bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Air Filter Coating with Plant Extracts Against Airborne Microbes
Authors: Byun Ha Ram , Park Seon Young , Hwang Ee Taek , Sang Byoung In , Min Jiho , Sung Daekyung , Choi Won Il , Kim Sunghyun , Lee Jin Hyung
Published: December 2020

Antimicrobial air filters are required to protect humans from the risk of secondary bioaerosol pollution as well as airborne particles. Three plant extracts (tea-tree oil, rosemary, and garlic) were selected to replace antimicrobial chemicals in air filters. The antimicrobial activity of plant extracts was investigated using Micrococcus luteus and Escherichia coli. Phytochemicals present in the three plant extracts were identified using a gas chromatograph coupled with a mass spectrometer. The extracts were spray-coated on polyethylene terephthalate filter surfaces using silicate polymeric coating and evaluated via X-ray photoelectron spectroscopy and a scanning electron microscope with energy dispersive spectroscopy. After coating, an increase of 9.1% in the pressure drop was observed. The strain Micrococcus luteus was used to evaluate the antimicrobial activity of the air filter. After bioaerosol exposure, the tea-tree oil-coated filters immediately induced M. luteus cell inactivation (40–55%), whereas the rosemary and garlic coated filters did not. However, 48 h after exposure, a significant M. luteus inactivation of 99.99%, 99.0%, and 99.9% was recorded for concentrations of 2.89, 6.73, and 11.51 mg/cm2 for the tea-tree, rosemary, and garlic extracts, respectively. The coated filters exhibited high antimicrobial activity, thereby indicating significant potential for application as self-cleaning air filters.
Correlating Natural, Dry, and Saturated Ultrasonic Pulse Velocities with the Mechanical Properties of Rock for Various Sample Diameters
Authors: Arman Hasan , Paramban Safwan
Published: December 2020

P-wave velocity is employed in various fields of engineering to estimate the mechanical properties of rock, as its measurement is reliable, convenient, rapid, nondestructive, and economical. The present study aimed to (i) correlate natural, dry, and saturated P-wave velocities with the mechanical properties of limestone and (ii) investigate how the ultrasonic P-wave velocities and mechanical properties of limestone are affected by the sample diameter. This study reveals that P-wave velocities under different environmental conditions can be correlated with the mechanical properties of limestone. Further, the R-value variations with different P-wave velocities for a given sample diameter are (i) negligible in terms of the uniaxial compressive strength (UCS) excluding 63.2 mm, (ii) limited for the diametrical point load index (PLID) except for 53.9 mm, (iii) perceived in case of the axial point load index (PLIA) for 47.7 mm, (iv) observed for the indirect tensile strength (ITS), but generally insignificant, and (v) detected in terms of Schmidt hammer value (SHV) except for 47.7 mm.
The Problem of Accounting for Heat Exchange between the Flow and the Flow Part Surfaces When Modeling a Viscous Flow in Low-Flow Stages of a Centrifugal Compressor
Authors: Kartashov Sergey , Kozhukhov Yuri , Ivanov Vycheslav , Danilishin Aleksei , Yablokov Aleksey , Aksenov Aleksey , Yanin Ivan , Nguyen Minh Hai
Published: December 2020

In this paper, we review the problem of accounting for heat exchange between the flow and the flow part surfaces when creating a calculation model for modeling the workflow process of low-flow stages of a centrifugal compressor using computational fluid dynamics (CFD). The objective selected for this study was a low-flow intermediate type stage with the conditional flow coefficient Փ = 0.008 and the relative width at the impeller exit b2/D2 = 0.0133. We show that, in the case of modeling with widespread adiabatic wall simplification, the calculated temperature in the gaps between the impeller and the stator elements is significantly overestimated. Modeling of the working process in the flow part was carried out with a coupled heat exchanger, as well as with simplified accounting for heat transfer by setting the temperatures of the walls. The gas-dynamic characteristics of the stage were compared with the experimental data, the heat transfer influence on the disks friction coefficient was estimated, and the temperature distributions in the gaps between disks and in the flow part of the stage were analyzed. It is shown that the main principle when modeling the flow in low-flow stage is to ensure correct temperature distribution in the gaps.
Comparing Approaches for Reconstructing Groundwater Levels in the Mountainous Regions of Interior British Columbia, Canada, Using Tree Ring Widths
Authors: Hunter Stephanie C. , Allen Diana M. , Kohfeld Karen E.
Published: December 2020

Observed groundwater level records are relatively short (<100 years), limiting long-term studies of groundwater variability that could provide valuable insight into climate change effects. This study uses tree ring data from the International Tree Ring Database (ITRDB) and groundwater level data from 22 provincial observation wells to evaluate different approaches for reconstructing groundwater levels from tree ring widths in the mountainous southern interior of British Columbia, Canada. The twenty-eight reconstruction models consider the selection of observation wells (e.g., regional average groundwater level vs. wells classified by recharge mechanism) and the search area for potential tree ring records (climate footprint vs. North American Ecoregions). Results show that if the climate footprint is used, reconstructions are statistically valid if the wells are grouped according to recharge mechanism, with streamflow-driven and high-elevation recharge-driven wells (both snowmelt-dominated) producing valid models. Of all the ecoregions considered, only the Coast Mountain Ecoregion models are statistically valid for both the regional average groundwater level and high-elevation recharge-driven systems. No model is statistically valid for low-elevation recharge-driven systems (rainfall-dominated). The longest models extend the groundwater level record to the year 1500, with the highest confidence in the later portions of the reconstructions going back to the year 1800.
Increases in Biogenic Volatile Organic Compound Concentrations Observed after Rains at Six Forest Sites in Non-Summer Periods
Authors: Miyama Takafumi , Morishita Tomoaki , Kominami Yuji , Noguchi Hironori , Yasuda Yukio , Yoshifuji Natsuko , Okano Michiaki , Yamanoi Katsumi , Mizoguchi Yasuko , Takanashi Satoru , Kitamura Kenzo , Matsumoto Kazuho
Published: December 2020

Since biogenic volatile organic compounds (BVOCs) are important precursors of ozone, the monitoring of the BVOC concentration distributions is needed. In general, forest BVOC concentrations increase in summer as well as in other seasons. This study aims to detect temporally sporadic increases in BVOC concentrations in the non-summer months and to analyze the occurring climatic conditions. Using a uniform sampling system and shared gas chromatography–mass spectrometry, the concentrations of isoprene and monoterpenes in six Japanese forests were observed approximately once a month for 3 years. Using the observed data, the relations between the BVOC concentration increases and meteorological factors were evaluated. Twenty instances of temporal increases in BVOC concentrations were observed. These mainly occurred in spring for isoprene and in autumn for monoterpenes. Most of the increases in the non-summer months were observed after a rainfall event, when the daily temperature range was large, suggesting that wind, rain, and a rapid diurnal temperature rise could be factors in the non-summer months. Thus, the network monitoring of BVOC concentrations might be effective for understanding the effects of factors other than temperature, and the mechanisms and frequency of the temporal increases, on the BVOC concentrations in various forests.
Unification Theories: Means and Generalized Euler Formulas
Authors: Iordanescu Radu , Nichita Florin Felix , Pasarescu Ovidiu
Published: December 2020

The main concepts in this paper are the means and Euler type formulas; the generalized mean which incorporates the harmonic mean, the geometric mean, the arithmetic mean, and the quadratic mean can be further generalized. Results on the Euler’s formula, the (modified) Yang–Baxter equation, coalgebra structures, and non-associative structures are also included in the current paper.
Genome Sequences of Serratia Strains Revealed Common Genes in Both Serratomolides Gene Clusters
Authors: Marques-Pereira Catarina , Proença Diogo Neves , Morais Paula V.
Published: December 2020

Serratia strains are ubiquitous microorganisms with the ability to produce serratomolides, such as serrawettins. These extracellular lipopeptides are described as biocides against many bacteria and fungi and may have a nematicidal activity against phytopathogenic nematodes. Serrawettins W1 and W2 from different strains have different structures that might be correlated with distinct genomic organizations. This work used comparative genomics to determine the distribution and the organization of the serrawettins biosynthetic gene clusters in all the 84 publicly available genomes of the Serratia genus. The serrawettin W1 and W2 gene clusters’ organization was established using antiSMASH software and compared with single and short data previously described for YD25TSerratia. Here, the serrawettin W1 gene clusters’ organization is reported for the first time. The serrawettin W1 biosynthetic gene swrW was present in 17 Serratia genomes. Eighty different coding sequence (CDS) were assigned to the W1 gene cluster, 13 being common to all clusters. The serrawettin W2 swrA gene was present in 11 Serratia genomes. The W2 gene clusters included 68 CDS with 24 present in all the clusters. The genomic analysis showed the swrA gene constitutes five modules, four with three domains and one with four domains, while the swrW gene constitutes one module with four domains. This work identified four genes common to all serrawettin gene clusters, highlighting their essential potential in the serrawettins biosynthetic process.
A Descriptive Overview of the Medical Uses Given to Mentha Aromatic Herbs throughout History
Authors: Silva Henrique
Published: December 2020

Mints have been among the most widely used herbs for medicinal purposes since ancient civilizations. They are still presently used for numerous purposes, including non-medicinal, which makes them economically relevant herbs. Information regarding the medical and scientific uses given to mints throughout history are vastly scattered and/or incomplete. The aim of this paper is to provide an extensive descriptive overview of the medical uses given to these herbs, highlighting both the authors in medical culture responsible for their dissemination, as well as their major galenic formulations. Databases on medical science, reference textbooks on medical history, botanics (aromatic herbs), and pharmacognosy were consulted. The use of mints remotes to Classical Antiquity, with major contributions from Pliny the Elder. In the Middle Ages, the increased knowledge surrounding mints came from Byzantine physicians, while, in the Modern Age, technological developments allowed the production of mint-based products which have become part of elaborate galenic formulas employed by an increasing number of physicians, as well as have also stimulated both scientific and artistic interests alike. In present-day medicine, several mints and mint-based products are being researched as potential therapeutic alternatives for many diseases, while also being vastly employed in food and cosmetic industries.
Role of Ferrous Sulfate (FeSO4) in Resistance to Cadmium Stress in Two Rice (Oryza sativa L.) Genotypes
Authors: Afzal Javaria , Saleem Muhammad Hamzah , Batool Fatima , Elyamine Ali Mohamed , Rana Muhammad Shoaib , Shaheen Asma , El-Esawi Mohamed A. , Tariq Javed Muhammad , Ali Qasim , Arslan Ashraf Muhammad , Hussain Ghulam Sabir , Hu Chengxiao
Published: December 2020

The impact of heavy metal, i.e., cadmium (Cd), on the growth, photosynthetic pigments, gas exchange characteristics, oxidative stress biomarkers, and antioxidants machinery (enzymatic and non-enzymatic antioxidants), ions uptake, organic acids exudation, and ultra-structure of membranous bounded organelles of two rice (Oryza sativa L.) genotypes (Shan 63 and Lu 9803) were investigated with and without the exogenous application of ferrous sulfate (FeSO4). Two O. sativa genotypes were grown under different levels of CdCl2 [0 (no Cd), 50 and 100 µM] and then treated with exogenously supplemented ferrous sulfate (FeSO4) [0 (no Fe), 50 and 100 µM] for 21 days. The results revealed that Cd stress significantly (p < 0.05) affected plant growth and biomass, photosynthetic pigments, gas exchange characteristics, affected antioxidant machinery, sugar contents, and ions uptake/accumulation, and destroy the ultra-structure of many membranous bounded organelles. The findings also showed that Cd toxicity induces oxidative stress biomarkers, i.e., malondialdehyde (MDA) contents, hydrogen peroxide (H2O2) initiation, and electrolyte leakage (%), which was also manifested by increasing the enzymatic antioxidants, i.e., superoxidase dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) and non-enzymatic antioxidant compounds (phenolics, flavonoids, ascorbic acid, and anthocyanin) and organic acids exudation pattern in both O. sativa genotypes. At the same time, the results also elucidated that the O. sativa genotypes Lu 9803 are more tolerant to Cd stress than Shan 63. Although, results also illustrated that the exogenous application of ferrous sulfate (FeSO4) also decreased Cd toxicity in both O. sativa genotypes by increasing antioxidant capacity and thus improved the plant growth and biomass, photosynthetic pigments, gas exchange characteristics, and decrease oxidative stress in the roots and shoots of O. sativa genotypes. Here, we conclude that the exogenous supplementation of FeSO4 under short-term exposure of Cd stress significantly improved plant growth and biomass, photosynthetic pigments, gas exchange characteristics, regulate antioxidant defense system, and essential nutrients uptake and maintained the ultra-structure of membranous bounded organelles in O. sativa genotypes.
Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature
Authors: Cinque Luigia , Angeletti Cristina , Orrico Alfredo , Castellana Stefano , Ferrito Lucia , Ciuoli Cristina , Mazza Tommaso , Castori Marco , Guarnieri Vito
Published: December 2020

Background. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, AIRE, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Thus, early recognition of the syndrome is often delayed, mostly in cases with atypical presentation, and the molecular confirm through the genetic analysis of the AIRE gene might be of great benefit. Methods. Our methods were to investigate, with a multigene panel next generation sequencing approach, two clinical cases, both presenting with idiopathic hypoparathyroidism, also comprising the AIRE gene; as well as to comment our findings as part of a more extensive review of literature data. Results. In the first clinical case, two compound heterozygote pathogenic variants of the AIRE gene were identified, thus indicating an autosomal recessive inheritance of the disease. In the second case, only one AIRE gene variant was found and an atypical dominant negative form of APS-1 suggested, later confirmed by further medical ascertainments. Conclusions. APS-1 might present with variable and sometimes monosymptomatic presentations and, if not recognized, might associate with severe complications. In this context, next generation diagnostics focused on a set of genes causative of partially overlapping disorders may allow early diagnosis.
STAT3 and p53: Dual Target for Cancer Therapy
Authors: Pham Thu-Huyen , Park Hyo-Min , Kim Jinju , Hong Jin Tae , Yoon Do-Young
Published: December 2020

The tumor suppressor p53 is considered the “guardian of the genome” that can protect cells against cancer by inducing cell cycle arrest followed by cell death. However, STAT3 is constitutively activated in several human cancers and plays crucial roles in promoting cancer cell proliferation and survival. Hence, STAT3 and p53 have opposing roles in cellular pathway regulation, as activation of STAT3 upregulates the survival pathway, whereas p53 triggers the apoptotic pathway. Constitutive activation of STAT3 and gain or loss of p53 function due to mutations are the most frequent events in numerous cancer types. Several studies have reported the association of STAT3 and/or p53 mutations with drug resistance in cancer treatment. This review discusses the relationship between STAT3 and p53 status in cancer, the molecular mechanism underlying the negative regulation of p53 by STAT3, and vice versa. Moreover, it underlines prospective therapies targeting both STAT3 and p53 to enhance chemotherapeutic outcomes.
Advanced Glycation End Products (AGE) and Soluble Forms of AGE Receptor: Emerging Role as Mortality Risk Factors in CKD
Authors: Dozio Elena , Vettoretti Simone , Caldiroli Lara , Nerini-Molteni Silvia , Tacchini Lorenza , Ambrogi Federico , Messa Piergiorgio , Corsi Romanelli Massimiliano M.
Published: December 2020

Advanced glycation end-products (AGE) can promote chronic kidney disease (CKD) progression and CKD-related morbidities. The soluble receptor for AGE (sRAGE) is a potential biomarker of inflammation and oxidative stress. Here, we explored the role of AGE, glycated albumin, sRAGE and its different forms, cRAGE and esRAGE, as prognostic factors for mortality in 111 advanced CKD patients. The median follow-up time was 39 months. AGE were quantified by fluorescence, sRAGE and its forms by ELISA. Malnutrition was screened by the Malnutrition Inflammation Score (MIS). The Cox proportional hazards regression model was used to assess the association of variables with all-cause mortality. Mean levels of sRAGE, esRAGE and cRAGE were 2318 ± 1224, 649 ± 454 and 1669 ± 901 pg/mL. The mean value of cRAGE/esRAGE was 2.82 ± 0.96. AGE were 3026 ± 766 AU and MIS 6.0 ± 4.7. eGFR correlated negatively with AGE, sRAGE, esRAGE and cRAGE, but not with cRAGE/esRAGE. Twenty-eight patients died. No difference was observed between diabetic and non-diabetic patients. Starting dialysis was not associated with enhanced risk of death. AGE, esRAGE and cRAGE/esRAGE were independently associated with all-cause mortality. AGE, esRAGE and cRAGE/esRAGE may help to stratify overall mortality risk. Implementing the clinical evaluation of CKD patients by quantifying these biomarkers can help to improve patient outcomes.
Post-COVID-19 Fatigue: Potential Contributing Factors
Authors: Rudroff Thorsten , Fietsam Alexandra C. , Deters Justin R. , Bryant Andrew D. , Kamholz John
Published: December 2020

Much of the spotlight for coronavirus disease 2019 (COVID-19) is on the acute symptoms and recovery. However, many recovered patients face persistent physical, cognitive, and psychological symptoms well past the acute phase. Of these symptoms, fatigue is one of the most persistent and debilitating. In this “perspective article,” we define fatigue as the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors due to the COVID-19 disease and propose a model to explain potential factors contributing to post-COVID-19 fatigue. According to our model, fatigue is dependent on conditional and physiological factors. Conditional dependency comprises the task, environment, and physical and mental capacity of individuals, while physiological factors include central, psychological, and peripheral aspects. This model provides a framework for clinicians and researchers. However, future research is needed to validate our proposed model and elucidate all mechanisms of fatigue due to COVID-19.
Carbonaceous Materials Investigated by Small-Angle X-ray and Neutron Scattering
Authors: Härk Eneli , Ballauff Matthias
Published: December 2020

Carbonaceous nanomaterials have become important materials with widespread applications in battery systems and supercapacitors. The application of these materials requires precise knowledge of their nanostructure. In particular, the porosity of the materials together with the shape of the pores and the total internal surface must be known accurately. Small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) present the methods of choice for this purpose. Here we review our recent investigations using SAXS and SANS. We first describe the theoretical basis of the analysis of carbonaceous material by small-angle scattering. The evaluation of the small-angle data relies on the powerful concept of the chord length distribution (CLD) which we explain in detail. As an example of such an evaluation, we use recent analysis by SAXS of carbide-derived carbons. Moreover, we present our SAXS analysis on commercially produced activated carbons (ACN, RP-20) and provide a comparison with small-angle neutron scattering data. This comparison demonstrates the wealth of additional information that would not be obtained by the application of either method alone. SANS allows us to change the contrast, and we summarize the main results using different contrast matching agents. The pores of the carbon nanomaterials can be filled gradually by deuterated p-xylene, which leads to a precise analysis of the pore size distribution. The X-ray scattering length density of carbon can be matched by the scattering length density of sulfur, which allows us to see the gradual filling of the nanopores by sulfur in a melt-impregnation procedure. This process is important for the application of carbonaceous materials as cathodes in lithium/sulfur batteries. All studies summarized in this review underscore the great power and precision with which carbon nanomaterials can be analyzed by SAXS and SANS.
Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma
Authors: Eun Jung Woo , Seo Chul Won , Baek Geum Ok , Yoon Moon Gyeong , Ahn Hye Ri , Son Ju A. , Sung Suna , Kim Do Wan , Kim Soon Sun , Cho Hyo Jung , Cheong Jae Youn
Published: December 2020

Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group (p = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression (p < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial–mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.
Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients
Authors: Zielinska Hanna A. , Daly Carl S. , Alghamdi Ahmad , Bahl Amit , Sohail Muhammed , White Paul , Dean Sarah R. , Holly Jeff M. P. , Perks Claire M.
Published: December 2020

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.
Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection
Authors: Miller Hannah , Czigany Zoltan , Lurje Isabella , Reichelt Sophie , Bednarsch Jan , Strnad Pavel , Trautwein Christian , Roderburg Christoph , Tacke Frank , Gaisa Nadine Therese , Knüchel-Clarke Ruth , Neumann Ulf Peter , Lurje Georg
Published: December 2020

Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)–restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of “high-expression” variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients’ individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.
Clinical and Genetic Tumor Characteristics of Responding and Non-Responding Patients to PD-1 Inhibition in Hepatocellular Carcinoma
Authors: Spahn Stephan , Roessler Daniel , Pompilia Radu , Gabernet Gisela , Gladstone Beryl Primrose , Horger Marius , Biskup Saskia , Feldhahn Magdalena , Nahnsen Sven , Hilke Franz J. , Scheiner Bernhard , Dufour Jean-François , De Toni Enrico N. , Pinter Matthias , Malek Nisar P. , Bitzer Michael
Published: December 2020

Immune checkpoint inhibitors (ICIs) belong to the therapeutic armamentarium in advanced hepatocellular carcinoma (HCC). However, only a minority of patients benefit from immunotherapy. Therefore, we aimed to identify indicators of therapy response. This multicenter analysis included 99 HCC patients. Progression-free (PFS) and overall survival (OS) were studied by Kaplan-Meier analyses for clinical parameters using weighted log-rank testing. Next-generation sequencing (NGS) was performed in a subset of 15 patients. The objective response (OR) rate was 19% median OS (mOS)16.7 months. Forty-one percent reached a PFS > 6 months; these patients had a significantly longer mOS (32.0 vs. 8.5 months). Child-Pugh (CP) A and B patients showed a mOS of 22.1 and 12.1 months, respectively. Ten of thirty CP-B patients reached PFS > 6 months, including 3 patients with an OR. Tumor mutational burden (TMB) could not predict responders. Of note, antibiotic treatment within 30 days around ICI initiation was associated with significantly shorter mOS (8.5 vs. 17.4 months). Taken together, this study shows favorable outcomes for OS with low AFP, OR, and PFS > 6 months. No specific genetic pattern, including TMB, could identify responders. Antibiotics around treatment initiation were associated with worse outcome, suggesting an influence of the host microbiome on therapy success.
Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer
Authors: Tanabe Shihori , Quader Sabina , Ono Ryuichi , Cabral Horacio , Aoyagi Kazuhiko , Hirose Akihiko , Yokozaki Hiroshi , Sasaki Hiroki
Published: December 2020

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.
Acquired Resistance to PD-1/PD-L1 Blockade in Lung Cancer: Mechanisms and Patterns of Failure
Authors: Pathak Ranjan , Pharaon Rebecca R. , Mohanty Atish , Villaflor Victoria M. , Salgia Ravi , Massarelli Erminia
Published: December 2020

Immunotherapy is now the preferred treatment for most lung cancer patients. It is used to treat unresectable stage III non-small-cell lung cancer and is the first-line therapy for non-oncogene-driven advanced/metastatic non-small-cell lung cancer patients (either alone or in combination with chemotherapy). Unfortunately, most patients that respond initially to immunotherapy develop resistance over time, thus limiting the durability of immunotherapy. A better understanding of the mechanisms of acquired resistance is urgently needed to expand the benefit of immunotherapy in lung cancer patients. This review aims to summarize the mechanisms and clinical outcomes of acquired resistance of anti-PD-1/PD-L1 therapies in non-small-cell lung cancer patients.
Influence of Remaining Acid Sites of an Amorphous Aluminosilicate on the Oligomerization of n-Butenes after Impregnation with Nickel Ions
Authors: Nadolny Fabian , Alscher Felix , Peitz Stephan , Borovinskaya Ekaterina , Franke Robert , Reschetilowski Wladimir
Published: December 2020

Highly linear octene isomers can be produced from n-butene on industrial scale by using Ni-containing aluminosilicates as heterogeneous catalysts. These catalysts can be prepared by impregnating an aluminosilicate with a Ni(II) salt solution. This leads to a competition between acid-catalyzed and nickel-catalyzed reactions. In this study it is shown that some octene isomers are exclusively formed via an acid-catalyzed mechanism as a result of methyl group migration at the surface of a mesoporous catalyst. Specifically, the isomers 4,4-dimethylhexene (4,4-DMH) and 3-ethyl-2-methylpentene (3E-2MP) exhibit a systematic correlation compared to the amount of 3,4-dimethylhexene (3,4-DMH) formed at acid sites. By analyzing the ratio of 4,4-DMH and/or 3E-2MP to 3,4-DMH in the product spectrum before and after impregnation with a nickel precursor, the extend of acid site covered by nickel ions can be evaluated.
Right Place at the Right Time: How Changes in Protocadherins Affect Synaptic Connections Contributing to the Etiology of Neurodevelopmental Disorders
Authors: Mancini Maria , Bassani Silvia , Passafaro Maria
Published: December 2020

During brain development, neurons need to form the correct connections with one another in order to give rise to a functional neuronal circuitry. Mistakes during this process, leading to the formation of improper neuronal connectivity, can result in a number of brain abnormalities and impairments collectively referred to as neurodevelopmental disorders. Cell adhesion molecules (CAMs), present on the cell surface, take part in the neurodevelopmental process regulating migration and recognition of specific cells to form functional neuronal assemblies. Among CAMs, the members of the protocadherin (PCDH) group stand out because they are involved in cell adhesion, neurite initiation and outgrowth, axon pathfinding and fasciculation, and synapse formation and stabilization. Given the critical role of these macromolecules in the major neurodevelopmental processes, it is not surprising that clinical and basic research in the past two decades has identified several PCDH genes as responsible for a large fraction of neurodevelopmental disorders. In the present article, we review these findings with a focus on the non-clustered PCDH sub-group, discussing the proteins implicated in the main neurodevelopmental disorders.
Histone Variant H3.3 Mutations in Defining the Chromatin Function in Mammals
Authors: Trovato Matteo , Patil Vibha , Gehre Maja , Noh Kyung Min
Published: December 2020

The systematic mutation of histone 3 (H3) genes in model organisms has proven to be a valuable tool to distinguish the functional role of histone residues. No system exists in mammalian cells to directly manipulate canonical histone H3 due to a large number of clustered and multi-loci histone genes. Over the years, oncogenic histone mutations in a subset of H3 have been identified in humans, and have advanced our understanding of the function of histone residues in health and disease. The oncogenic mutations are often found in one allele of the histone variant H3.3 genes, but they prompt severe changes in the epigenetic landscape of cells, and contribute to cancer development. Therefore, mutation approaches using H3.3 genes could be relevant to the determination of the functional role of histone residues in mammalian development without the replacement of canonical H3 genes. In this review, we describe the key findings from the H3 mutation studies in model organisms wherein the genetic replacement of canonical H3 is possible. We then turn our attention to H3.3 mutations in human cancers, and discuss H3.3 substitutions in the N-terminus, which were generated in order to explore the specific residue or associated post-translational modification.
Pericapillary Edema Assessment by Means of the Nailfold Capillaroscopy and Laser Scanning Microscopy
Authors: Yakimov Boris P. , Gurfinkel Yury I. , Davydov Denis A. , Allenova Anastasia S. , Budylin Gleb S. , Vasiliev Vladimir Yu. , Soldatova Vera Yu. , Kamalov Armais A. , Matskeplishvili Simon T. , Priezzhev Alexander V. , Shirshin Evgeny A.
Published: December 2020

Edema, i.e., fluid accumulation in the interstitial space, accompanies numerous pathological states of the human organism, including heart failure (HF), inflammatory response, and lymphedema. Nevertheless, techniques for quantitative assessment of the edema’s severity and dynamics are absent in clinical practice, and the analysis is mainly limited to physical examination. This fact stimulates the development of novel methods for fast and reliable diagnostics of fluid retention in tissues. In this work, we focused on the possibilities of two microscopic techniques, nailfold video capillaroscopy (NVC) and confocal laser scanning microscopy (CLSM), in the assessment of the short-term and long-term cutaneous edema. We showed that for the patients with HF, morphological parameters obtained by NVC—namely, the apical diameter of capillaries and the size of the perivascular zone—indicate long-term edema. On the other hand, for healthy volunteers, the application of two models of short-term edema, venous occlusion, and histamine treatment of the skin, did not reveal notable changes in the capillary parameters. However, a significant reduction of the NVC image sharpness was observed in this case, which was suggested to be due to water accumulation in the epidermis. To verify these findings, we made use of CLSM, which provides the skin structure with cellular resolution. It was observed that for the histamine-treated skin, the areas of the dermal papillae become hyporefractive, leading to the loss of contrast and the lower visibility of capillaries. Similar effect was observed for patients undergoing infusion therapy. Collectively, our results reveal the parameters can be used for pericapillary edema assessment using the NVC and CLSM, and paves the way for their application in a clinical set-up.
CNN2Gate: An Implementation of Convolutional Neural Networks Inference on FPGAs with Automated Design Space Exploration
Authors: Ghaffari Alireza , Savaria Yvon
Published: December 2020

Convolutional Neural Networks (CNNs) have a major impact on our society, because of the numerous services they provide. These services include, but are not limited to image classification, video analysis, and speech recognition. Recently, the number of researches that utilize FPGAs to implement CNNs are increasing rapidly. This is due to the lower power consumption and easy reconfigurability that are offered by these platforms. Because of the research efforts put into topics, such as architecture, synthesis, and optimization, some new challenges are arising for integrating suitable hardware solutions to high-level machine learning software libraries. This paper introduces an integrated framework (CNN2Gate), which supports compilation of a CNN model for an FPGA target. CNN2Gate is capable of parsing CNN models from several popular high-level machine learning libraries, such as Keras, Pytorch, Caffe2, etc. CNN2Gate extracts computation flow of layers, in addition to weights and biases, and applies a “given” fixed-point quantization. Furthermore, it writes this information in the proper format for the FPGA vendor’s OpenCL synthesis tools that are then used to build and run the project on FPGA. CNN2Gate performs design-space exploration and fits the design on different FPGAs with limited logic resources automatically. This paper reports results of automatic synthesis and design-space exploration of AlexNet and VGG-16 on various Intel FPGA platforms.
Small-Footprint Wake Up Word Recognition in Noisy Environments Employing Competing-Words-Based Feature
Authors: Yoon Ki-Mu , Kim Wooil
Published: December 2020

This paper proposes a small-footprint wake-up-word (WUW) recognition system for real noisy environments by employing the competing-words-based feature. Competing-words-based features are generated using a ResNet-based deep neural network with small parameters using the competing-words dataset. The competing-words dataset consists of the most acoustically similar and dissimilar words to the WUW used for our system. The obtained features are used as input to the classification network, which is developed using the convolutional neural network (CNN) model. To obtain sufficient data for training, data augmentation is performed by using a room impulse response filter and adding sound signals of various television shows as background noise, which simulates an actual living room environment. The experimental results demonstrate that the proposed WUW recognition system outperforms the baselines that employ CNN and ResNet models. The proposed system shows 1.31% in equal error rate and 1.40% false rejection rate at a 1.0% false alarm rate, which are 29.57% and 50.00% relative improvements compared to the ResNet system, respectively. The number of parameters used for the proposed system is reduced by 83.53% compared to the ResNet system. These results prove that the proposed system with the competing-words-based feature is highly effective at improving WUW recognition performance in noisy environments with a smaller footprint.
Degradation Rate Location Dependency of Photovoltaic Systems
Authors: Frick Alexander , Makrides George , Schubert Markus , Schlecht Matthias , Georghiou George E.
Published: December 2020

A main challenge towards ensuring improved lifetime performance and reduction of financial risks of photovoltaic (PV) technologies remains the accurate degradation quantification of field systems and the dependency of this performance loss rate to climatic conditions. The purpose of this study is to address these technological issues by presenting a unified methodology for accurately calculating the degradation rate (RD) of PV systems and provide evidence that degradation mechanisms are location dependent. The method followed included the application of data inference and time series analytics, in the scope of comparing the long-term RD of different crystalline Silicon (c-Si) PV systems, installed at different climatic locations. The application of data quality and filtering steps ensured data fidelity for the RD analysis. The yearly RD results demonstrated that the adopted time series analytical techniques converged after 7 years and were in close agreement to the degradation results obtained from indoor standardized procedures. Finally, the initial hypothesis that the RD is location dependent was verified, since the multicrystalline silicon (multi-c-Si) systems at the warm climatic region exhibited higher degradation compared to the respective systems at the moderate climate. For the investigated monocrystalline silicon (mono-c-Si) systems the location-dependency is also affected by the manufacturing technology.
Use of Remote Sensing Data to Improve the Efficiency of National Forest Inventories: A Case Study from the United States National Forest Inventory
Authors: Lister Andrew J. , Andersen Hans , Frescino Tracey , Gatziolis Demetrios , Healey Sean , Heath Linda S. , Liknes Greg C. , McRoberts Ronald , Moisen Gretchen G. , Nelson Mark , Riemann Rachel , Schleeweis Karen , Schroeder Todd A. , Westfall James , Wilson B. Tyler
Published: December 2020

Globally, forests are a crucial natural resource, and their sound management is critical for human and ecosystem health and well-being. Efforts to manage forests depend upon reliable data on the status of and trends in forest resources. When these data come from well-designed natural resource monitoring (NRM) systems, decision makers can make science-informed decisions. National forest inventories (NFIs) are a cornerstone of NRM systems, but require capacity and skills to implement. Efficiencies can be gained by incorporating auxiliary information derived from remote sensing (RS) into ground-based forest inventories. However, it can be difficult for countries embarking on NFI development to choose among the various RS integration options, and to develop a harmonized vision of how NFI and RS data can work together to meet monitoring needs. The NFI of the United States, which has been conducted by the USDA Forest Service’s (USFS) Forest Inventory and Analysis (FIA) program for nearly a century, uses RS technology extensively. Here we review the history of the use of RS in FIA, beginning with general background on NFI, FIA, and sampling statistics, followed by a description of the evolution of RS technology usage, beginning with paper aerial photography and ending with present day applications and future directions. The goal of this review is to offer FIA’s experience with NFI-RS integration as a case study for other countries wishing to improve the efficiency of their NFI programs.
Photosynthetic and Morphological Acclimation to High and Low Light Environments in Petasites japonicus subsp. giganteus
Authors: Deguchi Ray , Koyama Kohei
Published: December 2020

Within each species, leaf traits such as light-saturated photosynthetic rate or dark respiration rate acclimate to local light environment. Comparing only static physiological traits, however, may not be sufficient to evaluate the effects of such acclimation in the shade because the light environment changes diurnally. We investigated leaf photosynthetic and morphological acclimation for a perennial herb, butterbur (Petasites japonicus (Siebold et Zucc.) Maxim. subsp. giganteus (G.Nicholson) Kitam.) (Asteraceae), in both a well-lit clearing and a shaded understory of a temperate forest. Diurnal changes in light intensity incident on the leaves were also measured on a sunny day and an overcast day. Leaves in the clearing were more folded and upright, whereas leaves in the understory were flatter. Leaf mass per area (LMA) was approximately twofold higher in the clearing than in the understory, while light-saturated photosynthetic rate and dark respiration rate per unit mass of leaf were similar between the sites. Consequently, both light-saturated photosynthetic rate and dark respiration rate per unit area of leaf were approximately twofold higher in the clearing than in the understory, consistent with previous studies on different species. Using this experimental dataset, we performed a simulation in which sun and shade leaves were hypothetically exchanged to investigate whether such plasticity increased carbon gain at each local environment. As expected, in the clearing, the locally acclimated sun leaves gained more carbon than the hypothetically transferred shade leaves. By contrast, in the understory, the daily net carbon gain was similar between the simulated sun and shade leaves on the sunny day due to the frequent sunflecks. Lower LMA and lower photosynthetic capacity in the understory reduced leaf construction cost per area rather than maximizing net daily carbon gain. These results indicate that information on static photosynthetic parameters may not be sufficient to evaluate shade acclimation in forest understories.