bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological Effects of Low Salinity Exposure on Bottlenose Dolphins (Tursiops truncatus)
Authors: McClain Abby M. , Daniels Risa , Gomez Forrest M. , Ridgway Sam H. , Takeshita Ryan , Jensen Eric D. , Smith Cynthia R.
Published: November 2020

Bottlenose dolphins (Tursiops truncatus) have a worldwide distribution in temperate and tropical waters and often inhabit estuarine environments, indicating their ability to maintain homeostasis in low salinity for limited periods of time. Epidermal and biochemical changes associated with low salinity exposure have been documented in stranded bottlenose dolphins; however, these animals are often found severely debilitated or deceased and in poor condition. Dolphins in the U.S. Navy Marine Mammal Program travel globally, navigating varied environments comparable to those in which free-ranging dolphins are observed. A retrospective analysis was performed of medical records from 46 Navy dolphins and blood samples from 43 Navy dolphins exposed to a variety of salinity levels for different durations over 43 years (from 1967–2010). Blood values from samples collected during low salinity environmental exposure (salinity ranging from 0–30 parts per thousand (ppt) were compared to samples collected while those same animals were in a seawater environment (31–35 ppt). Epidermal changes associated with low salinity exposure were also assessed. Significant decreases in serum sodium, chloride, and calculated serum osmolality and significant increases in blood urea nitrogen and aldosterone were observed in blood samples collected during low salinity exposure. Epidermal changes were observed in 35% of the animals that spent time in low salinity waters. The prevalence of epidermal changes was inversely proportional to the level of salinity to which the animals were exposed. Future work is necessary to fully comprehend the impacts of low salinity exposure in bottlenose dolphins, but the physiological changes observed in this study will help improve our understanding of the upper limit of duration and the lower limit of salinity in which a bottlenose dolphin can maintain homeostasis.
Efficiency of DNA Isolation Methods Based on Silica Columns and Magnetic Separation Tested for the Detection of Mycobacterium avium Subsp. Paratuberculosis in Milk and Faeces
Authors: Husakova Marketa , Kralik Petr , Babak Vladimir , Slana Iva
Published: November 2020

Timely and reliable detection of animals shedding Mycobacterium avium subsp. paratuberculosis (MAP) should help to effectively identify infected animals and limit infection transmission at early stages to ensure effective control of paratuberculosis. The aim of the study was to compare DNA extraction methods and evaluate isolation efficiency using milk and faecal samples artificially contaminated by MAP with a focus on modern instrumental automatic DNA isolation procedures based on magnetic separation. In parallel, an automatic and manual version of magnetic separation and two methods of faecal samples preparation were compared. Commercially available DNA isolation kits were evaluated, and the selected kits were used in a trial of automatic magnetic beads-based isolation and compared with the manual version of each kit. Detection of the single copy element F57 was performed by qPCR to quantify MAP and determine the isolation efficiency. The evaluated kits showed significant differences in DNA isolation efficiencies. The best results were observed with the silica column Blood and Tissue kit for milk and Zymo Research for faeces. The highest isolation efficiency for magnetic separation was achieved with MagMAX for both matrices. The magnetic separation and silica column isolation methods used in this study represent frequently used methods in mycobacterial diagnostics.
Enhanced Magneto-Optic Properties in Sputtered Bi- Containing Ferrite Garnet Thin Films Fabricated Using Oxygen Plasma Treatment and Metal Oxide Protective Layers
Authors: Kotov V. , Nur-E-Alam M. , Vasiliev M. , Alameh K. , Balabanov D. , Burkov V.
Published: November 2020

Magneto-optic (MO) imaging and sensing are at present the most developed practical applications of thin-film MO garnet materials. However, in order to improve sensitivity for a range of established and forward-looking applications, the technology and component-related advances are still necessary. These improvements are expected to originate from new material system development. We propose a set of technological modifications for the RF-magnetron sputtering deposition and crystallization annealing of magneto-optic bismuth-substituted iron-garnet films and investigate the improved material properties. Results show that standard crystallization annealing for the as-deposited ultrathin (sputtered 10 nm thick, amorphous phase) films resulted in more than a factor of two loss in the magneto-optical activity of the films in the visible spectral region, compared to the liquid-phase grown epitaxial films. Results also show that an additional 10 nm-thick metal-oxide (Bi2O3) protective layer above the amorphous film results in ~2.7 times increase in the magneto-optical quality of crystallized iron-garnet films. On the other hand, the effects of post-deposition oxygen (O2) plasma treatment on the magneto-optical (MO) properties of Bismuth substituted iron garnet thin film materials are investigated. Results show that in the visible part of the electromagnetic spectrum (at 532 nm), the O2 treated (up to 3 min) garnet films retain higher specific Faraday rotation and figures of merit compared to non-treated garnet films.
Elucidating the Sound Absorption Characteristics of Foxtail Millet (Setariaitalica) Husk
Authors: Balasubramanian Dhayalini , Rajendran Senthil , Srinivasan Bhuvanesh , Angamuthu Nirmalakumari
Published: November 2020

The current study deals with the analysis of sound absorption characteristics of foxtail millet husk powder. Noise is one the most persistent pollutants which has to be dealt seriously. Foxtail millet is a small seeded cereal cultivated across the world and its husk is less explored for its utilization in polymer composites. The husk is the outer protective covering of the seed, rich in silica and lingo-cellulose content making it suitable for sound insulation. The acoustic characterization is done for treated foxtail millet husk powder and polypropylene composite panels. The physical parameters like fiber mass content, density, and thickness of the composite panel were varied and their influence over sound absorption was mapped. The influence of porosity, airflow resistance, and tortuosity was also studied. The experimental result shows that 30-mm thick foxtail millet husk powder composite panel with 40% fiber mass content, 320 kg/m3 density showed promising sound absorption for sound frequency range above 1000 Hz. We achieved noise reduction coefficient (NRC) value of 0.54. In view to improve the performance of the panel in low-frequency range, we studied the efficiency of incorporating air gap and rigid backing material to the designed panel. We used foxtail millet husk powder panel of density 850 kg/m3 as rigid backing material with varying air gap thickness. Thus the composite of 320 kg/m3 density, 30-mm thick when provided with 35-mm air gap and backing material improved the composite’s performance in sound frequency range 250 Hz to 1000 Hz. The overall sound absorption performance was improved and the NRC value and average sound absorption coefficient (SAC) were increased to 0.7 and 0.63 respectively comparable with the commercial acoustic panels made out of the synthetic fibers. We have calculated the sound absorption coefficient values using Delany and Bezlay model (D&B model) and Johnson–Champoux–Allard model (JCA model) and compared them with the measured sound absorption values.
Load Controlled Fatigue Behaviour of Microplasma Arc Welded Thin Titanium Grade 5 (6Al-4V) Sheets
Authors: Szusta Jaroslaw , Tüzün Nail , Karakaş Özler
Published: November 2020

The current study investigates the load controlled fatigue properties of the microplasma arc welded thin titanium Grade 5 (6Al-4V) sheets. In order to explore the effect of weld geometry on the fatigue, two different welded joints were used in the experimental studies. Load controlled fatigue test results were evaluated to present an outlook on the behaviour of microplasma welded titanium alloy Grade 5 sheets under cyclic loading. Even though the previously published monotonic tests showed successful use of microplasma arc welding to join thin titanium Grade 5 sheets with mechanical properties comparable to the base metal, fatigue life of the welded joints was lower than the lives of samples without welds. In particular, the fatigue performance of overlap joints was very poor. This was presumed to be due to the changed material properties of the heat affected zone which was formed by the excess heat of the welding process as fractures often occurred at such locations. Based on experimental findings and fractographic observations, a clear adverse effect of welding process in material behaviour was discovered. Despite the concentrated heat of microplasma arc welding, post-weld heat treatment of the weld area is recommended to improve the mechanical behaviour of the welded joints.
Effects of Multiple-Hole Baffle Arrangements on Flow Fields in a Five-Strand Asymmetric Tundish
Authors: Zhang Binglong , Liu Fuhai , Zhu Rong , Zhu Jinfeng
Published: November 2020

This paper reports on the re-engineering of standard five-strand tundish designs into a five-strand asymmetric tundish, which resulted in a non-uniform rate and bias for each strand. We sought to improve the casting conditions by optimizing the liquid steel flow-field in the tundish. Both a water modelling experiment and a numerical simulation were performed to analyze the flow-field according to various diversion hole diameters and injection angles. The results showed that the average residence time decreased as the diameter of the diversion holes increased. As the injection angle was increased, the average residence time initially decreased and then increased. The liquid steel from the ladle shroud rapidly extended to the #2 and #3 strands in the original tundish, which reduced the likelihood of inclusion collision and coalescence.
The Importance of Phase Composition for Corrosion Resistance of Borided Layers Produced on Nickel Alloys
Authors: Makuch Natalia
Published: November 2020

The plasma paste boriding process was used for production of the borided layers on pure nickel and nickel-chromium alloys. The produced layers consisted of nickel borides only (in the case of nickel) or a nickel and chromium borides mixture (in the case Ni–Cr alloys). The objective of this investigation was to indicate the importance of the presence of chromium for corrosion resistance of non-borided alloys, as well as to indicate the influence of phase composition of borided layers on their corrosion resistance. Pure nickel was characterized by higher corrosion resistance, in comparison to the nickel-based alloys. Increased chromium content in nickel alloys resulted in their high susceptibility for pitting corrosion. All borided samples were characterized by higher corrosion resistance than the non-borided samples. However, the phase composition of borided layers influenced their corrosion resistance. Due to the microstructure which consisted of one type of borides (nickel borides), borided nickel had the highest resistance to corrosion, whereas the presence of chromium borides in layers produced on nickel-chromium alloys caused a decrease in corrosion resistance.
Ten-Coordinate Lanthanide [Ln(HL)(L)] Complexes (Ln = Dy, Ho, Er, Tb) with Pentadentate N3O2-Type Schiff-Base Ligands: Synthesis, Structure and Magnetism
Authors: Bazhenova Tamara A. , Yakushev Ilya A. , Lyssenko Konstantin A. , Maximova Olga V. , Mironov Vladimir S. , Manakin Yuriy V. , Kornev Alexey B. , Vasiliev Alexander N. , Yagubskii Eduard B.
Published: November 2020

A series of five neutral mononuclear lanthanide complexes [Ln(HL)(L)] (Ln = Dy3+, Ho3+ Er3+ and Tb3+) with rigid pentadentate N3O2-type Schiff base ligands, H2LH (1-Dy, 3-Ho, 4-Er and 6-Tb complexes) or H2LOCH3, (2-Dy complex) has been synthesized by reaction of two equivalents of 1,1′-(pyridine-2,6-diyl)bis(ethan-1-yl-1-ylidene))dibenzohydrazine (H2LH, [H2DAPBH]) or 1,1′-(pyridine-2,6-diyl)bis(ethan-1-yl-1-ylidene))di-4-methoxybenzohydrazine (H2LOCH3, [H2DAPMBH]) with common lanthanide salts. The terbium complex [Tb(LH)(NO3)(H2O)2](DME)2 (5-Tb) with one ligand H2LH was also obtained and characterized. Single crystal X-ray analysis shows that complexes 1–4 have the composition {[Ln3+(HL)−(L)2−] solv} and similar molecular structures. In all the compounds, the central Ln3+ ion is chelated by two interlocked pentadentate ligands resulting in the coordination number of ten. Each lanthanide ion is coordinated by six nitrogen atoms and four oxygen atoms of the two N3O2 chelating groups forming together a distorted bicapped square antiprismatic polyhedron N6O4 with two capping pyridyl N atoms in the apical positions. The ac magnetic measurements reveal field-induced single-molecule magnet (SMM) behavior of the two dysprosium complexes (with barriers of Ueff = 29 K at 800 Oe in 1-Dy and Ueff = 70 K at 300 Oe in 2-Dy) and erbium complex (Ueff = 87 K at 1500 Oe in 4-Er); complex 3-Ho with a non-Kramers Ho3+ ion is SMM-silent. Although 2-Dy differs from 1-Dy only by a distant methoxy-group in the phenyl ring of the ligand, their dynamic magnetic properties are markedly different. This feature can be due to the difference in long-range contributions (beyond the first coordination sphere) to the crystal-field (CF) potential of 4f electrons of Dy3+ ion that affects magnetic characteristics of the ground and excited CF states. Magnetic behavior and the electronic structure of Ln3+ ions of 1–4 complexes are analyzed in terms of CF calculations.
The Magnetic Band-Structures of Ordered PtxFe1−x, PtxCo1−x, and PtxNi1−x (x = 0.25, 0.50, and 0.75)
Authors: Shuttleworth Ian
Published: November 2020

The electronic band structures of the ordered L12 and L10 phases of the PtxM1−x (M = Fe, Co and Ni) alloys were investigated using spin-polarized density functional theory (DFT). The relative contributions of both itinerant (Stoner) and localized magnetism at the high-symmetry k-points were determined and discussed qualitatively. Significant directional effects were identified along the A and R directions of the L10 and L12 alloys, respectively, and are discussed in terms of charge channeling effects.
Do Randomized Algorithms Improve the Efficiency of Minimal Learning Machine?
Authors: Linja Joakim , Hämäläinen Joonas , Nieminen Paavo , Kärkkäinen Tommi
Published: November 2020

Minimal Learning Machine (MLM) is a recently popularized supervised learning method, which is composed of distance-regression and multilateration steps. The computational complexity of MLM is dominated by the solution of an ordinary least-squares problem. Several different solvers can be applied to the resulting linear problem. In this paper, a thorough comparison of possible and recently proposed, especially randomized, algorithms is carried out for this problem with a representative set of regression datasets. In addition, we compare MLM with shallow and deep feedforward neural network models and study the effects of the number of observations and the number of features with a special dataset. To our knowledge, this is the first time that both scalability and accuracy of such a distance-regression model are being compared to this extent. We expect our results to be useful on shedding light on the capabilities of MLM and in assessing what solution algorithms can improve the efficiency of MLM. We conclude that (i) randomized solvers are an attractive option when the computing time or resources are limited and (ii) MLM can be used as an out-of-the-box tool especially for high-dimensional problems.
Probabilistic Jacobian-Based Saliency Maps Attacks
Authors: Combey Théo , Loison António , Faucher Maxime , Hajri Hatem
Published: November 2020

Neural network classifiers (NNCs) are known to be vulnerable to malicious adversarial perturbations of inputs including those modifying a small fraction of the input features named sparse or L0 attacks. Effective and fast L0 attacks, such as the widely used Jacobian-based Saliency Map Attack (JSMA) are practical to fool NNCs but also to improve their robustness. In this paper, we show that penalising saliency maps of JSMA by the output probabilities and the input features of the NNC leads to more powerful attack algorithms that better take into account each input’s characteristics. This leads us to introduce improved versions of JSMA, named Weighted JSMA (WJSMA) and Taylor JSMA (TJSMA), and demonstrate through a variety of white-box and black-box experiments on three different datasets (MNIST, CIFAR-10 and GTSRB), that they are both significantly faster and more efficient than the original targeted and non-targeted versions of JSMA. Experiments also demonstrate, in some cases, very competitive results of our attacks in comparison with the Carlini-Wagner (CW) L0 attack, while remaining, like JSMA, significantly faster (WJSMA and TJSMA are more than 50 times faster than CW L0 on CIFAR-10). Therefore, our new attacks provide good trade-offs between JSMA and CW for L0 real-time adversarial testing on datasets such as the ones previously cited.
High Temperature Anti-Oxidation Behavior and Mechanical Property of Radio Frequency Magnetron Sputtered Cr Coating
Authors: Li Guangbin , Liu Yanhong , Zhang Yingchun , Li Huailin , Wang Xiaojing , Zheng Mingmin , Li Yusha
Published: November 2020

A dense and uniform Cr coating was fabricated on the zirconium alloys fuel claddings by radio frequency (RF) magnetron sputtering to improve the mechanical and anti-oxidation properties under 1200 °C steam environment. The phase composition and the micro and macro morphologies of the specimens were investigated by X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), scanning electron microscope (SEM) and optical-microtopography (OM) analyses, and the high-temperature oxidation behavior was evaluated at 1200 °C steam environment for 3000 s. In this paper, there exists a positive correlation between thickness and Vickers hardness (HV), and a negative correlation between surface roughness and bonding force. Radial tensile was introduced to investigate the deformation-resistant performance, and the displacement of the Cr-coated specimen was as low as 2.32 mm, which was much lower than the uncoated zircaloy cladding (3.05 mm). Different thicknesses of Cr coatings were deposited to investigate the oxidation degrees of zircaloy cladding under a high-temperature steam environment. The optimal 6 μm Cr-coated zirconium alloys cladding exhibited an excellent anti-oxidation property, and the weight gain was as low as ~4.12 mg/cm2, which was almost one-third of the uncoated specimen.
Enteroviruses from Humans and Great Apes in the Republic of Congo: Recombination within Enterovirus C Serotypes
Authors: Amona Inestin , Medkour Hacène , Akiana Jean , Davoust Bernard , Tall Mamadou Lamine , Grimaldier Clio , Gazin Celine , Zandotti Christine , Levasseur Anthony , Scola Bernard La , Raoult Didier , Fenollar Florence , Banga-Mboko Henri , Mediannikov Oleg
Published: November 2020

Enteroviruses (EVs) are viruses of the family Picornaviridae that cause mild to severe infections in humans and in several animal species, including non-human primates (NHPs). We conducted a survey and characterization of enteroviruses circulating between humans and great apes in the Congo. Fecal samples (N = 24) of gorillas and chimpanzees living close to or distant from humans in three Congolese parks were collected, as well as from healthy humans (N = 38) living around and within these parks. Enteroviruses were detected in 29.4% of gorilla and 13.15% of human feces, including wild and human-habituated gorillas, local humans and eco-guards. Two identical strains were isolated from two humans coming from two remote regions. Their genomes were similar and all genes showed their close similarity to coxsackieviruses, except for the 3C, 3D and 5′-UTR regions, where they were most similar to poliovirus 1 and 2, suggesting recombination. Recombination events were found between these strains, poliovirus 1 and 2 and EV-C99. It is possible that the same EV-C species circulated in both humans and apes in different regions in the Congo, which must be confirmed in other investigations. In addition, other studies are needed to further investigate the circulation and genetic diversity of enteroviruses in the great ape population, to draw a definitive conclusion on the different species and types of enteroviruses circulating in the Republic of Congo.
Review on the Compositional Variation of Eudialyte-Group Minerals in the Ilímaussaq Complex (South Greenland)
Authors: Marks Michael A.W. , Eggenkamp Hans G.M. , Atanasova Petya , Mundel Felicitas , Kümmel Sascha , Hagen Matthias , Wenzel Thomas , Markl Gregor
Published: November 2020

We review the compositional variation of eudialyte-group minerals (EGM) from the Ilímaussaq complex in South Greenland. Investigated samples cover all major rock units and associated pegmatites and aplites. The whole data set (>3000 analyses from >250 samples) exhibits variable XMn (0.1–0.5), REE (0.2–1.7 apfu), Nb (0.1–0.4), and Cl contents (0.4–1.6 apfu). Most EGM compositions are Na-rich (13–15 apfu), while deviations to Na-rich but also to Na-poor compositions occur because of a combination of primary features (peralkalinity, water activity) and secondary alteration. During magma evolution, REE contents in EGM cores generally increase and reach their highest contents in the most evolved rock units of the complex. This points to the moderate compatibility of REE in EGM and a bulk D (cEGM/cmelt) value of <1 during magma differentiation. Chlorine contents in EGM cores continuously decrease, and are lowest at the rims of individual crystals, suggesting a continuous decrease of Cl activity in the magmas by large-scale EGM and sodalite extraction during the orthomagmatic stage and water enrichment during the late-magmatic stage. The overall variations of XMn across stratigraphy are only minor and likely influenced by the co-crystallization of sodic pyroxene and amphibole (c.f. aegirine, arfvedsonite) and local phase proportions. Similarly, Nb and Ti contents are influenced by co-crystallizing aenigmatite, rinkite, and others. Their presence buffers Ti and Nb contents to rather constant and low values, while their absence may cause variable enrichment on a local scale. Very low Sr contents (<0.1 apfu) in magmatic EGM from Ilímaussaq are related to the basaltic nature of the parental magmas of the complex, as large-scale plagioclase fractionation occurred prior to the formation of the Ilímaussaq magmas, effectively removing Sr from the system. This is in line with very strong negative Eu anomalies in EGM from Ilímaussaq. Consistently, Sr contents in EGM from alkaline complexes, for which foiditic parental magmas are assumed, are much higher and, in such cases, negative Eu anomalies are generally absent.
A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro
Authors: Ben Toumia Imene , Sobeh Mansour , Ponassi Marco , Banelli Barbara , Dameriha Anas , Wink Michael , Chekir Ghedira Leila , Rosano Camillo
Published: November 2020

Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.
ATP Analogues for Structural Investigations: Case Studies of a DnaB Helicase and an ABC Transporter
Authors: Lacabanne Denis , Wiegand Thomas , Wili Nino , Kozlova Maria I. , Cadalbert Riccardo , Klose Daniel , Mulkidjanian Armen Y. , Meier Beat H. , Böckmann Anja
Published: November 2020

Nucleoside triphosphates (NTPs) are used as chemical energy source in a variety of cell systems. Structural snapshots along the NTP hydrolysis reaction coordinate are typically obtained by adding stable, nonhydrolyzable adenosine triphosphate (ATP) -analogues to the proteins, with the goal to arrest a state that mimics as closely as possible a physiologically relevant state, e.g., the pre-hydrolytic, transition and post-hydrolytic states. We here present the lessons learned on two distinct ATPases on the best use and unexpected pitfalls observed for different analogues. The proteins investigated are the bacterial DnaB helicase from Helicobacter pylori and the multidrug ATP binding cassette (ABC) transporter BmrA from Bacillus subtilis, both belonging to the same division of P-loop fold NTPases. We review the magnetic-resonance strategies which can be of use to probe the binding of the ATP-mimics, and present carbon-13, phosphorus-31, and vanadium-51 solid-state nuclear magnetic resonance (NMR) spectra of the proteins or the bound molecules to unravel conformational and dynamic changes upon binding of the ATP-mimics. Electron paramagnetic resonance (EPR), and in particular W-band electron-electron double resonance (ELDOR)-detected NMR, is of complementary use to assess binding of vanadate. We discuss which analogues best mimic the different hydrolysis states for the DnaB helicase and the ABC transporter BmrA. These might be relevant also to structural and functional studies of other NTPases.
Influence of Chitin Source and Polymorphism on Powder Compression and Compaction: Application in Drug Delivery
Authors: Al-Hmoud Linda , Abu Fara Deeb , Rashid Iyad , Chowdhry Babur Z. , Badwan Adnan A.
Published: November 2020

The objective of the research reported herein is to compare the compaction properties of three different chitin extracts from the organisms most used in the seafood industry; namely crabs, shrimps and squids. The foregoing is examined in relation to their polymorphic forms as well as compression and compaction behavior. Chitin extracted from crabs and shrimps exhibits the α-polymorphic form whilst chitin extracted from squid pins displays a β-polymorphic form. These polymorphs were characterized using FTIR, X-ray powder diffraction and scanning electron microscopy. Pore diameter and volume differ between the two polymorphic powder forms. The β form is smaller in pore diameter and volume. Scanning electron microscopy of the two polymorphic forms shows clear variation in the arrangement of chitin layers such that the α form appears more condensed due to the anti-parallel arrangement of the polymer chains. True, bulk and tapped densities of these polymorphs and their mixtures indicated poor flowability. Nevertheless, compression and compaction properties obtained by applying Heckle and Kawakita analyses indicated that both polymorphs are able to be compacted with differences in the extent of compaction. Chitin compacts, regardless of their origin, showed a very high crushing strength with very fast dissolution which makes them suitable for use as fast mouth dissolving tablets. Moreover, when different chitin powders are granulated with two model drugs, i.e., metronidazole and spiramycin they yielded high crushing strength and their dissolution profiles were in accordance with compendial requirements. It is concluded that the source of chitin extraction is as important as the polymorphic form when compression and compaction of chitin powders is carried out.
Impact of Brewing Methods on Total Phenolic Content (TPC) in Various Types of Coffee
Authors: Olechno Ewa , Puścion-Jakubik Anna , Markiewicz-Żukowska Renata , Socha Katarzyna
Published: November 2020

Coffee is a widely consumed beverage, both in Europe, where its consumption is highest, and on other continents. It provides many compounds, including phenolic compounds. The aim of the study was to assess the effect of various brewing methods on the total phenolic content (TPC) in the infusion. Research material comprised commercially available coffees: Instant Arabica and Robusta, freshly ground Arabica and Robusta (immediately prior to the analysis), ground Arabica and Robusta, decaffeinated Arabica, and green Arabica and Robusta. The following preparation methods were used: Pouring hot water over coffee grounds or instant coffee, preparing coffee in a percolator and using a coffee machine. Additional variables which were employed were water temperature (90 or 100 °C) and its type (filtered or unfiltered). In order to determine the impact of examined factors, 225 infusion were prepared. Total phenolic content was determined by the spectrophotometric method using the Folin-Ciocalteu reagent and the obtained results were expressed in mg gallic acid (GAE) per 100 g of brewed coffee. The highest value was obtained for 100% Arabica ground coffee prepared in a coffee percolator using unfiltered water at a temperature of 100 °C: 657.3 ± 23 mg GAE/100 g of infusion. High values were also observed for infusions prepared in a coffee machine, where the highest TPC value was 363.8 ± 28 mg GAE/100 g for ground Arabica. In turn, the lowest TPC was obtained for Arabica green coffee in opaque packaging, brewed with filtered water at a temperature of 100 °C: 19.5 ± 1 mg GAE/100 g of infusion. No significant effect of temperature and water type on the TPC within one type of coffee was observed. Due to its high content of phenolic compounds, Arabica coffee brewed in a coffee percolator should be the most popular choice for coffee drinkers.
Cancer Research in the “Chemical Biology” Section of the Journal Molecules
Authors: Corson Timothy W.
Published: November 2020

The Chemical Biology Section of Molecules, like the discipline it represents, is diverse, dynamic, and growing rapidly [...]
Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents
Authors: Mbaba Mziyanda , Golding Taryn M. , Smith Gregory S.
Published: November 2020

In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.
Machine Learning Methods in Drug Discovery
Authors: Patel Lauv , Shukla Tripti , Huang Xiuzhen , Ussery David W. , Wang Shanzhi
Published: November 2020

The advancements of information technology and related processing techniques have created a fertile base for progress in many scientific fields and industries. In the fields of drug discovery and development, machine learning techniques have been used for the development of novel drug candidates. The methods for designing drug targets and novel drug discovery now routinely combine machine learning and deep learning algorithms to enhance the efficiency, efficacy, and quality of developed outputs. The generation and incorporation of big data, through technologies such as high-throughput screening and high through-put computational analysis of databases used for both lead and target discovery, has increased the reliability of the machine learning and deep learning incorporated techniques. The use of these virtual screening and encompassing online information has also been highlighted in developing lead synthesis pathways. In this review, machine learning and deep learning algorithms utilized in drug discovery and associated techniques will be discussed. The applications that produce promising results and methods will be reviewed.
Signalling Properties of Inositol Polyphosphates
Authors: Maffucci Tania , Falasca Marco
Published: November 2020

Several studies have identified specific signalling functions for inositol polyphosphates (IPs) in different cell types and have led to the accumulation of new information regarding their cellular roles as well as new insights into their cellular production. These studies have revealed that interaction of IPs with several proteins is critical for stabilization of protein complexes and for modulation of enzymatic activity. This has not only revealed their importance in regulation of several cellular processes but it has also highlighted the possibility of new pharmacological interventions in multiple diseases, including cancer. In this review, we describe some of the intracellular roles of IPs and we discuss the pharmacological opportunities that modulation of IPs levels can provide.
Silane Coupling Agent Modifies the Mechanical Properties of a Chitosan Microfiber
Authors: Shirosaki Yuki , Okabayashi Toshinobu , Yasutomi Saki
Published: November 2020

Chitosan microfibers are widely used in medical applications because they have favorable inherent properties. However, their mechanical properties require further improvement. In the present study, a trimethoxysilane aldehyde (TMSA) crosslinking agent was added to chitosan microfibers to improve their tensile strength. The chitosan microfibers were prepared using a coagulation method. The tensile strength of the chitosan microfibers was improved by crosslinking them with TMSA, even when only a small amount was used (less than 1%). TMSA did not change the orientation of the chitosan molecules. Furthermore, aldehyde derived from TMSA did not remain, and siloxane units were formed in the microfibers.
Virtual Screening and In Vitro Evaluation of PD-L1 Dimer Stabilizers for Uncoupling PD-1/PD-L1 Interaction from Natural Products
Authors: Lung Jrhau , Hung Ming-Szu , Lin Yu-Ching , Hung Chien-Hui , Chen Chih-Cheng , Lee Kuan-Der , Tsai Ying
Published: November 2020

Genetic mutations accumulated overtime could generate many growth and survival advantages for cancer cells, but these mutations also mark cancer cells as targets to be eliminated by the immune system. To evade immune surveillance, cancer cells adopted different intrinsic molecules to suppress immune response. PD-L1 is frequently overexpressed in many cancer cells, and its engagement with PD-1 on T cells diminishes the extent of cytotoxicity from the immune system. To resume immunity for fighting cancer, several therapeutic antibodies disrupting the PD-1/PD-L1 interaction have been introduced in clinical practice. However, their immunogenicity, low tissue penetrance, and high production costs rendered these antibodies beneficial to only a limited number of patients. PD-L1 dimer formation shields the interaction interface for PD-1 binding; hence, screening for small molecule compounds stabilizing the PD-L1 dimer may make immune therapy more effective and widely affordable. In the current study, 111 candidates were selected from over 180,000 natural compound structures through virtual screening, contact fingerprint analysis, and pharmacological property prediction. Twenty-two representative candidates were further evaluated in vitro. Two compounds were found capable of inhibiting the PD-1/PD-L1 interaction and promoting PD-L1 dimer formation. Further structure optimization and clinical development of these lead inhibitors will eventually lead to more effective and affordable immunotherapeutic drugs for cancer patients.
Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations
Authors: Zorkina Yana , Abramova Olga , Ushakova Valeriya , Morozova Anna , Zubkov Eugene , Valikhov Marat , Melnikov Pavel , Majouga Alexander , Chekhonin Vladimir
Published: November 2020

Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.
Design Strategies of Conductive Hydrogel for Biomedical Applications
Authors: Xu Junpeng , Tsai Yu-Liang , Hsu Shan-hui
Published: November 2020

Conductive hydrogel, with electroconductive properties and high water content in a three-dimensional structure is prepared by incorporating conductive polymers, conductive nanoparticles, or other conductive elements, into hydrogel systems through various strategies. Conductive hydrogel has recently attracted extensive attention in the biomedical field. Using different conductivity strategies, conductive hydrogel can have adjustable physical and biochemical properties that suit different biomedical needs. The conductive hydrogel can serve as a scaffold with high swelling and stimulus responsiveness to support cell growth in vitro and to facilitate wound healing, drug delivery and tissue regeneration in vivo. Conductive hydrogel can also be used to detect biomolecules in the form of biosensors. In this review, we summarize the current design strategies of conductive hydrogel developed for applications in the biomedical field as well as the perspective approach for integration with biofabrication technologies.
Combination Antitumor Effect of Sorafenib via Calcium-Dependent Deactivation of Focal Adhesion Kinase Targeting Colorectal Cancer Cells
Authors: Jeong Keun-Yeong , Park Minhee , Sim Jae-Jun , Kim Hwan Mook
Published: November 2020

Sorafenib has been recently used for the treatment of patients with advanced colorectal cancer (CRC) and is recognized for its therapeutic value. However, the continuous use of sorafenib may cause resistance in the treatment of cancer patients. In this study, we investigated whether sorafenib exerts an enhanced anticancer effect on CRC cells via the calcium-mediated deactivation of the focal adhesion kinase (FAK) signaling pathways. The appropriate dose of sorafenib and lactate calcium salt (CaLa) for a combination treatment were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Then, cell cycle analysis was performed following treatment with 2.5 μM sorafenib and/or 2.5 mM CaLa. CRC cells were found to be in the G1 phase by sorafenib treatment, and they accumulated in the sub-G1 phase with CaLa treatment. Western blots and enzyme-linked immunosorbent assays were performed to analyze the elements of the recombinant activated factor (RAF) and focal adhesion kinase (FAK) signaling cascades. Sorafenib-inhibited RAF-dependent signaling in CRC cells, however, either did not affect the expression of Akt or increased it. As the upstream signaling of FAK was suppressed by CaLa, we observed that the expression of the sub-signaling phospho (p) AKT and p-mammalian target of rapamycin was also suppressed. Treatment with a combination of sorafenib and CaLa enhanced the antitumor activity of CRC cells. The % viability of CRC cells was significantly decreased compared to the single treatment with sorafenib or CaLa, and the accumulation of Sub G1 of CRC cells was clearly confirmed. The migration ability of CRC cells was significantly reduced. The findings of this study indicate that sorafenib will show further improved antitumor efficacy against CRC due to overcoming resistance through the use of CaLa.
Approach to the Dynamic of Carbamazepine and its Main Metabolites in Soil Contamination through the Reuse of Wastewater and Sewage Sludge
Authors: Malvar José Luis , Santos Juan Luis , Martín Julia , Aparicio Irene , Alonso Esteban
Published: November 2020

The release of pharmaceutically active compounds to the soils through the application of sewage sludge and the irrigation with wastewater, or even with surface water, is constant. The adsorption of these compounds onto the soil is one of the key factors affecting their fate in the environment and their potential environmental risks. In this work, the adsorption of carbamazepine (CBZ) and its metabolites, 3-hydroxy-carbamazepine (3OH-CBZ), carbamazepine-10,11-dihydro-10,11-epoxide (EP-CBZ), and 10,11-dihydro-10-hydroxycarbamazepine (10OH-CBZ), in three Mediterranean soils was evaluated using single-solute and four-solute experiments. The highest adsorptions were measured for 3OH-CBZ, followed by CBZ, EP-CBZ, and 10OH-CBZ, in that order. A high influence of the physicochemical characteristics of the compounds, pH, and soil characteristics in the adsorption of the studied compounds was observed and corroborated by the statistical analysis of the results. Moreover, a good fit was observed in the three isotherm models evaluated (linear, Freundlich, and Langmuir) in single-solute experiments (R2 > 0.90). However, a decrease of the measured adsorptions and a worse fit to the isotherm models were observed in the case of multiple-solute experiments. This could be mainly due to the competition established between the studied compounds for the active sites of the soils.
Timing and Frequency of Daily Energy Intake in Adults with Prediabetes and Overweight or Obesity and Their Associations with Body Fat
Authors: Mogensen Christina Sonne , Færch Kristine , Bruhn Lea , Amadid Hanan , Tetens Inge , Quist Jonas Salling , Clemmensen Kim Katrine Bjerring
Published: November 2020

Knowledge on how energy intake and macronutrients are distributed during the day and the role of daily eating patterns in body composition among adults with overweight/obesity and prediabetes is lacking. Therefore, we evaluated the diurnal dietary intake and studied the associations of daily eating patterns with body fat percentage. A total of 119 adults with prediabetes were included (mean (SD) HbA1c 41 (2.3) mmol/mol, BMI 31.5 (5.0) kg/m2, age 57.8 (9.3) years, 44% men). Information on dietary intake was obtained from self-reported food records for three consecutive days. All foods and beverages (except water) were registered with information on time of ingestion. Body fat was measured by dual-energy X-ray absorptiometry. A total of 60.5% of the participants reported a daily eating window of 12 or more hours/day, and almost half of the daily total energy intake was reported in the evening. In analyses adjusted for age, gender, and total daily energy intake, having the first daily energy intake one hour later was associated with slightly higher body fat percentage (0.64% per hour, 95% CI: 0.28; 1.01; p < 0.001), whereas higher meal frequency was associated with slightly lower body fat percentage (0.49% per extra daily meal, 95% CI: −0.81; −0.18; p = 0.002). Prospective studies are warranted to address the clinical implications of daily eating patterns on body fat and cardiometabolic health.
The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development
Authors: Rozner Reut , Vernikov Janna , Griess-Fishheimer Shelley , Travinsky Tamar , Penn Svetlana , Schwartz Betty , Mesilati-Stahy Ronit , Argov-Argaman Nurit , Shahar Ron , Monsonego-Ornan Efrat
Published: November 2020

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.