bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors for Marketing Innovation in Portuguese Firms CIS 2014
Authors: Monteiro Patrícia , Correia Aldina , Braga Vítor
Published: November 2019

Globalization, radical and frequent changes as well as the increasing importance of applying knowledge through the efficient implementation of innovation is critical under the current circumstances. Innovation has been the source of businesses competitive advantage, but it is not restricted to technological innovations, and thus marketing innovation also plays a central role. This is a significant topic in the marketing field and not yet deeply analysed in academic research. The main objective of this study is to understand what factors influence marketing innovation and to establish a business profile of firms that innovate or do not in marketing. We used multivariate statistical techniques, such as, multiple linear regression (with the Marketing Innovation Index as dependent variable) and discriminant analysis where the dependent variable is a dummy variable indicating if the firm innovates or not in marketing. The results suggest that there are several factors explaining marketing innovation, although in this study, we find that the factors contributing the most for marketing innovation are: the Organizational Innovation Index, customer and/or user suggestions, and intellectual property rights and licensing (IPRL). Most of the literature has studied these factors separately. This research studied such factors together, and it is clear that both organizational innovation and IPRL play an important role that drives firms to innovate in marketing, which differs from some literature; customer suggestions help in the process of marketing innovation, as some authors argue that customers do not always know what they want until they have it. In parallel, this study proved to be useful in understanding that the different values for the Marketing Innovation Index display no influence on the results, since they were equivalent when a dummy variable (innovated/not innovated in marketing) was used as a dependent variable. In practice, we realize that the factors are useful to clarify what Portuguese firms innovate or not in marketing, with no different results when we the four marketing innovation levels (design, distribution, advertising and price) are considered.
Prevention of Pathological Fracture of the Proximal Femur: A Systematic Review of Surgical and Percutaneous Image-Guided Techniques Used in Interventional Oncology
Authors: Rodrigues Laëtitia , Cornelis François H. , Reina Nicolas , Chevret Sylvie
Published: November 2019

Background and objectives: Patients suffering from bone metastasis are at high risk for pathological fractures and especially hip fractures. Osteolytic metastases can induce a high morbidity rate (i.e., pain, facture risk, mobility impairment), and operation on them can be difficult in this frail population having a reduced life expectancy. Several medical devices have been investigated for the prevention of these pathological hip fractures. Materials and Methods: To investigate these solutions, a literature review and a meta-analysis of primary studies was performed. Data sources included electronic databases (PubMed, CENTRAL and ClinicalTrials.gov) from 1990 until 1 January 2019. Titles, abstracts and full-text articles were reviewed in order to select only studies evaluating the performance of the studied solution to prevent osteoporotic and/or pathological hip fracture. The main outcomes were the occurrence of hip fracture, pain evaluation (VAS score) and adverse events occurrence (including severe adverse events and deaths). All randomised controlled trials (RCTs) and cohort studies were considered. A Bayesian cumulative meta-analysis was undertaken on the primary studies conducted in patients with bone metastasis. Results: A total of 12 primary studies were identified, all were cohort studies without a control group, and one compared two devices, and were thereafter considered separately. In those 12 samples, 255 patients were included, mean age 61.7 years. After implantation, the cumulative risk of fracture was 5.5% (95% confidence interval, 3.0% to 8.6%), and adverse event occurrence was 17.4% (95%CI, 12.6 to 22.8%), with a median follow-up of 10 months. The posterior probability of a fracture rate below 5% was 40.3%. Conclusions: The literature about medical devices evaluation for preventing hip fractures in metastatic patients is poor and mostly based on studies with a limited level of evidence. However, this systematic review shows promising results in terms of efficacy and tolerance of these devices in patients with bone metastases. This treatment strategy requires further investigations.
Influence of Pain on Knee Joint Movement and Moment during the Stance Phase in Patients with Severe Bilateral Knee Osteoarthritis: A Pilot Study
Authors: Fukaya Takashi , Mutsuzaki Hirotaka , Mori Koichi
Published: November 2019

Background and Objectives: The purpose of this study was to compare the side-to-side differences in knee joint movement and moment for the degree of pain in the walking stance phase in patients with bilateral knee osteoarthritis (KOA) of comparable severity. We hypothesized that knee joint movement and moment on the side with strong pain were lower compared with the side with weak pain. Materials and Methods: We included 11 patients diagnosed with bilateral severe KOA. In all patients’ left and right knees, the Kellgren–Lawrence radiographic scoring system grade was level 4, and the femorotibial angle and knee range of motion were equivalent. Following patients’ interviews with an orthopedic surgeon, we performed a comparative study with KOA with strong pain (KOAs) as the strong painful side and KOA with weak pain (KOAw) as the weak painful side. Data for changes in bilateral knee joint angles in three dimensions during the stance phase and bilateral knee sagittal and frontal moments exerted in the early and late stance phases were extracted from kinematics and kinetics analyses. Results: Three-dimensional joint movements in the knee joint were not significantly different in all phases between KOAs and KOAw. Knee extensor moment in the early stance phase in KOAs was significantly smaller than that in KOAw. Knee abductor moment in the early and late stance phase was not significantly different between KOAs and KOAw. Conclusions: Although we found no difference in joint motion in bilateral knee joints, knee extensor moment on the side with strong pain was decreased. In patients with bilateral severe KOA, it was suggested that the magnitude of knee pain contributed to the decrease in knee joint function.
Effect of the Average Energy on WC Grain Growth of WC-10Co-4Cr Composite by Laser Cladding
Authors: López-Baltazar Enrique A. , Ruiz-Luna Haideé , Baltazar-Hernández Víctor H. , Ruiz-Mondragón José Jorge , Ibarra-Medina Juansethi , Alvarado-Orozco Juan Manuel
Published: November 2019

In the present study, the microstructure evolution of WC-10Co-4Cr powder deposited on AISI-SAE 1020 steel substrate by laser cladding was evaluated, considering the effect of average energy per unit area. Single tracks were obtained by employing a Yb: YAG laser system with selected processing parameters. All samples were sectioned in the transverse direction for further characterization of the cladding. Results showed that dilution lay within 15% and 25%, whereas porosity was measured below 12%. According to microstructural analyses, considerable grain growth is developed within the central area of the cladding (namely, the inner region); additionally, the development of a triangular and/or polygonal morphology for WC particles along with a clear reduction in hardness was observed when employing a high average energy. It is worth noting that, in spite of the rapid thermal cycles developed during laser cladding of WC-10Co-4Cr, grain growth is attributed to a coalescence mechanism due to complete merging of WC into larger particles. Finally, the presence of small round or ellipsoidal particles within the inner region of the cladding suggested that non-merged particles occurred due to both an inhomogeneous dispersion and the lack of faced-shaped WC particles.
Investigation of Primary Carbides in a Commercial-Sized Electroslag Remelting Ingot of H13 Steel
Authors: Wang Xijie , Li Guangqiang , Liu Yu , Cao Yulong , Wang Fang , Wang Qiang
Published: November 2019

The characteristics of primary carbides in a commercial-sized (one ton) electroslag remelting (ESR) ingot of AISI H13 steel were investigated. The interaction between the primary carbides and inclusions was also clarified. The results indicate that there are two types of primary carbides, V-rich and Mo-rich primary carbides, in the H13 ESR ingot. The quantity, the area fraction, and the size of the two primary carbides tend to decrease from the center of the H13 ESR ingot to the outer surface. Additionally, the V-rich primary carbide is obviously larger than the Mo-rich primary carbide. The Al2O3 inclusion can promote the precipitation of the V-rich primary carbide, while the MnS inclusion encourages the precipitation of Mo-rich primary carbide. The CaO∙Al2O3 inclusion cannot act as the nucleation site for the precipitation of the two primary carbides. The solid fraction that the V-rich primary carbide begins to precipitate ranges from 0.965 to 0.983, and that for the Mo-rich primary carbide and the MnS inclusion change from 0.9990 to 0.9998 and from 0.989 to 0.990, respectively.
Flow Stress and Hot Deformation Activation Energy of 6082 Aluminium Alloy Influenced by Initial Structural State
Authors: Schindler Ivo , Kawulok Petr , Očenášek Vladivoj , Opěla Petr , Kawulok Rostislav , Rusz Stanislav
Published: November 2019

Stress-strain curves of the EN AW 6082 aluminium alloy with 1.2 Si-0.51 Mg-0.75 Mn (wt.%) were determined by the uniaxial compression tests at temperatures of 450–550 °C with a strain rate of 0.5–10 s−1. The initial structure state corresponded to three processing types: as-cast structure non-homogenized or homogenized at 500 °C, and the structure after homogenization and hot extrusion. Significantly higher flow stress appeared as a result of low temperature forming of the non-homogenized material. Hot deformation activation energy Q-values varied between 99 and 122 kJ·mol−1 for both homogenized materials and from 200 to 216 kJ·mol−1 for the as-cast state, while the Q-values calculated from the measured steady-state stress were always higher than those calculated from the peak stress values. For the extruded state of the 6082 alloy, the physically-based model was developed to reliably predict the flow stress influenced by dynamic softening, temperature, strain rate, and true strain up to 0.6.
Investigation on the Effect of Roasting and Leaching Parameters on Recovery of Gallium from Solid Waste Coal Fly Ash
Authors: Huang Jing , Wang Yingbin , Zhou Guanxuan , Gu Yu
Published: November 2019

Coal fly ash (CFA) provides important resources of gallium, which is regarded as an irreplaceable material in many technologies. A prospective roasting reagent assisted acid leaching process was proposed for the purpose of extracting gallium. The extraction efficiency of gallium by NaF (sodium fluoride) roasting followed by HNO3 (nitric acid) leaching process was demonstrated. The effect of roasting temperature, roasting time, the NaF-CFA mass ratio, acid leaching temperature, acid leaching time, and acid concentration were investigated. The results revealed that under optimal conditions (roasting temperature of 800 °C, roasting time of 10 min, acid leaching in 2 mol/L HNO3 for 1 h, and the NaF-CFA mass ratio of 0.75:1), 94% of gallium was extracted. Compared to previous studies, the process is a cost-effective method which can greatly shorten reaction time. It can reduce environmental pollution as it requires fewer acid reagents with low concentration and additives. It is expected to provide a method for the extraction of gallium from CFA.
Serum Steroid Profiling by Liquid Chromatography–Tandem Mass Spectrometry for the Rapid Confirmation and Early Treatment of Congenital Adrenal Hyperplasia: A Neonatal Case Report
Authors: Cicalini Ilaria , Tumini Stefano , Guidone Paola Irma , Pieragostino Damiana , Zucchelli Mirco , Franchi Sara , Lisi Gabriele , Lelli Chiesa Pierluigi , Stuppia Liborio , De Laurenzi Vincenzo , Rossi Claudia
Published: November 2019

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in some cases, of mineralocorticoids. A variety of clinical presentations accompany a range of severities, which are described as different forms of CAH, and are the result of these hormonal imbalances. The incidence of CAH worldwide is approximately 1 in 15,000 live births, and is population-dependent; thus, its inclusion in neonatal screening tests is widely discussed. Diagnosis of CAH is based on the quantification of 17-hydroxyprogesterone, usually by immunoassay, which has low specificity and high false-positive rates, resulting in a relatively high demand for a second-tier confirmation test. We report a case of a newborn recognized as female at birth, but showing ambiguous genitalia and other CAH clinical features, including hypernatremia, in the first days of life. In addition to the classical assays, liquid chromatography–tandem mass spectrometry was used to determine the serum steroid profile, allowing for the accurate and simultaneous quantification of seven steroids in the same analysis. Such an application immediately revealed an alteration in the levels of specific steroids related to CAH, leading to an early intervention by hormone replacement therapy. Subsequently, the diagnosis of classic CAH due to 21-hydroxylase deficiency was further confirmed by molecular testing.
Diversity of 2D Acoustofluidic Fields in an Ultrasonic Cavity Generated by Multiple Vibration Sources
Authors: Tang Qiang , Zhou Song , Huang Liang , Chen Zhong
Published: November 2019

Two-dimensional acoustofluidic fields in an ultrasonic chamber actuated by segmented ring-shaped vibration sources with different excitation phases are simulated by COMSOL Multiphysics. Diverse acoustic streaming patterns, including aggregation and rotational modes, can be feasibly generated by the excitation of several sessile ultrasonic sources which only vibrate along radial direction. Numerical simulation of particle trajectory driven by acoustic radiation force and streaming-induced drag force also demonstrates that micro-scale particles suspended in the acoustofluidic chamber can be trapped in the velocity potential well of fluid flow or can rotate around the cavity center with the circumferential acoustic streaming field. Preliminary investigation of simple Russian doll- or Matryoshka-type configurations (double-layer vibration sources) provide a novel method of multifarious structure design in future researches on the combination of phononic crystals and acoustic streaming fields. The implementation of multiple segmented ring-shaped vibration sources offers flexibility for the control of acoustic streaming fields in microfluidic devices for various applications. We believe that this kind of acoustofluidic design is expected to be a promising tool for the investigation of rapid microfluidic mixing on a chip and contactless rotational manipulation of biosamples, such as cells or nematodes.
Physical Characteristics of and Transient Response from Thin Cylindrical Piezoelectric Transducers Used in a Petroleum Logging Tool
Authors: Fa Lin , Tu Nan , Qu Hao , Wu Yingrui , Sun Ke , Zhang Yandong , Liang Meng , Fang Xiangrong , Zhao Meishan
Published: November 2019

We report on a transient response model of thin cylindrical piezoelectric transducers used in the petroleum logging tools, parallel to a recently established transient response model of thin spherical-shell transducers. Established on a series of parallel-connected equivalent-circuits, this model provides insightful information on the physical characteristics of the thin cylindrical piezoelectric transducers, i.e., the transient response, center-frequency, and directivity of the transducer. We have developed a measurement system corresponding to the new model to provide a state-of-the-art comparison between theory and experiment. We found that the measured results were in good agreement with those of theoretical calculations.
Phenotypes Associated with Pathogenicity: Their Expression in Arctic Fungal Isolates
Authors: Perini Laura , Mogrovejo Diana C. , Tomazin Rok , Gostinčar Cene , Brill Florian H. H. , Gunde-Cimerman Nina
Published: November 2019

Around 85% of the environments on Earth are permanently or seasonally colder than 5 °C. Among those, the poles constitute unique biomes, which harbor a broad variety of microbial life, including an abundance of fungi. Many fungi have an outstanding ability to withstand extreme conditions and play vital ecosystem roles of decomposers as well as obligate or facultative symbionts of many other organisms. Due to their dispersal capabilities, microorganisms from cryosphere samples can be distributed around the world. Such dispersal involves both species with undefined pathogenicity and potentially pathogenic strains. Here we describe the isolation of fungal species from pristine Arctic locations in Greenland and Svalbard and the testing of the expression of characteristics usually associated with pathogenic species, such as growth at 37 °C, hemolytic ability, and susceptibility to antifungal agents. A total of 320 fungal isolates were obtained, and 24 of the most abundant and representative species were further analyzed. Species known as emerging pathogens, like Aureobasidium melanogenum, Naganishia albida, and Rhodotorula mucilaginosa, were able to grow at 37 °C, showed beta-hemolytic activity, and were intrinsically resistant to commonly used antifungals such as azoles and echinocandins. Antifungal resistance screening revealed a low susceptibility to voriconazole in N. albida and Penicillium spp. and to fluconazole in Glaciozyma watsonii and Glaciozyma-related taxon.
Identification, Genotyping and Antimicrobial Susceptibility Testing of Brucella spp. Isolated from Livestock in Egypt
Authors: Khan Aman Ullah , Shell Waleed S. , Melzer Falk , Sayour Ashraf E. , Ramadan Eman Shawkat , Elschner Mandy C. , Moawad Amira A. , Roesler Uwe , Neubauer Heinrich , El-Adawy Hosny
Published: November 2019

Brucellosis is a highly contagious zoonosis worldwide with economic and public health impacts. The aim of the present study was to identify Brucella (B.) spp. isolated from animal populations located in different districts of Egypt and to determine their antimicrobial resistance. In total, 34-suspected Brucella isolates were recovered from lymph nodes, milk, and fetal abomasal contents of infected cattle, buffaloes, sheep, and goats from nine districts in Egypt. The isolates were identified by microbiological methods and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Differentiation and genotyping were confirmed using multiplex PCR for B. abortus, Brucella melitensis, Brucella ovis, and Brucella suis (AMOS) and Bruce-ladder PCR. Antimicrobial susceptibility testing against clinically used antimicrobial agents (chloramphenicol, ciprofloxacin, erythromycin, gentamicin, imipenem, rifampicin, streptomycin, and tetracycline) was performed using E-Test. The antimicrobial resistance-associated genes and mutations in Brucella isolates were confirmed using molecular tools. In total, 29 Brucella isolates (eight B. abortus biovar 1 and 21 B. melitensis biovar 3) were identified and typed. The resistance of B. melitensis to ciprofloxacin, erythromycin, imipenem, rifampicin, and streptomycin were 76.2%, 19.0%, 76.2%, 66.7%, and 4.8%, respectively. Whereas, 25.0%, 87.5%, 25.0%, and 37.5% of B. abortus were resistant to ciprofloxacin, erythromycin, imipenem, and rifampicin, respectively. Mutations in the rpoB gene associated with rifampicin resistance were identified in all phenotypically resistant isolates. Mutations in gyrA and gyrB genes associated with ciprofloxacin resistance were identified in four phenotypically resistant isolates of B. melitensis. This is the first study highlighting the antimicrobial resistance in Brucella isolated from different animal species in Egypt. Mutations detected in genes associated with antimicrobial resistance unravel the molecular mechanisms of resistance in Brucella isolates from Egypt. The mutations in the rpoB gene in phenotypically resistant B. abortus isolates in this study were reported for the first time in Egypt.
Viscoelastic Behaviour from Complementary Forced-Oscillation and Microcreep Tests
Authors: Jackson Ian
Published: November 2019

There is an important complementarity between experimental methods for the study of high-temperature viscoelasticity in the time and frequency domains that has not always been fully exploited. Here, we show that the parallel processing of forced-oscillation data and microcreep records, involving the consistent use of either Andrade or extended Burgers creep function models, yields a robust composite modulus-dissipation dataset spanning a broader range of periods than either technique alone. In fitting this dataset, the alternative Andrade and extended Burgers models differ in their partitioning of strain between the anelastic and viscous contributions. The extended Burgers model is preferred because it involves a finite range of anelastic relaxation times and, accordingly, a well-defined anelastic relaxation strength. The new strategy offers the prospect of better constraining the transition between transient and steady-state creep or, equivalently, between anelastic and viscous behaviour.
Total Synthesis of the Proposed Structure of Paraphaeosphaeride C
Authors: Kobayashi Kenichi , Kunimura Risako , Kogen Hiroshi
Published: November 2019

Paraphaeosphaeride C is a demethoxy derivative of phaeosphaeride A and exhibits STAT3 inhibitory activity. Our previous papers reported the total synthesis of phaeosphaeride A using a diastereoselective vinyl anion aldol reaction as the key step to construct the dihydropyran ring. In this work, the first total synthesis of the proposed structure of paraphaeosphaeride C was achieved via a similar synthetic strategy. The synthetic compound was characterized through extensive nuclear magnetic resonance (NMR) analysis but the 1H and 13C-NMR data for this compound did not correspond to those reported in the literature for paraphaeosphaeride C.
Effects of Melatonin Treatment of Postharvest Pear Fruit on Aromatic Volatile Biosynthesis
Authors: Liu Jianlong , Liu Hanting , Wu Ting , Zhai Rui , Yang Chengquan , Wang Zhigang , Ma Fengwang , Xu Lingfei
Published: November 2019

Aroma affects the sensory quality of fruit and, consequently, consumer satisfaction. Melatonin (MT) is a plant growth regulator used to delay senescence in postharvest fruit during storage; however, its effect on aroma of pear fruit remains unclear. In this study, we assessed the effects of 0.1 mmol L−1 MT on volatiles and associated gene expression in the fruit of pear cultivars ‘Korla’ (Pyrus brestschneideri Rehd) and ‘Abbé Fetel’ (Pyrus communis L.). MT mainly affected the production of C6 aromatic substances in the two varieties. In ‘Korla’, MT inhibited expression of PbHPL, and reduced hydroperoxide lyase (HPL) activity and content of hexanal and (E)-hex-2-enal. In contrast, MT inhibited activity of lipoxygenase (LOX), reduced expression of PbLOX1 and PbLOX2, promoted PbAAT gene expression, increased alcohol acyltransferase (AAT) activity, and increased propyl acetate, and hexyl acetate content in ‘Abbé Fetel’ that similarly led to the reduction in content of hexanal and (E)-hex-2-enal. Content of esters in ‘Abbé Fetel’ pear increased with increasing postharvest storage period. Although mechanisms differed between the two varieties, effects on aroma volatiles mediated by MT were driven by expression of genes encoding LOX, HPL, and AAT enzymes.
Impact of Citral and Phloretin, Alone and in Combination, on Major Virulence Traits of Streptococcus pyogenes
Authors: Adil Mohd , Baig Mohd Hassan , Rupasinghe H.P. Vasantha
Published: November 2019

Streptococcus pyogenes is well documented as a multi-virulent and exclusively human pathogen. The LuxS-based signaling in these bacteria has a crucial role in causing several infections through pathways that are pathogenic. This study evaluated the individual and synergistic effects of citral and phloretin against S. pyogenes in relation to major virulence traits. The in vitro synergy of citral and phloretin was evaluated by the checkerboard method. The fractional inhibitory concentration (FIC) values were calculated to determine the interactions between the inhibitors. The bacteria’s virulence properties were tested in the presence of the molecules, individually as well as in combination. Molecules’ cytotoxicity was tested using human tonsil epithelial cells. The synergistic effects of the molecules on the expression of biofilm and quorum sensing genes were tested using quantitative real-time polymerase chain reaction (qRT-PCR). The molecules were also tested for their impact on LuxS protein by molecular docking, modeling, and free-energy calculations. When the two molecules were assessed in combination (synergistic effect, FIC Index of 0.5), a stronger growth inhibitory activity was exhibited than the individual molecules. The cell surface hydrophobicity, as well as genes involved in quorum sensing and biofilm formation, showed greater suppression when the molecules were tested in combination. The in silico findings also suggest the inhibitory potential of the two molecules against LuxS protein. The binding orientation and the binding affinity of citral and phloretin well support the notion that there is a synergistic effect of citral and phloretin. The data reveal the combination of citral and phloretin as a potent antibacterial agent to combat the virulence of S. pyogenes.
Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease
Authors: Afzal Mohammad , Redha Amina , AlHasan Redha
Published: November 2019

Anthocyanins (ANTs) are plant pigments that belong to a flavanol class of polyphenols and have diverse pharmacological properties. These compounds are primarily found in fruits and vegetables, with an average daily intake of 180 mgd−1 of these compounds in the developed world. ANTs are potent antioxidants that might regulate the free radical-mediated generation of amyloid peptides (Abeta-amyloids) in the brain, which causes Alzheimer’s disease (AD). This study presents a literature review of ANTs from different berries and their potential therapeutic value, with particular emphasis on neurodegenerative AD, which owing to oxidative stress. This review also highlights reactive oxygen species (ROS) generation through energy metabolism, nitrogen reactive species, the role of transition metals in generating ROS, and the radical-quenching mechanisms of natural antioxidants, including ANTs. The current status of the bioavailability, solubility, and structure activity relationship of ANTs is discussed herein.
Isolation of a Halogen-Bonded Complex Formed between Methane and Chlorine Monofluoride and Characterisation by Rotational Spectroscopy and Ab Initio Calculations
Authors: Legon Anthony C. , Lister David G. , Holloway John H. , Mani Devendra , Arunan Elangannan
Published: November 2019

A halogen-bonded complex formed between methane and chlorine monofluoride has been isolated in the gas phase before the reaction between the components and has been characterised through its rotational spectrum, which is of the symmetric-top type but only exhibits K = 0 type transitions at the low effective temperature of the pulsed-jet experiment. Spectroscopic constants for two low-lying states that result from internal rotation of the CH4 subunit were detected for each of the two isotopic varieties H4C···35ClF and H4C···37ClF and were analysed to show that ClF lies on the symmetry axis with Cl located closer than F to the C atom, at the distance r0(C···Cl) ≅ 3.28 Å and with an intermolecular stretching force constant kσ ≅ 4 N m−1. Ab initio calculations at the explicitly correlated level CCSD(T)(F12c)/cc-pVTZ-F12 show that in the equilibrium geometry, the ClF molecule lies along a C3 axis of CH4 and Cl is involved in a halogen bond. The Cl atom points at the nucleophilic region identified on the C3 axis, opposite the unique C–H bond and somewhere near the C atom and the tetrahedron face centre, with re(C···Cl) = 3.191 Å. Atoms-in-molecules (AIM) theory shows a bond critical point between Cl and C, confirming the presence of a halogen bond. The energy that is required to dissociate the complex from the equilibrium conformation into its CH4 and ClF components is only De ≅ 5 kJ mol−1. A likely path for the internal rotation of the CH4 subunit is identified by calculations at the same level of theory, which also provide the variation of the energy of the system as a function of the motion along that path. The barrier to the motion along the path is only ≅ 20 cm−1.
Natural Bioactive Compounds As Protectors Of Mitochondrial Dysfunction In Cardiovascular Diseases And Aging
Authors: Arauna Diego , Furrianca María , Espinosa-Parrilla Yolanda , Fuentes Eduardo , Alarcón Marcelo , Palomo Iván
Published: November 2019

Diet, particularly the Mediterranean diet, has been considered as a protective factor against the development of cardiovascular diseases, the main cause of death in the world. Aging is one of the major risk factors for cardiovascular diseases, which have an oxidative pathophysiological component, being the mitochondria one of the key organelles in the regulation of oxidative stress. Certain natural bioactive compounds have the ability to regulate oxidative phosphorylation, the production of reactive oxygen species and the expression of mitochondrial proteins; but their efficacy within the mitochondrial physiopathology of cardiovascular diseases has not been clarified yet. The following review has the purpose of evaluating several natural compounds with evidence of mitochondrial effect in cardiovascular disease models, ascertaining the main cellular mechanisms and their potential use as functional foods for prevention of cardiovascular disease and healthy aging.
Effects of Ultrasonic-Assisted Extraction on the Physicochemical Properties of Different Walnut Proteins
Authors: Lv Siyi , Taha Ahmed , Hu Hao , Lu Qi , Pan Siyi
Published: November 2019

The effects of ultrasonic-assisted extraction (UAE, 200 W, 20 min) on the yield and physicochemical properties of different walnut proteins (WNPs, including albumin, globulin, and glutelin) were investigated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that UAE could result in protein molecular fragmentation of albumin, but did not affect the major bands of globulin and glutelin. The CD spectra demonstrated that different WNPs obtained by UAE had different changes in their secondary structure. Under UAE, there was an increase in surface hydrophobicity (H0) of albumin and gluten and no change in the fluorescence intensity, while decreases were observed in the H0 and fluorescence intensity of globulin; and the contents of total and surface free sulfhydryl in albumin dramatically decreased. UAE reduced the size of the particles and the dimension of the microstructures in albumin and gluten, indicating that ultrasound could unfold protein aggregates. In addition, UAE increased the solubility, emulsifying activity (EA), foaming capacity (FC), and foam stability (FS) of the obtained proteins. The above results indicate that ultrasound extraction is a promising approach to improve the extraction yield and properties of walnut proteins.
Effects of l-Carnitine in Patients with Autism Spectrum Disorders: Review of Clinical Studies
Authors: Malaguarnera Michele , Cauli Omar
Published: November 2019

Carnitine is an amino acid derivative, which plays several important roles in human physiology, in the central nervous system, and for mitochondrial metabolism, in particular. Altered carnitine metabolic routes have been associated with a subgroup of patients with autism spectrum disorders (ASD) and could add to the pathophysiology associated with these disorders. We review the current evidence about the clinical effects of carnitine administration in ASD in both non-syndromic forms and ASD associated with genetic disorders. Two randomized clinical trials and one open-label prospective trial suggest that carnitine administration could be useful for treating symptoms in non-syndromic ASD. The effect of carnitine administration in ASD associated with genetic disorders is not conclusive because of a lack of clinical trials and objectives in ASD evaluation, but beneficial effects have also been reported for other comorbid disorders, such as intellectual disability and muscular strength. Side effects observed with a dose of 200 mg/kg/day consisted of gastro-intestinal symptoms and a strong, heavy skin odor. Doses of about 50–100 mg/kg/day are generally well tolerated. Further clinical trials with the identification of the subgroup of ASD patients that would benefit from carnitine administration are warranted.
Novel Convenient Approach to the Solid-Phase Synthesis of Oligonucleotide Conjugates
Authors: Meschaninova Mariya I. , Novopashina Darya S. , Semikolenova Olga A. , Silnikov Vladimir N. , Venyaminova Alya G.
Published: November 2019

A novel and convenient approach for the solid-phase 5′-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5′-hydroxyl of polymer support-bound protected oligonucleotides by N,N′-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of closo-dodecaborate, estrone, cholesterol, and α-tocopherol were specially prepared. A wide range of oligonucleotide conjugates bearing closo-dodecaborate, short peptide, pyrene, lipophilic residues (cholesterol, α-tocopherol, folate, estrone), aliphatic diamines, and propargylamine were synthesized and characterized to demonstrate the versatility of the approach. The developed method is suitable for the conjugate synthesis of oligonucleotides of different types (ribo-, deoxyribo-, 2′-O-methylribo-, and others).
Novel Flavonoid Glycosides of Quercetin from Leaves and Flowers of Gaiadendron punctatum G.Don. (Violeta de Campo), used by the Saraguro Community in Southern Ecuador, Inhibit α-Glucosidase Enzyme
Authors: Cedeño Héctor , Espinosa Sandra , Andrade José Miguel , Cartuche Luis , Malagón Omar
Published: November 2019

Gaiadandendron punctatum G.Don. (violeta de campo) is a plant used in traditional medicine by the Saraguro people, an ancient indigenous group that lives in southern Ecuador. From samples collected in the region, six glycoside flavonoids, five with quercetin and one with kaempferol as aglycon, were isolated and characterized from hydroalcoholic extracts of leaves and flowers. Rutin (2) was found in flowers and leaves, nicotiflorin (1) was found in flowers, artabotryside A (3) was found in leaves, and three novel quercetin flavonoid glycosides were isolated, elucidated, and characterized via 1D and 2D NMR experiments (1H, 13C, COSY, DEPT, HMBC, HSQC, TOCSY, NOESY, ROESY), acid hydrolysis–derivatization–GC-MS analysis, HPLC-MS, IR, UV, and optical rotation. The new quercetin flavonoid glycosides were named hecpatrin (4) (isolated from leaves), gaiadendrin (5) (isolated from leaves), and puchikrin (6) (isolated from flowers). The hydroalcoholic extracts of the leaves presented antimicrobial activity against Micrococcus luteus, Staphylococcus aureus, and Enterococcus faecalis and the hydroalcoholic extract of the flowers was active against Micrococcus luteus. However, glycoside flavonoids presented scarce antimicrobial activity against bacteria. Hydroalcoholic extracts from leaves and flowers and their secondary metabolites showed inhibition against the α-glucosidase enzyme at different concentrations. Rutin, gaiadendrin, and nicotiflorin showed competitive α-glucosidase inhibition, while hecpatrin presented non-competitive inhibition.
Photocatalytic Performance of SiO2/CNOs/TiO2 to Accelerate the Degradation of Rhodamine B under Visible Light
Authors: Zhang Weike , Zhang Yanrong , Yang Kai , Yang Yanqing , Jia Jia , Guo Lijun
Published: November 2019

A silicon dioxide/carbon nano onions/titanium dioxide (SiO2/CNOs/TiO2) composite was synthesized by a simple sol-gel method and characterized by the methods of X-ray diffraction (XRD), scanning electronic microscope (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET), Fourier transform infrared (FTIR), thermogravimetric analysis (TG), differential scanning calorimeter (DSC) and UV-Vis diffuse reflectance spectra (UV-Vis DRS). In this work, the photocatalytic activity of the SiO2/CNOs/TiO2 photocatalyst was assessed by testing the degradation rate of Rhodamine B (RhB) under visible light. The results indicated that the samples exhibited the best photocatalytic activity when the composite consisted of 3% CNOs and the optimum dosage of SiO2/CNOs/TiO2(3%) was 1.5 g/L as evidenced by the highest RhB degradation rate (96%). The SiO2/CNOs/TiO2 composite greatly improved the quantum efficiency of TiO2. This work provides a new option for the modification of subsequent nanocomposite oxide nanoparticles.
Construction of A New Dose–Response Model for Staphylococcus aureus Considering Growth and Decay Kinetics on Skin
Authors: Esfahanian Elaheh , Adhikari Umesh , Dolan Kirk , Mitchell Jade
Published: November 2019

In order to determine the relationship between an exposure dose of Staphylococcus aureus (S. aureus) on the skin and the risk of infection, an understanding of the bacterial growth and decay kinetics is very important. Models are essential tools for understanding and predicting bacterial kinetics and are necessary to predict the dose of organisms post-exposure that results in a skin infection. One of the challenges in modeling bacterial kinetics is the estimation of model parameters, which can be addressed using an inverse problem approach. The objective of this study is to construct a microbial kinetic model of S. aureus on human skin and use the model to predict concentrations of S. aureus that result in human infection. In order to model the growth and decay of S. aureus on skin, a Gompertz inactivation model was coupled with a Gompertz growth model. A series of analyses, including ordinary least squares regression, scaled sensitivity coefficient analysis, residual analysis, and parameter correlation analysis were conducted to estimate the parameters and to describe the model uncertainty. Based on these analyses, the proposed model parameters were estimated with high accuracy. The model was then used to develop a new dose-response model for S. aureus using the exponential dose–response model. The new S. aureus model has an optimized k parameter equivalent to 8.05 × 10−8 with 95th percentile confidence intervals between 6.46 × 10−8 and 1.00 × 10−7.
Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo
Authors: Sari Gulce , van de Garde Martijn D.B. , van Schoonhoven Anne , Voermans Jolanda J.C. , van der Eijk Annemiek A. , de Man Robert A. , Boonstra Andre , Vanwolleghem Thomas , Pas Suzan D.
Published: November 2019

Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients.
Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam
Authors: Lachowicz Dorota , Mielczarek Przemyslaw , Wirecka Roma , Berent Katarzyna , Karewicz Anna , Szuwarzyński Michał , Zapotoczny Szczepan
Published: November 2019

A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were colloidally stable and their size and surface charge could be controlled by the polycation/polyanion ratio. The morphology of the obtained particles was visualized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The resulting structures were spherical, with hydrodynamic diameters in the range of 100–150 nm. The binding constant (Ka) of a model drug, piroxicam, to the cationic pullulan (C-PUL) was determined by spectrophotometric measurements. The value of Ka was calculated according to the Benesi—Hildebrand equation to be (3.6 ± 0.2) × 103 M−1. After binding to cationic pullulan, piroxicam was effectively entrapped inside the nanohydrogel particles and released in a controlled way. The obtained system was efficiently taken up by cells and was shown to be biocompatible.
Methyljasmonate Elicitation Increases Terpenoid Indole Alkaloid Accumulation in Rhazya stricta Hairy Root Cultures
Authors: Akhgari Amir , Laakso Into , Maaheimo Hannu , Choi Young Hae , Seppänen-Laakso Tuulikki , Oksman-Caldentey Kirsi-Marja , Rischer Heiko
Published: November 2019

Methyl jasmonate is capable of initiating or improving the biosynthesis of secondary metabolites in plants and therefore has opened up a concept for the biosynthesis of valuable constituents. In this study, the effect of different doses of methyl jasmonate (MeJA) elicitation on the accumulation of terpenoid indole alkaloids (TIAs) in the hairy root cultures of the medicinal plant, Rhazya stricta throughout a time course (one-seven days) was investigated. Gas chromatography-mass spectrometry (GC-MS) analyses were carried out for targeted ten major non-polar alkaloids. Furthermore, overall alterations in metabolite contents in elicited and control cultures were investigated applying proton nuclear magnetic resonance (1H NMR) spectroscopy. Methyl jasmonate caused dosage- and time course-dependent significant rise in the accumulation of TIAs as determined by GC-MS. The contents of seven alkaloids including eburenine, quebrachamine, fluorocarpamine, pleiocarpamine, tubotaiwine, tetrahydroalstonine, and ajmalicine increased compared to non-elicited cultures. However, MeJA-elicitation did not induce the accumulation of vincanine, yohimbine (isomer II), and vallesiachotamine. Furthermore, principal component analysis (PCA) of 1H NMR metabolic profiles revealed a discrimination between elicited hairy roots and control cultures with significant increase in total vindoline-type alkaloid content and elevated levels of organic and amino acids. In addition, elicited and control samples had different sugar and fatty acid profiles, suggesting that MeJA also influences the primary metabolism of R. stricta hairy roots. It is evident that methyl jasmonate is applicable for elevating alkaloid accumulation in “hairy root” organ cultures of R. strica.
Cellulose in Ionic Liquids and Alkaline Solutions: Advances in the Mechanisms of Biopolymer Dissolution and Regeneration
Authors: El Seoud Omar A. , Kostag Marc , Jedvert Kerstin , Malek Naved I.
Published: November 2019

This review is focused on assessment of solvents for cellulose dissolution and the mechanism of regeneration of the dissolved biopolymer. The solvents of interest are imidazole-based ionic liquids, quaternary ammonium electrolytes, salts of super-bases, and their binary mixtures with molecular solvents. We briefly discuss the mechanism of cellulose dissolution and address the strategies for assessing solvent efficiency, as inferred from its physico-chemical properties. In addition to the favorable effect of lower cellulose solution rheology, microscopic solvent/solution properties, including empirical polarity, Lewis acidity, Lewis basicity, and dipolarity/polarizability are determinants of cellulose dissolution. We discuss how these microscopic properties are calculated from the UV-Vis spectra of solvatochromic probes, and their use to explain the observed solvent efficiency order. We dwell briefly on use of other techniques, in particular NMR and theoretical calculations for the same purpose. Once dissolved, cellulose is either regenerated in different physical shapes, or derivatized under homogeneous conditions. We discuss the mechanism of, and the steps involved in cellulose regeneration, via formation of mini-sheets, association into “mini-crystals”, and convergence into larger crystalline and amorphous regions. We discuss the use of different techniques, including FTIR, X-ray diffraction, and theoretical calculations to probe the forces involved in cellulose regeneration.
Molecular Modeling of EUV Photoresist Revealing the Effect of Chain Conformation on Line-Edge Roughness Formation
Authors: Park Juhae , Lee Sung-Gyu , Vesters Yannick , Severi Joren , Kim Myungwoong , De Simone Danilo , Oh Hye-Keun , Hur Su-Mi
Published: November 2019

Extreme ultraviolet lithography (EUVL) is a leading-edge technology for pattern miniaturization and the production of advanced electronic devices. One of the current critical challenges for further scaling down the technology is reducing the line-edge roughness (LER) of the final patterns while simultaneously maintaining high resolution and sensitivity. As the target sizes of features and LER become closer to the polymer size, polymer chain conformations and their distribution should be considered to understand the primary sources of LER. Here, we proposed a new approach of EUV photoresist modeling with an explicit description of polymer chains using a coarse-grained model. Our new simulation model demonstrated that interface variation represented by width and fluctuation at the edge of the pattern could be caused by characteristic changes of the resist material during the lithography processes. We determined the effect of polymer chain conformation on LER formation and how it finally contributed to LER formation with various resist material parameters (e.g., Flory–Huggins parameter, molecular weight, protected site ratio, and Tg).