bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrial Cancer as a Metabolic Disease with Dysregulated PI3K Signaling: Shedding Light on Novel Therapeutic Strategies
Authors: Kyo Satoru , Nakayama Kentaro
Published: August 2020

Endometrial cancer (EC) is one of the most common malignancies of the female reproductive organs. The most characteristic feature of EC is the frequent association with metabolic disorders. However, the components of these disorders that are involved in carcinogenesis remain unclear. Accumulating epidemiological studies have clearly revealed that hyperinsulinemia, which accompanies these disorders, plays central roles in the development of EC via the insulin-phosphoinositide 3 kinase (PI3K) signaling pathway as a metabolic driver. Recent comprehensive genomic analyses showed that over 90% of ECs have genomic alterations in this pathway, resulting in enhanced insulin signaling and production of optimal tumor microenvironments (TMEs). Targeting PI3K signaling is therefore an attractive treatment strategy. Several clinical trials for recurrent or advanced ECs have been attempted using PI3K-serine/threonine kinase (AKT) inhibitors. However, these agents exhibited far lower efficacy than expected, possibly due to activation of alternative pathways that compensate for the PIK3-AKT pathway and allow tumor growth, or due to adaptive mechanisms including the insulin feedback pathway that limits the efficacy of agents. Overcoming these responses with careful management of insulin levels is key to successful treatment. Further interest in specific TMEs via the insulin PI3K-pathway in obese women will provide insight into not only novel therapeutic strategies but also preventive strategies against EC.
GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells
Authors: Bacelar Sacramento de Araújo Taís , de Oliveira Siquara da Rocha Leonardo , Torres Andion Vidal Manuela , Cerqueira Coelho Paulo Lucas , Galvão dos Reis Mitermayer , Solano de Freitas Souza Bruno , Botelho Pereira Soares Milena , Almeida Pereira Thiago , Della Coletta Ricardo , Pereira Bezerra Daniel , Borges Dias Rosane , Araújo Gurgel Rocha Clarissa
Published: August 2020

Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 µM) to the tested compound. The compound’s effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.
The Role of MicroRNAs in Bone Metabolism and Disease
Authors: Gao Yongguang , Patil Suryaji , Qian Airong
Published: August 2020

Bone metabolism is an intricate process involving various bone cells, signaling pathways, cytokines, hormones, growth factors, etc., and the slightest deviation can result in various bone disorders including osteoporosis, arthropathy, and avascular necrosis of femoral head. Osteoporosis is one of the most prevalent disorders affecting the skeleton, which is characterized by low bone mass and bone mineral density caused by the disruption in the balanced process of bone formation and bone resorption. The current pharmaceutical treatments such as bisphosphonates, selective estrogen receptor modulator, calcitonin, teriparatide, etc., could decrease the risk of fractures but have side-effects that have limited their long term applications. MicroRNAs (miRNAs) are one of many non-coding RNAs. These are single-stranded with a length of 19–25 nucleotides and can influence various cellular processes and play an important role in various diseases. Therefore, in this article, we review the different functions of different miRNA in bone metabolism and osteoporosis to understand their mechanism of action for the development of possible therapeutics.
CXCL13/CXCR5 Interaction Facilitates VCAM-1-Dependent Migration in Human Osteosarcoma
Authors: Liu Ju-Fang , Lee Chiang-Wen , Lin Chih-Yang , Chao Chia-Chia , Chang Tsung-Ming , Han Chien-Kuo , Huang Yuan-Li , Fong Yi-Chin , Tang Chih-Hsin
Published: August 2020

Osteosarcoma is the most common primary tumor of the skeletal system and is well-known to have an aggressive clinical outcome and high metastatic potential. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a vital role in the development of several cancers. However, the effect of CXCL13 in the motility of osteosarcoma cells remains uncertain. Here, we found that CXCL13 increases the migration and invasion potential of three osteosarcoma cell lines. In addition, CXCL13 expression was upregulated in migration-prone MG-63 cells. Vascular cell adhesion molecule 1 (VCAM-1) siRNA and antibody demonstrated that CXCL13 promotes migration via increasing VCAM-1 production. We also show that CXCR5 receptor controls CXCL13-mediated VCAM-1 expression and cell migration. Our study identified that CXCL13/CXCR5 axis facilitate VCAM-1 production and cell migration in human osteosarcoma via the phospholipase C beta (PLCβ), protein kinase C α (PKCα), c-Src, and nuclear factor-κB (NF-κB) signaling pathways. CXCL13 and CXCR5 appear to be a novel therapeutic target in metastatic osteosarcoma.
Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy
Authors: Held Patrice K. , Bird Ian M. , Heather Natasha L.
Published: August 2020

Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.
A Robust Method of Eye Torsion Measurement for Medical Applications
Authors: Jin Nan , Mavromatis Sébastien , Sequeira Jean , Curcio Stéphane
Published: August 2020

The detection of eye torsion is an important element for diagnosis of balance disorders, although it is rarely available in existing eye tracking systems. A novel method is proposed in this paper to provide robust measurement of torsional eye movements. A numerical approach is presented to estimate the iris boundary only according to the gaze direction, so the segmentation of the iris is more robust against occlusions and ambiguities. The perspective distortion of the iris pattern at eccentric eye positions is also corrected, benefiting from the transformation relation that is established for the iris estimation. The angle of the eye torsion is next measured on the unrolled iris patterns via a TM (Template Matching) technique. The principle of the proposed method is validated and its robustness in practice is assessed. A very low mean FPR (False Positive Rate) is reported (i.e., 3.3%) in a gaze test when testing on five participants with very different eye morphologies. The present method always gave correct measurement on the iris patterns with simulated eye torsions and rarely provided mistaken detections in the absence of eye torsion in practical conditions. Therefore, it shows a good potential to be further applied in medical applications.
Predicting the Invasion Potential of the Lily Leaf Beetle, Lilioceris lilii Scopoli (Coleoptera: Chrysomelidae), in North America
Authors: Freeman Maggie , Looney Chris , Orlova-Bienkowskaja Marina J. , Crowder David W.
Published: August 2020

Invasive species are among the leading threats to global ecosystems due to impacts on native flora and fauna through competition and predation. The lily leaf beetle, Lilioceris lilii Scopoli (Coleoptera: Chrysomelidae), is an invasive pest of lilies (Lilium spp.) and other genera of Liliaceae (Liliales). A habitat suitability model was created using Maxent, to help predict if L. lilii will be able to establish in locations were native North American Liliaceae species grow. The model was created using georeferenced occurrence records from the beetle’s native, naturalized, and invasive range. Model results indicate that precipitation in the driest quarter and annual average temperatures are most strongly correlated with L. lilii distribution, and suggest that the species will perform poorly in very dry, hot, or cold environments. The model also indicates that the beetle should be able to establish throughout the range of most North American Liliaceae genera, including species of special conservation concern. This model can be used by natural area managers to identify areas of high habitat suitability that overlap with vulnerable North American Liliaceae species, and prioritize L. lilii monitoring and control activities as the beetle continues to expand its range.
Genotype–Phenotype Correlations in Children with HHT
Authors: Kilian Alexandra , Latino Giuseppe , White Andrew , Clark Dewi , Chakinala Murali , Ratjen Felix , McDonald Jamie , Whitehead Kevin , Gossage James , Lin Doris , Henderson Katharine , Pollak Jeffrey , McWilliams Justin , Kim Helen , Lawton Michael , Faughnan Marie ,   the Brain Vascular Malformation Consortium HHT Investigator Group
Published: August 2020

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presence of a combined phenotype—defined as both pulmonary AVMs and brain VMs—was also associated with ENG mutation. Gastrointestinal bleeding was rare (4.4%), but was associated with SMAD4 genotype (p < 0.001). We conclude that genotype–phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients with ENG mutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.
Intracranial Hemorrhage Complicating Acute Myocardial Infarction: An 18-Year National Study of Temporal Trends, Predictors, and Outcomes
Authors: Patlolla Sri Harsha , Sundaragiri Pranathi R. , Cheungpasitporn Wisit , Doshi Rajkumar , Barsness Gregory W. , Rabinstein Alejandro A. , Jaffe Allan S. , Vallabhajosyula Saraschandra
Published: August 2020

Background: There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI). This study sought to evaluate the temporal trends, predictors, and outcomes of ICH in AMI. Methods: The National Inpatient Sample (2000–2017) was used to identify adult (>18 years) AMI admissions with ICH. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy were used to estimate functional burden. Results: Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, the ICH cohort was on average older, female, of non-White race, had greater comorbidities, and had higher rates of arrhythmias (all p < 0.001). Female sex, non-White race, ST-segment elevation AMI presentation, use of fibrinolytics, mechanical circulatory support, and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%), as compared to those without (p < 0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 (95% CI 5.47–5.84); p < 0.001), longer hospital length of stay, higher hospitalization costs, and greater use of percutaneous endoscopic gastrostomy (all p < 0.001). Among ICH survivors (N = 13, 689), 81.3% had a poor functional outcome at discharge. Conclusions: ICH causes a substantial burden in AMI due to associated higher in-hospital mortality and poor functional outcomes.
Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation
Authors: Shah Neel , Farhat Abdelaziz , Tweed Jefferson , Wang Ziheng , Lee Jeon , McBeth Rafe , Skinner Michael , Tian Fenghua , Thiagarajan Ravi , Raman Lakshmi
Published: August 2020

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.
Increased First Pass Success with C-MAC Videolaryngoscopy in Prehospital Endotracheal Intubation—A Randomized Controlled Trial
Authors: Macke Christian , Gralla Felix , Winkelmann Marcel , Clausen Jan-Dierk , Haertle Marco , Krettek Christian , Omar Mohamed
Published: August 2020

Endotracheal intubation (ETI) with direct view laryngoscopy (DL) is the gold standard for airway management. Videolaryngoscopy (VL) can improve glottis visualization, thus facilitating ETI. The aim of this monocentric, randomized, prospective study on a physician staffed German air ambulance is to compare DL and VL for ETI in terms of number of attempts and time as well as visualization of the glottis in a prehospital setting in a physician-based rescue system in adult patients. A power analysis was performed à priori. We used consecutive on-scene randomization with a sealed envelope system for the DL and VL-group. Successful ETI with first pass success was significantly more frequent with VL than DL and three seconds faster. The percentage of glottis opening and the Cormack & Lehane classification were significantly better with VL than DL. Regarding improved first pass success in ETI with the VL, we would recommend the use of VL for prehospital airway management in physician-based rescue systems.
Evaluation of the Reliability, Reproducibility and Validity of Digital Orthodontic Measurements Based on Various Digital Models among Young Patients
Authors: Park Seo-Hyun , Byun Soo-Hwan , Oh So-Hee , Lee Hye-Lim , Kim Ju-Won , Yang Byoung-Eun , Park In-Young
Published: August 2020

The advantages of intraoral model scanning have yielded recent developments. However, few studies have explored the orthodontic clinical use of this technique particularly among young patients. This study aimed to evaluate the reliability, reproducibility and validity of the orthodontic measurements: tooth width, arch length and arch length discrepancy in each digital model obtained by model scanner and intraoral scanner, relative to a plaster model. Arch length measured using two methods: curved arch length (CAL) measured automatically by digital program and sum of sectional liner arch length (SLAL) measured sum of anterior and posterior liner arch lengths. Arch length discrepancy calculated each arch length measurement methods: curved arch length discrepancy (CALD) and sum of sectional liner arch length discrepancy (SLALD). Forty young patients were eligible for the study. A plaster model (P), model-scanned digital model (MSD) and intraoral scanned digital model (ISD) were acquired from each patient. The reliability of the measurements was evaluated using Pearson’s correlation coefficient, while the reproducibility was evaluated using the intraclass correlation coefficient. The validity was assessed by a paired t-test. All measurements measured in P, MSD and ISD exhibited good reliability and reproducibility. Most orthodontic measurements despite of CAL in MSD exhibited high validity. Only the SLAL and SLALD in ISD group differed significantly, despite the good validity of the tooth width, CAL and CALD. The measurements based on the digital program appeared high reliability, reproducibility and accurate than conventional measurement. However, SLAL and SLALD in ISD group appeared shorter because of distortion during intraoral scanning. However, this could be compensated by using digital programed curved arch. Although the validity of SLAL and SLALD in the ISD group differed statistically, the difference is not considered clinically significant. Although MSD and ISD are acceptable for a clinical space analysis, clinicians should be aware of digital model-induced errors.
Metastatic Burden Defines Clinically and Biologically Distinct Subgroups of Stage 4 High-Risk Neuroblastoma
Authors: Seo Eun Seop , Lee Eun-jin , Lee Boram , Shin Muheon , Cho Young-Seok , Hyun Ju Kyung , Cho Hee Won , Ju Hee Young , Yoo Keon Hee , Koo Hong Hoe , Lee Ji Won , Sung Ki Woong
Published: August 2020

This study aimed to identify the prognostic subgroups of stage 4 high-risk neuroblastoma based on metastatic burden and explore their distinct clinical and genomic features. Patients aged ≥18 months with stage 4 and metaiodobenzylguanidine-avid neuroblastoma were enrolled. One hundred and thirty eligible patients were treated under the tandem high-dose chemotherapy scheme. Prognostic significance of metastatic burden measured by the modified Curie score was analyzed using a competing risk approach, and the optimal cut-point was determined. Metastasis-specific subgroups (cut-point: 26) were compared using clinicopathological variables, and differential gene expression analysis and gene set variation analysis (GSVA) were performed using RNA sequencing (RNA-seq). Metastatic burden at diagnosis showed a progressive association with relapse/progression. After applying the cut-point, patients with high metastatic burden showed >3-fold higher risk of relapse/progression than those with low metastatic burden. Moreover, patients with high metastatic burden showed smaller primary tumors and higher biochemical marker levels than those with low metastatic burden. In the genomic analysis, 51 genes were found to be differentially expressed based on the set criteria. GSVA revealed 55 gene sets, which significantly distinguished patients with high metastatic burden from those with low metastatic burden at a false discovery rate <0.25. The results indicated the prognostic significance of metastatic burden in stage 4 high-risk neuroblastoma, and we identified the distinct clinicopathological and genomic features based on metastatic burden. This study may aid in the better understanding and risk-stratification of stage 4 high-risk neuroblastoma patients.
Late Outcome after Surgery for Type-A Aortic Dissection
Authors: Jormalainen Mikko , Raivio Peter , Biancari Fausto , Mustonen Caius , Honkanen Hannu-Pekka , Venermo Maarit , Vento Antti , Juvonen Tatu
Published: August 2020

The aim of this study was to evaluate all-cause mortality and aortic reoperations after surgery for Stanford type A aortic dissection (TAAD). We evaluated the late outcome of patients who underwent surgery for acute TAAD from January 2005 to December 2017 at the Helsinki University Hospital, Finland. We studied 309 patients (DeBakey type I TAAD: 89.3%) who underwent repair of TAAD. Aortic root repair was performed in 94 patients (30.4%), hemiarch repair in 264 patients (85.4%) and partial/total aortic arch repair in 32 patients (10.4%). Hospital mortality was 13.6%. At 10 years, all-cause mortality was 34.9%, and the cumulative incidence of aortic reoperation or late aortic-related death was 15.6%, of any aortic reoperation 14.6%, reoperation on the aortic root 6.6%, on the aortic arch, descending thoracic and/or abdominal aorta 8.7%, on the descending thoracic and/or abdominal aorta 6.4%, and on the abdominal aorta 3.8%. At 10 years, cumulative incidence of reoperation on the distal aorta was higher in patients with a diameter of the descending thoracic aorta ≥35 mm at primary surgery (cumulative incidence in the overall series: 13.2% vs. 4.0%, SHR 3.993, 95%CI 1.316–12.120; DeBakey type I aortic dissection: 13.6% vs. 4.5%, SHR 3.610, 95%CI 1.193–10.913; patients with dissected descending thoracic aorta: 15.8% vs. 5.9%, SHR 3.211, 95%CI 1.067–9.664). In conclusion, surgical repair of TAAD limited to the aortic segments involved by the intimal tear was associated with favorable survival and a low rate of aortic reoperations. However, patients with enlarged descending thoracic aorta at primary surgery had higher risk of late reoperation. Half of the distal aortic reinterventions were performed on the abdominal aorta.
Assessment of Several Ocean Reanalyzes about North Equatorial Current at 160° E
Authors: Wang Jiahao , Mao Kefeng , Chen Xi
Published: August 2020

Three ocean reanalyzes including Simple Ocean Data Assimilation (SODA), Hybrid Coordinate Ocean Model, and the Navy Coupled Ocean Data Assimilation (HYCOM+NCODA) analysis, and the Ocean General Circulation Model for the Earth Simulator (OFES) are assessed about their ability of depicting the structure of North Equatorial Current (NEC) at 160° E. We found that these products could reflect the structure of NEC relatively well at the whole section, but not at the single point through comparing their results with mooring and cruising measurement, and the OFES is the best choice to study mesoscale processes versus the other two reanalyzes through comparing their results with satellite measurement.
Land Cover Influences on LST in Two Proposed Smart Cities of India: Comparative Analysis Using Spectral Indices
Authors: Ramaiah Manish , Avtar Ram , Rahman Md. Mustafizur
Published: August 2020

Elucidating the impact of Land Surface Temperature (LST) is an important aspect of urban studies. The impact of urbanization on LST has been widely studied to monitor the Urban Heat Island (UHI) phenomenon. However, the sensitivity of various urban factors such as urban green spaces (UGS), built-up area, and water bodies to LST is not sufficiently resolved for many urban settlements. By using remote sensing techniques, this study aimed to quantify the influence of urban factors on LST in the two traditional cities (i) Panaji and (ii) Tumkur of India, proposed to be developed as smart cities. Landsat data were used to extract thematic and statistical information about urban factors using the Enhanced Built-up and Bareness Index (EBBI), Modified Normalized Difference Water Index (MNDWI), and Soil Adjusted Vegetation Index (SAVI). The multivariate regression model revealed that the value of adjusted R2 was 0.716 with a standard error of 1.97 for Tumkur city, while it was 0.698 with a standard error of 1.407 for Panaji city. The non-parametric correlation test brought out a strong negative correlation between MNDWI and LST with a value of 0.83 for Panaji, and between SAVI and LST with a value of 0.77 for Tumkur. The maximum percentage share of cooling surfaces are water bodies in Panaji with 35% coverage and green spaces in Tumkur with 25% coverage. Apparently, the UGS and water bodies can help in bringing down the LST, as well as facilitating healthy living conditions and aesthetic appeal. Therefore, the significance of ecosystem services (green spaces and water bodies) should be given priority in the decision-making process of sustainable and vibrant city development.
Microgravity Modulates Effects of Chemotherapeutic Drugs on Cancer Cell Migration
Authors: Prasanth Devika , Suresh Sindhuja , Prathivadhi-Bhayankaram Sruti , Mimlitz Michael , Zetocha Noah , Lee Bong , Ekpenyong Andrew
Published: August 2020

Microgravity or the condition of apparent weightlessness causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. These organ and system-level dysfunctions correlate with changes induced at the single cell level both by simulated microgravity on earth as well as microgravity conditions in outer space (as in the international space station). Reported changes in single bone cells, muscle cells and white blood cells include structural/morphological abnormalities, changes in gene expression, protein expression, metabolic pathways and signaling pathways, suggesting that cells mount some response or adjustment to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear largely because the primary mechanism of gravity sensing in animal cells is unknown. Here, we used a rotary cell culture system developed by NASA to subject leukemic and erythroleukemic cancer cells to microgravity for 48 h and then quantified their innate immune response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dot-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration (p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 g). However, cells treated with doxorubicin showed enhanced migration both in 1 g and following µg. Our results show that microgravity modulates cancer cell response to chemotherapy in a drug-dependent manner. These results suggest using simulated microgravity as an immunomodulatory tool for the development of new immunotherapies for both space and terrestrial medicine.
Ceramization Mechanism of Ceramizable Silicone Rubber Composites with Nano Silica at Low Temperature
Authors: Li Penghu , Jin Haiyun , Wei Shichao , Liu Huaidong , Gao Naikui , Shi Zhongqi
Published: August 2020

Ceramizable composite is a kind of polymer matrix composite that can turn into ceramic material at a high temperature. It can be used for the ceramic insulation of a metal conductor because of its processability. However, poor low-temperature ceramization performance is a problem of ceramizable composites. In this paper, ceramizable composites were prepared by using silicone rubber as a matrix. Ceramic samples were sintered at different temperatures no more than 1000 °C, according to thermogravimetric analysis results of the composites. The linear contraction and flexural strength of the ceramics were measured. The microstructure and crystalline phase of ceramics were analyzed using scanning electron microscope (SEM) and X-ray diffraction (XRD). The results show that the composites turned into ceramics at 800 °C, and a new crystal and continuous microstructure formed in the samples. The flexural strength of ceramics was 46.76 MPa, which was more than twice that of similar materials reported in other research sintered at 1000 °C. The maximum flexural strength was 54.56 MPa, when the sintering temperature was no more than 1000 °C. Moreover, glass frit and nano silica played important roles in the formation of the ceramic phase in this research. A proper content of nano silica could increase the strength of the ceramic samples.
Numerical Evaluation on Analysis Methods of Trapping Site Density in Steels Based on Hydrogen Permeation Curve
Authors: Yang Bangshu , Li Li , Cheng Lin
Published: August 2020

Hydrogen permeation techniques have been widely utilized to extract hydrogen effective diffusivity, as well as hydrogen trapping site characteristics in steels. Several methods have been proposed to examine reversible and irreversible trapping site characteristics. However, the inappropriate utilization of these simplified models, as well as incorrect value assignment to the key parameters, can result in several orders of magnitude difference in hydrogen trapping site density. Therefore, in order to evaluate these models and verify their application prerequisites, a serial of hydrogen permeation tests were numerically simulated and examined, separately considering reversible and irreversible hydrogen trapping sites. In the meantime, suggestions were given to conduct hydrogen permeation test more effectively, and evaluate hydrogen trapping site characteristics more precisely.
On the Microstructure and Properties of Nb-12Ti-18Si-6Ta-5Al-5Cr-2.5W-1Hf (at.%) Silicide-Based Alloys with Ge and Sn Additions
Authors: Zhao Jiang , Utton Claire , Tsakiropoulos Panos
Published: August 2020

The microstructures and properties of the alloys JZ3 (Nb-12.4Ti-17.7Si-6Ta-2.7W-3.7Sn-4.8Ge-1Hf-4.7Al-5.2Cr) and JZ3+(Nb-12.4Ti-19.7Si-5.7Ta-2.3W-5.7Sn-4.9Ge-0.8Hf-4.6Al-5.2Cr) were studied. The densities of both alloys were lower than the densities of Ni-based superalloys and many of the refractory metal complex concentrated alloys (RCCAs) studied to date. Both alloys had Si macrosegregation and the same phases in their as cast and heat treated microstructures, namely βNb5Si3, αNb5Si3, A15-Nb3X (X = Al, Ge, Si, Sn), C14-Cr2Nb and solid solution. W-rich solid solutions were stable in both alloys. At 800 °C only the alloy JZ3 did not show pest oxidation, and at 1200 °C a thin and well adhering scale formed only on JZ3+. The alloy JZ3+ followed parabolic oxidation with rate constant one order of magnitude higher than the single crystal Ni-superalloy CMSX-4 for the first 14 h of oxidation. The oxidation of both alloys was superior to that of RCCAs. Both alloys were predicted to have better creep at the creep goal condition compared with the superalloy CMSX-4. Calculated Si macrosegregation, solid solution volume fractions, chemical compositions of solid solution and Nb5Si3, weight changes in isothermal oxidation at 800 and 1200 °C using the alloy design methodology NICE agreed well with the experimental results.
In Situ Mo(Si,Al)2-Based Composite through Selective Laser Melting of a MoSi2-30 wt.% AlSi10Mg Mixture
Authors: Minasyan Tatevik , Aydinyan Sofiya , Toyserkani Ehsan , Hussainova Irina
Published: August 2020

The laser power bed fusion approach has been successfully employed to manufacture Mo(Si,Al)2-based composites through the selective laser melting of a MoSi2-30 wt.% AlSi10Mg mixture for high-temperature structural applications. Composites were manufactured by leveraging the in situ reaction of the components during printing at 150–300 W laser power, 500–1000 mm·s−1 laser scanning speed, and 100–134 J·mm−3 volumetric energy density. Microcomputed tomography scans indicated a negligible induced porosity throughout the specimens. The fully dense Mo(Si1-x,Alx)2-based composites, with hardness exceeding 545 HV1 and low roughness for both the top (horizontal) and side (vertical) surfaces, demonstrated that laser-based additive manufacturing can be exploited to create unique structures containing hexagonal Mo(Si0.67Al0.33)2.
The Discrete and Continuous Retardation and Relaxation Spectrum Method for Viscoelastic Characterization of Warm Mix Crumb Rubber-Modified Asphalt Mixtures
Authors: Zhang Fei , Wang Lan , Li Chao , Xing Yongming
Published: August 2020

To study the linear viscoelastic (LVE) of crumb rubber-modified asphalt mixtures before and after the warm mix additive was added methods of obtaining the discrete and continuous spectrum are presented. Besides, the relaxation modulus and creep compliance are constructed from the discrete and continuous spectrum, respectively. The discrete spectrum of asphalt mixtures can be obtained from dynamic modulus test results according to the generalized Maxwell model (GMM) and the generalized Kelvin model (GKM). Similarly, the continuous spectrum of asphalt mixtures can be obtained from the dynamic modulus test data via the inverse integral transformation. In this paper, the test procedure for all specimens was ensured to be completed in the LVE range. The results show that the discrete spectrum and the continuous spectrum have similar shapes, but the magnitude and position of the spectrum peaks is different. The continuous spectrum can be considered as the limiting case of the discrete spectrum. The relaxation modulus and creep compliance constructed by the discrete and continuous spectrum are almost indistinguishable in the reduced time range of 10−5 s–103 s. However, there are more significant errors outside the time range, and the maximum error is up to 55%.
Novel III-V Nitride Polymorphs in the P42/mnm and Pbca Phases
Authors: Fan Qingyang , Ai Xin , Zhou Junni , Yu Xinhai , Zhang Wei , Yun Sining
Published: August 2020

In this work, the elastic anisotropy, mechanical stability, and electronic properties for P42/mnm XN (XN = BN, AlN, GaN, and InN) and Pbca XN are researched based on density functional theory. Here, the XN in the P42/mnm and Pbca phases have a mechanic stability and dynamic stability. Compared with the Pnma phase and Pm-3n phase, the P42/mnm and Pbca phases have greater values of bulk modulus and shear modulus. The ratio of the bulk modulus (B), shear modulus (G), and Poisson’s ratio (v) of XN in the P42/mnm and Pbca phases are smaller than those for Pnma XN and Pm-3n XN, and larger than those for c-XN, indicating that Pnma XN and Pm-3n XN are more ductile than P42/mnm XN and Pbca XN, and that c-XN is more brittle than P42/mnm XN and Pbca XN. In addition, in the Pbca phases, XN can be considered a semiconductor material, while in the P42/mnm phase, GaN and InN have direct band-gap, and BN and AlN are indirect wide band gap materials. The novel III-V nitride polymorphs in the P42/mnm and Pbca phases may have great potential for application in visible light detectors, ultraviolet detectors, infrared detectors, and light-emitting diodes.
Stochastic Order for a Multivariate Uniform Distributions Family
Authors: Catana Luigi-Ionut , Raducan Anisoara
Published: August 2020

In this article we give sufficient conditions for stochastic order of multivariate uniform distributions on closed convex sets.
An Iteration Function Having Optimal Eighth-Order of Convergence for Multiple Roots and Local Convergence
Authors: Behl Ramandeep , Argyros Ioannis K. , Argyros Michael , Salimi Mehdi , Alsolami Arwa Jeza
Published: August 2020

In the study of dynamics of physical systems an important role is played by symmetry principles. As an example in classical physics, symmetry plays a role in quantum physics, turbulence and similar theoretical models. We end up having to deal with an equation whose solution we desire to be in a closed form. But obtaining a solution in such form is achieved only in special cases. Hence, we resort to iterative schemes. There is where the novelty of our study lies, as well as our motivation for writing it. We have a very limited literature with eighth-order convergent iteration functions that can handle multiple zeros m≥1. Therefore, we suggest an eighth-order scheme for multiple zeros having optimal convergence along with fast convergence and uncomplicated structure. We develop an extensive convergence study in the main theorem that illustrates eighth-order convergence of our scheme. Finally, the applicability and comparison was illustrated on real life problems, e.g., Van der Waal’s equation of state, Chemical reactor with fractional conversion, continuous stirred reactor and multi-factor problems, etc., with existing schemes. These examples further show the superiority of our schemes over the earlier ones.
Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in Pseudomonas aeruginosa
Authors: Hegazy Wael A. H. , Khayat Maan T. , Ibrahim Tarek S. , Nassar Majed S. , Bakhrebah Muhammed A. , Abdulaal Wesam H. , Alhakamy Nabil A. , Bendary Mahmoud M.
Published: August 2020

Pseudomonas aeruginosa is a significant human pathogen, it possesses almost all of the known antimicrobial resistance mechanisms. Quorum sensing (QS) is an intercellular communication system that orchestrates bacterial virulence and its targeting is an effective approach to diminish its pathogenesis. Repurposing of drugs is an advantageous strategy, in this study we aimed to repurpose the anti-diabetic drugs sitagliptin, metformin and vildagliptin as anti-QS in P. aeruginosa. The effects of sub-inhibitory concentrations of the tested drugs on the expression of QS-encoding genes and QS-regulated virulence factors were assessed. The protective activity of tested drugs on P. aeruginosa pathogenesis was evaluated in vivo on mice. In silico analysis was performed to evaluate the interference capabilities of the tested drugs on QS-receptors. Although the three drugs reduced the expression of QS-encoding genes, only sitagliptin inhibited the P. aeruginosa virulence in vitro and protected mice from it. In contrast, metformin showed significant in vitro anti-QS activities but failed to protect mice from P. aeruginosa. Vildagliptin did not show any in vitro or in vivo efficacy. Sitagliptin is a promising anti-QS agent because of its chemical nature that hindered QS-receptors. Moreover, it gives an insight to consider their similar chemical structures as anti-QS agents or even design new chemically similar anti-QS pharmacophores.
Effects of Lentil Genotype on the Colonization of Beneficial Trichoderma Species and Biocontrol of Aphanomyces Root Rot
Authors: Bazghaleh Navid , Prashar Pratibha , Woo Sheridan , Vandenberg Albert
Published: August 2020

Trichoderma species are opportunistic plant symbionts that are common in the root and rhizosphere ecosystems. Many Trichoderma species may enhance plant growth, nutrient acquisition, and disease resistance, and for these reasons, they are widely used in agriculture as biofertilizers or biocontrol agents. Host plant genotype and other microorganisms, such as root pathogens, may influence the efficacy of Trichoderma inoculants. Aphanomyces euteiches is an important soil-borne oomycete in western Canada that causes root rot in legume crops such as lentil and pea, and there is not yet any significantly resistant varieties or effective treatments available to control the disease. In this study, the composition of root-associated fungal communities and the abundance of Trichoderma species, T. harzianum strain T-22 and T. virens strain G41, was determined in the roots of eight Lens genotypes based on internal transcribed spacer (ITS) Illumina MiSeq paired-end sequencing, both in the presence and the absence of the root rot pathogen Aphanomyces euteiches. Biocontrol effects of T. harzianum on A. euteiches was also examined. Significant genotypic variations were observed in the composition of root-associated fungal communities and the abundance of the different Trichoderma species in the lentil roots. The presence of A. euteiches altered the composition of Trichoderma found associated to the lentil genotypes. Biocontrol of A. euteiches by T. harzianum T22 species was observed in vitro and positive correlations between the abundance of Trichoderma and plant root and shoot biomass were observed in vivo. These findings revealed that lentil genotype and infection by the phytopathogen A. euteiches greatly influenced the colonization of root-associated fungi and the abundance of the Trichoderma species, as well as the effect on plant growth promotion. The multipartite interactions observed among lentil genotypes, Trichoderma species and A. euteiches suggest possibilities to select compatible host-beneficial microbe combinations in lentil breeding programs and to develop application strategies to harness the beneficial effects of Trichoderma inoculants in sustainable crop production systems.
A Geospatial Database for Effective Mine Rehabilitation in Australia
Authors: Werner Tim , Bach Peter , Yellishetty Mohan , Amirpoorsaeed Fatemeh , Walsh Stuart , Miller Alec , Roach Matthew , Schnapp Andrew , Solly Philippa , Tan Youming , Lewis Chloe , Hudson Ehren , Heberling Kim , Richards Thomas , Chia Han , Truong Melissa , Gupta Tushar , Wu Xiaoling
Published: August 2020

The Australian landscape is affected by abandoned mines that pose environmental, public health and safety risks. To promote the beneficial reuse, rehabilitation and/or remediation of these sites and understand their spatial arrangement, we compiled, classified and analysed a country-wide geospatial database of all known inactive hard rock mine sites. Following extensive review and classification of disparate records of such sites that have been terminated, neglected or classified as heritage, plus those under care and maintenance in Australia, we assessed state-by-state reporting and cross-border rehabilitation requirements. This was enabled by the development of the Mining Incidence Documentation & Assessment Scheme (MIDAS) that can be used to catalogue and compare active or inactive mine data regardless of reporting conventions. At a national level, and with four case studies, we performed GIS-based spatial analyses and environmental risk assessments to demonstrate potential uses of our database. Analyses considered the proximity of sites to factors such as infrastructure and sensitive environmental receptors. As Australia struggles to manage the ongoing technical, socioeconomic and environmental challenges of effective mine rehabilitation, the insights enabled by this national-level spatial database may be key to developing coordinated responses that extend beyond state boundaries. Our classification and methodology are easily transferable, thereby encouraging more formalized, systematic and widespread documentation of abandoned mines worldwide.
Thermal Conductivities of Choline Chloride-Based Deep Eutectic Solvents and Their Mixtures with Water: Measurement and Estimation
Authors: Ibrahim Taleb H. , Sabri Muhammad A. , Abdel Jabbar Nabil , Nancarrow Paul , Mjalli Farouq S. , AlNashef Inas
Published: August 2020

The thermal conductivities of selected deep eutectic solvents (DESs) were determined using the modified transient plane source (MTPS) method over the temperature range from 295 K to 363 K at atmospheric pressure. The results were found to range from 0.198 W·m−1·K−1 to 0.250 W·m−1·K−1. Various empirical and thermodynamic correlations present in literature, including the group contribution method and mixing correlations, were used to model the thermal conductivities of these DES at different temperatures. The predictions of these correlations were compared and consolidated with the reported experimental values. In addition, the thermal conductivities of DES mixtures with water over a wide range of compositions at 298 K and atmospheric pressure were measured. The standard uncertainty in thermal conductivity was estimated to be less than ± 0.001 W·m−1·K−1 and ± 0.05 K in temperature. The results indicated that DES have significant potential for use as heat transfer fluids.
Integral Representation of Electrostatic Interactions inside a Lipid Membrane
Authors: Bossa Guilherme Volpe , May Sylvio
Published: August 2020

Interactions between charges and dipoles inside a lipid membrane are partially screened. The screening arises both from the polarization of water and from the structure of the electric double layer formed by the salt ions outside the membrane. Assuming that the membrane can be represented as a dielectric slab of low dielectric constant sandwiched by an aqueous solution containing mobile ions, a theoretical model is developed to quantify the strength of electrostatic interactions inside a lipid membrane that is valid in the linear limit of Poisson-Boltzmann theory. We determine the electrostatic potential produced by a single point charge that resides inside the slab and from that calculate charge-charge and dipole-dipole interactions as a function of separation. Our approach yields integral representations for these interactions that can easily be evaluated numerically for any choice of parameters and be further simplified in limiting cases.
k-Oligocarrageenan Promoting Growth of Hybrid Maize: Influence of Molecular Weight
Authors: San Pham Trung , Khanh Chau Minh , Khanh Huynh Hoang Nhu , Khoa Truong Anh , Hoang Nguyen , Nhung Le Thi , Trinh Nguyen Thi Kieu , Nguyen Thanh-Danh
Published: August 2020

k-Oligocarrageenan (OC) is an effective biostimulator and a protector against disease infections for plants. However, the effect of OC molecular weight (MW) on plant growth is not fully understood. In this work, OCs with three different MWs (42, 17 and 4 kDa) was prepared by varying the degradation reaction time using ascorbic acid as a reagent. The product structure was confirmed by Fourier-transform infrared spectroscopy (FTIR) data. The growth promotion for maize (Zea mays L.) plants was investigated by foliar spray application of the prepared OCs. Field trials were carried out in two years, 2018 and 2019. The results showed that among treatments, OC with 4 kDa exhibited the best performance in both crop growth and grain yield parameters which indicated increases compared to the control in plant height (6.9–19.9%), length of ears (12.2%), diameter of ears (9.1%), fresh grain weight (17.8%), dry grain weight (20.0%) and grain yield (21.3%). Moreover, low MW OC augmented NP uptake in the plant growth while no effect on K uptake was observed. Therefore, OC with low MWs is potentially promising to apply as a promoter to enhance yield of crops.