bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance
Authors: Mitani Seiichiro , Kawakami Hisato
Published: February 2020

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.
Milk Fat Globule-EGF Factor 8 Contributes to Progression of Hepatocellular Carcinoma
Authors: Ko Duck Sung , Kim Su Hyun , Park Ji Young , Lee Gyunggyu , Kim Hyo Jin , Kim Gyeongmin , Chi Kyun You , Kim Ilsoo , Lee Jinseok , Won Kyu-Yeoun , Han Jiyou , Son Jeongsang , Woo Dong-Hun , Han Choongseong , Kim Jong-Hoon
Published: February 2020

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer.
Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma
Authors: Terai Mizue , Londin Eric , Rochani Ankit , Link Emma , Lam Bao , Kaushal Gagan , Bhushan Alok , Orloff Marlana , Sato Takami
Published: February 2020

Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment. Here, we have investigated the role of tryptophan 2,3-dioxygenase (TDO) in UM. Both TDO and indoleamine 2,3-dioxygenase (IDO) catalyze tryptophan and produce kynurenine, which could cause inhibition of T cell immune responses. We first studied the expression of TDO on tumor tissue specimens obtained from UM hepatic metastasis. High expression of TDO protein was confirmed in all hepatic metastasis. TDO was positive in both normal hepatocytes and the tumor cells with relatively higher expression in tumor cells. On the other hand, IDO protein remained undetectable in all of the MUM specimens. UM cell lines established from metastasis also expressed TDO protein and increasing kynurenine levels were detected in the supernatant of MUM cell culture. In TCGA database, higher TDO2 expression in primary UM significantly correlated to BAP1 mutation and monosomy 3. These results indicate that TDO might be one of the key mechanisms for resistance to immunotherapy in UM.
Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen
Authors: Yang Ming-Hui , Chen Marcelo , Mo Hsiao-Hsuan , Tsai Wan-Chi , Chang Yu-Chi , Chang Chin-Chuan , Chen Ko-Chin , Wu Hsin-Yi , Yuan Cheng-Hui , Lee Che-Hsin , Chen Yi-Ming Arthur , Tyan Yu-Chang
Published: February 2020

Hepatocellular carcinoma (HCC) is among the ten most commonly diagnosed cancers and the fourth leading cause of cancer-related death. Patients with hepatitis B virus (HBV) infection are prone to developing chronic liver diseases (i.e., fibrosis and cirrhosis), and the HBV X antigen plays an important role in the development of HCC. The difficulty in detecting HCC at the early stages is one of the main reasons that the death rate approximates the incidence rate. The regulators controlling the downstream liver protein expression from HBV infection are unclear. Mass spectrometric techniques and customized programs were used to identify differentially expressed proteins which may be involved in the development of liver fibrosis and HCC progression in hepatitis B virus X protein transgenic mice (HBx mice). FSTL1, CTSB, and TGF-β enhanced the signaling pathway proteins during the pathogenesis of HBx. Missing proteins can be essential in cell growth, differentiation, apoptosis, migration, metastasis or angiogenesis. We found that LHX2, BMP-5 and GDF11 had complex interactions with other missing proteins and BMP-5 had both tumor suppressing and tumorigenic roles. BMP-5 may be involved in fibrosis and tumorigenic processes in the liver. These results provide us an understanding of the mechanism of HBx-induced disorders, and may serve as molecular targets for liver treatment.
Correction: Møller, P.; et al. Causes for Frequent Pathogenic BRCA1 Variants Include Low Penetrance in Fertile Ages, Recurrent De-Novo Mutations and Genetic Drift. Cancers 2019, 11, 132
Authors: Møller Pål , Dominguez-Valentin Mev , Rødland Einar Andreas , Hovig Eivind
Published: February 2020

The authors wish to make the following corrections to this paper [1]: The authors would like to replace Table 3 in [1]. The corrections are correcting typographical errors when translating our database in BIC format to HGVS nomenclature, and removing four carriers which had zero follow-up time. [...]
HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women
Authors: Oltra Sara S. , Cejalvo Juan Miguel , Tormo Eduardo , Albanell Marta , Ferrer Ana , Nacher Marta , Bermejo Begoña , Hernando Cristina , Chirivella Isabel , Alonso Elisa , Burgués Octavio , Peña-Chilet Maria , Eroles Pilar , Lluch Ana , Ribas Gloria , Martinez María Teresa
Published: February 2020

Background: Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: HDAC5 expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.
Rh-induced Support Transformation and Rh Incorporation in Titanate Structures and Their Influence on Catalytic Activity
Authors: Kiss János , Sápi András , Tóth Mariann , Kukovecz Ákos , Kónya Zoltán
Published: February 2020

Rh is one of the most effective metals in several technologically important heterogeneous catalytic reactions, like the hydrogenation of CO2, and CO, the CO+H2O reaction, and methane and ethanol transformations. Titania and titanates are among the most frequently studied supports for Rh nanoparticles. The present study demonstrates that the nature of the support has a marked influence on the specific activity. For comparison, the catalytic activity of TiO2 P25 is also presented. It is pointed out that a certain amount of Rh can be stabilized as cation (Rh+) in ion-exchange positions (i.e., in atomic scale distribution) of the titanate framework. This ionic form does not exists on TiO2. We pay distinguished attention not only to the electronic interaction between Rh metal and the titania/titanate support, but also to the Rh-induced phase transitions of one-dimensional titanate nanowires (TiONW) and nanotubes (TiONT). Support transformation phenomena can be observed in Rh-loaded titanates. Rh decorated nanowires transform into the TiO2(B) phase, whereas their pristine counterparts recrystallize into anatase. The formation of anatase is dominant during the thermal annealing process in both acid-treated and Rh-decorated nanotubes; Rh catalysis this transformation. We demonstrate that the phase transformations and the formation of Rh nanoclusters and incorporated Rh ions affect the conversion and the selectivity of the reactions. The following initial activity order was found in the CO2 + H2, CO + H2O and C2H5OH decomposition reactions: Rh/TiO2 (Degussa P25) ≥ Rh/TiONW > Rh/TiONT. On the other hand it is remarkable that the hydrogen selectivity in ethanol decomposition was two times higher on Rh/TiONW and Rh/TiO(NT) catalysts than on Rh/TiO2 due to the presence of Rh+ cations incorporated into the framework of the titanate structures.
Active Expression of Membrane-Bound L-Amino Acid Deaminase from Proteus mirabilis in Recombinant Escherichia coli by Fusion with Maltose-Binding Protein for Enhanced Catalytic Performance
Authors: Zhang Dan-Ping , Jing Xiao-Ran , Fan An-Wen , Liu Huan , Nie Yao , Xu Yan
Published: February 2020

L-amino acid deaminases (LAADs) are membrane flavoenzymes that catalyze the deamination of neutral and aromatic L-amino acids to α-keto acids and ammonia. LAADs can be used to develop many important biotechnological applications. However, the transmembrane α-helix of LAADs restricts its soluble active expression and purification from a heterologous host, such as Escherichia coli. Herein, through fusion with the maltose-binding protein (MBP) tag, the recombinant E. coli BL21 (DE3)/pET-21b-MBP-PmLAAD was constructed and the LAAD from Proteus mirabilis (PmLAAD) was actively expressed as a soluble protein. After purification, the purified MBP-PmLAAD was obtained. Then, the catalytic activity of the MBP-PmLAAD fusion protein was determined and compared with the non-fused PmLAAD. After fusion with the MBP-tag, the catalytic efficiency of the MBP-PmLAAD cell lysate was much higher than that of the membrane-bound PmLAAD whole cells. The soluble MBP-PmLAAD cell lysate catalyzed the conversion of 100 mM L-phenylalanine (L-Phe) to phenylpyruvic acid (PPA) with a 100% yield in 6 h. Therefore, the fusion of the MBP-tag not only improved the soluble expression of the PmLAAD membrane-bound protein, but also increased its catalytic performance.
Mercury(II)-Catalyzed Cleavage, Isomerization and Depurination of RNA and DNA Model Compounds and Desulfurization of Their Phosphoromonothioate Analogs
Authors: Saleh Lange Yakubu , Ora Mikko , Lönnberg Tuomas
Published: February 2020

The potential of Hg(II), a metal ion so-far overlooked in the development of artificial nucleases, to cleave RNA and DNA has been assessed. Accordingly, Hg(II)-promoted cleavage and isomerization of the RNA model compound adenylyl-3′,5′-(2′,3′-O-methyleneadenosine) and depurination of 2′-deoxyadenosine were followed by HPLC as a function of pH (5.0–6.0) and the desulfurization of both diastereomers of the phosphoromonothioate analog of adenylyl-3′,5′-(2′,3′-O-methyleneadenosine) at a single pH (6.9). At 5 mM [Hg(II)], cleavage of the RNA model compound was accelerated by two orders of magnitude at the low and by one order of magnitude at the high end of the pH range. Between 0 and 5 mM [Hg(II)], the cleavage rate showed a sigmoidal dependence on [Hg(II)], suggesting the participation of more than one Hg(II) in the reaction. Isomerization and depurination were also facilitated by Hg(II), but much more modestly than cleavage, less than 2-fold over the entire pH range studied. Phosphoromonothioate desulfurization was by far the most susceptible reaction to Hg(II) catalysis, being accelerated by more than four orders of magnitude.
Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond
Authors: Wang Xiaoli , Lv Chunyu , Guo Ying , Yuan Shuiqiao
Published: February 2020

Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction.
Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy
Authors: Nguyen Hong-My , Guz-Montgomery Kirsten , Saha Dipongkor
Published: February 2020

Oncolytic viruses (OVs) are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce anti-tumor immunity. OV-induced tumor immunity can be enhanced through viral expression of anti-tumor cytokines such as interleukin 12 (IL-12). IL-12 is a potent anti-cancer agent that promotes T-helper 1 (Th1) differentiation, facilitates T-cell-mediated killing of cancer cells, and inhibits tumor angiogenesis. Despite success in preclinical models, systemic IL-12 therapy is associated with significant toxicity in humans. Therefore, to utilize the therapeutic potential of IL-12 in OV-based cancer therapy, 25 different IL-12 expressing OVs (OV-IL12s) have been genetically engineered for local IL-12 production and tested preclinically in various cancer models. Among OV-IL12s, oncolytic herpes simplex virus encoding IL-12 (OHSV-IL12) is the furthest along in the clinic. IL-12 expression locally in the tumors avoids systemic toxicity while inducing an efficient anti-tumor immunity and synergizes with anti-angiogenic drugs or immunomodulators without compromising safety. Despite the rapidly rising interest, there are no current reviews on OV-IL12s that exploit their potential efficacy and safety to translate into human subjects. In this article, we will discuss safety, tumor-specificity, and anti-tumor immune/anti-angiogenic effects of OHSV-IL12 as mono- and combination-therapies. In addition to OHSV-IL12 viruses, we will also review other IL-12-expressing OVs and their application in cancer therapy.
Dynamics and Regulations of BimEL Ser65 and Thr112 Phosphorylation in Porcine Granulosa Cells during Follicular Atresia
Authors: Yang Feng , Chen Yanhong , Liu Qiang , Dai Shizhen , Zeng Shenming
Published: February 2020

BimEL protein is involved in follicular atresia by regulating granulosa cell apoptosis, but the dynamic changes of BimEL phosphorylation during follicular atresia are poorly understood. The aim of this study was to explore the changes of key BimEL phosphorylation sites and their upstream regulatory pathways. First, the levels of BimEL-Ser65 and BimEL-Thr112 phosphorylation (p-BimEL-S65, p-BimEL-T112) in granulosa cells (GC) from healthy (H), slightly-atretic (SA), and atretic (A) follicles and in cultured GC after different treatments were detected by Western blotting. Next, the effects of the corresponding site mutations of BIM on apoptosis of GC were investigated. Finally, the pathways of two phosphorylation sites were investigated by kinase inhibitors. The results revealed that p-BimEL-S65 levels were higher in GC from H than SA and A, whereas p-BimEL-T112 was reversed. The prosurvival factors like FSH and IGF-1 upregulated the level of p-BimEL-S65, while the proapoptotic factor, heat stress, increased the level of p-BimEL-T112 in cultured GC. Compared with the overexpression of wild BimEL, the apoptotic rate of the GC overexpressed BimEL-S65A (replace Ser65 with Ala) mutant was significantly higher, but the apoptotic rate of the cells overexpressing BimEL-T112A did not differ. In addition, inhibition of the ERK1/2 or JNK pathway by specific inhibitors reduced the levels of p-BimEL-S65 and p-BimEL-T112. In conclusion, the levels of p-BimEL-S65 and p-BimEL-T112 were reversed during follicular atresia. Prosurvival factors promote p-BimEL-S65 levels via ERK1/2 to inhibit GC apoptosis, whereas proapoptotic factor upregulates the level of p-BimEL-T112 via JNK to induce GC apoptosis.
mTOR Regulation of Metabolism in Hematologic Malignancies
Authors: Mirabilii Simone , Ricciardi Maria Rosaria , Tafuri Agostino
Published: February 2020

Neoplastic cells rewire their metabolism, acquiring a selective advantage over normal cells and a protection from therapeutic agents. The mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular activities, including the control of metabolic processes. mTOR is hyperactivated in a large number of tumor types, and among them, in many hematologic malignancies. In this article, we summarized the evidence from the literature that describes a central role for mTOR in the acquisition of new metabolic phenotypes for different hematologic malignancies, in concert with other metabolic modulators (AMPK, HIF1α) and microenvironmental stimuli, and shows how these features can be targeted for therapeutic purposes.
ER-to-Golgi Trafficking and Its Implication in Neurological Diseases
Authors: Wang Bo , Stanford Katherine R. , Kundu Mondira
Published: February 2020

Membrane and secretory proteins are essential for almost every aspect of cellular function. These proteins are incorporated into ER-derived carriers and transported to the Golgi before being sorted for delivery to their final destination. Although ER-to-Golgi trafficking is highly conserved among eukaryotes, several layers of complexity have been added to meet the increased demands of complex cell types in metazoans. The specialized morphology of neurons and the necessity for precise spatiotemporal control over membrane and secretory protein localization and function make them particularly vulnerable to defects in trafficking. This review summarizes the general mechanisms involved in ER-to-Golgi trafficking and highlights mutations in genes affecting this process, which are associated with neurological diseases in humans.
miRNAs as Key Players in the Management of Cutaneous Melanoma
Authors: Lorusso Celeste , De Summa Simona , Pinto Rosamaria , Danza Katia , Tommasi Stefania
Published: February 2020

The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other “druggable” targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.
c-Jun, Foxo3a, and c-Myc Transcription Factors are Key Regulators of ATP-Mediated Angiogenic Responses in Pulmonary Artery Vasa Vasorum Endothelial Cells †
Authors: Strassheim Derek , Karoor Vijaya , Nijmeh Hala , Weston Philip , Lapel Martin , Schaack Jerome , Sullivan Timothy , Dempsey Edward C. , Stenmark Kurt R. , Gerasimovskaya Evgenia
Published: February 2020

Angiogenic vasa vasorum (VV) expansion plays an essential role in the pathogenesis of hypoxia-induced pulmonary hypertension (PH), a cardiovascular disease. We previously showed that extracellular ATP released under hypoxic conditions is an autocrine/paracrine, the angiogenic factor for pulmonary artery (PA) VV endothelial cells (VVECs), acting via P2Y purinergic receptors (P2YR) and the Phosphoinositide 3-kinase (PI3K)-Akt-Mammalian Target of Rapamycin (mTOR) signaling. To further elucidate the molecular mechanisms of ATP-mediated VV angiogenesis, we determined the profile of ATP-inducible transcription factors (TFs) in VVECs using a TranSignal protein/DNA array. C-Jun, c-Myc, and Foxo3 were found to be upregulated in most VVEC populations and formed nodes connecting several signaling networks. siRNA-mediated knockdown (KD) of these TFs revealed their critical role in ATP-induced VVEC angiogenic responses and the regulation of downstream targets involved in tissue remodeling, cell cycle control, expression of endothelial markers, cell adhesion, and junction proteins. Our results showed that c-Jun was required for the expression of ATP-stimulated angiogenic genes, c-Myc was repressive to anti-angiogenic genes, and Foxo3a predominantly controlled the expression of anti-apoptotic and junctional proteins. The findings from our study suggest that pharmacological targeting of the components of P2YR-PI3K-Akt-mTOR axis and specific TFs reduced ATP-mediated VVEC angiogenic response and may have a potential translational significance in attenuating pathological vascular remodeling.
Human Plasmacytoid Dendritic Cells and Cutaneous Melanoma
Authors: Monti Matilde , Consoli Francesca , Vescovi Raffaella , Bugatti Mattia , Vermi William
Published: February 2020

The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high amount of type I Interferon (I-IFN), through the Toll-like receptor (TLR) 7 and 9 signaling pathway activation. However, published data indicate that melanoma-associated escape mechanisms are in place to hijack pDC functions. We have recently reported that pDC recruitment is recurrent in the early phases of melanoma, but the entire pDC compartment collapses over melanoma progression. Here, we summarize recent advances on pDC biology and function within the context of melanoma immunity.
Creating a Consistent Multi-Decadal Oceanic TRMM-GPM Brightness Temperature Record with Estimated Calibration Uncertainty
Authors: Chen Ruiyao , Jones W. Linwood
Published: February 2020

The National Aeronautics and Space Administration’s (NASA) Precipitation Measurement Missions (PMMs) include two earth satellite missions, namely, the Tropical Rainfall Measuring Mission (TRMM, 1997–2015) and the Global Precipitation Measurement (GPM, 2014-present). To generate a consistent multi-decadal brightness temperature (Tb) record that spans the TRMM and GPM eras, it is highly desirable to perform a comprehensive intercalibration of the TRMM Microwave Imager (TMI) and the GPM Microwave Imager (GMI) Tb measurements. Unfortunately, GMI and TMI share a limited common operational period of only 13 months. Fortunately, the WindSat polarimetric radiometer (2003-present) has been shown to be well calibrated and radiometrically stable relative to TMI for a period of over 5 years. Therefore, this paper describes the use of overlapping WindSat Tb measurements as the calibration bridge to achieve a seamless transfer joining the TMI and GMI Tb time series. Also, the development of the Tb measurement uncertainty estimation model is presented, which incorporates all relevant sources of uncertainty. Afterwards, this model was applied to three intercalibration processes: TMI to GMI, TMI to WindSat, and WindSat to GMI, and results are presented that quantify the corresponding Tb channel measurements biases and associated uncertainties associated with the merged TMI-GMI Tb record. This is an important accomplishment because this study can enable improved future Earth Science and global climate change investigations by making a long-term Tb record with estimated uncertainty available.
Heat Transfer Effect on Viscoelastic Fluid Used as a Coating Material for Wire with Variable Viscosity
Authors: Khan Zeeshan , Rasheed Haroon Ur , Islam Saeed , Noor Sahib , Khan Ilyas , Abbas Tariq , Khan Waris , Seikh Asiful H. , Sherif El-Sayed M. , Nisar Kottakkaran Sooppy
Published: February 2020

This article examines a wire coating technique using a viscoelastic Eyring–Powell fluid in which magnetohydrodynamic (MHD) flow, thermal transfer, and Joule heating effects are studied. Temperature-dependent, variable-viscosity models are used. Flexible-viscosity models which are temperature dependent are also considered. The interface of the thermal boundary layer which describe the flux and thermal convection phenomena, are evaluated by using a dominant numerical technique known as the fourth-order Runge–Kutta method. In particular, this article takes into account the impact of a permeable matrix which behaves like a dielectric in order to avoid heat dissipation. The effect of thermal generation is also explained, since it controls power. The novel effects for the numerous parameters which affect the velocity and temperature profiles on the wire coating process are investigated through graphs explained in detail. These include non-Newtonian, hydromagnetic, permeability, and heat source/sink effects. For validation purposes, the numerical scheme is also compared with a semi-numerical technique HAM and BVPh2 software, and found a closed agreement with the numerical results.
A New Alternative Electrochemical Process for a Pre-Deposited UPD-Mn Mediated the Growth of Cu(Mn) Film by Controlling the Time during the Cu-SLRR
Authors: Fang Jau-Shiung , Sie Yu-Fei , Cheng Yi-Lung , Chen Giin-Shan
Published: February 2020

A layer-by-layer deposition is essential for fabricating the Cu interconnects in a nanoscale-sized microelectronics because the gap-filling capability limits the film deposition step coverage on trenches/vias. Conventional layer-by-layer electrochemical deposition of Cu typically works by using two electrolytes, i.e., a sacrificial Pb electrolyte and a Cu electrolyte. However, the use of a Pb electrolyte is known to cause environmental issues. This study presents an Mn monolayer, which mediated the electrochemical growth of Cu(Mn) film through a sequence of alternating an underpotential deposition (UPD) of Mn, replacing the conventionally used UPD-Pb, with a surface-limited redox replacement (SLRR) of Cu. The use of the sacrificial Mn monolayer uniquely provides redox replacement by Cu2+ owing to the standard reductive potential differences. Repeating the sequence of the UPD-Mn followed by the SLRR-Cu enables Cu(Mn) film growth in an atomic layer growth manner. Further, controlling the time of open circuit potential (OCP) during the Cu-SLRR yields a technique to control the content of the resultant Cu(Mn) film. A longer OCP time caused more replacement of the UPD-Mn by the Cu2+, thus resulting in a Cu(Mn) film with a higher Cu concentration. The proposed layer-by-layer growth method offers a wet, chemistry-based deposition capable of fabricating Cu interconnects without the use of the barrier layer and can be of interest in microelectronics.
Optimization of Rice Husk Ash-Based Geopolymers Coating Composite for Enhancement in Flexural Properties and Microstructure Using Response Surface Methodology
Authors: Basri Mohd Salahuddin Mohd , Mustapha Faizal , Mazlan Norkhairunnisa , Ishak Mohd Ridzwan
Published: February 2020

If the coating is sufficiently flexible, no tears, cracks, or debond will occur. Although geopolymers have a great potential as a coating material, research on the flexural properties is very limited. In this study, a three-point bending test and scanning electron microscope were used to investigate the flexural properties and microstructure of the geopolymer composite coating (GCC), respectively. Response Surface Methodology (RSM) consists of a combination of mathematical and statistical techniques, which is useful in modelling, analyzing, and optimizing responses that are influenced by several factors. It was used in determining the relationship between each factor and determining the best composition for the composite coating. Several factors were considered including ratio of activated alkaline (AA) solution (V1), RHA/AA ratio (V2), and curing temperature (V3). Results showed that the RHA/AA ratio mostly influenced the response, followed by curing temperature while the ratio of AA was not significant. Lower V2 and V3 values provided the highest flexural strength and modulus. The optimum composition which provided the best coating of flexural properties were V1 = 3.5, V2 = 0.39, and V3 = 45.7 °C. Microscopic images showed that coating with high flexural properties (ductile coating) exhibited minor and rough cracks as compared to that of coating with low flexural properties (brittle coating) which displayed a crack with a clean linear cut. Brittle coating was highly agglomerated and has a significant negative effect on the flexural properties. By developing the optimum composition, the GCC may potentially be a good alternative as a building construction coating material.
Multidisciplinary Diagnostic Algorithm for Evaluation of Patients Presenting with a Prosthetic Problem in the Hip or Knee: A Prospective Study
Authors: Khalid Vesal , Schønheyder Henrik Carl , Larsen Lone Heimann , Nielsen Poul Torben , Kappel Andreas , Thomsen Trine Rolighed , Aleksyniene Ramune , Lorenzen Jan , Ørsted Iben , Simonsen Ole , Jordal Peter Lüttge , Rasmussen Sten
Published: February 2020

The predominant indications for revision surgery after total hip (THA) or knee arthroplasty (TKA) are an aseptic failure (AF) and prosthetic joint infection (PJI). Accurate diagnosis is crucial. Therefore, we evaluated prospectively a multidisciplinary diagnostic algorithm including multi-modal radionucleid imaging (RNI) and extended microbiological diagnostics. If the surgeon suspected PJI or AF, revision surgery was performed with multiple samples obtained in parallel for special culture procedures and later molecular analyses. Alternatively, if the underlying cause was not evident, RNI was scheduled comprising 99Tc—HDP SPECT/CT, 111In-labeled white blood cells combined with 99Tc-nanocoll bone marrow SPECT/CT, and 18F-FDG PET/CT. A multidisciplinary clinical team made a recommendation on the indication for a diagnostic procedure guided by RNI images or revision surgery. A total of 156 patients with 163 arthroplasties were included. Fifty-five patients underwent RNI. In all, 118 revision surgeries were performed in 112 patients: 71 on the indication of AF and 41 revision of PJI. Thirty-four patients were concluded with chronic pain, and revision surgery refrained. The effective median follow-up period was 13 months. A structured approach offered by the algorithm was useful for the clinician in the evaluation of patients with a failing TKA or THA. Surgical revision was possibly obviated in approximately 20% of patients where an explanation or cause of failure was not found. The algorithm served as an effective tool.
Emergence of Network Motifs in Deep Neural Networks
Authors: Zambra Matteo , Maritan Amos , Testolin Alberto
Published: February 2020

Network science can offer fundamental insights into the structural and functional properties of complex systems. For example, it is widely known that neuronal circuits tend to organize into basic functional topological modules, called network motifs. In this article, we show that network science tools can be successfully applied also to the study of artificial neural networks operating according to self-organizing (learning) principles. In particular, we study the emergence of network motifs in multi-layer perceptrons, whose initial connectivity is defined as a stack of fully-connected, bipartite graphs. Simulations show that the final network topology is shaped by learning dynamics, but can be strongly biased by choosing appropriate weight initialization schemes. Overall, our results suggest that non-trivial initialization strategies can make learning more effective by promoting the development of useful network motifs, which are often surprisingly consistent with those observed in general transduction networks.
Measuring Characteristics of Explanations with Element Maps
Authors: Wagner Steffen , Kok Karel , Priemer Burkhard
Published: February 2020

What are the structural characteristics of written scientific explanations that make them good? This is often difficult to measure. One approach to describing and analyzing structures is to employ network theory. With this research, we aim to describe the elementary structure of written explanations, their qualities, and the differences between those made by experts and students. We do this by converting written explanations into networks called element maps and measure their characteristics: size, the ratio of diameter to size, and betweenness centrality. Our results indicate that experts give longer explanations with more intertwinement, organized around a few central key elements. Students’ explanations vary widely in size, are less intertwined, and often lack a focus around key elements. We have successfully identified and quantified the characteristics that can be a starting point for guiding students towards generating expert-like written explanations.
A Compact UWB Bandpass Chip Filter on a GaAs Substrate with Modified Chebyshev Structure
Authors: Hu Shanwen , Hu Yunqing , Gao Yiting , Zhang Xiaodong , Zhang Xinlei , Wang Zixuan , Zhou Bo , Cai Zhikuang , Guo Yufeng
Published: February 2020

Ultra-Wideband (UWB) systems are widely used in low-power, high-speed, high-security short-range wireless communication systems throughout digital homes and offices. In the RF front-end of a UWB system, bandpass filters (BPFs) are used to put through the passband signals and reject the stopband signals. Most UWB BPFs are designed with dielectric materials on circuit boards or LTCC technology. In this paper, a very compact fully integrated UWB chip filter is proposed and designed on a GaAs substrate with nitride as dielectric layers to meet the small size requirement of portable devices for next-generation UWB applications. The filter is constructed with a modified Chebyshev structure. The final filter circuit contains only four inductors instead of six for the conventional Chebyshev filter, which makes the chip more compact and cost effective. The filter is designed and fabricated on a 0.25 μm GaAs pHEMT technology with a chip size of only 0.73 mm × 0.51 mm including the chip edge and scribe line area, while the filter core area is only 0.61 mm × 0.39 mm, including bonding PADs. The measurement results illustrated that the proposed BPF shows a passband covering the frequency range of 3.1–9.0 GHz, the minimum passband insertion loss is only 1.5 dB, the stopband rejection is better than −30 dB throughout frequencies below 2 GHz and above 12 GHz, S11 is less than −16 dB, and S22 is better than −11 dB during the whole passband range. It demonstrated that the proposed filter can be considered as one of the most compact UWB filters.
Dual Fuel Reaction Mechanism 2.0 including NOx Formation and Laminar Flame Speed Calculations Using Methane/Propane/n-Heptane Fuel Blends
Authors: Schuh Sebastian , Winter Franz
Published: February 2020

This study presents the further development of the TU Wien dual fuel mechanism, which was optimized for simulating ignition and combustion in a rapid compression expansion machine (RCEM) in dual fuel mode using diesel and natural gas at pressures higher than 60 bar at the start of injection. The mechanism is based on the Complete San Diego mechanism with n-heptane extension and was attuned to the RCEM measurements to achieve high agreement between experiments and simulation. This resulted in a specific application area. To obtain a mechanism for a wider parameter range, the Arrhenius parameter changes performed were analyzed and updated. Furthermore, the San Diego nitrogen sub-mechanism was added to consider NOx formation. The ignition delay time-reducing effect of propane addition to methane was closely examined and improved. To investigate the propagation of the flame front, the laminar flame speed of methane–air mixtures was simulated and compared with measured values from literature. Deviations at stoichiometric and fuel-rich conditions were found and by further mechanism optimization reduced significantly. To be able to justify the parameter changes performed, the resulting reaction rate coefficients were compared with data from the National Institute of Standards and Technology chemical kinetics database.
Post-Harvest Stand Dynamics over Five Years in Selectively Logged Production Forests in Bago, Myanmar
Authors: Khai Tual Cin , Mizoue Nobuya , Ota Tetsuji
Published: February 2020

Understanding the stand dynamics of tropical production forests is essential for determining the sustainability of a polycyclic selective logging system, but limited related studies have addressed the impacts of illegal logging over time. Myanmar faces the extensive degradation of traditional production forests with a 160-year logging history, but the cause of this degradation and how to balance legal and/or illegal disturbances with recovery in over-logged forests remain unclear. The present study investigated stand structural changes over 5 years after official legal logging operations using two 1-ha (100 × 100 m) sample plots. For 5 years after logging, the volume of trees with a diameter at breast height (DBH) ≥ 20 cm decreased by 46.0% from 121 to 65.1 m3 ha−1, with a significant loss of the first- and second-grade species group (Tectona grandis Linn. f. and Xylia xylocarpa (Roxb.) Taub.) from 48.3 to 6.8 m3 ha−1. The total tree loss owing to official logging operations, mainly targeting the second- and fourth-grade species group, was 29.3 m3 ha−1. A similar level of total tree loss (28.0 m3 ha−1) was attributed to illegal logging that targeted the first- and second-grade species group. The mean annual recruitment rate of 3.1% was larger than the reported values for tropical forests, but there were no and only 1.5 trees ha−1 recruitments s for T. grandis and X. xylocarpa, respectively. The mean annual mortality rate of 2.5% was within the values reported in the related literature, and the volume loss from the mortality was relatively similar to the gain from the increment of living trees for all species groups. We concluded that the effects of illegal disturbances for 5 years post-harvest were equivalent to those of legal disturbances and larger than those of natural change, and are a major cause of the substantial reduction in stocking levels, especially for commercial species.
Identification of Grafting-Responsive MicroRNAs Associated with Growth Regulation in Pecan [Carya illinoinensis (Wangenh.) K. Koch]
Authors: Liu Zhuangzhuang , Li Fengda , Peng Fangren , Tan Pengpeng , Zhu Kaikai , Feng Gang , Mo Zhenghai , Li Yongrong
Published: February 2020

Pecan [Carya illinoinensis (Wangenh.) K. Koch] is an economically important nut tree and grafting is often used for clonal propagation of cultivars. However, there is a lack of research on the effects of rootstocks on scions, which are meaningful targets for directed breeding of pecan grafts. MicroRNAs (miRNAs) play an important role in many biological processes, but the mechanism underlying the involvement of miRNAs in grafting-conferred physiological changes is unclear. To identify the grafting-responsive miRNAs that may be involved in the regulation of growth in grafted pecan, six small RNA libraries were constructed from the phloem of two groups of grafts with significantly different growth performance on short and tall rootstocks. A total of 441 conserved miRNAs belonging to 42 miRNA families and 603 novel miRNAs were identified. Among the identified miRNAs, 24 (seven conserved and 17 novel) were significantly differentially expressed by the different grafts, implying that they might be responsive to grafting and potentially involved in the regulation of graft growth. Ninety-five target genes were predicted for the differentially expressed miRNAs; gene annotation was available for 33 of these. Analysis of their targets suggested that the miRNAs may regulate auxin transport, cell activity, and inorganic phosphate (Pi) acquisition, and thereby, mediate pecan graft growth. Use of the recently-published pecan genome enabled identification of a substantial population of miRNAs, which are now available for further research. We also identified the grafting-responsive miRNAs and their potential roles in pecan graft growth, providing a basis for research on long-distance regulation in grafted pecan.
Dietary Grape Pomace Supplementation in Dairy Cows: Effect on Nutritional Quality of Milk and Its Derived Dairy Products
Authors: Ianni Andrea , Martino Giuseppe
Published: February 2020

Grape pomace (GP) is the main solid by-product of winemaking and represents a rich source of potent bioactive compounds which could display a wide range of beneficial effects in human health for their association with reduced risk of several chronic diseases. Several studies have proposed the use of GP as a macro-ingredient to obtain economically worthwhile animal feedstuffs naturally enriched by polyphenols and dietary fibers. Moreover, the research carried out in this field in the last two decades evidences the ability of GP to induce beneficial effects in cow milk and its derived dairy products. First of all, a general increase in concentration of polyunsaturated fatty acids (PUFA) was observed, and this could be considered the reflection of the high content of these compounds in the by-product. Furthermore, an improvement in the oxidative stability of dairy products was observed, presumably as a direct consequence of the high content of bioactive compounds in GP that are credited with high and well-characterized antioxidant functions. Last but not least, particularly in ripened cheeses, volatile compounds (VOCs) were identified, arising both from lipolytic and proteolytic processes and commonly associated with pleasant aromatic notes. In conclusion, the GP introduction in the diet of lactating cows made it possible to obtain dairy products characterized by improved nutritional properties and high health functionality. Furthermore, the presumable improvement of organoleptic properties seems to be effective in contributing to an increase in the consumer acceptability of the novel products. This review aims to evaluate the effect of the dietary GP supplementation on the quality of milk and dairy products deriving from lactating dairy cows.
Could Western Attitudes towards Edible Insects Possibly be Influenced by Idioms Containing Unfavourable References to Insects, Spiders and other Invertebrates?
Authors: Meyer-Rochow Victor Benno , Kejonen Aimo
Published: February 2020

It is known that idioms, proverbs, and slogans can become integrated into feelings like irritation, contemptuous attitudes, and even anger and disgust. Idioms making reference to insects, spiders, and other invertebrates occur in all languages, but they convey mostly negative content in people of Western cultural orientation. By analyzing a subgroup of insect and spider idioms related to food, eating, and digestion, the authors suggest that mirror neurons are activated in people that are exposed to the largely unfavorable content of such idioms. This could then lead the listener of such idioms to adopt the kind of negative attitude towards insects that is expressed in the idioms and to project it towards edible species.