bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Characterization of Resistance to Powdery Mildew of VvTIFY9 from Vitis vinifera
Authors: Yu Yihe , Wan Yutong , Jiao Zeling , Bian Lu , Yu Keke , Zhang Guohai , Guo Dalong
Published: September 2019

Powdery mildew is a disease caused by fungal pathogens that harms grape leaves and fruits. The TIFY gene family is a plant-specific super-family involved in the process of plants’ development and their biotic and abiotic stress responses. This study aimed to learn the function of the VvTIFY9 gene to investigate molecular mechanisms of grape resistance to powdery mildew. A VvTIFY9 protein encoding a conserved motif (TIF[F/Y]XG) was characterized in grape (Vitis vinifera). Sequence analysis confirmed that VvTIFY9 contained this conserved motif (TIF[F/Y]XG). Quantitative PCR analysis of VvTIFY9 in various grape tissues demonstrated that the expression of VvTIFY9 was higher in grape leaves. VvTIFY9 was induced by salicylic acid (SA) and methyl jasmonate (MeJA) and it also quickly responded to infection with Erysiphe necator in grape. Analysis of the subcellular localization and transcriptional activation activity of VvTIFY9 showed that VvTIFY9 located to the nucleus and had transcriptional activity. Arabidopsis that overexpressed VvTIFY9 were more resistant to Golovinomyces cichoracearum, and quantitative PCR revealed that two defense-related genes, AtPR1 and AtPDF1.2, were up-regulated in the overexpressing lines. These results indicate that VvTIFY9 is intimately involved in SA-mediated resistance to grape powdery mildew. This study provides the basis for exploring the molecular mechanism of grape resistance to disease resistance and candidate genes for transgenic disease resistance breeding of grape plants.
TSLP Exacerbates Septic Inflammation via Murine Double Minute 2 (MDM2) Signaling Pathway
Authors: Han Na-Ra , Moon Phil-Dong , Kim Hyung-Min , Jeong Hyun-Ja
Published: September 2019

Thymic stromal lymphopoietin (TSLP) is crucial for Th2-mediated inflammation. Sepsis is a serious systemic inflammatory reaction with organ dysfunction by infection. However, the function of TSLP during sepsis is poorly understood. Thus, we investigated a role and regulatory mechanism of TSLP during sepsis. Sepsis was induced by lipopolysaccharides (LPS) or Escherichia coli DH5α injection in mice. TSLP levels were measured in human subjects, mice, and macrophages. TSLP deficiency or murine double minute 2 (MDM2) deficiency was induced using siRNA or an MDM2 inhibitor, nutlin-3a. We found that TSLP levels were elevated in serum of patients and mice with sepsis. TSLP deficiency lowered liver damage and inflammatory cytokine levels in mice with sepsis. TSLP was produced by the MDM2/NF-κB signaling pathway in LPS-stimulated macrophages. TSLP downregulation by an MDM2 inhibitor, nutlin-3a, alleviated clinical symptoms and septic inflammatory responses. Pharmacological inhibition of TSLP level by cisplatin reduced the septic inflammatory responses. Altogether, the present results show that TSLP exacerbates septic inflammation via the MDM2 signaling pathway, suggesting that TSLP may be a potential target for the treatment of sepsis.
A Prognostic Model for the Outcome of Nobel Biocare Dental Implants with Peri-Implant Disease after One Year
Authors: de Araújo Nobre Miguel , Salvado Francisco , Nogueira Paulo , Rocha Evangelista , Ilg Peter , Maló Paulo
Published: September 2019

Background: This investigation, based on a 1-year retrospective cohort study, aimed to estimate and validate a prognostic model for ailing and failing implants due to peri-implant disease. Methods: A total of 240 patients (male: 97; female: 143; average age of 57.3 years) with at least one ailing or failing implant were included: 120 patients for model derivation and 120 patients for model validation. The primary outcome measure was the implant status: success, defined as the arrest of the disease, or failure defined as implant extraction, prevalence or re-incidence of peri-implant disease). Potential prognostic risk indicators were collected at the baseline evaluation. The relative risk (RR) was estimated for the predictors through logistic regression and the c-statistic (95% confidence interval) was calculated for both derivation and validation sets. The significance level was set at 5%. Results: The risk model retrieved the prognostic factors age (RR = 1.04), history of Periodontitis (RR = 3.13), severe peri-implant disease status (RR = 3.26), implant length (RR = 3.52), early disease development (RR = 3.99), with good discrimination in both the derivation set (0.763 [0.679; 0.847]) and validation set (0.709 [0.616; 0.803]). Conclusions: A prognostic risk model for estimating the outcome of implants with peri-implant disease is available, with a good performance considering the c-statistic evaluation.
Comparison of Percutaneous Endoscopic Surgery and Traditional Anterior Open Surgery for Treating Lumbar Infectious Spondylitis
Authors: Fu Tsai-Sheng , Wang Ying-Chih , Lin Tung-Yi , Chang Chia-Wei , Wong Chak-Bor , Su Juin-Yih
Published: September 2019

Minimally invasive surgery is becoming popular for treating spinal disorders. The advantages of percutaneous endoscopic debridement and drainage (PEDD) for infectious spondylitis include direct observation of the lesion, direct pus drainage, and earlier pain relief. We retrospectively reviewed 37 patients who underwent PEDD and 31 who underwent traditional anterior open debridement and interbody fusion with bone grafting from 2004 to 2012. The causative organisms were isolated from 30 patients (81.1%) following PEDD, and from 25 patients (80.6%) following open surgery (p = 0.48). Staphylococcus aureus was the most common pathogen (38.2%). In the PEDD group, blood loss (<50 mL versus 585 ± 428 mL, p < 0.001) was significantly lesser and the duration of hospitalization (24.4 ± 12.5 days versus 31.5 ± 14.6 days, p = 0.03) was shorter than that in the open surgery group. Serologically, there were significantly faster C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) normalization rates in the PEDD group (p < 0.001, p = 0.009, respectively). In the two-year follow-up radiographs, 26 out of 30 (86.7%) open surgery patients showed bony fusions of the infected segments. On the contrary, sclerotic change of the destructive endplates was observed and the motion of infected spinal segments was still preserved in the PEDD group. There was no significant difference in the change of sagittal profile, including primary correction gain, correction loss, and actual correction gain/loss. PEDD is an effective alternative option and should be considered prior to traditional extensive spinal surgery—particularly for patients with early-stage spinal infection or serious complicated medical conditions.
Mitochondrial Structural Changes in the Pathogenesis of Diabetic Retinopathy
Authors: Roy Sayon , Kim Dongjoon , Sankaramoorthy Aravind
Published: September 2019

At the core of proper mitochondrial functionality is the maintenance of its structure and morphology. Physical changes in mitochondrial structure alter metabolic pathways inside mitochondria, affect mitochondrial turnover, disturb mitochondrial dynamics, and promote mitochondrial fragmentation, ultimately triggering apoptosis. In high glucose condition, increased mitochondrial fragmentation contributes to apoptotic death in retinal vascular and Müller cells. Although alterations in mitochondrial morphology have been detected in several diabetic tissues, it remains to be established in the vascular cells of the diabetic retina. From a mechanistic standpoint, our current work supports the notion that increased expression of fission genes and decreased expression of fusion genes are involved in promoting excessive mitochondrial fragmentation. While mechanistic insights are only beginning to reveal how high glucose alters mitochondrial morphology, the consequences are clearly seen as release of cytochrome c from fragmented mitochondria triggers apoptosis. Current findings raise the prospect of targeting excessive mitochondrial fragmentation as a potential therapeutic strategy for treatment of diabetic retinopathy. While biochemical and epigenetic changes have been reported to be associated with mitochondrial dysfunction, this review focuses on alterations in mitochondrial morphology, and their impact on mitochondrial function and pathogenesis of diabetic retinopathy.
Dynamics Simulation for Process Risk Evolution on the Bunker Operation of an LNG-fueled Vessel with Catastrophe Mathematical Models
Authors: Xuan Shaoyong , Hu Shenping , Li Zhuang , Li Wei , Li Boyin
Published: September 2019

Liquefied nature gas (LNG) is a green energy. LNG-fueled vessels are extremely complex engineering systems. In view of the inherent hazardous properties of LNG fuel, LNG fueling is not only an important part, but it is also full of high risks in the operation of LNG-fueled vessels (LNGFVs). Therefore, it is necessary to study the risk factors, and the intrinsic relationship among them between the LNG and the vessel, and to simulate the system dynamics in the process of LNGFV operation. During the process of fueling of LNGFV, at every moment the vessel interacts with the energy and information of the surrounding environment. First, the impact of the three interactions of the fueling operation process, ship factors, and environmental factors were analyzed on the risk of fueling operation, and a complete node system was proposed as to the complex system dynamics mode. Second, by analyzing the boundary conditions of the system, the relationship of factors was established via the tools of system dynamics (SD). Based on the catastrophe theory (CA), the dynamics model for the fueling of LNG is set up to study the system’s risk mutation phenomenon. Third, combined with the simulation results of the case analysis, the risk evolution mode of the LNGFV during the fueling process was obtained, and constructive opinions were put forward for improving the safe fueling of the LNGFV. Application examples show that formal description of risk emergence and transition is a prerequisite for the quantitative analysis of the risk evolution mode. In order to prevent accidents, the coupling synchronization of risk emergence should be weakened, and meanwhile risk control should be implemented.
Effect of Carbonation on Abrasion Resistance of Alkali-Activated Slag with Various Activators
Authors: Kim Hyeong-Ki , Song Keum-Il , Song Jin-Kyu , Jang Jeong Gook
Published: September 2019

The effect of carbonation on the abrasion resistance of alkali-activated slag (AAS) was investigated. Various activator sets were selected for synthesizing AAS specimens, and the compressive strength was measured before and after carbonation. The abrasion resistance of the specimens was measured in accordance with the ASTM C944 test method. The relationship between the mass loss caused by abrasion and compressive strength was analyzed to understand the effect of matrix strength on abrasion resistance. Test results showed that the decrease in compressive strength of AAS specimens by carbonation reduced their abrasion resistance. In addition, the abrasion resistance of AAS before and after carbonation was sensitively influenced by activator type. It can be concluded that additional caution is required when using AAS where abrasion may have occurred.
Difference Mappings Associated with Nonsymmetric Monotone Types of Fejér’s Inequality
Authors: Rostamian Delavar Mohsen , De La Sen Manuel
Published: September 2019

Two mappings L w and P w , in connection with Fejér’s inequality, are considered for the convex and nonsymmetric monotone functions. Some basic properties and results along with some refinements for Fejér’s inequality according to these new settings are obtained. As applications, some special means type inequalities are given.
Extending the Applicability of a Two-Step Chord-Type Method for Non-Differentiable Operators
Authors: Argyros Ioannis K. , Gupta Neha , Jaiswal J. P.
Published: September 2019

The semi-local convergence analysis of a well defined and efficient two-step Chord-type method in Banach spaces is presented in this study. The recurrence relation technique is used under some weak assumptions. The pertinency of the assumed method is extended for nonlinear non-differentiable operators. The convergence theorem is also established to show the existence and uniqueness of the approximate solution. A numerical illustration is quoted to certify the theoretical part which shows that earlier studies fail if the function is non-differentiable.
On a New Formula for Fibonacci’s Family m-step Numbers and Some Applications
Authors: Alfuraidan Monther Rashed , Joudah Ibrahim Nabeel
Published: September 2019

In this work, we obtain a new formula for Fibonacci’s family m-step sequences. We use our formula to find the nth term with less time complexity than the matrix multiplication method. Then, we extend our results for all linear homogeneous recurrence m-step relations with constant coefficients by using the last few terms of its corresponding Fibonacci’s family m-step sequence. As a computational number theory application, we develop a method to estimate the square roots.
Bathyptilones: Terpenoids from an Antarctic Sea Pen, Anthoptilum grandiflorum (Verrill, 1879)
Authors: Thomas Santana A.L. , Sanchez Anthony , Kee Younghoon , Wilson Nerida G. , Baker Bill J.
Published: September 2019

An Antarctic coral belonging to the order Pennatulacea, collected during the 2013 austral autumn by trawl from 662 to 944 m depth, has yielded three new briarane diterpenes, bathyptilone A-C (1–3) along with a trinorditerpene, enbepeanone A (4), which bears a new carbon skeleton. Structure elucidation was facilitated by one- and two-dimensional NMR spectroscopy, mass spectrometry and confirmed by X-ray crystallography. The three compounds were screened in four cancer cell lines. Bathyptilone A displayed selective nanomolar cytotoxicity against the neurogenic mammalian cell line Ntera-2.
Verruculosins A–B, New Oligophenalenone Dimers from the Soft Coral-Derived Fungus Talaromyces verruculosus
Authors: Wang Minghui , Yang Longhe , Feng Liubin , Hu Fan , Zhang Fang , Ren Jie , Qiu Yan , Wang Zhaokai
Published: September 2019

In an effort to discover new bioactive anti-tumor lead compounds, a specific tyrosine phosphatase CDC25B and an Erb family receptor EGFR were selected as drug screening targets. This work led to the investigation of the soft coral-derived fungus Talaromyces verruculosus and identification of two new oligophenalenone dimers, verruculosins A–B (1–2), along with three known analogues, bacillisporin F (3), duclauxin (4), and xenoclauxin (5). Compound 1 was the first structure of the oligophenalenone dimer possessing a unique octacyclic skeleton. The detailed structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic data, X-ray crystallography, optical rotation, Electronic Circular Dichroism (ECD) analysis, and nuclear magnetic resonance (NMR) calculations. Among which, compounds 1, 3, and 5 exhibited modest inhibitory activity against CDC25B with IC50 values of 0.38 ± 0.03, 0.40 ± 0.02, and 0.26 ± 0.06 µM, respectively.
Analytical Investigation of the Micro Groove Surface Topography by Micro-Milling
Authors: Zhang Jinfeng , Feng Chao , Wang Hao , Gong Yadong
Published: September 2019

Micro-milling is an emerging processing technology for machining micro- and high-precision three dimensional parts that require the use of various materials (with sizes ranging from tens of micrometers to a few millimeters) in the field of advanced manufacturing. Therefore, it can be applied to manufacture the micro parts, but new challenges are raised about parts with high surface quality. Herein, both surface formation and micro machined surface roughness models are studied, with the aim of solving complicated problems regarding the quality of surface finish when micro-milling metallic materials. From a theoretical point of view, the first model for surface formation processes considering the strain gradient plasticity theory was built in the area around the cutting edge, and the minimum uncut chip thickness equation was derived. The model accounts for the properties of the work material in tertiary and quaternary zones on the minimum chip thickness. A second model for micro machined surface roughness based on the relationship of kinematics between cutting process and cutter edge was also developed, which takes the influences of tool run out into account. Both proposed models were introduced to analyze the tendency of surface roughness for micro grooves. Both models were also used to justify experimental results. The results show that the developed surface roughness model could be useful in predicting both roughness parameters and trends as a function of cutting parameters.
Multi-Seam Coal Deposit Modeling via Principal Component Analysis & GIS
Authors: Louloudis Georgios , Roumpos Christos , Theofilogiannakos Konstantinos , Stathopoulos Nikolaos
Published: September 2019

Spatial modeling and evaluation is a critical step for planning the exploitation of mineral deposits. In this work, a methodology for the investigation of a multi-seam coal deposit spatial variability is proposed. The study area includes the Klidi (Florina, Greece) multi-seam lignite deposit which is suitable for surface mining. The analysis is based on the original data of 76 exploratory drill-holes in an area of 10 km2, in conjunction with the geological and geomorphological data of the deposit. The analytical methods include drill-hole data analysis and evaluation based on an appropriate algorithm, principal component analysis and geographic information techniques. The results proved to be very satisfactory for the explanation of the maximum variance of the initial data values as well as the identification of the deposit structure and the optimum planning of mine development. The proposed analysis can be also helpful for minimizing cost and optimizing efficiency of surface mining operations. Furthermore, the provided methods could be applied in other areas of geosciences, indicating the theoretical value as well as the important practical implications of the analysis.
Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression
Authors: Gabe Vika , Kacergius Tomas , Abu-Lafi Saleh , Zeidan Mouhammad , Abu-Farich Basheer , Austys Donatas , Masalha Mahmud , Rayan Anwar
Published: September 2019

The accumulation of biofilm by Streptococcus mutans bacteria on hard tooth tissues leads to dental caries, which remains one of the most prevalent oral diseases. Hence, the development of new antibiofilm agents is of critical importance. The current study reports the results from testing the effectiveness of octyl gallate (C8-OG) against: (1) S. mutans biofilm formation on solid surfaces (polystyrene, glass), (2) acidogenicity, (3) and the expression of biofilm-related genes. The amount of biofilm formed by S. mutans bacteria was evaluated using the colorimetric method and optical profilometry. The pH of the biofilm growth medium was measured with microelectrode. A quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the expression of genes encoding glucan binding protein B (gbpB), glucosyltransferases B, -C, -D (gtfB, -C, -D), and the F-ATPase β subunit of the F1 protein (atpD). The results show that C8-OG significantly diminished biofilm formation by exposed S. mutans on solid surfaces and suppressed acidogenicity in a dose-dependent manner, compared to unexposed bacteria (p < 0.05). The C8-OG concentration of 100.24 µM inhibited S. mutans biofilm development on solid surfaces by 100% and prevented a decrease in pH levels by 99%. In addition, the RT-qPCR data demonstrate that the biofilm-producing bacteria treated with C8-OG underwent a significant reduction in gene expression in the case of the four genes under study (gbpB, gtfC, gtfD, and atpD), and there was a slight decrease in expression of the gtfB gene. However, C8-OG treatments did not produce significant expression change compared to the control for the planktonic cells, although there was a significant increase for the atpD gene. Therefore, C8-OG might be a potent antibiofilm and/or anticaries agent for oral formulations that aim to reduce the prevalence of dental caries.
New Artificial Biomimetic Enzyme Analogues Based on Iron(II/III) Schiff Base Complexes: An Effect of (Benz)imidazole Organic Moieties on Phenoxazinone Synthase and DNA Recognition ‡
Authors: Bocian Aleksandra , Szymańska Martyna , Brykczyńska Daria , Kubicki Maciej , Wałęsa-Chorab Monika , Roviello Giovanni N. , Fik-Jaskółka Marta A. , Gorczyński Adam , Patroniak Violetta
Published: September 2019

Elucidation of the structure and function of biomolecules provides us knowledge that can be transferred into the generation of new materials and eventually applications in e.g., catalysis or bioassays. The main problems, however, concern the complexity of the natural systems and their limited availability, which necessitates utilization of simple biomimetic analogues that are, to a certain degree, similar in terms of structure and thus behaviour. We have, therefore, devised a small library of six tridentate N-heterocyclic coordinating agents (L1–L6), which, upon complexation, form two groups of artificial, monometallic non-heme iron species. Utilization of iron(III) chloride leads to the formation of the 1:1 (Fe:Ln) ‘open’ complexes, whereas iron(II) trifluoromethanosulfonate allows for the synthesis of 1:2 (M:Ln) ‘closed’ systems. The structural differences between the individual complexes are a result of the information encoded within the metallic centre and the chosen counterion, whereas the organic scaffold influences the observed properties. Indeed, the number and nature of the external hydrogen bond donors coming from the presence of (benz)imidazole moieties in the ligand framework are responsible for the observed biological behaviour in terms of mimicking phenoxazinone synthase activity and interaction with DNA.
Biomimetic Non-Heme Iron-Catalyzed Epoxidation of Challenging Terminal Alkenes Using Aqueous H2O2 as an Environmentally Friendly Oxidant
Authors: Fingerhut Anja , Vargas-Caporali Jorge , Leyva-Ramírez Marco Antonio , Juaristi Eusebio , Tsogoeva Svetlana B.
Published: September 2019

Catalysis mediated by iron complexes is emerging as an eco-friendly and inexpensive option in comparison to traditional metal catalysis. The epoxidation of alkenes constitutes an attractive application of iron(III) catalysis, in which terminal olefins are challenging substrates. Herein, we describe our study on the design of biomimetic non-heme ligands for the in situ generation of iron(III) complexes and their evaluation as potential catalysts in epoxidation of terminal olefins. Since it is well-known that active sites of oxidases might involve imidazole fragment of histidine, various simple imidazole derivatives (seven compounds) were initially evaluated in order to find the best reaction conditions and to develop, subsequently, more elaborated amino acid-derived peptide-like chiral ligands (10 derivatives) for enantioselective epoxidations.
Quantifying Fluorescently Labeled Ceramide Levels in Human Sarcoma Cell Lines in Response to a Sphingomyelin Synthase Inhibitor
Authors: Pashikanti Srinath , Afrin Farjana , Meldrum Trevor C. , Stegelmeier John L. , Pavek Adriene , Habashi Yashar A. , Fatema Kaniz , Barrott Jared J.
Published: September 2019

Sphingolipid metabolism is an important process in sustaining the growth needs of rapidly dividing cancer cells. Enzymes that synthesize sphingolipids have become attractive targets in cancer pharmacology. Ceramide is a precursor for synthesizing sphingolipids such as sphingomyelin, sphingosine-1-phosphate, and glucosylceramide. Sphingomyelin synthase (SMS) is the enzyme that transfers a phosphatidylcholine to ceramide to generate sphingomyelin. To test the inhibition of SMS, scientists assess the buildup of ceramide in the cell, which is cytotoxic. Because ceramide is a small lipid molecule, there are limited tools like antibodies to detect its presence. Alternatively, designated machines for small-molecule separation coupled with mass spectrometry detection can be used; however, these can be cost-prohibitive. We used a commercially available NBD-ceramide to apply to human cancer cell lines in the presence or absence of a known SMS inhibitor, jaspine B. After short incubation times, we were able to collect cell lysates and using solvent extraction methods, run the cellular material on a thin-layer chromatography plate to determine the levels of intact fluorescently labeled ceramide. Brighter fluorescence on the TLC plate correlated to greater SMS inhibition. Small molecules can then be screened quantifiably to determine the biological impact of inhibiting the sphingolipid metabolism pathways involving ceramide.
GLIM Criteria Using Hand Grip Strength Adequately Predict Six-Month Mortality in Cancer Inpatients
Authors: Contreras-Bolívar Victoria , Sánchez-Torralvo Francisco José , Ruiz-Vico María , González-Almendros Inmaculada , Barrios Manuel , Padín Susana , Alba Emilio , Olveira Gabriel
Published: September 2019

Protein-calorie malnutrition is very frequent in cancer patients and is associated with an increase in morbidity and mortality. Recently, the Global Leadership Initiative on Malnutrition (GLIM) criteria were proposed to standardize the diagnosis of malnutrition. Nevertheless, these criteria were not validated in prospective studies. Our objective is to determine the prevalence of malnutrition in cancer inpatients using different diagnostic classifications, including GLIM criteria, and to establish their association with length of stay and mortality. Hence, we designed a prospective study. Within the first 24 hours of admission to the Inpatient Oncology Unit, subjective global assessment (SGA) was carried out, and anthropometric data (body mass index (BMI), mid-arm circumference (MAC), arm muscle circumference (AMC), fat-free mass index (FFMI)) and hand grip strength (HGS) were obtained to assess the reduction of muscle mass according to GLIM criteria. Length of stay, biomarkers (albumin, prealbumin, C-reactive protein (CRP)), and in-hospital and six-month mortality were evaluated. Regarding the 282 patients evaluated, their mean age was 60.4 ± 12.6 years, 55.7% of them were male, and 92.9% had an advanced-stage tumor (17.7% stage III, 75.2% stage IV). According to SGA, 81.6% of the patients suffered from malnutrition (25.5% moderate malnutrition, and 56.1% severe malnutrition), and, based on GLIM criteria, malnutrition rate was between 72.2 and 80.0% depending on the used tool. Malnourished patients (regardless of the tool used) showed significantly worse values concerning BMI, length of stay, and levels of CRP/albumin, albumin, and prealbumin than normally nourished patients. In logistic regression, adjusted for confounding variables, the odds ratio of death at six months was significantly associated with malnutrition by SGA (odds ratio 2.73, confidence interval (CI) 1.35–5.52, p = 0.002), and by GLIM criteria calculating muscle mass with HGS (odds ratio 2.72, CI 1.37–5.40, p = 0.004) and FFMI (odds ratio 1.87, CI 1.01–3.48, p = 0.047), but not by MAC or AMC. The prevalence of malnutrition in advanced-stage cancer inpatients is very high. SGA and GLIM criteria, especially with HGS, are useful tools to diagnose malnutrition and have a similar predictive value regarding six-month mortality in cancer inpatients.
Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc
Authors: Loepfe Moira , Duss Anja , Zafeiropoulou Katerina-Alexandra , Björgvinsdóttir Oddny , D’Este Matteo , Eglin David , Fortunato Giuseppino , Klasen Juergen , Ferguson Stephen J. , Wuertz-Kozak Karin , Krupkova Olga
Published: September 2019

Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER™ technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.
Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies
Authors: Sartorius Rossella , D’Apice Luciana , Prisco Antonella , De Berardinis Piergiuseppe
Published: September 2019

The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, our laboratory focused its efforts in the study of antigen delivery strategies based on the filamentous bacteriophage ‘fd’, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses. We showed that fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently, we described the display of immunologically active lipids. In this review, we will provide an overview of the reported applications of the bacteriophage carriers and describe the advantages of exploiting this technology for delivery strategies.
Toll-Like Receptors and Relevant Emerging Therapeutics with Reference to Delivery Methods
Authors: Javaid Nasir , Yasmeen Farzana , Choi Sangdun
Published: September 2019

The built-in innate immunity in the human body combats various diseases and their causative agents. One of the components of this system is Toll-like receptors (TLRs), which recognize structurally conserved molecules derived from microbes and/or endogenous molecules. Nonetheless, under certain conditions, these TLRs become hypofunctional or hyperfunctional, thus leading to a disease-like condition because their normal activity is compromised. In this regard, various small-molecule drugs and recombinant therapeutic proteins have been developed to treat the relevant diseases, such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, systemic lupus erythematosus, and allergy. Some drugs for these diseases have been clinically approved; however, their efficacy can be enhanced by conventional or targeted drug delivery systems. Certain delivery vehicles such as liposomes, hydrogels, nanoparticles, dendrimers, or cyclodextrins can be employed to enhance the targeted drug delivery. This review summarizes the TLR signaling pathway, associated diseases and their treatments, and the ways to efficiently deliver the drugs to a target site.
Physicochemical Properties of a New PEGylated Polybenzofulvene Brush for Drug Encapsulation
Authors: Paolino Marco , Reale Annalisa , Razzano Vincenzo , Giuliani Germano , Donati Alessandro , Giorgi Gianluca , Boccia Antonella Caterina , Mendichi Raniero , Piovani Daniele , Botta Chiara , Salvini Laura , Samperi Filippo , Savoca Cristina , Licciardi Mariano , Paccagnini Eugenio , Gentile Mariangela , Cappelli Andrea
Published: September 2019

A new polymer brush was synthesized by spontaneous polymerization of benzofulvene macromonomer 6-MOEG-9-T-BF3k bearing a nona(ethylene glycol) side chain linked to the 3-phenylindene scaffold by means of a triazole heterocycle. The polymer structure was studied by SEC-MALS, NMR spectroscopy, and MALDI-TOF MS techniques, and the results supported the role of oligomeric initiatory species in the spontaneous polymerization of polybenzofulvene derivatives. The aggregation features of high molecular weight poly-6-MOEG-9-T-BF3k-FE were investigated by pyrene fluorescence analysis, dynamic light scattering studies, and transmission electron microscopy, which suggested a tendency towards the formation of spherical objects showing dimensions in the range of 20–200 nm. Moreover, poly-6-MOEG-9-T-BF3k-FE showed an interesting cytocompatibility in the whole concentration range tested that, besides its aggregation features, makes this polybenzofulvene brush a good polymer candidate for nanoencapsulation and delivery of drug molecules. Finally, the photo-physical features of poly-6-MOEG-9-T-BF3k-FE could allow the biodistribution of the resulting drug delivery systems to be monitored by fluorescence microscopy techniques.
Skin-on-a-Chip Device for Ex Vivo Monitoring of Transdermal Delivery of Drugs—Design, Fabrication, and Testing
Authors: Lukács Bence , Bajza Ágnes , Kocsis Dorottya , Csorba Attila , Antal István , Iván Kristóf , Laki András József , Erdő Franciska
Published: September 2019

To develop proper drug formulations and to optimize the delivery of their active ingredients through the dermal barrier, the Franz diffusion cell system is the most widely used in vitro/ex vivo technique. However, different providers and manufacturers make various types of this equipment (horizontal, vertical, static, flow-through, smaller and larger chambers, etc.) with high variability and not fully comparable and consistent data. Furthermore, a high amount of test drug formulations and large size of diffusion skin surface and membranes are important requirements for the application of these methods. The aim of our study was to develop a novel Microfluidic Diffusion Chamber device and compare it with the traditional techniques. Here the design, fabrication, and a pilot testing of a microfluidic skin-on-a chip device are described. Based on this chip, further developments can also be implemented for industrial purposes to assist the characterization and optimization of drug formulations, dermal pharmacokinetics, and pharmacodynamic studies. The advantages of our device, beside the low costs, are the small drug and skin consumption, low sample volumes, dynamic arrangement with continuous flow mimicking the dermal circulation, as well as rapid and reproducible results.
Hydrophilic Molecularly Imprinted Chitosan Based on Deep Eutectic Solvents for the Enrichment of Gallic Acid in Red Ginseng Tea
Authors: Li Guizhen , Rwo Kyung Ho
Published: September 2019

Hydrophilic molecularly imprinted chitosan (HMICS) were synthesized based on hydrophilic deep eutectic solvents (DESs) and the DESs was used as both a template and functional monomer for the enrichment of gallic acid (GA) from red ginseng tea using a solid phase microextraction (SPME) method. Using the response surface methodology (RSM) strategy, the optimal extraction amount (8.57 mg·g−1) was found to be an extraction time of 30 min, a solid to liquid ratio of 20 mg·mL−1, and five adsorption/desorption cycles. Compared to traditional methods, the produced HMICS-SPME exhibited the advantages of simplicity of operation, higher recovery and selectivity, improved analytical characteristics and reduced sample and reagent consumption, and it is expected to promote the rapid development and wide applications of molecular imprinting.
Performance and Economic Analysis of Concentrated Solar Power Generation for Pakistan
Authors: Soomro Mujeeb Iqbal , Mengal Abdullah , Memon Yasir Aftab , Khan Muhammad Waris Ali , Shafiq Qadir Nawaz , Mirjat Nayyar Hussain
Published: September 2019

In Pakistan, the utilization of renewable energy sources is increasing in order to reduce the electricity supply and demand gap. However, concentrated solar power (CSP) generation has not been considered in the country even though it has gained considerable attention worldwide. This study, as such, investigates the potential, performance, and economic analyses of four CSP technologies for different locations in Pakistan. Initially, an assessment of CSP sites, including solar resource, land, and water availability, was undertaken. Then, performance simulations of CSP technologies for four different locations of Pakistan, namely Quetta, Hyderabad, Multan, and Peshawar, were examined. For all cases, highest energy production was achieved in summers and lowest in winters, and CSP plants with evaporative cooling were found to be efficient compared to air cooling. The results also revealed that the Quetta and Hyderabad regions were promising for CSP development while parabolic tough (PT) and solar power tower (SPT) were the suitable CSP technologies for these regions. Specifically, the SPT plant with air cooling could be a favorable option for energy production in Quetta. Lastly, economic analyses revealed the financial feasibility of CSP plants in Pakistan since the levelized cost of energy is found to be significantly low.
Penalising Unexplainability in Neural Networks for Predicting Payments per Claim Incurred
Authors: H. L. Poon Jacky
Published: September 2019

In actuarial modelling of risk pricing and loss reserving in general insurance, also known as P&C or non-life insurance, there is business value in the predictive power and automation through machine learning. However, interpretability can be critical, especially in explaining to key stakeholders and regulators. We present a granular machine learning model framework to jointly predict loss development and segment risk pricing. Generalising the Payments per Claim Incurred (PPCI) loss reserving method with risk variables and residual neural networks, this combines interpretable linear and sophisticated neural network components so that the ‘unexplainable’ component can be identified and regularised with a separate penalty. The model is tested for a real-life insurance dataset, and generally outperformed PPCI on predicting ultimate loss for sufficient sample size.
Synergy of Satellite, In Situ and Modelled Data for Addressing the Scarcity of Water Quality Information for Eutrophication Assessment and Monitoring of Swedish Coastal Waters
Authors: Kratzer Susanne , Kyryliuk Dmytro , Edman Moa , Philipson Petra , Lyon Steve
Published: September 2019

Monthly CHL-a and Secchi Depth (SD) data derived from the full mission data of the Medium Resolution Imaging Spectrometer (MERIS; 2002–2012) were analysed along a horizontal transect from the inner Bråviken bay and out into the open sea. The CHL-a values were calibrated using an algorithm derived from Swedish lakes. Then, calibrated Chl-a and Secchi Depth (SD) estimates were extracted from MERIS data along the transect and compared to conventional monitoring data as well as to data from the Swedish Coastal zone Model (SCM), providing physico-biogeochemical parameters such as temperature, nutrients, Chlorophyll-a (CHL-a) and Secchi depth (SD). A high negative correlation was observed between satellite-derived CHL-a and SD (ρ = −0.91), similar to the in situ relationship established for several coastal gradients in the Baltic proper. We also demonstrate that the validated MERIS-based estimates and data from the SCM showed strong correlations for the variables CHL-a, SD and total nitrogen (TOTN), which improved significantly when analysed on a monthly basis across basins. The relationship between satellite-derived CHL-a and modelled TOTN was also evaluated on a monthly basis using least-square linear regression models. The predictive power of the models was strong for the period May-November (R2: 0.58–0.87), and the regression algorithm for summer was almost identical to the algorithm generated from in situ data in Himmerfjärden bay. The strong correlation between SD and modelled TOTN confirms that SD is a robust and reliable indicator to evaluate changes in eutrophication in the Baltic proper which can be assessed using remote sensing data. Amongst all three assessed methods, only MERIS CHL-a was able to correctly depict the pattern of phytoplankton phenology that is typical for the Baltic proper. The approach of combining satellite data and physio-biogeochemical models could serve as a powerful tool and value-adding complement to the scarcely available in situ data from national monitoring programs. In particular, satellite data will help to reduce uncertainties in long-term monitoring data due to its improved measurement frequency.
Mapping with Pléiades—End-to-End Workflow
Authors: Perko Roland , Raggam Hannes , Roth Peter M.
Published: September 2019

In this work, we introduce an end-to-end workflow for very high-resolution satellite-based mapping, building the basis for important 3D mapping products: (1) digital surface model, (2) digital terrain model, (3) normalized digital surface model and (4) ortho-rectified image mosaic. In particular, we describe all underlying principles for satellite-based 3D mapping and propose methods that extract these products from multi-view stereo satellite imagery. Our workflow is demonstrated for the Pléiades satellite constellation, however, the applied building blocks are more general and thus also applicable for different setups. Besides introducing the overall end-to-end workflow, we need also to tackle single building blocks: optimization of sensor models represented by rational polynomials, epipolar rectification, image matching, spatial point intersection, data fusion, digital terrain model derivation, ortho rectification and ortho mosaicing. For each of these steps, extensions to the state-of-the-art are proposed and discussed in detail. In addition, a novel approach for terrain model generation is introduced. The second aim of the study is a detailed assessment of the resulting output products. Thus, a variety of data sets showing different acquisition scenarios are gathered, allover comprising 24 Pléiades images. First, the accuracies of the 2D and 3D geo-location are analyzed. Second, surface and terrain models are evaluated, including a critical look on the underlying error metrics and discussing the differences of single stereo, tri-stereo and multi-view data sets. Overall, 3D accuracies in the range of 0.2 to 0.3 m in planimetry and 0.2 to 0.4 m in height are achieved w.r.t. ground control points. Retrieved surface models show normalized median absolute deviations around 0.9 m in comparison to reference LiDAR data. Multi-view stereo outperforms single stereo in terms of accuracy and completeness of the resulting surface models.
Extracting Raft Aquaculture Areas from Remote Sensing Images via an Improved U-Net with a PSE Structure
Authors: Cui Binge , Fei Dong , Shao Guanghui , Lu Yan , Chu Jialan
Published: September 2019

Remote sensing has become a primary technology for monitoring raft aquaculture products. However, due to the complexity of the marine aquaculture environment, the boundaries of the raft aquaculture areas in remote sensing images are often blurred, which will result in ‘adhesion’ phenomenon in the raft aquaculture areas extraction. The fully convolutional network (FCN) based methods have made great progress in the field of remote sensing in recent years. In this paper, we proposed an FCN-based end-to-end raft aquaculture areas extraction model (which is called UPS-Net) to overcome the ‘adhesion’ phenomenon. The UPS-Net contains an improved U-Net and a PSE structure. The improved U-Net can simultaneously capture boundary and contextual information of raft aquaculture areas from remote sensing images. The PSE structure can adaptively fuse the boundary and contextual information to reduce the ‘adhesion’ phenomenon. We selected laver raft aquaculture areas in eastern Lianyungang in China as the research region to verify the effectiveness of our model. The experimental results show that compared with several state-of-the-art models, the proposed UPS-Net model performs better at extracting raft aquaculture areas and can significantly reduce the ‘adhesion’ phenomenon.
Development and Intercomparison Study of an Atmospheric Motion Vector Retrieval Algorithm for GEO-KOMPSAT-2A
Authors: Oh Soo Min , Borde Régis , Carranza Manuel , Shin In-Chul
Published: September 2019

We derived an atmospheric motion vector (AMV) algorithm for the Geostationary Korea Multipurpose Satellite (GEO-KOMPSAT-2A; GK-2A) launched on 4 December 2018, using the Advanced Himawari Imager (AHI) onboard Himawari-8, which is very similar to the Advanced Meteorological Imager onboard GK-2A. This study clearly describes the main steps in our algorithm and optimizes it for the target box size and height assignment methods by comparing AMVs with numerical weather prediction (NWP) and rawinsonde profiles for July 2016 and January 2017. Target box size sensitivity tests were performed from 8 × 8 to 48 × 48 pixels for three infrared channels and from 16 × 16 to 96 × 96 pixels for one visible channel. The results show that the smaller box increases the speed, whereas the larger one slows the speed without quality control. The best target box sizes were found to be 16 × 16 for CH07, 08, and 13, and 48 × 48 pixels for CH03. Height assignment sensitivity tests were performed for several methods, such as the cross-correlation coefficient (CCC), equivalent blackbody temperature (EBBT), infrared/water vapor (IR/WV) intercept, and CO2 slicing methods for a cloudy target as well as normalized total contribution (NTC) and normalized total cumulative contribution (NTCC) for a clear-air target. For a cloudy target, the CCC method is influenced by the quality of the cloud’s top pressure. Better results were found when using EBBT and IR/WV intercept methods together rather than individually. Furthermore, CO2 slicing had the best statistics. For a clear-air target, the combined use of NTC and NTCC had the best statistics. Additionally, the mean vector difference, root-mean-square (RMS) vector difference, bias, and RMS error (RMSE) between GK-2A AMVs and NWP or rawinsonde were smaller by approximately 18.2% on average than in the case of the Communication, Ocean and Meteorology Satellite (COMS) AMVs. In addition, we verified the similarity between GK-2A and Meteosat Third Generation (MTG) AMVs using the AHI of Himawari-8 from 21 July 2016. This similarity can provide evidence that the GK-2A algorithm works properly because the GK-2A AMV algorithm borrows many methods of the MTG AMV algorithm for geostationary data and inversion layer corrections. The Pearson correlation coefficients in the speed, direction, and height of the prescribed GK-2A and MTG AMVs were larger than 0.97, and the corresponding bias/RMSE were0.07/2.19 m/s, 0.21/14.8°, and 2.61/62.9 hPa, respectively, considering common quality indicator with forecast (CQIF) > 80.