bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumhuriyet Döneminde Türkiye’de Liman ve İskele Politikaları (1923-1960)
Authors: Yurtoğlu Nadir
Published: November 2019

Cumhuriyetin ilk yıllarından itibaren 1960 yılına kadar Türkiye’de liman ve iskele politikaları ile bu politikaların ekonomiye olan yansımaları çalışmanın konusunu teşkil etmektedir. Konu, Cumhuriyetin ilk döneminde liman ve iskele politikaları (1923-1950); Demokrat Parti (DP) döneminde liman ve iskele politikaları (1950-1960) ile sınırlandırılarak iki dönem halinde ele alınmıştır. Türkiye’de liman ve iskele politikaları ile bu politikaların ekonomiye olan katkıları sayısal veriler ışığında değerlendirilmiştir. Çalışmanın kaynak materyalini, Cumhuriyet arşivi belgeleri, resmi yayınlardan; zabıt ceridesi, kanunlar ve tutanak dergileri, resmi gazete, istatistik yıllıkları ve ayın tarihinin yanı sıra dönemin süreli yayınları arasında bulunan ekonomi dergilerinin makaleleri oluşturmaktadır. Konu incelenirken, deniz ticaretinin geliştirilmesinde liman ve iskelelerin yaptığı katkılar göz önüne getirilerek gerekli değerlendirilmelerde bulunulmuştur. Çalışmada elde edilen sonuç şudur: Cumhuriyetin ilk yıllarından itibaren yabancılar tarafından yürütülen liman hizmetleri 1925 yılında Türk sermayesi ile kurulan şirketlere devredilmiştir. 1939 yılında liman hizmetlerini devletin üstlenmesiyle Devlet Limanları İşletme Umum Müdürlüğü teşkil edilmiş, bu kurum 1944 yılında Devlet Denizyolları ve Limanları İşletme Umum Müdürlüğüne dönüştürülmüştür. Ayrıca çıkarılan kanunlarla liman ve iskeleler konusunda yasal boşluklar giderilmiştir. DP döneminde ise liman ve iskelelerin iç ve dış finans kaynakları artırılıp yeniden inşa, ıslah ve genişletilme çalışmalarına girilmesi ve limanların donanımlı hale getirilmesiyle yükleme-boşaltma kapasiteleri artırılmıştır. Bu suretle Türkiye’nin dış ülkelerle yapılan deniz ticaret hacmi genişletilerek millî ekonomiye önemli katkılar sağlanmıştır.
HUBUNGAN LINGKUNGAN KERJA DAN RELIGIUSITAS DENGAN PENERAPAN K3 DI RUMAH SAKIT “X”
Authors: Sari Devitasari
Published: November 2019

Upaya Kesehatan dan Keselamatan Kerja harus diselenggarakan untuk mewujudkan produktivitas kerja yang optimal di semua tempat kerja termasuk di dalam Rumah Sakit. Salah satu instalasi di Rumah Sakit yang perlu mendapatkan perhatian lingkungan kerja dan penerapan K3 yaitu instalasi gizi, hal ini karena berdasarkan data studi pendahuluan terdapat kejadian kecelakaan kerja ringan sampai dengan sedang.

Desain penelitian yang digunakan pada penelitian ini adalah menggunakan metode analisis kuantitatif dengan pendekatan Cross-sectional. Sampel 42 orang karyawan bagian produksi di instalasi gizi RS “X” dengan metode total sampling. Sedangkan uji statistik yang digunakan adalah uji korelasi spearman.

Hasil uji bivariat menggunakan korelasi spearman didapatkan bahwa ada hubungan antara lingkungan kerja dan religiusitas dengan penerapan K3 (p=0.000;p=0.042). Lingkungan kerja denga penerapan K3 menunjukan tingkat hubungan yang cukup kuat yaitu sebesar 0.599, sedangkan untuk religiusitas dengan penerapan K3 menunjukan tingkat hubungan yang lemah atau rendah yaitu sebesar 0.316. Secara keseluruhan karyawan bagian produksi di instalasi Gizi RS “X” merasa nyaman dengan lingkungan kerja yang ada pada saat ini. Lingkungan kerja sudah memenuhi standard atau baku mutu peraturan. Sedangkan religiusitas lebih kepada privasi yang dipengaruhi oleh budaya organisasi dan budaya kerja.
PENGEMBANGAN BAHAN AJAR EVALUASI PEMBELAJARAN UNTUK PENDIDIKAN GURU SEKOLAH DASAR UNIVERSITAS KUNINGAN
Authors: Purnomo Heru , Wulandari Isnaini
Published: November 2019

Evaluation of Learning is one of the mandatory compulsory subjects that must be taken by students at PGSD FKIP Kuningan University in order to obtain assessment and evaluation skill. However, there is no teaching material for evaluating learning for PGSD that explicitly discusses the elementary school learning evaluation process. This study to develop instructional evaluation teaching materials on PGSD learning evaluation courses which are expected to equip students to be applied in primary schools when they become teachers. This research method is a research and development study by taking the object of research at the Kuningan University PGSD. The results of the validation of learning evaluation material experts obtained results with a total value of 74 of the 20 learning indicators that were assessed with a range of scores 1-5, so that a score of 3.7 from all assessment indicators in the learning evaluation instrument can be said with good category. The results of student responses to the feasibility of developing teaching materials obtained by 90.27% of students on the response Very good and good. Based on the results obtained from the response to the readability of the product development, it was obtained that the response of students was 93.65% in the Very Good and Good categories. Based on the categorization of the results of the gain score analysis in the Hake calculation table, the value of 0.59 is categorized as medium
IMPLEMENTASI STANDAR ISI DALAM KURIKULUM 2013 DI SEKOLAH DASAR
Authors: Oktaviani Ndaru Mukti , Wulandari Isnaini
Published: November 2019

The curriculum 2013 is a refinement of the previous curriculum KTSP. The curriculum development from KTSP to curriculum2013 had an impact on the changes in most learning systems. Changes in national education standards also affect the implementation of the curriculum 2013. In the implementation of the curriculum 2013 in primary schools, there were obstacles which, based on the results of the FGD with elementary school teachers in Kuningan, West Java, it was found that teachers were still experiencing difficulties in implementing the curriculum 2013. Content standards in the curriculum 2013 which are derived directly from graduate competency standards. This condition certainly hindered the achievement of the overall  curriculum 2013 goals.The research method used in this research is case study. The study was conducted at public elementary schools located in Kuningan Regency, SDN Dukuhdalem, Japara District, SDN 1 Manislor, Jalaksana District, and SDN 1 Purwawinangun, Kuningan District. There are two types of research instruments used, observation sheets and interview guides. Qualitative data analysis is carried out interactively and takes place continuously at each stage of the study so that it is complete, and the data is saturated.The results of the study note that the money scope of the material on the spiritual attitude competence and social attitude competence face obstacles in terms of time in its implementation, the scope of the material on the competency of expertise faces obstacles in terms of costs in its implementation. As well as the scope of the material on knowledge competence faces obstacles in terms of monotonous material, the breadth of the material that is considered to be insufficient so that it does not meet the material requirements in the learning process, as well as the material which is considered incomplete in its implementation
SYNTHESIS AND CRYSTALLOCHEMICAL PROPERTIES OF Ce-SUBSTITUTED NANOPARTICLES OF MANGANITE (La,Sr)MnO3
Authors: Timashkov Illia , Shlapa Yulia , Solopan Sergiy , Belous Anatoliy
Published: November 2019

Serious of Ce-substituted lanthanum-strontium man-ganites La0.7–xSr0.3CexMnO3 (x = 0–0.2) nanoparticles were synthesized by sol-gel method with further heat treatment of precursors at 800 °C. Crystallographic properties of obtained nanoparticles were investiga-ted by X-ray diffraction method. According to XRD data, it was established that the substitution of lan-thanum ions by cerium in the crystalline structure and formation of single-phased nanoparticles occurs only up to 5 % mol. of Ce regardless of the heating temperature. Linear decreasing the cell volume of nanoparticles in this concentration range of Ce satis-fies the Vegard law and indicates on the formation of a continuous series of solid solutions with the dis-torted perovskite up to 5 % of Ce. At higher concen-trations of Ce there are additional peaks on the XRD patterns, which point on the formation of an addi-tional phase of CeO2. According to TEM studies, it was calculated that the average size of was 30–40 nm. To estimate heating efficiency of synthesized nanoparticles in the alternating magnetic field, mag-netic fluids based on the synthesized nanoparticles and aqueous dextran solution were prepared. It was shown that they effectively heated up to controlled temperatures in an alternating magnetic field, and their heating efficiency was directly proportional to the increase of the concentration of cerium. Accor-ding to the results of the complex studies, it was shown the possibility to synthesize single-phase Ce-substituted nanoparticles of manganite with a pe-rovskite structure. It was established that cerium does not significantly influence on the change of magnetic properties of such nanoparticles and they are promising for further investigations as the in-ducers of magnetic hyperthermia, as well as for the biological tests.
CATHODE MATERIALS OF ROCK SALT DERIVATIVE STRUCTURES FOR SODIUM-ION SECONDARY POWER SOURCES
Authors: Malovanyy Sergiy
Published: November 2019

The rechargeable lithium-ion batteries have been dominating the portable electronic market for the past two decades with high energy density and long cycle-life. However, applications of lithium-ion batteries in large-scale stationary energy storage are likely to be limited by the high cost and availability of lithium resources. The room temperature Na-ion secondary battery have received extensive investigations for large-scale energy storage systems (EESs) and smart grids lately due to similar chemistry of “rocking-chair” sodium storage mechanism, lower price and huge abundance. They are considered as an alternative to lithium-ion batteries for large-scale applications, bringing an increasing research interests in materials for sodium-ion batteries. Although there are many obstacles to overcome before the Na-ion battery becomes commercially available, recent research discoveries corroborate that some of the cathode materials for the Na-ion battery have indeed advantages over its Li-ion competitors. Layered oxides are promising cathode materials for sodium ion batteries because of their high theoretical capacities. In this publication, a review of layered oxides (NaxMO2, M = V, Cr, Mn, Fe, Co, Ni, and a mixture of 2 or 3 elements) as a Na-ion battery cathode is presented. O3 and P2 layered sodium transition metal oxides  NaxMO2 are a promising class of cathode materials for Na secondary battery applications. These materials, however, all suffer from capacity decline when the extraction of Na exceeds certain capacity limits. Understanding the causes of this capacity decay is critical to unlocking the potential of these materials for battery applications.  Single layered oxide systems are well characterized not only for their electrochemical performance, but also for their structural transitions during the cycle. Binary oxides systems are investigated in order to address issues regarding low reversible capacity, capacity retention, operating voltage, and structural stability. Some materials already have reached high energy density, which is comparable to that of LiFePO4. On the other hand, the carefully chosen elements in the electrodes also largely determine the cost of SIBs. Therefore, earth abundant-based compounds are ideal candidates for reducing the cost of electrodes. Among all low-cost metal elements, cathodes containing iron, chromium and manganese are the most representative ones. The aim of the article is to present the development of Na layered oxide materials in the past as well as the state of the art today.
DETERMINATION OF Cu(II) CONCENTRATION IN AQUEOUS MEDIUM USING INVERSION ELECTROCHEMICAL METHOD
Authors: Vorobets Vera , Kolbasov Gennadii , Fomanyuk Sergii , Smirnova Nataliia , Linnik Oksana
Published: November 2019

Electrode materials based on titanium dioxide modified with zinc ions and gold nanoparticles, synthesized by sol-gel method, were used to determine the concentration of Cu (II) in liquids by stripping voltammetry method. Determination of Cu (II) was done using background solutions based on 0.4 M formic acid and ammonium acetate buffer (pH = 7.5) using the standard addition method with a potential scanning speed of 50 mV•s-1. The solution was stirred during the preliminary electrolysis at a potential of -1400 mV (vs silver-chloride reference electrode) for 120 seconds and then the potential was scanned from -1200 mV to + 200 mV. It is shown that the background solution based on ammonium acetate buffer provides a higher sensitivity and a good selectivity of peaks for the determination of copper compared to the background solution based on formic acid. Determined that value of the analytical signal of copper in the studied model solutions based on ammonium acetate and formic acid is proportional to the concentration of copper ions in the solution. To increase the selectivity of stripping voltammetry method in determining copper concentrations in solutions, an inversion spectral photoelectrochemical method was proposed, the essence of which is preliminary electroconcentration of the elements under investigation in the cathode potential region and subsequent measurement of the spectral photoelectrochemical characteristics of electroconcentration products. It has been found that in solutions of 1M ammonium acetate containing Cu2+ ions, the cathodic polarization of TiO2-based photoelectrode leads to the appearance of a cathode photocurrent and the values of photocurrent quantum yield increase with increasing content of copper ions in the solution. The spectral sensitivity of the surface layer corresponds to the absorption spectrum of Cu2O. The sensitivity of stripping voltammetry method to copper Cu (II) using the materials studied was 0.3 mg•l-1. It is shown that the inversion photoelectrochemical method is promising in the selective determination of copper concentration in liquids.
Precariedad laboral y construcción social de la “ilegalidad”: familias indígenasecuatorianas en Nueva York
Authors: Herrera Mosquera Gioconda
Published: November 2019

This article examines the migration of Ecuadorian indigenous families to New York City in the context of the 2008 Financial Crisis and the tightening of immigration policies in the United States. Migration trajectories show increasingly risky travel conditions, and significant changes in labor market integration as well as settlement. The article shows that job insecurity and the social condition of illegality are mutually connected in the different stages of the migration trajectory and constitute a different experience from that of Ecuadorians who emigrated in previous decades.
Impact of Row Distance and Seed Density on Grain Yield, Quality Traits, and Free Asparagine of Organically Grown Wheat
Authors: Stockmann Falko , Weber Ernst Albrecht , Merkt Nikolaus , Schreiter Pat , Claupein Wilhelm , Graeff-Hönninger Simone
Published: November 2019

Organic farming faces challenges providing sufficient nutrient supply as manure and crop rotations are often the major nutrient inputs. Larger row distances and fewer seed densities can support nitrogen availability by giving more space to the single plant. As free asparagine (Asn) the main precursor of acrylamide (AA) in plants is closely related to nitrogen uptake and storage, the question arose whether free Asn will be affected by row distance and seed densities in organic farming. This study investigated the effect of row distance and seed density on yield, yield components, baking quality, and free Asn in organic farming. A two-year field trial was carried out including two winter wheat cultivars, two row distances, and two seed densities. Year and cultivar highly influenced all traits. The impact of both treatments was mainly caused by interaction. Nevertheless, enlarged row distances raised baking quality, while free Asn was changed to a minor extent. Thus, we recommend larger row distances for raising baking quality without increasing free Asn. Seed density is of minor relevance. The close relation found between free Asn and grains per spike (R2 = 0.72) indicates that smaller grains contain more Asn than bigger grains. This opens new insights into Asn synthesis during grain development and offers a potential prediction of Asn amounts.
Immunoglobulin for Treating Bacterial Infections: One More Mechanism of Action
Authors: Sawa Teiji , Kinoshita Mao , Inoue Keita , Ohara Junya , Moriyama Kiyoshi
Published: November 2019

The mechanisms underlying the effects of immunoglobulins on bacterial infections are thought to involve bacterial cell lysis via complement activation, phagocytosis via bacterial opsonization, toxin neutralization, and antibody-dependent cell-mediated cytotoxicity. Nevertheless, recent advances in the study of the pathogenicity of Gram-negative bacteria have raised the possibility of an association between immunoglobulin and bacterial toxin secretion. Over time, new toxin secretion systems like the type III secretion system have been discovered in many pathogenic Gram-negative bacteria. With this system, the bacterial toxins are directly injected into the cytoplasm of the target cell through a special secretory apparatus without any exposure to the extracellular environment, and therefore with no opportunity for antibodies to neutralize the toxin. However, antibodies against the V-antigen, which is located on the needle-shaped tip of the bacterial secretion apparatus, can inhibit toxin translocation, thus raising the hope that the toxin may be susceptible to antibody targeting. Because multi-drug resistant bacteria are now prevalent, inhibiting this secretion mechanism is an attractive alternative or adjunctive therapy against lethal bacterial infections. Thus, it is not unreasonable to define the blocking effect of anti-V-antigen antibodies as the fifth mechanism for immunoglobulin action against bacterial infections.
Novel Small-molecule Antibacterials against Gram-positive Pathogens of Staphylococcus and Enterococcus Species
Authors: Seethaler Marius , Hertlein Tobias , Wecklein Björn , Ymeraj Alba , Ohlsen Knut , Lalk Michael , Hilgeroth Andreas
Published: November 2019

Defeat of the antibiotic resistance of pathogenic bacteria is one great challenge today and for the future. In the last century many classes of effective antibacterials have been developed, so that upcoming resistances could be met with novel drugs of various compound classes. Meanwhile, there is a certain lack of research of the pharmaceutical companies, and thus there are missing developments of novel antibiotics. Gram-positive bacteria are the most important cause of clinical infections. The number of novel antibacterials in clinical trials is strongly restricted. There is an urgent need to find novel antibacterials. We used synthetic chemistry to build completely novel hybrid molecules of substituted indoles and benzothiophene. In a simple one-pot reaction, two novel types of thienocarbazoles were yielded. Both indole substituted compound classes have been evaluated as completely novel antibacterials against the Staphylococcus and Enterococcus species. The evaluated partly promising activities depend on the indole substituent type. First lead compounds have been evaluated within in vivo studies. They confirmed the in vitro results for the new classes of small-molecule antibacterials.
Dynamic Analysis of Modified Duffing System via Intermittent External Force and Its Application
Authors: He Jianbin , Cai Jianping
Published: November 2019

Over the past century, a tremendous amount of work on the Duffing system has been done with continuous external force, including analytical and numerical solution methods, and the dynamic behavior of physical systems. However, hows does the Duffing oscillator behave if the external force is intermittent? This paper investigates the Duffing oscillator with intermittent external force, and a modified Duffing chaotic system is proposed. Different from the continuous-control method, an intermittent external force of cosine function was designed to control the Duffing oscillator, such that the modified Duffing (MD) system could behave chaotically. The dynamic characteristics of MD system, such as the strange attractors, Lyapunov exponent spectra, and bifurcation diagram spectra were outlined with numerical simulations. Numerical results showed that there existed a positive Lyapunov exponent in some parameter intervals. Furthermore, by combining it with chaos scrambling and chaos XOR encryption, a chaos-based encryption algorithm was designed via the pseudorandom sequence generated from the MD. Finally, feasibility and validity were verified by simulation experiments of image encryption.
Evaluation of Molecular Polarizability and of Intensity Carrying Modes Contributions in Circular Dichroism Spectroscopies
Authors: Zanchi Chiara , Longhi Giovanna , Abbate Sergio , Pellegrini Giovanni , Biagioni Paolo , Tommasini Matteo
Published: November 2019

We re-examine the theory of electronic and vibrational circular dichroism spectroscopy in terms of the formalism of frequency-dependent molecular polarizabilities. We show the link between Fermi’s gold rule in circular dichroism and the trace of the complex electric dipole–magnetic dipole polarizability. We introduce the C++ code polar to compute the molecular polarizability complex tensors from quantum chemistry outputs, thus simulating straightforwardly UV-visible absorption (UV-Vis)/electronic circular dichroism (ECD) spectra, and infrared (IR)/vibrational circular dichroism (VCD) spectra. We validate the theory and the code by referring to literature data of a large group of chiral molecules, showing the remarkable accuracy of density functional theory (DFT) methods. We anticipate the application of this methodology to the interpretation of vibrational spectra in various measurement conditions, even in presence of metal surfaces with plasmonic properties. Our theoretical developments aim, in the long run, at embedding the quantum-mechanical details of the chiroptical spectroscopic response of a molecule into the simulation of the electromagnetic field distribution at the surface of plasmonic devices. Such simulations are also instrumental to the interpretation of the experimental spectra measured from devices designed to enhance chiroptical interactions by the surface plasmon resonance of metal nanostructures.
Simultaneous Analysis of Heavy Metal Concentration in Soil Samples
Authors: Śliwińska Anna , Smolinski Adam , Kucharski Piotr
Published: November 2019

The application of Fourier transform infrared spectroscopy to the simultaneous analysis of heavy metal concentration in soil samples was demonstrated in this paper. Two spectral techniques, namely, attenuated total reflectance (ATR) and diffuse reflectance (DRIFT), were applied and the whole infrared spectral region, i.e., far IR, mid IR, and near IR were considered in this work. Spectral data with reference to the results of laboratory analysis enabled the development of calibration partial least squares (PLS) models. The PLS models for the ATR near IR were characterized by a good fit and good prediction abilities. According to the results obtained, the most accurate description and prediction were realized in the case of mid/far and near IR for the mercury and nickel concentration in soil. Application of far IR slightly improved the prediction possibilities of the model. The construction of PLS models based on the Fourier-transform infrared (FT-IR) spectra enables the perception of FT-IR spectroscopy as a supplementary method that is useful in the estimation and monitoring of the contamination level in soils.
GNSS Ionosphere Sounding of Equatorial Plasma Bubbles
Authors: Ma Guanyi , Hocke Klemens , Li Jinghua , Wan Qingtao , Lu Weijun , Fu Weizheng
Published: November 2019

Ground- and space-based Global Navigation Satellite System (GNSS) receivers can provide three-dimensional (3D) information about the occurrence of equatorial plasma bubbles (EPBs). For this study, we selected March 2014 data (during solar maximum of cycle 24) for the analysis. The timing and the latitudinal dependence of the EPBs occurrence rate are derived by means of the rate of the total electron content (TEC) index (ROTI) data from GNSS receivers in China, whereas vertical profiles of the scintillation index S4 are provided by COSMIC (Constellation Observing System for Meteorology, Ionosphere and Climate). The GNSS receivers of the low Earth orbit satellites give information about the occurrence of amplitude scintillations in limb sounding geometry where the focus is on magnetic latitudes from 20° S to 20° N. The occurrence rates of the observed EPB-induced scintillations are generally smaller than those of the EPB-induced ROTI variations. The timing and the latitude dependence of the EPBs occurrence rate agree between the ground-based and spaceborne GNSS data. We find that EPBs occur at 19:00 LT and they are mainly situated above the F2 peak layer which descended from 450 km at 20:00 LT to 300 km at 24:00 LT in the equatorial ionosphere. At the same time, the spaceborne GNSS data also show, for the first time, a high occurrence rate of post-sunset scintillations at 100 km altitude, indicating the coexistence of equatorial sporadic E with EPBs.
Effect of Caffeine and Other Methylxanthines on Aβ-Homeostasis in SH-SY5Y Cells
Authors: Janitschke Daniel , Nelke Christopher , Lauer Anna , Regner Liesa , Winkler Jakob , Thiel Andrea , Grimm Heike , Hartmann Tobias , Grimm Marcus
Published: November 2019

Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine. Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial properties in neurodegenerative diseases, however, the mechanisms of action are not completely understood. Here we investigate the effect of the naturally occurring caffeine, theobromine and theophylline and the synthetic propentofylline and pentoxifylline on processes involved in Alzheimer’s disease (AD). All MTXs decreased amyloid-β (Aβ) level by shifting the amyloid precursor protein (APP) processing from the Aβ-producing amyloidogenic to the non-amyloidogenic pathway. The α-secretase activity was elevated whereas β-secretase activity was decreased. Breaking down the molecular mechanism, caffeine increased protein stability of the major α-secretase ADAM10, downregulated BACE1 expression and directly decreased β-secretase activity. Additionally, APP expression was reduced. In line with literature, MTXs reduced oxidative stress, decreased cholesterol and a decreased in Aβ1-42 aggregation. In conclusion, all MTXs act via the pleiotropic mechanism resulting in decreased Aβ and show beneficial properties with respect to AD in neuroblastoma cells. However, the observed effect strength was moderate, suggesting that MTXs should be integrated in a healthy diet rather than be used exclusively to treat or prevent AD.
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response
Authors: Itami-Matsumoto Saori , Hayakawa Michiyo , Uchida-Kobayashi Sawako , Enomoto Masaru , Tamori Akihiro , Mizuno Kazuyuki , Toyoda Hidenori , Tamura Takeyuki , Akutsu Tatsuya , Ochiya Takahiro , Kawada Norifumi , Murakami Yoshiki
Published: November 2019

Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1–5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC.
Fully Automated Microsystem for Unmediated Electrochemical Characterization, Visualization and Monitoring of Bacteria on Solid Media; E. coli K-12: A Case Study
Authors: Hernandez Cesar A. , Beni Valerio , Osma Johann F.
Published: November 2019

In this paper, we present a non-fluidic microsystem for the simultaneous visualization and electrochemical evaluation of confined, growing bacteria on solid media. Using a completely automated platform, real-time monitoring of bacterial and image-based computer characterization of growth were performed. Electrochemical tests, using Escherichia coli K-12 as the model microorganism, revealed the development of a faradaic process at the bacteria–microelectrode interface inside the microsystem, as implied by cyclic voltammetry and electrochemical impedance spectrometry measurements. The electrochemical information was used to determine the moment in which bacteria colonized the electrode-enabled area of the microsystem. This microsystem shows potential advantages for long-term electrochemical monitoring of the extracellular environment of cell culture and has been designed using readily available technologies that can be easily integrated in routine protocols. Complementarily, these methods can help elucidate fundamental questions of the electron transfer of bacterial cultures and are potentially feasible to be integrated into current characterization techniques.
The Practical Use of White Cell Inflammatory Biomarkers in Prediction of Postoperative Delirium after Cardiac Surgery
Authors: Kotfis Katarzyna , Ślozowska Justyna , Safranow Krzysztof , Szylińska Aleksandra , Listewnik Mariusz
Published: November 2019

Introduction: Postoperative delirium (POD) is associated with unfavorable outcomes. It may result from neuroinflammation and oxidative stress. The aim of this study was to evaluate the role of routinely available inflammatory markers derived from white blood cell count (WBC), for prognostic value in diagnosing delirium after cardiac surgery. Methods: We performed an analysis of data collected from patients undergoing planned coronary artery bypass grafting (CABG). Differential WBC and CRP (C-reactive protein) concentration were evaluated preoperatively (T0) and postoperatively at day 1 (T1), 3 (T3), 5 (T5) after CABG. Differences in neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet-to-WBC ratio (PWR) between patients with (Del +) and without delirium (Del −) were evaluated. Patients were screened using CAM-ICU. Results: We included 968 patients in the study. Incidence of delirium was 13.3%. In the group with POD, the majority of patients were men (87/129, 67.44%), and the mean age was 72 years. Preoperative WBC (8.21 ± 3.04 G/l vs. 7.55 ± 1.86 G/l, p = 0.029) were higher and mean platelet count was lower (217.7 ± 69.07 G/l vs. 227.44 ± 59.31 G/l, p = 0.031) in patients with POD. Lower pre-operative PLR values (109.87 ± 46.38 vs. 120.36 ± 52.98, p = 0.026) and PWR values (27.69 ± 7.50 vs. 31.32 ± 9.88 p < 0.001) were found in patients with POD. Association was strongest for PWR and remained significant at T1 (p < 0.001), T3 (p < 0.001) and T5 (p < 0.001). Basing on coefficients of logistic regression a model for optimal prediction of POD was calculated: CARDEL Index (CARdiac DELirium Index) = 0.108 × Age + 0.341 × HBA1C − 0.049 × PWR with AUC of 0.742 (p < 0.001). Conclusions: The results of this study show that lower pre-operative levels of PLR and PWR were associated with POD after cardiac surgery. Pre-operative PWR showed strongest correlation with POD and may be a potential new biomarker associated with postoperative delirium. CARDEL prognosis index composed of age, HbA1c and PWR is good at predicting development of delirium after CABG.
Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics
Authors: Capote-Moreno Ana , Ramos Eva , Egea Javier , López-Muñoz Francisco , Gil-Martín Emilio , Romero Alejandro
Published: November 2019

The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.
The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors
Authors: Meyers Daniel E. , Stukalin Igor , Vallerand Isabelle A. , Lewinson Ryan T. , Suo Aleksi , Dean Michelle , North Scott , Pabani Aliyah , Cheng Tina , Heng Daniel Y.C. , Bebb D. Gwyn , Morris Don G.
Published: November 2019

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined. We sought to determine whether LIPI is associated with overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled, real-world, retrospective cohort of patients with solid tumors treated with ICI. Of the total pooled cohort (N = 578), 47.2%, 38.2% and 14.5% of patients were stratified into good, intermediate and poor LIPI group, respectively. Median OS were 22.8 (95% CI 17.4–29.5), 7.8 (95% CI 6.6–9.6), and 2.5 months (95% CI 1.4–3.4) (p < 0.0001). Median PFS were 9.9 (95% CI 7.2–11.5), 3.6 (95% CI 2.7–4.3), and 1.4 months (95% CI 1.2–2.2) (p < 0.0001). ORR was also associated with LIPI group (p < 0.001). Intermediate and poor LIPI were independently prognostic of OS compared to good LIPI, with hazard ratios (HR) of 1.8 (95% CI 1.4–2.3, p < 0.001) and 3.6 (95% CI 2.5–5.1, p < 0.001), respectively. These data are the first to suggest that in a real-world setting, the prognostic value of LIPI may be tumor agnostic.
Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity
Authors: Mejbel Haider A. , Arudra Sri Krishna C. , Pradhan Dinesh , Torres-Cabala Carlos A. , Nagarajan Priyadharsini , Tetzlaff Michael T. , Curry Jonathan L. , Ivan Doina , Duose Dzifa Y. , Luthra Raja , Prieto Victor G. , Ballester Leomar Y. , Aung Phyu P.
Published: November 2019

Melanoma is a heterogeneous neoplasm at the histomorphologic, immunophenotypic, and molecular levels. Melanoma with extreme histomorphologic heterogeneity can pose a diagnostic challenge in which the diagnosis may predominantly rely on its immunophenotypic profile. However, tumor survival and response to therapy are linked to tumor genetic heterogeneity rather than tumor morphology. Therefore, understating the molecular characteristics of such melanomas become indispensable. In this study, DNA was extracted from 11 morphologically distinct regions in eight formalin-fixed, paraffin-embedded melanomas. In each region, mutations in 50 cancer-related genes were tested using next-generation sequencing (NGS). A tumor was considered genetically heterogeneous if at least one non-overlapping mutation was identified either between the histologically distinct regions of the same tumor (intratumor heterogeneity) or among the histologically distinct regions of the paired primary and metastatic tumors within the same patient (intertumor heterogeneity). Our results revealed that genetic heterogeneity existed in all tumors as non-overlapping mutations were detected in every tested tumor (n = 5, 100%; intratumor: n = 2, 40%; intertumor: n = 3, 60%). Conversely, overlapping mutations were also detected in all the tested regions (n = 11, 100%). Melanomas exhibiting histomorphologic heterogeneity are often associated with genetic heterogeneity, which might contribute to tumor survival and poor response to therapy.
Balancing STAT Activity as a Therapeutic Strategy
Authors: Polak Kelsey L. , Chernosky Noah M. , Smigiel Jacob M. , Tamagno Ilaria , Jackson Mark W.
Published: November 2019

Driven by dysregulated IL-6 family member cytokine signaling in the tumor microenvironment (TME), aberrant signal transducer and activator of transcription (STAT3) and (STAT5) activation have been identified as key contributors to tumorigenesis. Following transformation, persistent STAT3 activation drives the emergence of mesenchymal/cancer-stem cell (CSC) properties, important determinants of metastatic potential and therapy failure. Moreover, STAT3 signaling within tumor-associated macrophages and neutrophils drives secretion of factors that facilitate metastasis and suppress immune cell function. Persistent STAT5 activation is responsible for cancer cell maintenance through suppression of apoptosis and tumor suppressor signaling. Furthermore, STAT5-mediated CD4+/CD25+ regulatory T cells (Tregs) have been implicated in suppression of immunosurveillance. We discuss these roles for STAT3 and STAT5, and weigh the attractiveness of different modes of targeting each cancer therapy. Moreover, we discuss how anti-tumorigenic STATs, including STAT1 and STAT2, may be leveraged to suppress the pro-tumorigenic functions of STAT3/STAT5 signaling.
Editorial Catalysts: Special Issue on Trends in Catalytic Wet Peroxide Oxidation Processes
Authors: Quintanilla Asunción , Munoz Macarena
Published: November 2019

The catalytic wet peroxide oxidation (CWPO) process is an advanced oxidation technology that has shown great potential for the decontamination of wastewater [...]
The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation
Authors: Shcherbik Natalia , Pestov Dimitri G.
Published: November 2019

The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be chemically modified by reactive oxygen species, which may alter the ribosome′s functions or cause a complete loss of functionality. The oxidative damage that ribosomes accumulate during their lifespan in a cell may lead to reduced or faulty translation and contribute to various pathologies. However, remarkably little is known about the biological consequences of oxidative damage to the ribosome. Here, we provide a concise summary of the known types of changes induced by reactive oxygen species in rRNA and ribosomal proteins and discuss the existing experimental evidence of how these modifications may affect ribosome dynamics and function. We emphasize the special role that redox-active transition metals, such as iron, play in ribosome homeostasis and stability. We also discuss the hypothesis that redox-mediated ribosome modifications may contribute to adaptive cellular responses to stress.
yRACK1/Asc1 proxiOMICs—Towards Illuminating Ships Passing in the Night
Authors: Schmitt Kerstin , Valerius Oliver
Published: November 2019

Diverse signals and stress factors regulate the activity and homeostasis of ribosomes in all cells. The Saccharomyces cerevisiae protein Asc1/yRACK1 occupies an exposed site at the head region of the 40S ribosomal subunit (hr40S) and represents a central hub for signaling pathways. Asc1 strongly affects protein phosphorylation and is involved in quality control pathways induced by translation elongation arrest. Therefore, it is important to understand the dynamics of protein formations in the Asc1 microenvironment at the hr40S. We made use of the in vivo protein-proximity labeling technique Biotin IDentification (BioID). Unbiased proxiOMICs from two adjacent perspectives identified nucleocytoplasmic shuttling mRNA-binding proteins, the deubiquitinase complex Ubp3-Bre5, as well as the ubiquitin E3 ligase Hel2 as neighbors of Asc1. We observed Asc1-dependency of hr40S localization of mRNA-binding proteins and the Ubp3 co-factor Bre5. Hel2 and Ubp3-Bre5 are described to balance the mono-ubiquitination of Rps3 (uS3) during ribosome quality control. Here, we show that the absence of Asc1 resulted in massive exposure and accessibility of the C-terminal tail of its ribosomal neighbor Rps3 (uS3). Asc1 and some of its direct neighbors together might form a ribosomal decision tree that is tightly connected to close-by signaling modules.
Quantitative Analysis of Photon Density of States for One-Dimensional Photonic Crystals in a Rectangular Waveguide
Authors: Jao Ruei-Fu , Lin Ming-Chieh
Published: November 2019

Light propagation in one-dimensional (1D) photonic crystals (PCs) enclosed in a rectangular waveguide is investigated in order to achieve a complete photonic band gap (PBG) while avoiding the difficulty in fabricating 3D PCs. This work complements our two previous articles (Phys. Rev. E) that quantitatively analyzed omnidirectional light propagation in 1D and 2D PCs, respectively, both showing that a complete PBG cannot exist if an evanescent wave propagation is involved. Here, we present a quantitative analysis of the transmission functions, the band structures, and the photon density of states (PDOS) for both the transverse electric (TE) and transverse magnetic (TM) polarization modes of the periodic multilayer heterostructure confined in a rectangular waveguide. The PDOS of the quasi-1D photonic crystal for both the TE and TM modes are obtained, respectively. It is demonstrated that a “complete PBG” can be obtained for some frequency ranges and categorized into three types: (1) below the cutoff frequency of the fundamental TE mode, (2) within the PBG of the fundamental TE mode but below the cutoff frequency of the next higher order mode, and (3) within an overlap of the PBGs of either TE modes, TM modes, or both. These results are of general importance and relevance to the dipole radiation or spontaneous emission by an atom in quasi-1D periodic structures and may have applications in future photonic quantum technologies.
Integrated Information Theory and Isomorphic Feed-Forward Philosophical Zombies
Authors: Hanson Jake R. , Walker Sara I.
Published: November 2019

Any theory amenable to scientific inquiry must have testable consequences. This minimal criterion is uniquely challenging for the study of consciousness, as we do not know if it is possible to confirm via observation from the outside whether or not a physical system knows what it feels like to have an inside—a challenge referred to as the “hard problem” of consciousness. To arrive at a theory of consciousness, the hard problem has motivated development of phenomenological approaches that adopt assumptions of what properties consciousness has based on first-hand experience and, from these, derive the physical processes that give rise to these properties. A leading theory adopting this approach is Integrated Information Theory (IIT), which assumes our subjective experience is a “unified whole”, subsequently yielding a requirement for physical feedback as a necessary condition for consciousness. Here, we develop a mathematical framework to assess the validity of this assumption by testing it in the context of isomorphic physical systems with and without feedback. The isomorphism allows us to isolate changes in Φ without affecting the size or functionality of the original system. Indeed, the only mathematical difference between a “conscious” system with Φ > 0 and an isomorphic “philosophical zombie” with Φ = 0 is a permutation of the binary labels used to internally represent functional states. This implies Φ is sensitive to functionally arbitrary aspects of a particular labeling scheme, with no clear justification in terms of phenomenological differences. In light of this, we argue any quantitative theory of consciousness, including IIT, should be invariant under isomorphisms if it is to avoid the existence of isomorphic philosophical zombies and the epistemological problems they pose.
A Reference-Free Lossless Compression Algorithm for DNA Sequences Using a Competitive Prediction of Two Classes of Weighted Models
Authors: Pratas Diogo , Hosseini Morteza , Silva Jorge M. , Pinho Armando J.
Published: November 2019

The development of efficient data compressors for DNA sequences is crucial not only for reducing the storage and the bandwidth for transmission, but also for analysis purposes. In particular, the development of improved compression models directly influences the outcome of anthropological and biomedical compression-based methods. In this paper, we describe a new lossless compressor with improved compression capabilities for DNA sequences representing different domains and kingdoms. The reference-free method uses a competitive prediction model to estimate, for each symbol, the best class of models to be used before applying arithmetic encoding. There are two classes of models: weighted context models (including substitutional tolerant context models) and weighted stochastic repeat models. Both classes of models use specific sub-programs to handle inverted repeats efficiently. The results show that the proposed method attains a higher compression ratio than state-of-the-art approaches, on a balanced and diverse benchmark, using a competitive level of computational resources. An efficient implementation of the method is publicly available, under the GPLv3 license.