bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways
Authors: Zhao Qian , Zhu Hong-Ping , Xie Xin , Mao Qing , Liu Yan-Qing , He Xiang-Hong , Peng Cheng , Jiang Qing-Lin , Huang Wei
Published: March 2020

Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.
High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression
Authors: Xu Lei , Xia Hua , Ni Dongsheng , Hu Yanxia , Liu Jianing , Qin Yao , Zhou Qin , Yi Qiying , Xie Yajun
Published: March 2020

High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.
Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats
Authors: Xu Jie , Wang Jiao , Cao Yang , Jia Xiaotong , Huang Yujia , Cai Minghui , Lu Chunmei , Zhu Hui
Published: March 2020

Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placentas of streptozotocin-induced diabetic pregnant rats, which was associated with the decreased birthweight in the rats. A decreased placental efficiency and decreased placental mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity were also found in the rat model. In addition, hyperglycemia in vitro could inhibit amino acid transporter expression and mTORC1 activity in human trophoblast. Inhibition of mTORC1 activity led to reduced amino acid transporter expression in placental trophoblast. We concluded that reduced placental mTORC1 activity during pregnancy resulted in decreased placental amino acid transporter expression and, subsequently, contributed to fetal intrauterine growth restriction in pregnancies complicated with diabetes.
The GPR17 Receptor—A Promising Goal for Therapy and a Potential Marker of the Neurodegenerative Process in Multiple Sclerosis
Authors: Dziedzic Angela , Miller Elzbieta , Saluk-Bijak Joanna , Bijak Michal
Published: March 2020

One of the most important goals in the treatment of demyelinating diseases such as multiple sclerosis (MS) is, in addition to immunomodulation, reconstruction of the lost myelin sheath. The modulator of the central nervous system myelination is the metabotropic receptor coupled to the G-protein: GPR17. GPR17 receptors are considered to be sensors of local damage to the myelin sheath, and play a role in the reconstruction and repair of demyelinating plaques caused by ongoing inflammatory processes. GPR17 receptors are present on nerve cells and precursor oligodendrocyte cells. Under physiological conditions, they are responsible for the differentiation and subsequent maturation of oligodendrocytes, while under pathological conditions (during damage to nerve cells), their expression increases to become mediators in the demyelinating processes. Moreover, they are essential not only in both the processes of inducing damage and the death of neurons, but also in the local repair of the damaged myelin sheath. Therefore, GPR17 receptors may be recognized as the potential goal in creating innovative therapies for the treatment of the neurodegenerative process in MS, based on the acceleration of the remyelination processes. This review examines the role of GRP17 in pathomechanisms of MS development.
Reconstruction of the Evolutionary Histories of UGT Gene Superfamily in Legumes Clarifies the Functional Divergence of Duplicates in Specialized Metabolism
Authors: Krishnamurthy Panneerselvam , Tsukamoto Chigen , Ishimoto Masao
Published: March 2020

Plant uridine 5′-diphosphate glycosyltransferases (UGTs) influence the physiochemical properties of several classes of specialized metabolites including triterpenoids via glycosylation. To uncover the evolutionary past of UGTs of soyasaponins (a group of beneficial triterpene glycosides widespread among Leguminosae), the UGT gene superfamily in Medicago truncatula, Glycine max, Phaseolus vulgaris, Lotus japonicus, and Trifolium pratense genomes were systematically mined. A total of 834 nonredundant UGTs were identified and categorized into 98 putative orthologous loci (POLs) using tree-based and graph-based methods. Major key findings in this study were of, (i) 17 POLs represent potential catalysts for triterpene glycosylation in legumes, (ii) UGTs responsible for the addition of second (UGT73P2: galactosyltransferase and UGT73P10: arabinosyltransferase) and third (UGT91H4: rhamnosyltransferase and UGT91H9: glucosyltransferase) sugars of the C-3 sugar chain of soyasaponins were resulted from duplication events occurred before and after the hologalegina–millettoid split, respectively, and followed neofunctionalization in species-/ lineage-specific manner, and (iii) UGTs responsible for the C-22-O glycosylation of group A (arabinosyltransferase) and DDMP saponins (DDMPtransferase) and the second sugar of C-22 sugar chain of group A saponins (UGT73F2: glucosyltransferase) may all share a common ancestor. Our findings showed a way to trace the evolutionary history of UGTs involved in specialized metabolism.
Follow Me! A Tale of Avian Heart Development with Comparisons to Mammal Heart Development
Authors: Lansford Rusty , Rugonyi Sandra
Published: March 2020

Avian embryos have been used for centuries to study development due to the ease of access. Because the embryos are sheltered inside the eggshell, a small window in the shell is ideal for visualizing the embryos and performing different interventions. The window can then be covered, and the embryo returned to the incubator for the desired amount of time, and observed during further development. Up to about 4 days of chicken development (out of 21 days of incubation), when the egg is opened the embryo is on top of the yolk, and its heart is on top of its body. This allows easy imaging of heart formation and heart development using non-invasive techniques, including regular optical microscopy. After day 4, the embryo starts sinking into the yolk, but still imaging technologies, such as ultrasound, can tomographically image the embryo and its heart in vivo. Importantly, because like the human heart the avian heart develops into a four-chambered heart with valves, heart malformations and pathologies that human babies suffer can be replicated in avian embryos, allowing a unique developmental window into human congenital heart disease. Here, we review avian heart formation and provide comparisons to the mammalian heart.
Interstitial Lung Disease Associated with Lung Cancer: A Case–Control Study
Authors: Gibiot Quentin , Monnet Isabelle , Levy Pierre , Brun Anne-Laure , Antoine Martine , Chouaïd Christos , Cadranel Jacques , Naccache Jean-Marc
Published: March 2020

Interstitial lung disease (ILD) seems to be associated with an increased risk of lung cancer (LC) and to have a poorer prognosis than LC without ILD. The frequency of ILD in an LC cohort and its prognosis implication need to be better elucidated. This retrospective, observational, cohort study evaluated the frequency of ILD among LC patients (LC–ILD) diagnosed over a 2-year period. LC–ILD patients’ characteristics were compared to those with LC without ILD (LC–noILD). Lastly, we conducted a case–control study within this cohort, matching three LC–noILDs to each LC–ILD patient, to evaluate the ILD impact on LC patients’ prognoses. Among 906 LC patients, 49 (5.4%) also had ILD. Comparing LC–ILD to LC–noILD patients, respectively, more were men (85.7% vs. 66.2%; p = 0.02); adenocarcinomas were less frequent (47.1% vs. 58.7%, p = 0.08); median [range] and overall survival was shorter: (9 [range: 0.1–39.4] vs. 17.5 [range: 0.8–50.4] months; p = 0.01). Multivariate analysis (hazard ratio [95% confidence interval]) retained two factors independently associated with LC risk of death: ILD (1.79 [1.22–2.62]; p = 0.003) and standard-of-care management (0.49 [0.33–0.72]; p < 0.001). Approximately 5% of patients with a new LC diagnosis had associated ILD. ILD was a major prognosis factor for LC and should be taken into consideration for LC management. Further studies are needed to determine the best therapeutic strategy for the LC–ILD population.
The Development and Testing of a Chemotherapy-Induced Phlebitis Severity (CIPS) Scale for Patients Receiving Anthracycline Chemotherapy for Breast Cancer
Authors: Harris Valerie , Hughes Meinir , Roberts Rosie , Dolan Gina , Williams E. Mark
Published: March 2020

A chemotherapy induced phlebitis severity (CIPS) scale was developed in patients receiving anthracycline chemotherapy for breast cancer. A five-point severity scoring scale for chemotherapy-induced phlebitis was tested for inter-rater reliability. Ease of use was observed through timing assessments and a review of the completeness of documentation. A comparison of CIPS scale grade with participant reported severity scores was made. The final version was tested for inter-rater reliability, with 122 patient assessments. There was an 89.3% (109 of 122) agreement between the assessors (κ = 0.82, SE ± 0.042, 95% CI 0.74–0.90). Mean time to complete the scale was 1 min 36 s and documentation was fully completed for 98% of assessments. Patient reported severity closely matched the CIPS grade (κ = 0.54, SE ± 0.045, 95% CI 0.46–0.63). This new scale provides a list of symptoms associated with chemotherapy phlebitis, which can be scored quickly and accurately. It provides a reliable method for assessing chemotherapy-induced phlebitis, enabling a better understanding of its impact on patients’ quality of life, and to inform the appropriate choice of peripheral or central intravenous administration. Multicentre testing of the CIPS scale is recommended.
Sepsis-Associated Encephalopathy: From Delirium to Dementia?
Authors: Chung Ha-Yeun , Wickel Jonathan , Brunkhorst Frank M. , Geis Christian
Published: March 2020

Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy.
Relationship between Maternal Body Mass Index and Obstetric and Perinatal Complications
Authors: Ballesta-Castillejos Ana , Gómez-Salgado Juan , Rodríguez-Almagro Julián , Ortiz-Esquinas Inmaculada , Hernández-Martínez Antonio
Published: March 2020

Over the past few decades, overweight and obesity have become a growing health problem of particular concern for women of reproductive age as obesity in pregnancy has been associated with increased risk of obstetric and neonatal complications. The objective of this study is to describe the incidence of obstetric and perinatal complications in relation to maternal body mass index (BMI) at the time prior to delivery within the Spanish Health System. For this purpose, a cross-sectional observational study was conducted aimed at women who have been mothers between 2013 and 2018 in Spain. Data were collected through an online survey of 42 items that was distributed through lactation associations and postpartum support groups. A total of 5871 women answered the survey, with a mean age of 33.9 years (SD = 4.26 years). In the data analysis, crude odds ratios (OR) and adjusted odds ratios (AOR) were calculated through a multivariate analysis. A linear relationship was observed between the highest BMI figures and the highest risk of cephalopelvic disproportion (AOR of 1.79 for obesity type III (95% CI: 1.06–3.02)), preeclampsia (AOR of 6.86 for obesity type III (3.01–15.40)), labor induction (AOR of 1.78 for obesity type III (95% CI: 1.16–2.74)), emergency C-section (AOR of 2.92 for obesity type III (95% CI: 1.68–5.08)), morbidity composite in childbirth (AOR of 3.64 for obesity type III (95% CI: 2.13–6.24)), and macrosomia (AOR of 6.06 for obesity type III (95% CI: 3.17–11.60)), as compared with women with normoweight. Women with a higher BMI are more likely to develop complications during childbirth and macrosomia.
Influence of Preformed Antibodies in Liver Transplantation
Authors: Legaz Isabel , Boix Francisco , López Manuela , Alfaro Rafael , Galián José A. , Llorente Santiago , Campillo Jose A. , Botella Carmen , Ramírez Pablo , Sánchez-Bueno Francisco , Pons José A. , Moya-Quiles María R. , Minguela Alfredo , Muro Manuel
Published: March 2020

The significance of human leukocyte antigen (HLA) matching and preformed donor-specific antibodies (DSAs) in liver transplantation remains unclear. The aim of this study was to analyze the presence of DSAs in a large cohort of 810 liver recipients undergoing liver transplant to determine the influence on acute (AR) or chronic liver rejection (CR), graft loss and allograft survival. DSAs were identified using complement dependent cytotoxicity crossmatch (CDC-CM) and multiplexed solid-phase-based flow cytometry assay (Luminex). CDC-CM showed that a 3.2% of liver transplants were positive (+CDC-CM) with an AR frequency of 19.2% which was not different from that observed in negative patients (−CDC-CM, 22.3%). Only two patients transplanted with +CDC-CM (7.6%) developed CR and suffered re-transplant. +CDC-CM patients showed a significantly lower survival rate compared to −CDC-CM patients (23.1% vs. 59.1%, p = 0.0003), developing allograft failure within the first three months (p < 0.00001). In conclusion, we have demonstrated a relationship between the presence of preformed DSAs and the low graft liver survival, indicating the important role and the potential interest of performing this analysis before liver transplantation. Our results could help to detect patients with an increased risk of graft loss, a better choice of liver receptors as well as the establishment of individualized immunosuppressive regimens.
Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation
Authors: Xu Jin , Hassan-Ally Mohammad , Casas-Ferreira Ana María , Suvitaival Tommi , Ma Yun , Vilca-Melendez Hector , Rela Mohamed , Heaton Nigel , Jassem Wayel , Legido-Quigley Cristina
Published: March 2020

The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q < 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q < 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.
New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond
Authors: Demirkaya Erkan , Sahin Sezgin , Romano Micol , Zhou Qing , Aksentijevich Ivona
Published: March 2020

Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.
Calcium Kidney Stones are Associated with Increased Risk of Carotid Atherosclerosis: The Link between Urinary Stone Risks, Carotid Intima-Media Thickness, and Oxidative Stress Markers
Authors: Huang Ho Shiang , Liao Pao Chi , Liu Chan Jung
Published: March 2020

Previous studies have suggested that kidney stone formers are associated with a higher risk of cardiovascular events. To our knowledge, there have been no previous examinations of the relationship between carotid intima-media thickness (IMT) and urinary stone risk factors. This study was aimed toward an investigation of the association between dyslipidemia, IMT, and 24-hour urinalysis in patients with calcium oxalate (CaOx) or calcium phosphate (CaP) stones. We prospectively enrolled 114 patients with kidney stones and 33 controls between January 2016 and August 2016. All patients were divided into four groups, according to the stone compositions—CaOx ≥ 50% group, CaP group, struvite group, and uric acid stones group. Carotid IMT and the carotid score (CS) were evaluated using extracranial carotid artery doppler ultrasonography. The results of a multivariate analysis indicated that a higher serum total cholesterol (TC) and low-density lipoprotein (LDL) were all associated with lower urinary citrate and higher CS in both the CaOx ≥ 50% and CaP groups. Higher serum TC and LDL were also associated with increased serum 8-OHdG levels in both groups. The levels of carotid IMT and CS in the CaOx ≥ 50% and CaP groups were all significantly higher than in the controls. These findings suggest a strong link between dyslipidemia, carotid atherosclerosis, and calcium kidney stone disease.
A Numerical Study on Hydrodynamic Performance of an Inclined OWC Wave Energy Converter with Nonlinear Turbine–Chamber Interaction based on 3D Potential Flow
Authors: Kim Jeong-Seok , Nam Bo Woo , Kim Kyong-Hwan , Park Sewan , Shin Seung Ho , Hong Keyyong
Published: March 2020

In this study, a time-domain numerical method based on three-dimensional potential flow was developed to analyze the hydrodynamic characteristics of an inclined oscillating-water-column (OWC) wave energy converter (WEC). A finite element method was applied to solve the potential flow around and inside the OWC chamber. A turbine–chamber interaction was considered to take into account the pressure drop inside the OWC chamber, which is a nonlinear function of airflow speed via turbine operation. The instantaneous pressure drop was updated on the free-surface boundary condition inside the chamber in the time-domain to account for the coupling effect between the turbine and the chamber. The present numerical method was verified by comparing it with the model test results. The hydrodynamic characteristics of an inclined OWC chamber in terms of potential flow, such as the water column motion and the three-dimensional flow distribution around the chamber, were investigated. In terms of hydrodynamic performance, the energy conversion efficiency of the chamber showed a nonlinear response characteristic dependent on the incident wave height. In addition, numerical calculations were carried out to clarify the relationship between the main geometric parameters and the hydrodynamic response of the inclined OWC chamber.
An Efficient Method for Simulating Typhoon Waves Based on a Modified Holland Vortex Model
Authors: Wang Lvqing , Zhang Zhaozi , Liang Bingchen , Lee Dongyoung , Luo Shaoyang
Published: March 2020

A combination of the WAVEWATCH III (WW3) model and a modified Holland vortex model is developed and studied in the present work. The Holland 2010 model is modified with two improvements: the first is a new scaling parameter, bs, that is formulated with information about the maximum wind speed (vms) and the typhoon’s forward movement velocity (vt); the second is the introduction of an asymmetric typhoon structure. In order to convert the wind speed, as reconstructed by the modified Holland model, from 1-min averaged wind inputs into 10-min averaged wind inputs to force the WW3 model, a gust factor (gf) is fitted in accordance with practical test cases. Validation against wave buoy data proves that the combination of the two models through the gust factor is robust for the estimation of typhoon waves. The proposed method can simulate typhoon waves efficiently based on easily accessible data sources.
Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental Exserohilum rostratum Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System
Authors: Petraitiene Ruta , Petraitis Vidmantas , Maung BoBo Win , Naing Ethan , Kavaliauskas Povilas , Walsh Thomas J.
Published: March 2020

Phaeohyphomycosis of the central nervous system (CNS) is a life-threatening infection associated with severe morbidity. New approaches to treatment of CNS phaeohyphomycosis are critically needed. We therefore studied posaconazole with or without caspofungin for treatment of experimental CNS phaeohyphomycosis caused by Exserohilum rostratum. Each clinical isolate of E. rostratum isolate was inoculated intracisternally with 1.0 × 106 microconidia to fully anesthetized New Zealand White rabbits. Profound persistent neutropenia and immunosuppression were established and maintained using cytarabine and methylprednisolone, respectively. Study groups consisted of posaconazole suspension administered as oral formulation at 10 (PSC10) or 20 (PSC20) mg/kg, caspofungin (CFG) at 2 mg/kg intravenously (IV), combinations of PSC10+CFG or PSC20+CFG, and untreated controls (UC). Posaconazole produced a significant reduction of residual fungal burden of E. rostratum in cerebrum, cerebellum, spinal cord, and paravertebral muscle (p < 0.01), in comparison to UC. The combination of PSC10+CFG and PSC20+CFG achieved full clearance of residual fungal burden from cerebrum, while only PSC20+CFG treated rabbits demonstrated clearance from cerebellum, spinal cord, and paravertebral muscle (p < 0.01). These data correlated with the significant reduction of CSF (1→3)-β-d-glucan levels in rabbits treated with PSC20 and PSC20+CFG in comparison to those of UC (p < 0.05). Posaconazole alone or in combination with caspofungin demonstrated significant antifungal efficacy in the treatment of experimental E. rostratum meningoencephalitis and warrants further study for treatment of CNS phaeohyphomycosis.
Actors, Scales and Spaces Dynamics Linked to Groundwater Resources use for Agriculture Production in Haouaria Plain, Tunisia. A Territory Game Approach
Authors: Ferchichi Intissar , Mekki Insaf , Elloumi Mohamed , Arfa Lamia , Lardon Sylvie
Published: March 2020

Groundwater resources became a recognized enabler of important rural and socio-economic development in Mediterranean countries. However, the development of this groundwater economy is currently associated with an increased pressure on the available resource and negative implications on the socio-ecological system. Managing complex socio-ecological systems, such as those that occur in water resource management, is a multi-actor, multi-scale and dynamic decision-making process. This study aims to build a collective learning and collaborative construction tool through the territory game method. It was implemented in the Haouaria Plain, in Northern Tunisia, where farmers are currently dependent upon groundwater use for their livelihood and food security. After the diagnosis of the territorial issues, the drivers of change and a common spatial representation of the future trend of the territory, we dive into the dimensions that hinder or facilitate the implementation of scenarios and the pathways of actions. Thereafter, we analyzed these dimensions together again and reflect on the interactions among actors at different levels to transform the local territory. From the perspective of evolution scenarios for the Haouaria plain, the participants indicated the conditions that hinder or facilitate their implementation and they proposed twenty-three possible actions to be carried out in order to achieve the desired trends. They indicated how these propositions can be achieved, by whom, and where. The local stakeholders coordinate actors, activities and spaces on their territory. Spaces such as El Garâa basin, littoral forest or food processing companies are at stake to develop an integrated response to territorial issues.
Investigation of Anisotropic Subsequent Yield Behavior for 45 Steel by the Distortional Yield Surface Constitutive Model
Authors: Chang Yanjun , Kuang Zheng , Tang Runsen , Chen Jianyun , Song Qiao
Published: March 2020

The subsequent anisotropic yield behavior of 45 steel was predicted by the distortional yield surface constitutive model, which can describe the anisotropic subsequent yield and the cross effect of metal associating with loading history. The yield characteristics and plastic hardening behaviors of the 45 steel were simulated under three preloading paths including pre-torsion, pre-tension, and pre-tension–torsion. Based on the comparison between the experimental yield stresses and the simulation by the classical Chaboche model, the proposed model can describe the remarkable anisotropic yield behavior related to the loading history, which can effectively describe the sharp point of yield surface in pre-loading direction and the smaller curvature near its opposite direction. It was successfully simulated by the constitutive model proposed that the subsequent distortional yield surface defined by small offset strain and the degradation process of the distortion feature defined by large offset strain.
Microstructures Manufactured in Diamond by Use of Laser Micromachining
Authors: Dudek Mariusz , Rosowski Adam , Kozanecki Marcin , Jaszczak Malwina , Szymański Witold , Sharp Martin , Karczemska Anna
Published: March 2020

Different microstructures were created on the surface of a polycrystalline diamond plate (obtained by microwave plasma-enhanced chemical vapor deposition—MW PECVD process) by use of a nanosecond pulsed DPSS (diode pumped solid state) laser with a 355 nm wavelength and a galvanometer scanning system. Different average powers (5 to 11 W), scanning speeds (50 to 400 mm/s) and scan line spacings (“hatch spacing”) (5 to 20 µm) were applied. The microstructures were then examined using scanning electron microscopy, confocal microscopy and Raman spectroscopy techniques. Microstructures exhibiting excellent geometry were obtained. The precise geometries of the microstructures, exhibiting good perpendicularity, deep channels and smooth surfaces show that the laser microprocessing can be applied in manufacturing diamond microfluidic devices. Raman spectra show small differences depending on the process parameters used. In some cases, the diamond band (at 1332 cm−1) after laser modification of material is only slightly wider and shifted, but with no additional peaks, indicating that the diamond is almost not changed after laser interaction. Some parameters did show that the modification of material had occurred and additional peaks in Raman spectra (typical for low-quality chemical vapor deposition CVD diamond) appeared, indicating the growing disorder of material or manufacturing of the new carbon phase.
A Solar-Driven Flexible Electrochromic Supercapacitor
Authors: Zhang Danni , Sun Baolin , Huang Hui , Gan Yongping , Xia Yang , Liang Chu , Zhang Wenkui , Zhang Jun
Published: March 2020

Solar-driven electrochromic smart windows with energy-storage ability are promising for energy-saving buildings. In this work, a flexible photoelectrochromic device (PECD) was designed for this purpose. The PECD is composed of two flexible transparent conductive layers, a photocatalytic layer, an electrochromic material layer, and a transparent electrolyte layer. The photocatalytic layer is a dye-sensitized TiO2 thick film and the electrochromic layer is a WO3 thin film, which also possesses a supercapacitive property. Under illumination, dye-sensitized TiO2 thick film realizes photo-drive electrochromism that the WO3 changes from colorless to blue with large optical modulation. Meanwhile, the PECD has an electrochemical supercapacitance showing an energy storage property of 21 mF·cm−2 (114.9 F·g−1 vs the mass of WO3), stable mechanical performance and long cycle performance. The PECD can effectively adjust the transmittance of visible and near-infrared light without any external power supply, realizing zero energy consumption, and can convert solar energy into electrical energy for storage.
Tensile Properties and Thermal Stability of Unidirectionally <111>-Oriented Nanotwinned and <110>-Oriented Microtwinned Copper
Authors: Li Yu-Jin , Tu King-Ning , Chen Chih
Published: March 2020

Tensile tests on two kinds of electroplated copper foils with twins before and after annealing were performed. One electroplating parameter results in a microstructure of <110>-oriented microtwinned Cu (mt-Cu), and the other is <111>-oriented nanotwinned Cu (nt-Cu). The latter shows higher thermal stability than the former after annealing. Though the toughness for the two as-plated foils are quite close, the toughness for the <111> oriented nt-Cu increased from 34 to 74 MJ/m3 after annealing at 250 °C for 3 h. In comparison, the toughness of the <110>-oriented mt-Cu remained almost the same after annealing.
Effects of B2O3 on Melting Characteristics and Temperature-Dependent Viscosity of High-Basicity CaO–SiO2–FeOx–MgO Slag
Authors: Chong Junkai , Shen Yingying , Yang Peng , Tian Jianke , Zhang Wenjuan , Tang Xingchang , Du Xueyan
Published: March 2020

In order to reduce the amount of fluorite during the steelmaking process for environmental protection, it is essential to investigate the fluorine-free slag system. Thus, high-basicity CaO–SiO2–FeOx–MgO slag with B2O3 content from 0% to 15% was designed, and its melting characteristics and viscosity were investigated. The influence of B2O3 content on the phase diagram of the slag system was calculated using FactSage 7.3, and the break temperature was determined from the curves of temperature-dependent viscosity. The results show that, with the increase in B2O3 content, the melting characteristics of the CaO–SiO2–FeOx–MgO/B2O3 slag system, including liquidus temperature, flow temperature, softening temperature, and hemispheric temperature, all decreased; the main phase of the slag system transformed from Ca2SiO4 into borosilicate, and finally into borate; the viscous flow activation energy reduced from 690 kJ to 130 kJ; the break temperature reduced from 1590 °C to 1160 °C. Furthermore, the melting characteristics and the break temperature of the slag system with 5% and 8% B2O3 content were found to be the closest to the values of fluorine-containing steel slag.
Pseudo-random Path Generation Algorithms and Strategies for the Surface Quality Improvement of Optical Aspherical Components
Authors: Zha Jun , Zhang Hangcheng , Li Yipeng , Chen Yaolong
Published: March 2020

This study proposes two path generation algorithms to diminish the superposition of the convolution effect on the polishing path in computer-controlled optical surfacing. According to the polishing of aluminum-alloy based hyperboloid optical components, different proportions of polishing agents were blended. Then, the surface roughness of the optical components were determined through a validation experiment of the algorithms. Furthermore, the relationship between surface roughness and the polishing agent concentration, and the compensation strategies for surface roughness were analyzed. The results show that the two algorithms effectively compensated for surface waviness. The findings support the strategies for improving the surface quality of optical components with aspherical surfaces.
Experimental Study on Shear Capacity of High Strength Reinforcement Concrete Deep Beams with Small Shear Span–Depth Ratio
Authors: Zhang Jun-Hong , Li Shu-Shan , Xie Wei , Guo Yang-Dong
Published: March 2020

This study aimed to investigate the shear capacity performance for eight deep beams with HTRB600 reinforced high strength concrete under concentrated load to enable a better understanding of the effects of shear span–depth ratio, longitudinal reinforcement ratio, vertical stirrup ratio and in order to improve design procedures. The dimension of eight test specimens is 1600 mm × 200 mm × 600 mm. The effective span to height ratio l0/h is 2.0, the shear span–depth ratio λ is 0.3, 0.6 and 0.9, respectively. In addition, the longitudinal reinforcement ratio ρs is set to 0.67%, 1.05%, 1.27%, and the vertical stirrup ratio is taken to be 0%, 0.25%, 0.33%, 0.5%. Through measuring the strain of steel bar, the strain of concrete and the deflection of mid-span, the characteristics of the full process of shear capacity, the failure mode and the load deflection deformation curve were examined. The test results showed that the failure mode of deep beams with small shear span–depth ratio is diagonal compression failure, which is influenced by the layout and quantity of web reinforcement. The diagonal compression failure could be classified into two forms: crushing-strut and diagonal splitting. With decreasing of shear span–depth ratio and increasing longitudinal reinforcement ratio, the shear capacity of deep beams increases obviously, while the influence of vertical web reinforcement ratio on shear capacity is negligible. Finally, the shear capacity of eight deep beams based on GB 50010-2010 is calculated and compared with the calculation results of ACI 318-14, EN 1992-1-1:2004 and CSA A23.3-04, which are based on strut-and-tie model. The obtained results in this paper show a very good agreement with GB50010-2010 and ACI 318-14, while the results of EN 1992-1-1:2004 and CSA A23.3-04 are approved to be conservative.
Further Results on the Total Roman Domination in Graphs
Authors: Cabrera Martínez Abel , Cabrera García Suitberto , Carrión García Andrés
Published: March 2020

Let G be a graph without isolated vertices. A function f : V ( G ) → { 0 , 1 , 2 } is a total Roman dominating function on G if every vertex v ∈ V ( G ) for which f ( v ) = 0 is adjacent to at least one vertex u ∈ V ( G ) such that f ( u ) = 2 , and if the subgraph induced by the set { v ∈ V ( G ) : f ( v ) ≥ 1 } has no isolated vertices. The total Roman domination number of G, denoted γ t R ( G ) , is the minimum weight ω ( f ) = ∑ v ∈ V ( G ) f ( v ) among all total Roman dominating functions f on G. In this article we obtain new tight lower and upper bounds for γ t R ( G ) which improve the well-known bounds 2 γ ( G ) ≤ γ t R ( G ) ≤ 3 γ ( G ) , where γ ( G ) represents the classical domination number. In addition, we characterize the graphs that achieve equality in the previous lower bound and we give necessary conditions for the graphs which satisfy the equality in the upper bound above.
A Practical Traffic Assignment Model for Multimodal Transport System Considering Low-Mobility Groups
Authors: Zhang Tao , Yang Yang , Cheng Gang , Jin Minjie
Published: March 2020

In this study, we created a practical traffic assignment model for a multimodal transport system considering low-mobility groups with the aim of providing the foundation of transportation network design for low-mobility individuals. First, the route choice equilibrium for walking, non-vehicle, and private car modes is described using the logit function, which is formulated as a variational inequality problem considering different low-mobility groups. Then, the practicalities related to travel times at intersections, traffic barricades between different lanes, and fuel fees of private cars are integrated to design a generalized travel cost function. Last, the method of successive weight averages is used to solve the proposed model. The model and its solution are verified based on a real case study of the city of Wenling in China. The sensitivity of adjustment parameters related to travel costs are analyzed, the practicality of the proposed model is explored, and the results of traffic assignment for different low-mobility groups are discussed.
Competition-Independence Game and Domination Game
Authors: Worawannotai Chalermpong , Ruksasakchai Watcharintorn
Published: March 2020

The domination game is played on a graph by two players, Dominator and Staller, who alternately choose a vertex of G. Dominator aims to finish the game in as few turns as possible while Staller aims to finish the game in as many turns as possible. The game ends when all vertices are dominated. The game domination number, denoted by γ g ( G ) (respectively γ g ′ ( G ) ), is the total number of turns when both players play optimally and when Dominator (respectively Staller) starts the game. In this paper, we study a version of this game where the set of chosen vertices is always independent. This version turns out to be another game known as the competition-independence game. The competition-independence game is played on a graph by two players, Diminisher and Sweller. They take turns in constructing maximal independent set M, where Diminisher tries to minimize | M | and Sweller tries to maximize | M | . Note that, actually, it is the domination game in which the set of played vertices is independent. The competition-independence number, denoted by I d ( G ) (respectively I s ( G ) ) is the optimal size of the final independent set in the competition-independence game if Diminisher (respectively Sweller) starts the game. In this paper, we check whether some well-known results in the domination game hold for the competition-independence game. We compare the competition-independence numbers to the game domination numbers. Moreover, we provide a family of graphs such that many parameters are equal. Finally, we present a realization result on the competition-independence numbers.
Different Treatments in Patients with Temporomandibular Joint Disorders: A Comparative Randomized Study
Authors: Macedo De Sousa Bruno , López-Valverde Nansi , López-Valverde Antonio , Caramelo Francisco , Flores Fraile Javier , Herrero Payo Julio , Rodrigues María João
Published: March 2020

Background and Objectives: Temporomandibular joint disorders (TMJDs) are associated with pain and reduced jaw mobility. The aim of this study was to compare the outcome of patients with TMJ arthralgia when submitted to four different treatment modalities, in some cases using intra-articular injections of substances with anti-inflammatory properties and in others, a more conservative approach consisting only of a bite splint. Materials and Methods: The sample was made up of 80 patients, randomly distributed into 4 groups of 20 patients each. Each patient was given a nocturnal bite splint. One of the groups was treated with the bite splint only, while each patient in the other 3 was injected with betamethasone, sodium hyaluronate, or platelet-rich plasma in addition to using the bite splint. Two variables were assessed, namely pain intensity between 0 to 10 according to the visual analogue scale and maximum pain-free mouth opening in mm. The patients were evaluated at four different points: at the beginning of the treatment, as well as one week, one month and six months after initiation. Results: The results showed that maximum pain-free mouth opening improved in all the groups that made up the sample, with either a reduction in pain severity or with no pain. However, the group injected with platelet-rich plasma yielded the best results after six months, while patients treated with sodium hyaluronate or betamethasone obtained the best results at the end of the first week. Conclusions: We concluded that all the treatments used caused a reduction in pain and increased pain-free mouth opening. The splint combined with the platelet-rich plasma injection achieved long-term success.
Tribological Properties of Connecting Rod High Strength Screws Improved by Surface Peening Treatments
Authors: Croccolo Dario , De Agostinis Massimiliano , Fini Stefano , Olmi Giorgio , Paiardini Luca , Robusto Francesco
Published: March 2020

Bolted joints are highly loaded components and serious issues may arise from improper fastening and in particular from too high or too low preload. Friction at the underhead plays an important role, as it significantly affects the achievable preload for fixed and controlled tightening torque. In addition, multiple tightening is usually performed on connecting rod screws, which may be a further source of friction increment. This study investigates the effect of two surface treatments, shot-peening and deep-rolling, on the tribological properties upon bolt fastening. This topic was tackled experimentally and the campaign involved MJ9 X 1 4 g grade 13.9 36 NiCrMo connecting rod screws, in both lubricated and dry conditions. The results, processed by statistical tools, indicate that deep-rolling does not affect friction, whereas shot-peening yields significant benefits. As an effect of the generation of dimples and multiple contacts, it is able to lower (up to 25%) the bearing frictional coefficient in lubricated conditions, also making the friction level independent of the number of re-tightenings. For a dry surface, an even higher friction decrease (up to 30%) is achieved. Without lubrication, the friction coefficient keeps increasing for the incremented number of tightenings, but the increase rate is lowered with respect to the untreated surface.