bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity Profiles of Fractionated Radiotherapy, Contemporary Stereotactic Radiosurgery, and Transsphenoidal Surgery in Nonfunctioning Pituitary Macroadenomas
Authors: Chang Chia-Lun , Yuan Kevin Sheng-Po , Wu Alexander T.H. , Wu Szu-Yuan
Published: October 2019

Background: Here, we compared the toxicity profiles of contemporary stereotactic radiosurgery (SRS), modern fractionated radiotherapy (FRT), and transsphenoidal surgery used to treat nonfunctioning pituitary macroadenomas. Methods: We included the data of patients with nonfunctioning pituitary macroadenomas. To compare treatment outcomes, the patients were categorized groups 1 (those receiving modern FRT), 2 (those receiving contemporary SRS), and 3 (those receiving transsphenoidal surgery). The multivariable Cox proportional hazards regression analysis was performed to yielded adjusted hazard ratios (aHRs) and their 95% CIs for local recurrence in groups 2 and 3 compared with group 1. Results: We included the data of 248 patients with nonfunctioning pituitary macroadenomas. The analytical results revealed no significant differences in second primary brain or head and neck cancer, hypopituitarism, or optic nerve injury between the three cohorts. The multivariable Cox proportional hazards regression analysis revealed that compared with group 1, the aHRs (95% CIs) for stroke risk in groups 2 and 3 were 0.37 (0.14–0.99) and 0.51 (0.31–0.84), respectively. Conclusion: Contemporary SRS and transsphenoidal surgery for nonfunctioning pituitary macroadenoma treatment have equivalent toxicity profiles. However, modern FRT for nonfunctioning pituitary macroadenoma treatment might considerably increase stroke risk.
Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives
Authors: Martini Verena , Timme-Bronsert Sylvia , Fichtner-Feigl Stefan , Hoeppner Jens , Kulemann Birte
Published: October 2019

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer
Authors: Gamboa Adriana C. , Winer Joshua H.
Published: October 2019

The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy.
The Actin Binding Protein Plastin-3 Is Involved in the Pathogenesis of Acute Myeloid Leukemia
Authors: Velthaus Arne , Cornils Kerstin , Hennigs Jan K. , Grüb Saskia , Stamm Hauke , Wicklein Daniel , Bokemeyer Carsten , Heuser Michael , Windhorst Sabine , Fiedler Walter , Wellbrock Jasmin
Published: October 2019

Leukemia-initiating cells reside within the bone marrow in specialized niches where they undergo complex interactions with their surrounding stromal cells. We have identified the actin-binding protein Plastin-3 (PLS3) as potential player within the leukemic bone marrow niche and investigated its functional role in acute myeloid leukemia. High expression of PLS3 was associated with a poor overall and event-free survival for AML patients. These findings were supported by functional in vitro and in vivo experiments. AML cells with a PLS3 knockdown showed significantly reduced colony numbers in vitro while the PLS3 overexpression variants resulted in significantly enhanced colony numbers compared to their respective controls. Furthermore, the survival of NSG mice transplanted with the PLS3 knockdown cells showed a significantly prolonged survival in comparison to mice transplanted with the control AML cells. Further studies should focus on the underlying leukemia-promoting mechanisms and investigate PLS3 as therapeutic target.
IL-33 Promotes CD11b/CD18-Mediated Adhesion of Eosinophils to Cancer Cells and Synapse-Polarized Degranulation Leading to Tumor Cell Killing
Authors: Andreone Sara , Spadaro Francesca , Buccione Carla , Mancini Jacopo , Tinari Antonella , Sestili Paola , Gambardella Adriana Rosa , Lucarini Valeria , Ziccheddu Giovanna , Parolini Isabella , Zanetti Cristiana , D’Urso Maria Teresa , De Ninno Adele , Businaro Luca , Afferni Claudia , Mattei Fabrizio , Schiavoni Giovanna
Published: October 2019

Eosinophils are major effectors of Th2-related pathologies, frequently found infiltrating several human cancers. We recently showed that eosinophils play an essential role in anti-tumor responses mediated by immunotherapy with the ‘alarmin’ intereukin-33 (IL-33) in melanoma mouse models. Here, we analyzed the mechanisms by which IL-33 mediates tumor infiltration and antitumor activities of eosinophils. We show that IL-33 recruits eosinophils indirectly, via stimulation of tumor cell-derived chemokines, while it activates eosinophils directly, up-regulating CD69, the adhesion molecules ICAM-1 and CD11b/CD18, and the degranulation marker CD63. In co-culture experiments with four different tumor cell lines, IL-33-activated eosinophils established large numbers of stable cell conjugates with target tumor cells, with the polarization of eosinophil effector proteins (ECP, EPX, and granzyme-B) and CD11b/CD18 to immune synapses, resulting in efficient contact-dependent degranulation and tumor cell killing. In tumor-bearing mice, IL-33 induced substantial accumulation of degranulating eosinophils within tumor necrotic areas, indicating cytotoxic activity in vivo. Blocking of CD11b/CD18 signaling significantly reduced IL-33-activated eosinophils’ binding and subsequent killing of tumor cells, indicating a crucial role for this integrin in triggering degranulation. Our findings provide novel mechanistic insights for eosinophil-mediated anti-tumoral function driven by IL-33. Treatments enabling tumor infiltration and proper activation of eosinophils may improve therapeutic response in cancer patients.
A Cancer-Favoring, Engineered Vaccinia Virus for Cholangiocarcinoma
Authors: Yoo So Young , Badrinath Narayanasamy , Lee Hye Lim , Heo Jeong , Kang Dae-Hwan
Published: October 2019

While oncolytic vaccinia virus-based therapy has shown promising results for uncured patients with cancer, its effects on cholangiocarcinoma (CCA) remain unclear. Here, we evaluated the anti-cancer activity of the cancer-favoring oncolytic vaccinia virus (CVV), which was recognized as a promising therapy for stem cell-like colon cancer cells (SCCs) and metastatic hepatocellular carcinoma (HCC) in previous studies. CCA presents major challenges, such as clinical complexity, stem cell cancer characteristics, a high refractory rate, resistance to conventional therapy, and a dismal prognosis. In the present study, we confirmed the oncolytic activity of the CVV in CCA with a slightly alkaline microenvironment (pH 7–8), in which the CVV was stable and highly effective at infecting CCA. Taken together, our findings suggest that CVV-based therapy is highly suitable for the treatment of CCA.
Transcription Factor and miRNA Interplays Can Manifest the Survival of ccRCC Patients
Authors: Qin Shijie , Shi Xuejia , Wang Canbiao , Jin Ping , Ma Fei
Published: October 2019

Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-335-3p, hsa-miR-1269a). Secondly, we found that a signature containing these eight miRNAs showed obviously superior to a single miRNA in the prognostic effect and credibility for predicting the survival of ccRCC patients. Thirdly, we discovered that twenty-two transcription factors (TFs) interact with these eight miRNAs, and a signature combining nine TFs (TFAP2A, KLF5, IRF1, RUNX1, RARA, GATA3, IKZF1, POU2F2, and FOXM1) could promote the prognosis of ccRCC patients. Finally, we further identified eleven genes (hsa-miR-365b-3p, hsa-miR-223-3p, hsa-miR-1269a, hsa-miR-144-5p, hsa-miR-183-5p, hsa-miR-335-3p, TFAP2A, KLF5, IRF1, MYC, IKZF1) that could combine as a signature to improve the prognosis effect of ccRCC patients, which distinctly outperformed the eight-miRNA signature and the nine-TF signature. Overall, we identified several new prognosis factors for ccRCC, and revealed a potential mechanism that TFs and miRNAs interplay cooperatively or oppositely regulate a certain number of tumor suppressors, driver genes, and oncogenes to facilitate the survival of ccRCC patients.
Thyroid Bethesda Category AUS/FLUS in Our Microscopes: Three-Year-Experience and Cyto-Histological Correlation
Authors: Huhtamella Roope , Kholová Ivana
Published: October 2019

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) introduced a new category: Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) comprising of heterogenous lesions with a lesser degree of atypia. Its routine use is a bit controversial. The study cohort included AUS/FLUS thyroid cytopathological diagnoses signed out at Fimlab Laboratories from the period of 1 October 2013 to 31 December 2016. We analyzed all the AUS/FLUS cases, their cytology subclassification, and their cyto-histological correlation, when available. In total, there were 331 AUS/FLUS cases from 252 patients. The mean age was 59.8 years and there were 196 females and 56 males. Repeated AUS/FLUS was diagnosed in 75 (29.8%) cases. Out of 252 patients, 118 (46.8%) were operated on. Sixty-eight were operated on after the first AUS/FLUS diagnosis, 46 after 2 AUS/FLUS diagnoses, and 4 after 3 AUS/FLUS diagnoses. In total, there were 37 (14.7%) malignancies and 40 benign tumors. The risk of malignancy for AUS/FLUS (14.7%) is in agreement with the original TBSRTC risk of malignancy. The risk of neoplasia was 30.6% in our series.
Bystander Effects of Nitric Oxide in Cellular Models of Anti-Tumor Photodynamic Therapy
Authors: Bazak Jerzy , Korytowski Witold , Girotti Albert W.
Published: October 2019

Tumor cells exposed to stress-inducing radiotherapy or chemotherapy can send signals to non- or minimally exposed bystander cells. Bystander effects of ionizing radiation are well established, but little is known about such effects in non-ionizing photodynamic therapy (PDT). Our previous studies revealed that several cancer cell types upregulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate 5-aminolevulinic acid (ALA)-based PDT challenge. The NO signaled for cell resistance to photokilling as well as greater growth, migration and invasion of surviving cells. Based on this work, we hypothesized that diffusible NO produced by PDT-targeted cells in a tumor might elicit pro-growth/migration responses in non-targeted bystander cells. In the present study, we tested this using a novel approach, in which ALA-PDT-targeted human cancer cells on culture dishes (prostate PC3, breast MDA-MB-231, glioma U87, or melanoma BLM) were initially segregated from non-targeted bystanders via impermeable silicone-rimmed rings. Several hours after LED irradiation, rings were removed, and both cell populations analyzed for various post-hν responses. For a moderate and uniform level of targeted cell killing by PDT (~25%), bystander proliferation and migration were both enhanced. Enhancement correlated with iNOS/NO upregulation in surviving targeted cells in the following order: PC3 > MDA-MB-231 > U87 > BLM. If occurring in an actual tumor PDT setting and not suppressed (e.g., by iNOS activity or transcription inhibitors), then such effects could compromise treatment efficacy or even stimulate disease progression if PDT’s anti-tumor potency is not great enough.
Catalytic Oxidation Processes for the Upgrading of Terpenes: State-of-the-Art and Future Trends
Authors: Denicourt-Nowicki Audrey , Rauchdi Mariem , Ait Ali Mustapha , Roucoux Alain
Published: October 2019

Terpenic olefins constitute a relevant platform of renewable molecules, which could be used as key intermediates for the perfumery, flavoring, and pharmaceutical industries. The upgrading of these cheap and available agro-resources through catalytic oxidation processes remains of great interest, leading to the formation of either epoxides via the oxidation of the olefinic bond or α,β-unsaturated ketones by the Csp3-H functionalization at the α-position of the double bond. This critical review summarizes some of the most relevant homogeneous or heterogeneous catalysts designed for the oxidation of some abundant terpenic olefins in the last decade (2008–2018).
Deciphering the Effect of Microbead Size Distribution on the Kinetics of Heterogeneous Biocatalysts through Single-Particle Analysis Based on Fluorescence Microscopy
Authors: Muñoz-Morales Emilio , Velasco-Lozano Susana , Benítez-Mateos Ana I. , Marín María J. , Ramos-Cabrer Pedro , López-Gallego Fernando
Published: October 2019

Understanding the functionality of immobilized enzymes with spatiotemporal resolution and under operando conditions is an unmet need in applied biocatalysis, as well as priceless information to guide the optimization of heterogeneous biocatalysts for industrial purposes. Unfortunately, enzyme immobilization still relies on trial-and-error approximations that prevail over rational designs. Hence, a modern fabrication process to achieve efficient and robust heterogeneous biocatalysts demands comprehensive characterization techniques to track and understand the immobilization process at the protein–material interface. Recently, our group has developed a new generation of self-sufficient heterogeneous biocatalysts based on alcohol dehydrogenases co-immobilized with nicotinamide cofactors on agarose porous microbeads. Harnessing the autofluorescence of NAD+(P)H and using time-lapse fluorescence microscopy, enzyme activity toward the redox cofactors can be monitored inside the beads. To analyze these data, herein we present an image analytical tool to quantify the apparent Michaelis–Menten parameters of alcohol dehydrogenases co-immobilized with NAD(P)+/H at the single-particle level. Using this tool, we found a strong negative correlation between the apparent catalytic performance of the immobilized enzymes and the bead radius when using exogenous bulky substrates in reduction reactions. Therefore, applying image analytics routines to microscopy studies, we can directly unravel the functional heterogeneity of different heterogeneous biocatalyst samples tested under different reaction conditions.
Tailoring Celluclast® Cocktail’s Performance towards the Production of Prebiotic Cello-Oligosaccharides from Waste Forest Biomass
Authors: Karnaouri Anthi , Matsakas Leonidas , Bühler Saskja , Muraleedharan Madhu Nair , Christakopoulos Paul , Rova Ulrika
Published: October 2019

The main objective of this study focused on the sustainable production of cellobiose and other cellulose-derived oligosaccharides from non-edible sources, more specifically, from forest residues. For this purpose, a fine-tuning of the performance of the commercially available enzyme mixture Celluclast® was conducted towards the optimization of cellobiose production. By enzyme reaction engineering (pH, multi-stage hydrolysis with buffer exchange, addition of β-glucosidase inhibitor), a cellobiose-rich product with a high cellobiose to glucose ratio (37.4) was achieved by utilizing organosolv-pretreated birch biomass. In this way, controlled enzymatic hydrolysis combined with efficient downstream processing, including product recovery and purification through ultrafiltration and nanofiltration, can potentially support the sustainable production of food-grade oligosaccharides from forest biomass. The potential of the hydrolysis product to support the growth of two Lactobacilli probiotic strains as a sole carbon source was also demonstrated.
Effects of Additives and Metals on Crystallization of Nano-Sized HZSM-5 Zeolite for Glycerol Aromatization
Authors: Xu Wei , Gao Lijing , Xiao Guomin
Published: October 2019

Nano-sized HZSM-5 (n-HZSM-5) was synthesized and applied in the aromatization of glycerol. The effects of additives (carboxymethylcellulose sodium, NaCl, sodium alginate, etc.) on the chemical and physic properties of n-HZSM-5 during preparation were investigated. Metal modification was also investigated based on the synthesized n-HZSM-5. The results showed that the addition of carboxymethylcellulose sodium (CMC-Na), NaCl and sodium alginate (SA) led to forming smaller sizes of HZSM-5 and promoted the acid amounts of the catalysts, which increased its catalytic activities for obtaining BTX. The highest BTX yield of ~35% was obtained by SA derived n-HZSM-5, and the life of the catalyst were both obviously promoted by the additives with a highest of ~11 h by γ-(2,3-epoxypropoxy)propytrimethoxysilane (KH-560) derived n-HZSM-5. BTX yields could be improved by 40%by the addition of Zn and Cd in n-HZSM-5 while having little effect on the catalyst life.
The Use of a γ-Al2O3 and MgO Mixture in the Catalytic Conversion of 1,1,1,2-Tetrafluoroethane (HFC-134a)
Authors: Jeong Sangjae , Sudibya Gamal Luckman , Jeon Jong-Ki , Kim Young-Min , Swamidoss Caroline Mercy Andrew , Kim Seungdo
Published: October 2019

This paper reports the improved efficiency of 1,1,1,2-tetrafluoroethane (HFC-134a) decomposition by combined use of MgO with γ-Al2O3. While a high temperature (>900 °C) was required to achieve 90% conversion during non-catalytic pyrolysis of HFC-134a, 100% conversion of HFC-134a was achieved at 600 °C by the use of γ-Al2O3. Among the three catalysts (γ-Al2O3, MgO, and CaO) tested in this study, γ-Al2O3 showed the highest HFC-134a decomposition efficiency, followed by MgO and CaO, due to its large surface area and large amount of weak acid sites. Also with the longest lifetime among the catalysts, durability in maintaining complete decomposition of HFC-134a was shown in γ-Al2O3. The addition of MgO to γ-Al2O3 was effective in extending the lifetime of γ-Al2O3 due to the efficient interaction between HF and MgO, which can delay the deactivation of γ-Al2O3. Compared to the double bed γ-Al2O3-MgO configuration, the use of a mixed γ-Al2O3-MgO bed extended the catalyst lifetime more effectively.
Comprehensive Profiling of Surface Gangliosides Extracted from Various Cell Lines by LC-MS/MS
Authors: Lee Jua , Hwang Heeyoun , Kim Sumin , Hwang Jaeyun , Yoon Jaekyung , Yin Dongtan , Choi Sun Il , Kim Yun-Hee , Kim Yong-Sam , An Hyun Joo
Published: October 2019

Gangliosides act as a surface marker at the outer cellular membrane and play key roles in cancer cell invasion and metastasis. Despite the biological importance of gangliosides, they have been still poorly characterized due to the lack of effective analytical tools. Herein, we performed molecular profiling and structural elucidation of intact gangliosides in various cell lines including CFPAC1, A549, NCI-H358, MCF7, and Caski. We identified and quantified a total of 76 gangliosides on cell membrane using C18 LC-MS/MS. Gangliosides found in each cell line exhibited high complexity and diversity both qualitatively and quantitatively. The most abundant species was GM3(d34:1) in CFPAC1, NCI-H358, and MCF7, while GM2(d34:1) and GM1(d34:1) were major components in A549 and Caski, respectively. Notably, glycan moieties showed more diversity between cancer cell lines than ceramide moieties. In addition, noncancerous pancreatic cell line (hTERT/HPNE) could be distinguished by gangliosides containing different levels of sialic acid compared with cancerous pancreatic cell line (CFPAC1). These results clearly demonstrated the feasibility of our analytical platform to comprehensive profile of cell surface gangliosides for identifying cell types and subgrouping cancer cell types.
The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression
Authors: Chen Dishen , Le Thanh H. , Shahidipour Haleh , Read Scott A. , Ahlenstiel Golo
Published: October 2019

Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis.
Over-Activated Proteasome Mediates Neuroinflammation on Acute Intracerebral Hemorrhage in Rats
Authors: Liew Hock-Kean , Hu Wei-Fen , Lin Peter Bor-Chian , Wang Po-Kai , Tsai Andy Po-Yi , Pang Cheng-Yoong , Chen Tsung-Ying
Published: October 2019

Background: Neuroinflammation is a hallmark in intracerebral hemorrhage (ICH) that induces secondary brain injury, leading to neuronal cell death. ER stress-triggered apoptosis and proteostasis disruption caused neuroinflammation to play an important role in various neurological disorders. The consequences of ER stress and proteostasis disruption have rarely been studied during the course of ICH development. Methods: ICH was induced by collagenase VII-S intrastriatal infusion. Animals were sacrificed at 0, 3, 6, 24, and 72 h post-ICH. Rats were determined for body weight changes, hematoma volume, and neurological deficits. Brain tissues were harvested for molecular signaling analysis either for ELISA, immunoblotting, immunoprecipitation, RT-qPCR, protein aggregation, or for histological examination. A non-selective proteasome inhibitor, MG132, was administered into the right striatum three hours prior to ICH induction. Results: ICH-induced acute proteasome over-activation caused the early degradation of the endoplasmic reticulum (ER) chaperone GRP78 and IκB protein. These exacerbations were accompanied by the elevation of pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP) and pro-inflammatory cytokines expression via nuclear factor-kappa B (NF-κB) signal activation. Pre-treatment with proteasome inhibitor MG132 significantly ameliorated the ICH-induced ER stress/proteostasis disruption, pro-inflammatory cytokines, neuronal cells apoptosis, and neurological deficits. Conclusions: ICH induced rapid proteasome over-activation, leading to an exaggeration of the ER stress/proteostasis disruption, and neuroinflammation might be a critical event in acute ICH pathology.
Rewiring of Cancer Cell Metabolism by Mitochondrial VDAC1 Depletion Results in Time-Dependent Tumor Reprogramming: Glioblastoma as a Proof of Concept
Authors: Arif Tasleem , Stern Oriel , Pittala Srinivas , Chalifa-Caspi Vered , Shoshan-Barmatz Varda
Published: October 2019

Reprograming of the metabolism of cancer cells is an event recognized as a hallmark of the disease. The mitochondrial gatekeeper, voltage-dependent anion channel 1 (VDAC1), mediates transport of metabolites and ions in and out of mitochondria, and is involved in mitochondria-mediated apoptosis. Here, we compared the effects of reducing hVDAC1 expression in a glioblastoma xenograft using human-specific si-RNA (si-hVDAC1) for a short (19 days) and a long term (40 days). Tumors underwent reprograming, reflected in rewired metabolism, eradication of cancer stem cells (CSCs) and differentiation. Short- and long-term treatments of the tumors with si-hVDAC1 similarly reduced the expression of metabolism-related enzymes, and translocator protein (TSPO) and CSCs markers. In contrast, differentiation into cells expressing astrocyte or neuronal markers was noted only after a long period during which the tumor cells were hVDAC1-depleted. This suggests that tumor cell differentiation is a prolonged process that precedes metabolic reprograming and the “disappearance” of CSCs. Tumor proteomics analysis revealing global changes in the expression levels of proteins associated with signaling, synthesis and degradation of proteins, DNA structure and replication and epigenetic changes, all of which were highly altered after a long period of si-hVDAC1 tumor treatment. The depletion of hVDAC1 greatly reduced the levels of the multifunctional translocator protein TSPO, which is overexpressed in both the mitochondria and the nucleus of the tumor. The results thus show that VDAC1 depletion-mediated cancer cell metabolic reprograming involves a chain of events occurring in a sequential manner leading to a reversal of the unique properties of the tumor, indicative of the interplay between metabolism and oncogenic signaling networks.
4mCpred-EL: An Ensemble Learning Framework for Identification of DNA N4-Methylcytosine Sites in the Mouse Genome
Authors: Manavalan Balachandran , Basith Shaherin , Shin Tae Hwan , Lee Da Yeon , Wei Leyi , Lee Gwang
Published: October 2019

DNA N4-methylcytosine (4mC) is one of the key epigenetic alterations, playing essential roles in DNA replication, differentiation, cell cycle, and gene expression. To better understand 4mC biological functions, it is crucial to gain knowledge on its genomic distribution. In recent times, few computational studies, in particular machine learning (ML) approaches have been applied in the prediction of 4mC site predictions. Although ML-based methods are promising for 4mC identification in other species, none are available for detecting 4mCs in the mouse genome. Our novel computational approach, called 4mCpred-EL, is the first method for identifying 4mC sites in the mouse genome where four different ML algorithms with a wide range of seven feature encodings are utilized. Subsequently, those feature encodings predicted probabilistic values are used as a feature vector and are once again inputted to ML algorithms, whose corresponding models are integrated into ensemble learning. Our benchmarking results demonstrated that 4mCpred-EL achieved an accuracy and MCC values of 0.795 and 0.591, which significantly outperformed seven other classifiers by more than 1.5–5.9% and 3.2–11.7%, respectively. Additionally, 4mCpred-EL attained an overall accuracy of 79.80%, which is 1.8–5.1% higher than that yielded by seven other classifiers in the independent evaluation. We provided a user-friendly web server, namely 4mCpred-EL which could be implemented as a pre-screening tool for the identification of potential 4mC sites in the mouse genome.
Direct Laser Interference Patterning of Bioceramics: A Short Review
Authors: Fabris Douglas , Lasagni Andrés Fabián , Fredel Márcio C. , Henriques Bruno
Published: October 2019

Bioceramics are a great alternative to use in implants due to their excellent biocompatibility and good mechanical properties. Depending on their composition, bioceramics can be classified into bioinert and bioactive, which relate to their interaction with the surrounding living tissue. Surface morphology also has great influence on the implant biological behavior. Controlled texturing can improve osseointegration and reduce biofilm formation. Among the techniques to produce nano- and micropatterns, laser texturing has shown promising results due to its excellent accuracy and reproducibility. In this work, the use of laser techniques to improve surface morphology of biomaterials is reviewed, focusing on the application of direct laser interference patterning (DLIP) technique in bioceramics.
Modeling Hydrological Response to Climate Change in a Data-Scarce Glacierized High Mountain Astore Basin Using a Fully Distributed TOPKAPI Model
Authors: Atif Iqra , Iqbal Javed , Su Li-jun
Published: October 2019

Water scarcity is influencing environmental and socio-economic development on a global scale. Pakistan is ranked third among the countries facing water scarcity. This situation is currently generating intra-provincial water disputes and could lead to transboundary water conflicts. This study assessed the future water resources of Astore basin under representative concentration pathways (RCP) 4.5 and 8.5 scenarios using fully distributed TOPographic Kinematic APproximation and Integration (TOPKAPI) model. TOPKAPI model was calibrated and validated over five years from 1999–2003 with a Nash coefficient ranging from 0.93–0.97. Towards the end of the 21st century, the air temperature of Astore will increase by 3°C and 9.6 °C under the RCP4.5 and 8.5 scenarios, respectively. The rise in air temperature can decrease the snow cover with Mann Kendall trend of –0.12%/yr and –0.39%/yr (p ≥ 0.05) while annual discharge projected to be increased 11% (p ≤ 0.05) and 37% (p ≥ 0.05) under RCP4.5 and RCP8.5, respectively. Moreover, the Astore basin showed a different pattern of seasonal shifts, as surface runoff in summer monsoon season declined further due to a reduction in precipitation. In the spring season, the earlier onset of snow and glacier melting increased the runoff due to high temperature, regardless of the decreasing trend of precipitation. This increased surface runoff from snow/glacier melt of Upper Indus Basin (UIB) can potentially be utilized to develop water policy and planning new water harvesting and storage structures, to reduce the risk of flooding.
X-ray Single-Crystal Structural Analysis of a Magnetically Oriented Monoclinic Microcrystal Suspension of α-Glycine
Authors: Tanaka Tatsuya , Tsuboi Chiaki , Aburaya Kazuaki , Kimura Fumiko , Maeyama Masataka , Kimura Tsunehisa
Published: October 2019

We previously reported on a method for X-ray single-crystal structure determination from a powder sample via a magnetically oriented microcrystal suspension (MOMS). The method was successfully applied to orthorhombic microcrystals (L-alanine, P212121). In this study, we apply this method to monoclinic microcrystals. Unlike most of the orthorhombic MOMSs, monoclinic MOMSs exhibit two or four orientations with the same magnetic energy (we refer to this as twin orientations), making data processing difficult. In this paper, we perform a MOMS experiment for a powder sample of monoclinic microcrystal (α-glycine, P21/n) to show that our method can also be applied to monoclinic crystals. The single-crystal structure determined in this work is in good agreement with the reported one performed on a real single crystal. Furthermore, the relationship between the crystallographic and magnetic susceptibility axes is determined.
A Computational Study of Defects, Li-Ion Migration and Dopants in Li2ZnSiO4 Polymorphs
Authors: Perera Dilki , Ganeshalingam Sashikesh , Kuganathan Navaratnarajah , Chroneos Alexander
Published: October 2019

Lithium zinc silicate, Li2ZnSiO4, is a promising ceramic solid electrolyte material for Li-ion batteries. In this study, atomistic simulation techniques were employed to examine intrinsic defect processes; long range Li-ion migration paths, together with activation energies; and candidate substitutional dopants at the Zn and the Si sites in both monoclinic and orthorhombic Li2ZnSiO4 phases. The Li-Zn anti-site defect is the most energetically favourable defect in both phases, suggesting that a small amount of cation mixing would be observed. The Li Frenkel is the second lowest energy process. Long range Li-ion migration is observed in the ac plane in the monoclinic phase and the bc plane in the orthorhombic phase with activation energies of 0.88 eV and 0.90 eV, respectively, suggesting that Li-ion diffusivities in both phases are moderate. Furthermore, we show that Fe3+ is a promising dopant to increase Li vacancies required for vacancy-mediated Li-ion migration, and that Al3+ is the best dopant to introduce additional Li in the lattice required for increasing the capacity of this material. The favourable isovalent dopants are Fe2+ at the Zn site and Ge4+ at the Si site.
Growth and Photocatalytic Properties of Gallium Oxide Films Using Chemical Bath Deposition
Authors: Yeh Che-Yuan , Zhao Yi-Man , Li Hui , Yu Fei-Peng , Zhang Sam , Wuu Dong-Sing
Published: October 2019

Gallium oxide (Ga2O3) thin films were fabricated on glass substrates using a combination of chemical bath deposition and post-annealing process. From the field-emission scanning electron microscopy and x-ray diffraction results, the GaOOH nanorods precursors with better crystallinity can be achieved under higher concentrations (≥0.05 M) of gallium nitrate (Ga(NO3)3). It was found that the GaOOH synthesized from lower Ga(NO3)3 concentration did not transform into α-Ga2O3 among the annealing temperatures used (400–600 °C). Under higher Ga(NO3)3 concentrations (≥0.05 M) with higher annealing temperatures (≥500 °C), the GaOOH can be transformed into the Ga2O3 film successfully. An α-Ga2O3 sample synthesized in a mixed solution of 0.075 M Ga(NO3)3 and 0.5 M hexamethylenetetramine exhibited optimum crystallinity after annealing at 500 °C, where the α-Ga2O3 nanostructure film showed the highest aspect ratio of 5.23. As a result, the photodegeneration efficiencies of the α-Ga2O3 film for the methylene blue aqueous solution can reach 90%.
Bandwidth-Limited and Noisy Pulse Sequences for Single Qubit Operations in Semiconductor Spin Qubits
Authors: Ferraro Elena , De Michielis Marco
Published: October 2019

Spin qubits are very valuable and scalable candidates in the area of quantum computation and simulation applications. In the last decades, they have been deeply investigated from a theoretical point of view and realized on the scale of few devices in the laboratories. In semiconductors, spin qubits can be built confining the spin of electrons in electrostatically defined quantum dots. Through this approach, it is possible to create different implementations: single electron spin qubit, singlet–triplet spin qubit, or a three-electron architecture, e.g., the hybrid qubit. For each qubit type, we study the single qubit rotations along the principal axis of Bloch sphere including the mandatory non-idealities of the control signals that realize the gate operations. The realistic transient of the control signal pulses are obtained by adopting an appropriate low-pass filter function. In addition. the effect of disturbances on the input signals is taken into account by using a Gaussian noise model.
Gibbs Free Energy and Reaction Rate Acceleration in and on Microdroplets
Authors: Tuck Adrian F
Published: October 2019

Recent observations show that many reactions are accelerated in microdroplets compared to bulk liquid and gas media. This acceleration has been shown to feature Gibbs free energy changes, ΔG, that are negative and so reaction enabling, compared to the reaction in bulk fluid when it is positive and so reaction blocking. Here, we argue how these ΔG changes are relatable to the crowding enforced by microdroplets and to scale invariance. It is argued that turbulent flow is present in microdroplets, which span meso and macroscales. That enables scale invariant methods to arrive at chemical potentials for the substances involved. G and ΔG can be computed from the difference between the whole microdroplet and the bulk medium, and also for individual chemical species in both cases, including separately the microdroplet’s surface film and interior, provided sufficiently fine resolution is available in the observations. Such results can be compared with results computed by quantum statistical mechanics using molecular spectroscopic data. This proposed research strategy therefore offers a path to test its validity in comparing traditional equilibrium quantum statistical thermodynamic tests of microdroplets with those based on scale invariant analysis of both their 2D surface and 3D interior fluid flows.
Investigation of New Tsallis-Based Equation to Predict Shear Stress Distribution in Circular and Trapezoidal Channels
Authors: Sheikh Khozani Zohreh , Wan Mohtar Wan Hanna Melini
Published: October 2019

In this study, the entropy concept is employed to estimate the shear stress distribution in a circular channel with flat bed and trapezoidal channel. Using the principle of maximum entropy, the shear stress distribution is derived by maximizing the Tsallis entropy by assuming averaged shear stress as a random variable. The derived shear stress equation can describe the variation of shear stress along the wetted perimeter of channel. The developed model of shear stress distribution is tested with some credible experimental data and is also compared with equations obtained by other researchers based on the Shannon entropy concept. The present model has shown good agreement with the observed data and performed better than the Shannon-based model in both cross-sections with better results of several computed quantitative criteria. The model precision in estimating shear stress in the trapezoidal channel with mean root mean square error (RMSE) of 0.0158 was higher than the circular channel with flat bed with RMSE of 0.0679.
A Fuzzy Logic Approach for the Reduction of Mesh-Induced Error in CFD Analysis: A Case Study of an Impinging Jet
Authors: Sosnowski Marcin , Krzywanski Jaroslaw , Scurek Radomir
Published: October 2019

A crucial step in any computational fluid dynamics (CFD) analysis is the discretization of the domain because it influences truncation errors, numerical stability, and the convergence of the model. Therefore, the appropriate selection of numerical mesh parameters crucially contributes to the reliability of the obtained results. Therefore, an innovative approach to reducing the mesh-induced error in CFD analysis of an impinging jet using fuzzy logic is proposed within the paper. The flow parameters were obtained using the Reynolds-averaged Navier–Stokes calculations, based on the mesh parameters obtained using the grid convergence index and fuzzy logic, were compared to each other and to experimental research results. The fuzzy logic approach to define mesh parameters turned out to be a very promising method as it allowed us to obtain results that are qualitatively and quantitatively comparable to commonly used but far more time-consuming methods.
Effect of Incidence Angle on Entropy Generation in the Boundary Layers on the Blade Suction Surface in a Compressor Cascade
Authors: Shi Lei , Ma Hongwei
Published: October 2019

The entropy generation that occurs within boundary layers over a C4 blade at a Reynolds number of 24,000 and incidence angles (i) of 0°, 2.5°, 5°, 7.5°, and 10° are investigated experimentally using a particle image velocimetry (PIV) technique. To clarify the entropy generation process, the distribution of the entropy generation rates (EGR) and the unsteady flow structures within the PIV snapshots are analyzed. The results identify that for a higher incidence angle, the separation and transition occur further upstream, and the entropy generation in the boundary layer increases. When the separation takes place at the aft portion of the blade, the integral EGR decrease near the leading edge, remain minimal values in the middle portion of the blade, and increase sharply in the vicinity of the mean transition. More than 35% of the entropy generation is generated at the region downstream of the mean transition. When the separation occurs at the fore portion of the blade, the contributions of mean-flow viscous dissipation decrease to less than 20%. The entropy generation with elevated value can be detected over the entire blade. The entire integral entropy generation in the boundary layer increases sharply when the laminar separation bubble moves upstream to the leading edge.
Embedding Preference Uncertainty for Environmental Amenities in Climate Change Economic Assessments: A “Random” Step Forward
Authors: Skourtos Michalis , Damigos Dimitris , Kontogianni Areti , Tourkolias Christos , Hunt Alistair
Published: October 2019

While there is a considerable debate regarding the choice of proper discount rates for assessing climate change projects and policies, only a tiny body of literature emphasizes “what to discount”. Usually, climate change economic assessments rely on tools and methods that employ strong simplifications, assuming, among others, given and fixed preferences about the values of man-made and environmental goods. Aiming to fill a gap in the literature, this paper leaves aside the issue of discounting and focuses on the nature and impact of preference uncertainty on the economic estimates of future climate change damages on ecosystem non-market goods and services. To this end, a general random walk-based stochastic model is proposed, combining a number of parameters, e.g., the growth of income, depletion of environmental assets, the elasticity of income and demand, and the change in preferences towards the environment. The illustrative application of the model shows that the value of environmental losses is significantly affected by the change in preferences. By doing so, the model allows the analyst to visualize future paths of preference evolutions and to bring future values of damaged environmental assets realistically to the fore. If these elements are neglected when estimating climate change-related future damages to environmental goods and services, the results may be too narrow from a policy perspective.
Occupational Self-Efficacy and Psychological Capital Amongst Nursing Students: A Cross Sectional Study Understanding the Malleable Attributes for Success
Authors: Terry Daniel , Peck Blake , Smith Andrew , Nguyen Hoang
Published: October 2019

With a predicted shortfall in the worldwide nursing workforce, efforts to understand attributes that influence attrition and workforce longevity remain fundamental. Self-efficacy and the broader construct of psychological capital have been linked to positive workplace-based attributes in occupations. The aim of the study was to examine the relationship between general self-efficacy, occupational (nursing) self-efficacy, and psychological capital and their predictive factors among nursing students. A cross sectional design was used to address the aims of the study where all nursing students studying a three-year bachelor’s degree were invited to complete a questionnaire examining traits that might assist in the preparation for, and longevity in, a nursing career. Although the participating nursing students demonstrated high levels of general self-efficacy, their reported levels of nursing-specific self-efficacy were significantly lower. Psychological capital measures indicated that students had high levels of belief, hope, and resilience concerning their capacity to commit to and achieve goals, succeed now and into the future, and overcome obstacles. The findings suggest an opportunity exists for education providers to nurture the malleable aspects of self-efficacy and psychological capital, while developing greater capacity to bounce back and overcome the challenges that nursing students may encounter in their undergraduate academic training, and to reduce attrition as they prepare to enter the workplace.
On-Off Control of Range Extender in Extended-Range Electric Vehicle using Bird Swarm Intelligence
Authors: Wu Dongmei , Feng Liang
Published: October 2019

The bird swarm algorithm (BSA) is a bio-inspired evolution approach to solving optimization problems. It is derived from the foraging, defense, and flying behavior of bird swarm. This paper proposed a novel version of BSA, named as BSAII. In this version, the spatial distance from the center of the bird swarm instead of fitness function value is used to stand for their intimacy of relationship. We examined the performance of two different representations of defense behavior for BSA algorithms, and compared their experimental results with those of other bio-inspired algorithms. It is evident from the statistical and graphical results highlighted that the BSAII outperforms other algorithms on most of instances, in terms of convergence rate and accuracy of optimal solution. Besides the BSAII was applied to the energy management of extended-range electric vehicles (E-REV). The problem is modified as a constrained global optimal control problem, so as to reduce engine burden and exhaust emissions. According to the experimental results of two cases for the new European driving cycle (NEDC), it is found that turning off the engine ahead of time can effectively reduce its uptime on the premise of completing target distance. It also indicates that the BSAII is suitable for solving such constrained optimization problem.
Designing a Water-Immersed Rectangular Horn Antenna for Generating Underwater OAM Waves
Authors: Yang Yang , Wang Zhanliang , Wang Shaomeng , Zhou Qing , Shen Fei , Jiang Haibo , Wu Zhe , Zeng Baoqing , Guo Zhongyi , Gong Yubin
Published: October 2019

In order to extend the applications of vortex waves, we propose a water-immersed rectangular horn antenna array for generating underwater vortex waves carrying the orbital angular momentum (OAM). Firstly, a single dielectric-loaded rectangular horn antenna with the central frequency of 2.6 GHz was designed for generating underwater electromagnetic (EM) waves. Due to the supplementing dielectric-loaded waveguide in this single antenna, the problems with difficult sealing and fixation of the feed probe could be solved effectively. The simulation results show that it has a good impedance characteristics (S11 < −10 dB) and reasonable losses (less than 3.5 dB total for two antennas and a coaxial line) from 2.5 GHz to 2.7 GHz. Experiments on the single antenna were also carried out, which agree well with the simulations. Based on the designed single antenna, the water-immersed rectangular horn antenna array was proposed, and the phase gradient from 0~2π was fed to the horn antennas for generating underwater OAM waves. The simulation results demonstrate high fidelity of the generated OAM waves from the intensity and phase distributions. The purity of the generated OAM modes was also investigated and further verifies the high fidelity of the generated OAM waves. The generated high-quality OAM waves meet the requirements for underwater applications of OAM, such as underwater communication and underwater imaging.