bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter- and Intra-Species Communication of Emotion: Chemosignals as the Neglected Medium
Authors: Semin Gün R. , Scandurra Anna , Baragli Paolo , Lanatà Antonio , D’Aniello Biagio
Published: October 2019

Human body odors contain chemosignals that make species-specific communication possible. Such communication is without communicative intent and is generally below the threshold of consciousness. Human recipients of these chemosignals produced during emotional conditions display a simulacrum of the emotional state under which the chemosignal was produced. The investigation of an inter-species transfer of emotions via chemosignals was initiated by considerations of the historically anchored interdependence between humans and domesticated species, such as dogs and horses. Indeed, experiments with dogs have demonstrated that human body odors produced under emotional conditions of happiness and fear led dogs to manifest corresponding emotions to those experienced by humans. Preliminary data from horses also show that human body odors collected under fear and happiness conditions activate the autonomic nervous system of horses differentially. These studies indicate the possibility of a road to open our understanding of inter-species emotional communication via chemosignals.
How Can National Antimicrobial Stewardship Interventions in Primary Care Be Improved? A Stakeholder Consultation
Authors: Borek Aleksandra J. , Wanat Marta , Sallis Anna , Ashiru-Oredope Diane , Atkins Lou , Beech Elizabeth , Hopkins Susan , Jones Leah , McNulty Cliodna , Shaw Karen , Taborn Esther , Butler Christopher , Chadborn Tim , Tonkin-Crine Sarah
Published: October 2019

Many antimicrobial stewardship (AMS) interventions have been implemented in England, facilitating decreases in antibiotic prescribing. Nevertheless, there is substantial variation in antibiotic prescribing across England and some healthcare organizations remain high prescribers of antibiotics. This study aimed to identify ways to improve AMS interventions to further optimize antibiotic prescribing in primary care in England. Stakeholders representing different primary care settings were invited to, and 15 participated in, a focus group or telephone interview to identify ways to improve existing AMS interventions. Forty-five intervention suggestions were generated and 31 were prioritized for inclusion in an online survey. Fifteen stakeholders completed the survey appraising each proposed intervention using the pre-defined APEASE (i.e., Affordability, Practicability, Effectiveness, Acceptability, Safety, and Equity) criteria. The highest-rated nine interventions were prioritized as most promising and feasible, including: quality improvement, multidisciplinary peer learning, appointing AMS leads, auditing individual-level prescribing, developing tools for prescribing audits, improving inductions for new prescribers, ensuring consistent local approaches to antibiotic prescribing, providing online AMS training to all patient-facing staff, and increasing staff time available for AMS work with standardizing AMS-related roles. These prioritized interventions could be incorporated into existing national interventions or developed as stand-alone interventions to help further optimize antibiotic prescribing in primary care in England.
Influence of the Physical State of Spray-Dried Flavonoid-Inulin Microparticles on Oxidative Stability of Lipid Matrices
Authors: Morelo Guibeth , Giménez Begoña , Márquez-Ruiz Gloria , Holgado Francisca , Romero-Hasler Patricio , Soto-Bustamante Eduardo , Robert Paz
Published: October 2019

The effect of the physical state of flavonoid-inulin microparticles (semi-crystalline/amorphous) on the oxidative stability of lipid matrices was studied. Epicatechin (E) and quercetin (Q) microparticles with inulin were formulated at two infeed temperatures (15 °C and 90 °C) by spray drying. X-ray diffraction analyses showed that flavonoid-inulin microparticles obtained at feed temperature of 15 °C were semi-crystalline (E-In-15, 61.2% and Q-In-15, 60%), whereas those at 90 °C were amorphous (Q-In-90, 1.73 and Q-In-90 2.30%). Semi-crystalline state of flavonoid-inulin microparticles enhanced the EE (68.8 and 67.8% for E and Q, respectively) compared to amorphous state (41.6 and 51.1% for E and Q, respectively). However, amorphous Q-microparticles showed the highest antioxidant activity both in methyl linoleate and sunflower oil, increasing the induction period and decreasing the polar compounds and polymer triglyceride formation during long-term oxidation study. Therefore, the physical state of spray-dried flavonoid-inulin microparticles may determine their antioxidant activity in lipid matrices.
Hyperspectral Imaging and Hierarchical PLS-DA Applied to Asbestos Recognition in Construction and Demolition Waste
Authors: Bonifazi Giuseppe , Capobianco Giuseppe , Serranti Silvia
Published: October 2019

Asbestos-Containing Materials (ACMs) are hazardous and prohibited to be sold or used as recycled materials. In the past, asbestos was widely used, together with cement, to produce “asbestos cement-based” products. During the recycling process of Construction and Demolition waste (C&DW), ACM must be collected and deposited separately from other wastes. One of the main aims of the recycling strategies applied to C&DW was thus to identify and separate ACM from C&DW (e.g., concrete and brick). However, to obtain a correct recovery of C&DW materials, control methodologies are necessary to evaluate the quality and the presence of harmful materials, such as ACM. HyperSpectral Imaging (HSI)-based sensing devices allow performing the full detection of materials constituting demolition waste. ACMs are, in fact, characterized by a spectral response that nakes them is different from the “simple” matrix of the material/s not embedding asbestos. The described HSI quality control approach is based on the utilization of a platform working in the short-wave infrared range (1000–2500 nm). The acquired hyperspectral images were analyzed by applying different chemometric methods: Principal Component Analysis for data exploration and hierarchical Partial Least-Square-Discriminant Analysis (PLS-DA) to build classification models. Following this approach, it was possible to set up a repeatable, reliable and efficient technique able to detect ACM presence inside a C&DW flow stream. Results showed that it is possible to discriminate and identify ACM inside C&DW. The recognition is potentially automatic, non-destructive and does not need any contact with the investigated products.
Crack Initiation and Propagation Fatigue Life of Ultra High-Strength Steel Butt Joints
Authors: Ottersböck Markus J. , Leitner Martin , Stoschka Michael , Maurer Wilhelm
Published: October 2019

The division of the total fatigue life into different stages such as crack initiation and propagation is an important issue in regard to an improved fatigue assessment especially for high-strength welded joints. The transition between these stages is fluent, whereas the threshold between the two phases is referred to as technical crack initiation. This work presents a procedure to track crack initiation and propagation during fatigue tests of ultra high-strength steel welded joints. The method utilizes digital image correlation to calculate a distortion field of the specimens’ surface enabling the identification and measurement of cracks along the weld toe arising during the fatigue test. Hence, technical crack initiation of each specimen can be derived. An evaluation for ten ultra high-strength steel butt joints reveals, that for this superior strength steel grade more than 50% of fatigue life is spent up to a crack depth of 0.5 mm, which can be defined as initial crack. Furthermore, a notch-stress based fatigue assessment of these specimens considering the actual weld topography and crack initiation and propagation phase is performed. The results point out that two phase models considering both phases enable an increased accuracy of service life assessment.
Physiological Control Law for Rotary Blood Pumps with Full-State Feedback Method
Authors: Bakouri Mohsen
Published: October 2019

One concern about pulsatile rotary blood pumps is their physiological controller reactions when “venous return” changes. When a patient rises from a supine to a standing position, the blood volume in the leg veins is raised, owing to vasodilation, thus venous returns to the right atrium, and consequently, the left atrium is reduced. In this work, a physiological control law using a full-state feedback control method was developed in order to drive mechanical circulatory support. This strategy was used as a validated state-space pump model, to implement the controller and regulate the desired reference flow. The control law was assessed using a software model of the hemodynamical cardiovascular system interacting with the left ventricular assist device in different physiological conditions ranging from rest to exercise scenarios. Under these scenarios, heart failure disease was simulated by changing the hemodynamic parameters of the total blood volume, heart rate, cardiac contractility, and systemic peripheral resistance. The results were numerically observed during the postural changes. The rate of change in the physiological variables showed that the proposed control law can regulate the desired reference pump flow with minimal error within the acceptable clinical range in order to prevent suction and over perfusion.
Effects of Specific Parameters on Simulations of Energy Use and Air Temperatures in Offices Equipped with Radiant Heating/Cooling Panels
Authors: Jordan Sabina , Hafner Jože , Zbašnik-Senegačnik Martina , Legat Andraž
Published: October 2019

When creating a simulation model to assess the performance of buildings, there is usually a lack of feedback information. Only in the case of measurements of a real building is a direct comparison of the measured values and simulated results possible. Parameter data related to users’ behavior or other events can also be obtained. Their evaluated frequency, magnitude and duration, along with boundary conditions, are crucial for the results. It is clear that none of them can be predicted very accurately. Most of them, however, are needed for computer modeling. In this paper we analyzed the well-defined TRNSYS simulation model of offices equipped with radiant ceiling panels for heating and cooling. The model was based on real case offices and was validated based on measurements for 1 year. The analysis included simulations in order to define what effect the parameters related mainly to users have on the energy use and the indoor air temperatures. The study confirmed that specific human activities influence the annual energy use to a relatively small degree and that their effects often counteract. It also confirmed the even more important fact that although small, these activities can influence the thermal comfort of users. It is believed that despite the fact that this research was based on an analysis of offices equipped with radiant ceiling panels, most of the results could be applied generally.
Multi-Sensor Face Registration Based on Global and Local Structures
Authors: Li Wei , Dong Mingli , Lu Naiguang , Lou Xiaoping , Zhou Wanyong
Published: October 2019

The work reported in this paper aims at utilizing the global geometrical relationship and local shape feature to register multi-spectral images for fusion-based face recognition. We first propose a multi-spectral face images registration method based on both global and local structures of feature point sets. In order to combine the global geometrical relationship and local shape feature in a new Student’s t Mixture probabilistic model framework. On the one hand, we use inner-distance shape context as the local shape descriptors of feature point sets. On the other hand, we formulate the feature point sets registration of the multi-spectral face images as the Student’s t Mixture probabilistic model estimation, and local shape descriptors are used to replace the mixing proportions of the prior Student’s t Mixture Model. Furthermore, in order to improve the anti-interference performance of face recognition techniques, a guided filtering and gradient preserving image fusion strategy is used to fuse the registered multi-spectral face image. It can make the multi-spectral fusion image hold more apparent details of the visible image and thermal radiation information of the infrared image. Subjective and objective registration experiments are conducted with manual selected landmarks and real multi-spectral face images. The qualitative and quantitative comparisons with the state-of-the-art methods demonstrate the accuracy and robustness of our proposed method in solving the multi-spectral face image registration problem.
Characteristics of Arsenic Leached from Sediments: Agricultural Implications of Abandoned Mines
Authors: Hwang Soonho , Her Younggu , Jun Sang Min , Song Jung-Hun , Lee Goontaek , Kang Moonseong
Published: October 2019

Heavy metals, including arsenic from abandoned mines, are easily transported with sediment and deposited in waterbodies such as reservoirs and lakes, creating critical water quality issues when they are released. Understanding the leaching of heavy metals is necessary for developing efficient water quality improvement plans. This study investigated how arsenic leaches from different soil and sediment types and responds to hydrologic conditions to identify areas susceptible to arsenic contamination. In this study, batch- and column-leaching tests and sequential extraction procedures were used to examine arsenic leaching processes in detail. The results showed that most arsenic-loaded sediments accumulated in the vicinity of a reservoir inlet, and arsenic in reservoir beds have a higher leaching potential than those from agricultural land and stream beds. Arsenic deposited at the bottom of reservoirs had higher mobility than that in the other soils and sediments, and arsenic leaching was closely associated with the acidity of water. In addition, arsenic leaching was found to be responsive to seasons (wet or dry) as its mobilization is controlled by organic compounds that vary over time. The results suggested that temporal variations in the hydrochemical composition of reservoir water should be considered when defining a management plan for reservoir water quality.
Temporal Analysis of OMI-Observed Tropospheric NO2 Columns over East Asia during 2006–2015
Authors: Han Kyung M.
Published: October 2019

The study analyzed temporal variations of Ozone Monitoring Instrument (OMI)-observed NO2 columns, interregional correlation, and comparison between NO2 columns and NOx emissions during the period from 2006 to 2015. Regarding the trend of the NO2 columns, the linear lines were classified into four groups: (1) ‘upward and downward’ over six defined geographic regions in central-east Asia; (2) ‘downward’ over Guangzhou, Japan, and Taiwan; (3) ‘stagnant’ over South Korea; and (4) ‘upward’ over North Korea, Mongolia, Qinghai, and Northwestern Pacific ocean. In particular, the levels of NO2 columns in 2015 returned to those in 2006 over most of the polluted regions in China. Quantitatively, their relative changes in 2015 compared to 2006 were approximately 10%. From the interregional correlation analysis, it was found that unlike positive relationships between the polluted areas, the different variations of monthly NO2 columns led to negative relationships in Mongolia and Qinghai. Regarding the comparison between NO2 columns and NOx emission, the NOx emissions from the Copernicus Atmosphere Monitoring Service (CAMS) and Clean Air Policy Support System (CAPSS) inventories did not follow the year-to-year variations of NO2 columns over the polluted regions. In addition, the weekly effect was only clearly shown in South Korea, Japan, and Taiwan, indicating that the amounts of NOx emissions are significantly contributed to by the transportation sector.
Comparing Annoyance Potency Assessments for Odors from Different Livestock Animals
Authors: Moshammer Hanns , Oettl Dietmar , Mandl Michael , Kropsch Michael , Weitensfelder Lisbeth
Published: October 2019

(1) Background: When it comes to estimating the annoyance potency of odors, European countries relate to different guidelines. In a previous study we compared complaint rates for different agricultural odors, but due to different guidelines, the results we obtained are hard to generalize. (2) Methods: We compare our findings on complaint rates to Dutch and German findings on annoyance rates, using diverse regression models. We also discuss whether the use of the polarity profile for hedonic odor quality could improve annoyance potency assessment. This is demonstrated by comparing the graphical profiles of two different odor types (swine and cattle). (3) Results: Official complaint rates are comparable to a percentage of annoyed residents. Confounder variables such as personal variables do not greatly contribute to annoyance. However, individual emission sites also showed an important influence on complaints and hence on annoyance. Considering the hedonic quality of odors via the polarity profile method for improving an annoyance potency assessment cannot be recommended when using the given state of the method. This is particularly true when it comes to the rating of specific odors, as the method then seems to lack reliability. (4) Conclusions: Where data on annoyance rates are lacking, complaint data could be used instead.
A Comprehensive Survey on Parallel Submanifolds in Riemannian and Pseudo-Riemannian Manifolds
Authors: Chen Bang-Yen
Published: October 2019

A submanifold of a Riemannian manifold is called a parallel submanifold if its second fundamental form is parallel with respect to the van der Waerden–Bortolotti connection. From submanifold point of view, parallel submanifolds are the simplest Riemannian submanifolds next to totally geodesic ones. Parallel submanifolds form an important class of Riemannian submanifolds since extrinsic invariants of a parallel submanifold do not vary from point to point. In this paper, we provide a comprehensive survey on this important class of submanifolds.
Mechanism of Action and Interactions between Thyroid Peroxidase and Lipoxygenase Inhibitors Derived from Plant Sources
Authors: Habza-Kowalska Ewa , Gawlik-Dziki Urszula , Dziki Dariusz
Published: October 2019

This study focused on the effect of kaempferol, catechin, apigenin, sinapinic acid, and extracts from plants (i.e., parsley, cumin, mustard, green tea, and green coffee) on thyroid peroxidase (TPO) and lipoxygenase (LOX) activity, antiradical potential, as well as the result of interactions among them. Catechin, sinapinic acid, and kaempferol acted as a competitive TPO inhibitors, while apigenin demonstrated an uncompetitive mode of inhibitory action. Ethanol extracts from all plants acted as competitive TPO inhibitors, while, after in vitro digestion, TPO activation was found especially in the case of mustard (24%) and cumin (19.85%). Most importantly, TPO activators acted synergistically. The TPO effectors acted as LOX inhibitors. The most effective were potentially bioaccessible compounds from green tea and green coffee (IC50 = 29.73 mg DW/mL and 30.43 mg DW/mL, respectively). The highest free radical scavenging ability was determined for catechin and sinapinic acid (IC50 = 78.37 µg/mL and 84.33 µg/mL, respectively) and potentially bioaccessible compounds from mustard (0.42 mg DW/mL) and green coffee (0.87 mg DW/mL). Green coffee, green tea, cumin, and mustard contain potentially bioaccessible TPO activators that also act as effective LOX inhibitors, which indicate their potentially health-promoting effects for people suffering from Hashimoto’s disease.
Cell Fate Control by Translation: mRNA Translation Initiation as a Therapeutic Target for Cancer Development and Stem Cell Fate Control
Authors: Kim Hyun-Jung
Published: October 2019

Translation of mRNA is an important process that controls cell behavior and gene regulation because proteins are the functional molecules that determine cell types and function. Cancer develops as a result of genetic mutations, which lead to the production of abnormal proteins and the dysregulation of translation, which in turn, leads to aberrant protein synthesis. In addition, the machinery that is involved in protein synthesis plays critical roles in stem cell fate determination. In the current review, recent advances in the understanding of translational control, especially translational initiation in cancer development and stem cell fate control, are described. Therapeutic targets of mRNA translation such as eIF4E, 4EBP, and eIF2, for cancer treatment or stem cell fate regulation are reviewed. Upstream signaling pathways that regulate and affect translation initiation were introduced. It is important to regulate the expression of protein for normal cell behavior and development. mRNA translation initiation is a key step to regulate protein synthesis, therefore, identifying and targeting molecules that are critical for protein synthesis is necessary and beneficial to develop cancer therapeutics and stem cells fate regulation.
Carbon Emissions of Hotels: The Case of the Sri Lankan Hotel Industry
Authors: Abeydeera Lebunu Hewage Udara Willhelm , Karunasena Gayani
Published: October 2019

The need to mitigate climate change has become a major global concern, and greenhouse gas emissions are a major cause of global climate change. Therefore, the need to curb greenhouse gas emissions has been well recognized by global researchers, policymakers and academics. Carbon emissions of hotel operations have seized the attention of global researchers. However, carbon emissions of the hotels in developing countries remain to be a less explored domain. Therefore, carbon emissions of Sri Lankan hotels were explored using a case study approach. Five hotels in the Colombo suburb were explored, which revealed that each hotel released more than 7000 tons of carbon annually. Results further indicated the use of purchased electricity as the dominant source of carbon emissions. Emissions caused by transport activities were not included in the calculations due to the unavailability of data. Recommendations were made to overcome the issues identified during data collection as well as to reduce the carbon emissions from hotel operations. Wider adoption of the methodology used in this research will benefit the hotels to keep track of the carbon emissions using a systematic approach.
Radiomics Model Based on Non-Contrast CT Shows No Predictive Power for Complete Pathological Response in Locally Advanced Rectal Cancer
Authors: Hamerla Gordian , Meyer Hans-Jonas , Hambsch Peter , Wolf Ulrich , Kuhnt Thomas , Hoffmann Karl-Titus , Surov Alexey
Published: October 2019

(1) Background: About 15% of the patients undergoing neoadjuvant chemoradiation for locally advanced rectal cancer exhibit pathological complete response (pCR). The surgical approach is associated with major risks as well as a potential negative impact on quality of life and has been questioned in the past. Still, there is no evidence of a reliable clinical or radiological surrogate marker for pCR. This study aims to replicate previously reported response predictions on the basis of non-contrast CT scans on an independent patient cohort. (2) Methods: A total of 169 consecutive patients (126 males, 43 females) that underwent neoadjuvant chemoradiation and consecutive total mesorectal excision were included. The solid tumors were segmented on CT scans acquired on the same scanner for treatment planning. To quantify intratumoral 3D spatial heterogeneity, 1819 radiomics parameters were derived per case. Feature selection and algorithmic modeling were performed to classify pCR vs. non-pCR cases. A random forest model was trained on the dataset using 4-fold cross-validation. (3) Results: The model achieved an accuracy of 87%, higher than previously reported. Correction for the imbalanced distribution of pCR and non-PCR cases (13% and 87% respectively) was applied, yielding a balanced accuracy score of 0.5%. An additional experiment to classify a computer-generated random data sample using the same model led to comparable results. (4) Conclusions: There is no evidence of added value of a radiomics model based on on-contrast CT scans for prediction of pCR in rectal cancer. The imbalance of the target variable could be identified as a key issue, leading to a biased model and optimistic predictions.
Targeting STAT3 in Cancer with Nucleotide Therapeutics
Authors: K. Lau Yue-Ting , Ramaiyer Malini , E. Johnson Daniel , R. Grandis Jennifer
Published: October 2019

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in promoting the proliferation and survival of tumor cells. As a ubiquitously-expressed transcription factor, STAT3 has commonly been considered an “undruggable” target for therapy; thus, much research has focused on targeting upstream pathways to reduce the expression or phosphorylation/activation of STAT3 in tumor cells. Recently, however, novel approaches have been developed to directly inhibit STAT3 in human cancers, in the hope of reducing the survival and proliferation of tumor cells. Several of these agents are nucleic acid-based, including the antisense molecule AZD9150, CpG-coupled STAT3 siRNA, G-quartet oligodeoxynucleotides (GQ-ODNs), and STAT3 decoys. While the AZD9150 and CpG-STAT3 siRNA interfere with STAT3 expression, STAT3 decoys and GQ-ODNs target constitutively activated STAT3 and modulate its ability to bind to target genes. Both STAT3 decoy and AZD9150 have advanced to clinical testing in humans. Here we will review the current understanding of the structures, mechanisms, and potential clinical utilities of the nucleic acid-based STAT3 inhibitors.
NEDD9 Inhibition by miR-25-5p Activation Is Critically Involved in Co-Treatment of Melatonin- and Pterostilbene-Induced Apoptosis in Colorectal Cancer Cells
Authors: Jung Ji Hoon , Shin Eun Ah , Kim Ju-Ha , Sim Deok Yong , Lee Hyemin , Park Ji Eon , Lee Hyo-Jung , Kim Sung-Hoon
Published: October 2019

The underlying interaction between melatonin (MLT) and daily fruit intake still remains unclear to date, despite multibiological effects of MLT. Herein, the apoptotic mechanism by co-treatment of MLT and pterostilbene (Ptero) contained mainly in grape and blueberries was elucidated in colorectal cancers (CRCs). MLT and Ptero co-treatment (MLT+Ptero) showed synergistic cytotoxicity compared with MLT or Ptero alone, reduced the number of colonies and Ki67 expression, and also increased terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL) positive cells and reactive oxygen species (ROS) production in CRCs. Consistently, MLT+Ptero cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP), activated sex-determining region Y-Box10 (SOX10), and also attenuated the expression of Bcl-xL, neural precursor cell expressed developmentally downregulated protein 9 (NEDD9), and SOX9 in CRCs. Additionally, MLT+Ptero induced differentially expressed microRNAs (upregulation: miR-25-5p, miR-542-5p, miR-711, miR-4725-3p, and miR-4484; downregulation: miR-4504, miR-668-3p, miR-3121-5p, miR-195-3p, and miR-5194) in HT29 cells. Consistently, MLT +Ptero upregulated miR-25-5p at mRNA level and conversely NEDD9 overexpression or miR-25-5p inhibitor reversed the ability of MLT+Ptero to increase cytotoxicity, suppress colony formation, and cleave PARP in CRCs. Furthermore, immunofluorescence confirmed miR-25-5p inhibitor reversed the reduced fluorescence of NEDD9 and increased SOX10 by MLT+Ptero in HT29 cells. Taken together, our findings provided evidence that MLT+Ptero enhances apoptosis via miR-25-5p mediated NEDD9 inhibition in colon cancer cells as a potent strategy for colorectal cancer therapy.
Dual PDK1/Aurora Kinase A Inhibitors Reduce Pancreatic Cancer Cell Proliferation and Colony Formation
Authors: Casari Ilaria , Domenichini Alice , Sestito Simona , Capone Emily , Sala Gianluca , Rapposelli Simona , Falasca Marco
Published: October 2019

Deregulation of different intracellular signaling pathways is a common feature in cancer. Numerous studies indicate that persistent activation of the phosphoinositide 3-kinase (PI3K) pathway is often observed in cancer cells. 3-phosphoinositide dependent protein kinase-1 (PDK1), a transducer protein that functions downstream of PI3K, is responsible for the regulation of cell proliferation and migration and it also has been found to play a key role in different cancers, pancreatic and breast cancer amongst others. As PI3K is being described to be aberrantly expressed in several cancer types, designing inhibitors targeting various downstream molecules of PI3K has been the focus of anticancer agent development for a long time. In particular, dual inhibitory drugs targeting key signaling molecules in the PI3K pathway have attracted the attention of scientists. Several drugs have progressed to clinical trials, with limited success due to toxicity and bioavailability concerns. Very few anticancer drugs targeting the PI3K pathway have been approved for clinical use and their efficacy is particularly limited towards certain tumors such as pancreatic cancer. Here, we tested two drugs displaying dual inhibitory activity towards PDK1 and Aurora kinase A in a panel of pancreatic cancer cell lines and in two in vivo models of pancreatic cancer. Our data show that both inhibitors are able to impair cell proliferation and clonogenic potential in pancreatic cancer cells. However, the limited activity of both compounds in vivo indicates that further optimization of the pharmacokinetics properties is required.
Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes
Authors: Saxena Reshu , Klochkova Alena , Murray Mary Grace , Kabir Mohammad Faujul , Samad Safiyah , Beccari Tyler , Gang Julie , Patel Kishan , Hamilton Kathryn E. , Whelan Kelly A.
Published: October 2019

Esophageal cancer is among the most aggressive forms of human malignancy with five-year survival rates of <20%. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. While alterations in autophagy have been associated with carcinogenesis across tissues, cell type- and context-dependent roles for autophagy have been reported. Herein, we review the current knowledge related to autophagy in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the two most common subtypes of esophageal malignancy. We explore roles for autophagy in the development and progression of ESCC and EAC. We then continue to discuss molecular markers of autophagy as they relate to esophageal patient outcomes. Finally, we summarize current literature examining roles for autophagy in ESCC and EAC response to therapy and discuss considerations for the potential use of autophagy inhibitors as experimental therapeutics that may improve patient outcomes in esophageal cancer.
Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease
Authors: Reyes-Gordillo Karina , Shah Ruchi , Arellanes-Robledo Jaime , Cheng Ying , Ibrahim Joseph , Tuma Pamela L.
Published: October 2019

Akt kinase isoforms (Akt1, Akt2, and Akt3) have generally been thought to play overlapping roles in phosphoinositide 3-kinase (PI3K)-mediated-signaling. However, recent studies have suggested that they display isoform-specific roles in muscle and fat. To determine whether such isoform-specificity is observed with respect to alcoholic liver disease (ALD) progression, we examined the role of Akt1, Akt2, and Akt3 in hepatic inflammation, and pro-fibrogenic proliferation and migration using Kupffer cells, hepatic stellate cells (HSC), and hepatocytes in an ethanol and lipopolysaccharide (LPS)-induced two-hit model in vitro and in vivo. We determined that siRNA-directed silencing of Akt2, but not Akt1, significantly suppressed cell inflammatory markers in HSC and Kupffer cells. Although both Akt1 and Akt2 inhibited cell proliferation in HSC, only Akt2 inhibited cell migration. Both Akt1 and Akt2, but not Akt3, inhibited fibrogenesis in hepatocytes and HSC. In addition, our in vivo results show that administration of chronic ethanol, binge ethanol and LPS (EBL) in wild-type C57BL/6 mice activated all three Akt isoforms with concomitant increases in activated forms of phosphoinositide dependent kinase-1 (PDK1), mammalian target-of-rapamycin complex 2 (mTORC2), and PI3K, resulting in upregulation in expression of inflammatory, proliferative, and fibrogenic genes. Moreover, pharmacological blocking of Akt2, but not Akt1, inhibited EBL-induced inflammation while blocking of both Akt1 and Akt2 inhibited pro-fibrogenic marker expression and progression of fibrosis. Our findings indicate that Akt isoforms play unique roles in inflammation, cell proliferation, migration, and fibrogenesis during EBL-induced liver injury. Thus, close attention must be paid when targeting all Akt isoforms as a therapeutic intervention.
The ZIKA Virus Delays Cell Death Through the Anti-Apoptotic Bcl-2 Family Proteins
Authors: Turpin Jonathan , Frumence Etienne , Desprès Philippe , Viranaicken Wildriss , Krejbich-Trotot Pascale
Published: October 2019

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.
Feeding Entrainment of the Zebrafish Circadian Clock Is Regulated by the Glucocorticoid Receptor
Authors: Morbiato Elisa , Frigato Elena , Dinarello Alberto , Maradonna Francesca , Facchinello Nicola , Argenton Francesco , Carnevali Oliana , Dalla Valle Luisa , Bertolucci Cristiano
Published: October 2019

Glucocorticoids (GCs) are steroid hormones mainly acting as key regulators of body homeostasis and stress responses. Their activities are primarily based on the binding to the GC receptor (GR), a member of the nuclear receptor family, that regulates tissue-specific sets of genes. GCs secretion follows a circadian rhythmicity with a peak linked to the animal’s activity phase. In mammals, GCs are also implicated in feeding entrainment mechanisms as internal zeitgeber. Here, we investigated, by means of behavioural and molecular approaches, the circadian clock and its regulation by light and food in wild-type (WT) and null glucocorticoid receptor (gr−/−) zebrafish larvae, juveniles and adults. In both WT and gr−/− larvae and adults, behavioural activity and clock gene expression were entrained to the light–dark (LD) cycle and rhythmic in constant conditions. Differences in the pattern of clock genes’ expression indicated a modulatory role of GCs. A significant role of Gr was detected in the feeding entrainment which was absent or markedly dampened in mutants. Furthermore, the expression of two clock-regulated genes involved in glucidic and lipidic metabolism was altered, highlighting the participation of GCs in metabolic processes also in fish. Taken together, our results confirmed the role of GC-mediated Gr signaling in the feeding entrainment in a non-mammalian species, the zebrafish.
Glycobiology of Human Fungal Pathogens: New Avenues for Drug Development
Authors: Lee Danielle J. , O’Donnell Holly , Routier Françoise H. , Tiralongo Joe , Haselhorst Thomas
Published: October 2019

Invasive fungal infections (IFI) are an increasing threat to the developing world, with fungal spores being ubiquitous and inhaled every day. Some fungal species are commensal organisms that are part of the normal human microbiota, and, as such, do not pose a threat to the immune system. However, when the natural balance of this association is disturbed or the host’s immune system is compromised, these fungal pathogens overtake the organism, and cause IFI. To understand the invasiveness of these pathogens and to address the growing problem of IFI, it is essential to identify the cellular processes of the invading organism and their virulence. In this review, we will discuss the prevalence and current options available to treat IFI, including recent reports of drug resistance. Nevertheless, the main focus of this review is to describe the glycobiology of human fungal pathogens and how various components of the fungal cell wall, particularly cell wall polysaccharides and glycoconjugates, are involved in fungal pathogenicity, their biosynthesis and how they can be potentially exploited to develop novel antifungal treatment options. We will specifically describe the nucleotide sugar transporters (NSTs) that are important in fungal survival and suggest that the inhibition of fungal NSTs may potentially be useful to prevent the establishment of fungal infections.
A Matricryptic Conformation of the Integrin-Binding Domain of Fibronectin Regulates Platelet-Derived Growth Factor-Induced Intracellular Calcium Release
Authors: Farrar Christopher S. , Rouin Geoffrey T. , Miller Benjamin L. , Raeman Carol H. , Mooney Nancie A. , Hocking Denise C.
Published: October 2019

Platelet-derived growth factor (PDGF) signaling is dysregulated in a wide variety of diseases, making PDGF an attractive therapeutic target. However, PDGF also affects numerous signaling cascades essential for tissue homeostasis, limiting the development of PDGF-based therapies that lack adverse side-effects. Recent studies showed that fibroblast-mediated assembly of extracellular matrix (ECM) fibronectin fibrils attenuates PDGF-induced intracellular calcium release by selectively inhibiting phosphoinositol 3-kinase (PI3K) activation while leaving other PDGF-mediated signaling cascades intact. In the present study, a series of recombinant fibronectin-derived fusion proteins were used to localize the sequences in fibronectin that are responsible for this inhibition. Results demonstrate that attenuation of PDGF-induced intracellular calcium release by the fibronectin matrix mimetic, FNIII1H,8-10 requires α5β1 integrin ligation, but is not dependent upon the matricryptic, heparin-binding site of FNIII1. Intact cell-binding fibronectin fragments were also unable to attenuate PDGF-induced intracellular calcium release. In contrast, a novel integrin-binding fragment that adopts an extended and aligned conformational state, inhibited both PI3K activation and intracellular calcium release in response to PDGF. Taken together, these studies provide evidence that attenuation of PDGF-induced intracellular calcium release by fibronectin is mediated by a novel conformation of the α5β1 integrin-binding, FNIII9-10 modules, that is expressed by fibrillar fibronectin.
Metabolic, Physiological, and Transcriptomics Analysis of Batch Cultures of the Green Microalga Chlamydomonas Grown on Different Acetate Concentrations
Authors: Bogaert Kenny A. , Perez Emilie , Rumin Judith , Giltay Axel , Carone Michele , Coosemans Nadine , Radoux Michele , Eppe Gauthier , Levine Raphael D. , Remacle Francoise , Remacle Claire
Published: October 2019

Acetate can be efficiently metabolized by the green microalga Chlamydomonas reinhardtii. The regular concentration is 17 mM, although higher concentrations are reported to increase starch and fatty acid content. To understand the responses to higher acetate concentrations, Chlamydomonas cells were cultivated in batch mode in the light at 17, 31, 44, and 57 mM acetate. Metabolic analyses show that cells grown at 57 mM acetate possess increased contents of all components analyzed (starch, chlorophylls, fatty acids, and proteins), with a three-fold increased volumetric biomass yield compared to cells cultivated at 17 mM acetate at the entry of stationary phase. Physiological analyses highlight the importance of photosynthesis for the low-acetate and exponential-phase samples. The stationary phase is reached when acetate is depleted, except for the cells grown at 57 mM acetate, which still divide until ammonium exhaustion. Surprisal analysis of the transcriptomics data supports the biological significance of our experiments. This allows the establishment of a model for acetate assimilation, its transcriptional regulation and the identification of candidates for genetic engineering of this metabolic pathway. Altogether, our analyses suggest that growing at high-acetate concentrations could increase biomass productivities in low-light and CO2-limiting air-bubbled medium for biotechnology.
Chemical and Biological Roles of Zinc in a Porous Titanium Dioxide Layer Formed by Micro-Arc Oxidation
Authors: Shimabukuro Masaya , Tsutsumi Yusuke , Nozaki Kosuke , Chen Peng , Yamada Risa , Ashida Maki , Doi Hisashi , Nagai Akiko , Hanawa Takao
Published: October 2019

This study investigated the time transient effect of zinc (Zn) in the porous titanium dioxide formed by micro-arc oxidation (MAO) treatment routinely performed for Zn-containing electrolytes. The aim of our analysis was to understand the changes in both the chemical and biological properties of Zn in physiological saline. The morphology of the Zn-incorporated MAO surface did not change, and a small amount of Zn ions were released at early stages of incubation in saline. We observed a decrease in Zn concentration in the oxide layer because its release and chemical state (Zn2+ compound to ZnO) changed over time during incubation in saline. In addition, the antibacterial property of the Zn-incorporated MAO surface developed at late periods after the incubation process over a course of 28 days. Furthermore, osteogenic cells were able to proliferate and were calcified on the specimens with Zn. The changes related to Zn in saline had non-toxic effects on the osteogenic cells. In conclusion, the time transient effect of Zn in a porous titanium dioxide layer was beneficial to realize dual functions, namely the antibacterial property and osteogenic cell compatibility. Our study suggests the importance of the chemical state changes of Zn to control its chemical and biological properties.
A Novel Basalt Flake Epoxy Resin Coating Modified by Carbon Nanotubes
Authors: Luo Lida , Wang Qihui , Ma Qian , Wang Qingwei , Liu Jin , Ding Linfeng , Jiang Weizhong
Published: October 2019

As a new type of anticorrosive material, basalt flakes (BFs) have been widely used in the marine industry due to their good acid and alkali corrosion resistance and dispersion stability. In this work, the effect of carbon nanotubes (CNTs) addition on properties improvement of basalt flake epoxy resin (CNT-BF/EP) coating was studied. Firstly, 0–0.7 wt.% acidified CNTs was used to modify the surface of the BFs and the CNT-BF/EP coating was successfully prepared. Experimental results showed that the performance of the interfacial compatibility, the tensile strength, and acid and alkali resistance of the CNT-BF/EP coating were significantly improved with the addition of the CNTs. Particularly, the CNT-BF/EP coating achieved the best comprehensive properties (tensile strength increased to 30.3 MPa, surface weight loss rate of only 1.0 wt.% in the acid environment for 480 h, and water absorption of only 1.1 wt.% after 480 h) when the CNTs addition reached 0.5 wt.%. This work suggests a feasible way to enhance the mechanical properties and chemical durability of the basalt flakes coating.
Synthesis of an Adduct-Type Organic Ionic Crystal with Solid-State Ionic Conductivity from A Thiocyanate-Based Ionic Liquid and B(C6F5)3
Authors: Oki Yui , Moriya Makoto
Published: October 2019

We synthesized the novel adduct-type organic ionic crystal [C3mim][SCN·B(C6F5)3] (1) by the reaction of 1–methyl–3–propylimidazolium thiocyanate ([C3mim][SCN]), which is a room temperature ionic liquid, and B(C6F5)3, a bulky Lewis acid. The formation of a coordinative B–N bond between the SCN anion and the B(C6F5)3 in 1 was revealed by single-crystal X-ray diffractometry. We showed that 1 displays ionic conductivity in the crystalline state and that doping 1 with sodium thiocyanate and B(C6F5)3 results in a dramatic increase in ionic conductivity compared to that of 1.
Crystal Structure, Raman Spectroscopy and Dielectric Properties of New Semiorganic Crystals Based on 2-Methylbenzimidazole
Authors: Balashova E. V. , Svinarev F. B. , Zolotarev A. A. , Levin A. A. , Brunkov P. N. , Davydov V. Yu. , Smirnov A. N. , Redkov A. V. , Pankova G. A. , Krichevtsov B. B.
Published: October 2019

New single crystals, based on 2-methylbenzimidazole (MBI), of MBI-phosphite (C16H24N4O7P2), MBI-phosphate-1 (C16H24N4O9P2), and MBI-phosphate-2 (C8H16N2O9P2) were obtained by slow evaporation method from a mixture of alcohol solution of MBI crystals and water solution of phosphorous or phosphoric acids. Crystal structures and chemical compositions were determined by single crystal X-ray diffraction (XRD) analysis and confirmed by XRD of powders and elemental analysis. Raman spectroscopy of new crystals evidences the presence in crystals of MBI-, H3PO3-, or H3PO4- and water molecules. Dielectric properties of crystals reveal strong increase and low frequency dispersion of dielectric constant and losses at heating, indicating the appearance of proton conductivity. At low temperatures in MBI-phosphate-2, an increase of dielectric constant analogous to quantum paraelectric state is observed.
Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics
Authors: Evangelista Erin B. , Kwee Sandi A. , Sato Miles M. , Wang Lu , Rettenmeier Christoph , Xie Guoxiang , Jia Wei , Wong Linda L.
Published: October 2019

Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue.