioli Domenico , Meeus Pierre , Croce Sabrina , Chopin Nicolas , Rossi Lea , Floquet Anne , Rousset-Jablonski Christine , Tredan Olivier , Guyon Frédéric , Treilleux Isabelle , Rannou Corinne , Morfouace Marie , Ray-Coquard Isabelle
Published: January 2021

Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient’s tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in KRAS, KIT, ARID1A. Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
A Set of Cell Lines Derived from a Genetic Murine Glioblastoma Model Recapitulates Molecular and Morphological Characteristics of Human Tumors
Authors: Costa Barbara , Fletcher Michael N. C. , Boskovic Pavle , Ivanova Ekaterina L. , Eisemann Tanja , Lohr Sabrina , Bunse Lukas , Löwer Martin , Burchard Stefanie , Korshunov Andrey , Coltella Nadia , Cusimano Melania , Naldini Luigi , Liu Hai-Kun , Platten Michael , Radlwimmer Bernhard , Angel Peter , Peterziel Heike
Published: January 2021

Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for deciphering glioma biology and for the development of effective treatment options. The murine GBM cell lines currently available for engraftment in immunocompetent mice are not only exiguous but also inadequate in representing prominent characteristics of human GBM such as infiltrative behavior, necrotic areas, and pronounced tumor heterogeneity. Therefore, we generated a set of glioblastoma cell lines by repeated in vivo passaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts, they formed high-grade gliomas that faithfully recapitulated the histopathological features, invasiveness and immune cell infiltration characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioblastoma pathomechanism and to test novel treatments in an intact immune microenvironment.
Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC)
Authors: Simonaggio Audrey , Epaillard Nicolas , Pobel Cédric , Moreira Marco , Oudard Stéphane , Vano Yann-Alexandre
Published: January 2021

Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a combination with anti CTLA-4 or anti angiogenic therapies. In the face of these rising therapeutic options, the question of the therapeutic sequences is crucial. Predictive biomarkers are urgently required to provide a personalized treatment for each patient. Disappointingly, the usual ICI biomarkers, PD-L1 expression and Tumor Mutational Burden, approved in melanoma or non-small cell lung cancer (NSCLC) have failed to distinguish good and poor mccRCC responders to ICI. The tumor microenvironment is known to be involved in ICI response. Innovative technologies can be used to explore the immune contexture of tumors and to find predictive and prognostic biomarkers. Recent comprehensive molecular characterization of RCC has led to the development of robust genomic signatures, which could be used as predictive biomarkers. This review will provide an overview of the components of the RCC tumor microenvironment and discuss their role in disease progression and resistance to ICI. We will then highlight the current and future ICI predictive biomarkers assessed in mccRCC with a major focus on immunohistochemistry markers and genomic signatures.
Tampering of Viruses and Bacteria with Host DNA Repair: Implications for Cellular Transformation
Authors: Benedetti Francesca , Curreli Sabrina , Gallo Robert C. , Zella Davide
Published: January 2021

A reduced ability to properly repair DNA is linked to a variety of human diseases, which in almost all cases is associated with an increased probability of the development of cellular transformation and cancer. DNA damage, that ultimately can lead to mutations and genomic instability, is due to many factors, such as oxidative stress, metabolic disorders, viral and microbial pathogens, excess cellular proliferation and chemical factors. In this review, we examine the evidence connecting DNA damage and the mechanisms that viruses and bacteria have evolved to hamper the pathways dedicated to maintaining the integrity of genetic information, thus affecting the ability of their hosts to repair the damage(s). Uncovering new links between these important aspects of cancer biology might lead to the development of new targeted therapies in DNA-repair deficient cancers and improving the efficacy of existing therapies. Here we provide a comprehensive summary detailing the major mechanisms that viruses and bacteria associated with cancer employ to interfere with mechanisms of DNA repair. Comparing these mechanisms could ultimately help provide a common framework to better understand how certain microorganisms are involved in cellular transformation.
HSP90α Mediates Sorafenib Resistance in Human Hepatocellular Carcinoma by Necroptosis Inhibition under Hypoxia
Authors: Liao Yan , Yang Yue , Pan Di , Ding Youxiang , Zhang Heng , Ye Yuting , Li Jia , Zhao Li
Published: January 2021

As one of the most common malignancies worldwide, Hepatocellular carcinoma (HCC) has been treated by Sorafenib, which is the first approved target drug by FDA for advanced HCC. However, drug resistance is one of the obstacles to its application. As a typical characteristic of most solid tumors, hypoxia has become a key cause of resistance to chemotherapy and radiotherapy. It is important to elucidate the underlying mechanisms of Sorafenib resistance under hypoxia. In this study, the morphological changes of hepatocellular carcinoma cells were observed by Live Cell Imaging System and Transmission Electron Microscope; Sorafenib was found to induce necroptosis in liver cancer. Under hypoxia, the distribution of necroptosis related proteins was changed, which contributed to Sorafenib resistance. HSP90α binds with the necrosome complex and promotes chaperone-mediated autophagy (CMA) degradation, which leads necroptosis blocking and results in Sorafenib resistance. The patient-derived tumor xenograft (PDX) model has been established to investigate the potential therapeutic strategies to overcome Sorafenib resistance. 17-AAG inhibited HSP90α and presented obvious reversal effects of Sorafenib resistance in vivo and in vitro. All the results emphasized that HSP90α plays a critical role in Sorafenib resistance under hypoxia and 17-AAG combined with Sorafenib is a promising therapy for hepatocellular carcinoma.
Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions
Authors: Murcia Oscar , Martínez-Roca Alejandro , Juárez Miriam , Giner-Calabuig Mar , Alustiza Miren , Mira Cristina , Mangas-Sanjuan Carolina , Serrano Eva , Ruiz-Gómez Francisco Antonio , Baile-Maxia Sandra , Medina Lucía , Alenda Cristina , Payá Artemio , Rodriguez-Soler María , Zapater Pedro , Jover Rodrigo
Published: January 2021

The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of ≥10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of ≥10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78–11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33–4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance.
Chronic Myeloid Leukemia: A Model Disease of the Past, Present and Future
Authors: Minciacchi Valentina R. , Kumar Rahul , Krause Daniela S.
Published: January 2021

Chronic myeloid leukemia (CML) has been a “model disease” with a long history. Beginning with the first discovery of leukemia and the description of the Philadelphia Chromosome and ending with the current goal of achieving treatment-free remission after targeted therapies, we describe here the journey of CML, focusing on molecular pathways relating to signaling, metabolism and the bone marrow microenvironment. We highlight current strategies for combination therapies aimed at eradicating the CML stem cell; hopefully the final destination of this long voyage.
Monofluorophosphates—New Examples and a Survey of the PO3F2− Anion
Authors: Weil Matthias
Published: January 2021

During a systematic study of monofluorophosphates, i.e., compounds comprising the tetrahedral anion PO3F2−, twelve, for the most part new, compounds were obtained from aqueous solutions. Crystal structure refinements based on single crystal X-ray diffraction data revealed the previously unknown crystal structures of CdPO3F(H2O)2, Cr2(PO3F)3(H2O)18.8, Pb2(PO3F)Cl2(H2O), (NH4)2M(PO3F)2(H2O)2 (M = Mg, Mn, Co), NH4Cr(PO3F)2(H2O)6, NH4Cu2(H3O2)(PO3F)2, (NH4)2Zn(PO3F)2(H2O)0.2, and (NH4)2Zn3(PO3F)4(H2O), as well as redeterminations of ZnPO3F(H2O)2.5 and (NH4)2Ni(PO3F)2(H2O)6. From the previously unknown crystal structures, CdPO3F(H2O)2 (space group P1¯), Cr2(PO3F)3(H2O)18.8 (P1¯), Pb2(PO3F)Cl2(H2O) (Pnma), NH4Cr(PO3F)2(H2O)6 (R3¯m), (NH4)2Zn(PO3F)2(H2O)0.2 (C2/c), and (NH4)2Zn3(PO3F)4(H2O) (I4¯3d) each crystallizes in an unique crystal structure, whereas compounds (NH4)2M(PO3F)2(H2O)2 (M = Mg, Co) crystallize in the (NH4)2Cu(PO3F)2(H2O)2 type of structure (C2/m) and (NH4)2Mn(PO3F)2(H2O)2 in a subgroup thereof (P21/n, with a klassengleiche relationship of index 2), and NH4Cu2(H3O2)(PO3F)2 (C2/m) crystallizes isotypically with natrochalcite-type KCu2(H3O2)(SO4)2. A survey on the PO3F2− anion, including database entries of all inorganic compounds comprising this group, revealed mean bond lengths of P–O = 1.506(13) Å, P–F = 1.578(20) Å, and angles of O–P–O = 113.7(1.7)° and O–P–F = 104.8(1.7)°, using a dataset of 88 independent PO3F2− anions or entities. For those crystal structures of monofluorophosphates where hydrogen bonding is present, in the vast majority of cases, hydrogen bonds of the type D–H···F–P (D = O, N) are not developed.
Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory
Authors: Domingo Luis R. , Ríos-Gutiérrez Mar , Acharjee Nivedita
Published: January 2021

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD), with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity, have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G (d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol−1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study establishes the depopulation of the N–N–C core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.
Impact of Activity-Based Therapy on Respiratory Outcomes in a Medically Complex Child
Authors: Goode-Roberts MacKenzie , Bickel Scott G. , Stout Danielle L. , Calvery Margaret L. , Thompson Jennifer E. , Behrman Andrea L.
Published: January 2021

Introduction: Activity-based therapies (ABTs) focus on activating the neuromuscular system below the level of spinal cord injury (SCI) promoting neuromuscular capacity. Case description: A 2 year 7 month old with history of prematurity at 29 weeks, neonatal epidural abscess, resultant cervical SCI, respiratory failure, and global developmental delays presented for enrollment in an outpatient activity-based therapy program. Upon presentation to this program, he required nighttime mechanical ventilation via tracheostomy and daytime suctioning. He could not perform any age-appropriate activities and was described by his mother as ‘present’, neither engaged nor attentive. During and after 7 months of participation in ABTs including locomotor training and neuromuscular electrical stimulation, the patient demonstrated unexpected changes in his respiratory status leading to ventilator weaning with concomitant improvements in head and trunk control, participation, development, and quality of life. Discussion: ABT was not only safe for a medically complex child, but also this intervention had a remarkable effect on unresolved respiratory capacity and a more widespread impact on other functions as well as development. A child with a chronic, severe SCI demonstrated positive and impactful improvements in health, functional status, and quality of life during an episode of ABT.
Condylar Changes in Children with Posterior Crossbite after Maxillary Expansion: Tridimensional Evaluation
Authors: Fastuca Rosamaria , Turiaco Helga , Assandri Fausto , Zecca Piero A. , Levrini Luca , Caprioglio Alberto
Published: January 2021

(1) Background: To investigate condylar position in subjects with functional posterior crossbite comparing findings before and after rapid maxillary expansion (RME) treatment through 3D analysis; (2) Methods: Thirty-two Caucasian patients (14 males, mean age 8 y 8 m ± 1 y 2 m; 18 females mean age 8 y 2 m ± 1 y 4 m) with functional posterior crossbite (FPXB) diagnosis underwent rapid palatal expansion with a Haas appliance banded on second deciduous upper molars. Patients’ underwent CBCT scans before rapid palatal expansion (T0) and after 12 months (T1). The images were processed through 3D slicer software; (3) Results: The condylar position changes between T1 and T0 among the crossbite and non-crossbite sides were not statistically significant, except for the transversal axis. At T1, the condyles moved forward (y axis) and laterally (x axis), they also moved downward (z axis) but not significantly; (4) Conclusions: Condilar position in growing patients with functional posterior crossbite did not change significantly after rapid maxillary expansion.
Study of the Bond Capacity of FRCM- and SRG-Masonry Joints
Authors: Al-Lami Karrar , D’Antino Tommaso , Colombi Pierluigi
Published: January 2021

Fiber-reinforced cementitious matrix (FRCM) and steel-reinforced grout (SRG) have been increasingly applied as externally bonded reinforcement to masonry members in the last few years. Unlike fiber-reinforced polymer (FRP), FRCM and SRG have good performance when exposed to (relatively) high temperature and good compatibility with inorganic substrates, and they can be applied to wet surfaces and at (reasonably) low temperatures. Although numerous studies investigated the mechanical properties and bond performance of various FRCM and SRG, new composites have been developed recently, and their performance still needs to be assessed. In this study, the bond behavior of three FRCM composites and one SRG composite applied to a masonry substrate is investigated. Sixteen single-lap direct shear tests (four tests for each composite) are performed. The FRCM studied comprised one layer of carbon, PBO (polyparaphenylene benzobisoxazole), or alkali-resistant (AR)-glass bidirectional textile embedded within two cement-based matrices. The SRG composite comprised one layer of a unidirectional stainless-steel cord textile embedded within a lime-based matrix. The results show a peculiar bond behavior and failure mode for each composite. Based on these results, the behavior of the carbon and PBO FRCM is modeled solving the bond differential equation with a trilinear cohesive material law (CML).
Economic and Sustainability of Biodiesel Production—A Systematic Literature Review
Authors: Mizik Tamás , Gyarmati Gábor
Published: January 2021

As Earth’s fossil energy resources are limited, there is a growing need for renewable resources such as biodiesel. That is the reason why the social, economic and environmental impacts of biofuels became an important research topic in the last decade. Depleted stocks of crude oil and the significant level of environmental pollution encourage researchers and professionals to seek and find solutions. The study aims to analyze the economic and sustainability issues of biodiesel production by a systematic literature review. During this process, 53 relevant studies were analyzed out of 13,069 identified articles. Every study agrees that there are several concerns about the first-generation technology; however, further generations cannot be price-competitive at this moment due to the immature technology and high production costs. However, there are promising alternatives, such as wastewater-based microalgae with up to 70% oil content, fat, oils and grease (FOG), when production cost is below 799 USD/gallon, and municipal solid waste-volatile fatty acids technology, where the raw material is free. Proper management of the co-products (mainly glycerol) is essential, especially at the currently low petroleum prices (0.29 USD/L), which can only be handled by the biorefineries. Sustainability is sometimes translated as cost efficiency, but the complex interpretation is becoming more common. Common elements of sustainability are environmental and social, as well as economic, issues.
No-z Model for Magnetic Fields of Different Astrophysical Objects and Stability of the Solutions
Authors: Mikhailov Evgeny , Boneva Daniela , Pashentseva Maria
Published: January 2021

A wide range of astrophysical objects, such as the Sun, galaxies, stars, planets, accretion discs etc., have large-scale magnetic fields. Their generation is often based on the dynamo mechanism, which is connected with joint action of the alpha-effect and differential rotation. They compete with the turbulent diffusion. If the dynamo is intensive enough, the magnetic field grows, else it decays. The magnetic field evolution is described by Steenbeck—Krause—Raedler equations, which are quite difficult to be solved. So, for different objects, specific two-dimensional models are used. As for thin discs (this shape corresponds to galaxies and accretion discs), usually, no-z approximation is used. Some of the partial derivatives are changed by the algebraic expressions, and the solenoidality condition is taken into account as well. The field generation is restricted by the equipartition value and saturates if the field becomes comparable with it. From the point of view of mathematical physics, they can be characterized as stable points of the equations. The field can come to these values monotonously or have oscillations. It depends on the type of the stability of these points, whether it is a node or focus. Here, we study the stability of such points and give examples for astrophysical applications.
Geometrical Optimization of a Venturi-Type Microbubble Generator Using CFD Simulation and Experimental Measurements
Authors: Wilson Dillon Alexander , Pun Kul , Ganesan Poo Balan , Hamad Faik
Published: January 2021

Microbubble generators are of considerable importance to a range of scientific fields from use in aquaculture and engineering to medical applications. This is due to the fact the amount of sea life in the water is proportional to the amount of oxygen in it. In this paper, experimental measurements and computational Fluid Dynamics (CFD) simulation are performed for three water flow rates and three with three different air flow rates. The experimental data presented in the paper are used to validate the CFD model. Then, the CFD model is used to study the effect of diverging angle and throat length/throat diameter ratio on the size of the microbubble produced by the Venturi-type microbubble generator. The experimental results showed that increasing water flow rate and reducing the air flow rate produces smaller microbubbles. The prediction from the CFD results indicated that throat length/throat diameter ratio and diffuser divergent angle have a small effect on bubble diameter distribution and average bubble diameter for the range of the throat water velocities used in this study.