bluuebunny/crossref_metadata_2025 huggingface dataset:
On Neutrosophic αψ-Closed Sets
Authors: Parimala Mani , Smarandache Florentin , Jafari Saeid , Udhayakumar Ramalingam
Published: April 2018

The aim of this paper is to introduce the concept of α ψ -closed sets in terms of neutrosophic topological spaces. We also study some of the properties of neutrosophic α ψ -closed sets. Further, we introduce continuity and contra continuity for the introduced set. The two functions and their relations are studied via a neutrosophic point set.
How to Think Rationally about World Problems
Authors: Stanovich Keith E.
Published: April 2018

I agree with the target essay that psychology has something to offer in helping to address societal problems. Intelligence has helped meliorate some social problems throughout history, including the period of time that is covered by the Flynn effect, but I agree with Sternberg that other psychological characteristics may be contributing as well, particularly increases in rationality. I also believe that increasing human rationality could have a variety of positive societal affects at levels somewhat smaller in grain size than the societal problems that Sternberg focuses on. Some of the societal problems that Sternberg lists, however, I do not think would be remedied by increases in rationality, intelligence, or wisdom, because remedy might be the wrong word in the context of these issues. Issues such as how much inequality of income to tolerate, how much pollution to tolerate, and how much we should sacrifice economic growth for potential future changes in global temperature represent issues of clashing values, not the inability to process information, nor the lack of information, nor the failure to show wisdom.
Editorial Note: Review Papers for Journal of Risk and Financial Management (JRFM)
Authors: McAleer Michael
Published: April 2018

The Journal of Risk and Financial Management (JRFM) was inaugurated in 2008 and has continued publishing successfully with Volume 11 in 2018. Since the journal was established, JRFM has published in excess of 110 topical and interesting theoretical and empirical papers in financial economics, financial econometrics, banking, finance, mathematical finance, statistical finance, accounting, decision sciences, information management, tourism economics and finance, international rankings of journals in financial economics, and bibliometric rankings of journals in cognate disciplines. Papers published in the journal range from novel technical and theoretical papers to innovative empirical contributions. The journal wishes to encourage critical review papers on topical subjects in any of the topics mentioned above in financial economics and in cognate disciplines.
Low-Cycle Fatigue Behavior of 10CrNi3MoV High Strength Steel and Its Undermatched Welds
Authors: Song Wei , Liu Xuesong , Berto Filippo , Razavi Nima
Published: April 2018

The use of high strength steel allows the design of lighter, more slender and simpler structures due to high strength and favorable ductility. Nevertheless, the increase of yield strength does not guarantee the corresponding improvement of fatigue resistance, which becomes a major concern for engineering structure design, especially for the welded joints. The paper presents a comparison of the low cycle fatigue behaviors between 10CrNi3MoV high strength steel and its undermatched weldments. Uniaxial tension tests, Push-pull, strain-controlled fatigue tests were conducted on base metal and weldments in the strain range of 0.2–1.2%. The monotonic and cyclic stress-strain curves, stress-life, strain-life and energy-life in terms of these materials were analyzed for fatigue assessment of materials discrepancy. The stress-life results of base metal and undermatched weld metal exhibit cyclic softening behaviors. Furthermore, the shapes of 10CrNi3MoV steel hysteresis loops show a satisfactory Masing-type behavior, while the weld metal shows a non-Masing type behavior. Strain, plastic and total strain energy density amplitudes against the number of reversals to failure results demonstrate that the undermatched weld metal presents a higher resistance to fatigue crack initiation than 10CrNi3MoV high strength steel. Finally, fatigue fracture surfaces of specimens were compared by scanning electron microscopy to identify the differences of crack initiation and the propagation between them.
Influence of Surface Features for Increased Heat Dissipation on Tool Wear
Authors: Tamil Alagan Nageswaran , Beno Tomas , Hoier Philipp , Klement Uta , Wretland Anders
Published: April 2018

The critical problems faced during the machining process of heat resistant superalloys, (HRSA), is the concentration of heat in the cutting zone and the difficulty in dissipating it. The concentrated heat in the cutting zone has a negative influence on the tool life and surface quality of the machined surface, which in turn, contributes to higher manufacturing costs. This paper investigates improved heat dissipation from the cutting zone on the tool wear through surface features on the cutting tools. Firstly, the objective was to increase the available surface area in high temperature regions of the cutting tool. Secondly, multiple surface features were fabricated for the purpose of acting as channels in the rake face to create better access for the coolant to the proximity of the cutting edge. The purpose was thereby to improve the cooling of the cutting edge itself, which exhibits the highest temperature during machining. These modified inserts were experimentally investigated in face turning of Alloy 718 with high-pressure coolant. Overall results exhibited that surface featured inserts decreased flank wear, abrasion of the flank face, cutting edge deterioration and crater wear probably due to better heat dissipation from the cutting zone.
Effect of Inoculant Alloy Selection and Particle Size on Efficiency of Isomorphic Inoculation of Ti-Al
Authors: Kennedy Jacob , Rouat Bernard , Daloz Dominique , Bouzy Emmanuel , Zollinger Julien
Published: April 2018

The process of isomorphic inoculation relies on precise selection of inoculant alloys for a given system. Three alloys, Ti-10Al-25Nb, Ti-25Al-10Ta, and Ti-47Ta (at %) were selected as potential isomorphic inoculants for a Ti-46Al alloy. The binary Ti-Ta alloy selected was found to be ineffective as an inoculant due to its large density difference with the melt, causing the particles to settle. Both ternary alloys were successfully implemented as isomorphic inoculants that decreased the equiaxed grain size and increased the equiaxed fraction in their ingots. The degree of grain refinement obtained was found to be dependent on the number of particles introduced to the melt. Also, more new grains were formed than particles added to the melt. The grains/particle efficiency varied from greater than one to nearly twenty as the size of the particle increased. This is attributed to the breaking up of particles into smaller particles by dissolution in the melt. For a given particle size, Ti-Al-Ta and Ti-Al-Nb particles were found to have a roughly similar grain/particle efficiency.
Economic Model Predictive Control with Zone Tracking
Authors: Liu Su , Liu Jinfeng
Published: April 2018

In this work, we propose a framework for economic model predictive control (EMPC) with zone tracking. A zone tracking stage cost is incorporated into the existing EMPC framework to form a multi-objective optimization problem. We provide sufficient conditions for asymptotic stability of the optimal steady state and characterize the exact penalty for the zone tracking cost which prioritizes zone tracking objective over economic objective. Moreover, an algorithm to modify the target zone based on the economic performance and reachability of the optimal steady state is proposed. The modified target zone effectively decouples the dynamic zone tracking and economic objectives and simplifies parameter tuning.
Triphlorethol A, a Dietary Polyphenol from Seaweed, Decreases Sleep Latency and Increases Non-Rapid Eye Movement Sleep in Mice
Authors: Yoon Minseok , Cho Suengmok
Published: April 2018

In our previous studies, we have demonstrated that marine polyphenol phlorotannins promote sleep through the benzodiazepine site of the gamma-aminobutyric acid type A (GABAA) receptors. In this follow-up study, the sleep-promoting effects of triphlorethol A, one of the major phlorotannin constituents, were investigated. The effect of triphlorethol A on sleep-wake architecture and profiles was evaluated based on electroencephalogram and electromyogram data from C57BL/6N mice and compared with the well-known hypnotic drug zolpidem. Oral administration of triphlorethol A (5, 10, 25, and 50 mg/kg) dose-dependently decreased sleep latency and increased sleep duration during pentobarbital-induced sleep in imprinting control region mice. Triphlorethol A (50 mg/kg) significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in C57BL/6N mice, without affecting rapid eye movement sleep (REMS). There was no significant difference between the effects of triphlorethol A at 50 mg/kg and zolpidem at 10 mg/kg. Triphlorethol A had no effect on delta activity (0.5–4 Hz) of NREMS, whereas zolpidem significantly decreased it. These results not only support the sleep-promoting effects of marine polyphenol phlorotannins, but also suggest that the marine polyphenol compound triphlorethol A is a promising structure for developing novel sedative hypnotics.
Proteasomes and Proteasomal Gene Polymorphism in Association with Inflammation and Various Diseases
Authors: Žemeckienė Živilė , Vitkauskienė Astra , Sjakste Tatjana , Šitkauskienė Brigita , Sakalauskas Raimundas
Published: April 2018

A proteasome, a multicatalytic protein complex, is a central particle of the ubiquitinproteasome proteolytic pathway in all eukaryotic cells. Through the degradation of most intracellular proteins, proteasomes play a significant role in cell processes, such as cell cycle and division, posttranslational protein quality control, cell signaling, and apoptosis. Therefore, the ubiquitinproteasome system is necessary to ensure the normal functioning of cells and an organism. The associations between alterations in the ubiquitin-proteasome pathway and the development of various autoimmune, neurodegenerative, inflammatory and other diseases in humans have been established. Moreover, the findings of some studies suggest that proteasomes may participate in the pathogenesis of asthma through the regulation of the nuclear factor kappa B signaling pathway. Recently, much attention has been given to the associations between genes encoding the proteasome and their polymorphism, and various diseases. Associations between some proteasomal genes and myocardial infarction, type 2 diabetes mellitus, and other diseases have already been established. However, the results are inconclusive or conflicting and need further clarification.
The Most Important Throat-Related Symptoms Suggestive of Chronic Tonsillitis as the Main Indication for Adult Tonsillectomy
Authors: Pribuišienė Rūta , Kuzminienė Alina , Šarauskas Valdas , Šaferis Viktoras , Pribuišis Kipras , Rastenienė Ieva
Published: April 2018

Background and Objective. The literature lacks data about the evaluation of throatrelated symptoms proving chronic tonsillitis as the most common indication for adult tonsillectomy. Therefore, the aim of this study was to assess the most important throat-related symptoms suggestive of chronic tonsillitis in adults. Material and Methods. A prospective cohort study was carried out. The analysis of throatrelated symptoms (complaints, tonsillitis rate, pharyngeal signs, and antistreptolysin-O titer) in 81 adults with histologically confirmed chronic tonsillitis was conducted. Results. Recurrent tonsillitis was the most common complaint (74.1%). The mean number of tonsillitis episodes was 3.6 (SD, 1.9) times per year. There were no significant differences comparing the frequencies of all the analyzed pharyngeal signs (P>0.05). The antistreptolysin-O titer (mean, 279.8; SD, 211.6 UL) was pathological in 33.3% of patients. The study identified the most important throat-related symptoms revealing chronic tonsillitis: tonsillar cryptic debris (OR, 8.84; 95% CI, 1.93–40.53; P=0.005) and enlarged anterior cervical lymph nodes along with the frequency of tonsillitis episodes exceeding 3 times per year (OR, 8.27; 95% CI, 1.33–51.57; P=0.024). The classification accuracy of 85.2% was obtained. Conclusions. Tonsillar cryptic debris and enlarged regional lymph nodes along with recurrent tonsillitis could support the diagnosis of chronic tonsillitis in adults when considering tonsillectomy.
Possible Predisposing Factors for Late Intraocular Lens Dislocation After Routine Cataract Surgery
Authors: Krėpštė Lina , Kuzmienė Loreta , Miliauskas Arūnas , Janulevičienė Ingrida
Published: April 2018

Objective. The aim of this study was to evaluate possible risk factors for late intraocular lens (IOL) dislocation after routine cataract surgery. Material and Methods. A retrospective analysis of medical records of all the patients who were treated in the university hospital between 2011 and 2012 for late IOL dislocation requiring surgical management after routine cataract surgery was performed. In total, 58 patients (58 eyes) were included into the study. Results. The mean time between cataract surgery and late IOL dislocation was 67.8 months (SD, 34.9). A negative correlation was found between the patient age at cataract surgery and the time between cataract surgery and IOL dislocation (r=–0.29; P=0.042). Late in-the-bag dislocation occurred in 87.9% and late out-of-the-bag dislocation in 12.1% of the cases. Pseudoexfoliation was present in 56.9% and 42.9% of the eyes with in-the-bag and out-of-the-bag dislocation, respectively. The odds ratio for IOL dislocation within 43 months after complicated cataract surgery was 24.0 (95% confidence interval [95% CI] 4.5–127.4; P<0.001) and for in-the-bag IOL dislocation 24.9 (95% CI, 4.2–148.0; P<0.001). The odds ratio for in-the-bag IOL dislocation within 43 months after advanced cataract surgery was 18.8 (95% CI, 2.0–180.0; P=0.011). Moreover, in-the-bag IOL dislocation occurred earlier in the patients with past uveitis (P=0.020) or zonule laxity (P=0.037). Conclusions. Complicated cataract surgery increased the risk of both late in-the-bag and out-ofthe- bag IOL dislocation, and advanced cataract increased the risk of late in-the-bag IOL dislocation. The time to in-the-bag IOL dislocation shortens with pseudoexfoliation syndrome, advanced age, or past uveitis. These factors must be taken into account while planning a postoperative follow-up.
Perioperative Factors Affecting Length of Hospital Stay Among Elderly Patients
Authors: Damulevičienė Gytė , Lesauskaitė Vita , Macijauskienė Jūratė , Šmigelskas Kastytis , Venskutonis Donatas
Published: April 2018

Background and Objective. Timely assessment and prevention of risk factors for the main perioperative complications in elderly patients provide an opportunity to avoid them, decrease mortality, and diminish costs associated with longer hospital stay. The aim of this study was to estimate perioperative factors that could potentially predict the length of stay and to estimate their predictive value using a comprehensive geriatric assessment among elderly patients. Material and Methods. The study population comprised 99 surgical patients aged 65 and more. The patients were followed up until discharge. Study data analysis included questionnaires, anthropometric measurements before surgery, assessment and interviews after surgery, and case histories. Univariate and multivariate logistic regression analysis was performed. Results. Malnutrition was detected in 53.5% of the patients. Postoperative cognitive disorder was documented in 18.2% of elderly patients. The mean length of hospital stay was 10.1 days (SD, 9.14). Multivariate logistic regression analysis revealed that the best predictors for longer hospital stay in elderly patients were malnutrition (OR, 4.2; 95% CI, 1.5–11.8; P=0.007) together with postoperative cognitive impairment (OR, 9.2; 95% CI, 1.0–83.3; P=0.048). The total predictive value of the model was 70.5%. Conclusions. Malnutrition and a postoperative cognitive disorder were independent risk factors for longer hospital stay, while depression, cognitive impairment, functional dependence, and poor physical status were not independently associated with longer hospital stay. A comprehensive geriatric assessment can help assess the risk factors for longer treatment and predict the length of hospital stay, thus enabling the planning of optimal healthcare management of elderly patients.
Prognosis of In-Hospital Myocardial Infarction Course for Diabetic and Nondiabetic Patients Using a Noninvasive Evaluation of Hemodynamics and Heart Rate Variability
Authors: Ablonskytė-Dūdonienė Rūta , Bakšytė Giedrė , Čeponienė Indrė , Kriščiukaitis Algimantas , Drėgūnas Kęstutis , Ereminienė Eglė
Published: April 2018

Background and Objective. The objective of our study was to investigate whether the combination of markers of heart rate variability (HRV) and impedance cardiography (ICG) help evaluate the risk of in-hospital death, ventricular arrhythmia, or complicated course secondary to myocardial infarction (STEMI) and to clarify whether combined analysis of HRV and ICG improve prognosis of STEMI, comparing 3 groups: 1) diabetic, 2) nondiabetic, and 3) diabetes-unselected patients. Material and Methods. The parameters reflecting heart rate variability and central hemodynamics were estimated from a 24-hour synchronic electrocardiogram and thoracic impedance signal recordings in 232 patients (67 diabetic) on the third day after myocardial infarction. Logistic regression analysis was used to determine the predictors of selected outcomes. Different prognostic models were compared with the receiver operating characteristic curve analysis.Results. The model consisting of low- and high-frequency power ratio (LF/HF) and cardiac output (CO) was elaborated for the prognosis of in-hospital death in the group 3 (odds ratios [ORs] were 9.74 and 4.85, respectively). Very low-frequency power (VLF), cardiac index (CIN), and cardiac power output (CPO) were the predictors of ventricular arrhythmia in the group 2 (ORs of 1.005, 5.09, and 66.7, respectively) and the group 3 (ORs of 1.004, 3.84, and 37.04, respectively). The predictors of the complicated in-hospital course in the group 1 were the baseline width of the minimum square difference triangular interpolation of the highest peak of the histogram of all NN intervals (TINN) and stroke volume (SV) (ORs of 1.006, and 1.009, respectively); in the group 2, the mean of the standard deviations of all NN intervals for all 5-minute segments of the recording (SDNN index) and CPO (ORs of 1.06 and 2.44, respectively); and in the group 3, SDNN index, VLF, LF/HF, CIN (ORs of 1.04, 1.004, 2.3, and 3.49, respectively). Conclusions. The patients with decreased HRV and low estimates of central hemodynamics evaluated by ICG are at an increased risk of the adverse in-hospital course of STEMI. The combined analysis of HRV and ICG hemodynamic estimates contributes to the risk assessment of the complicated in-hospital course of STEMI, in-hospital hemodynamically significant ventricular arrhythmia, and in-hospital death secondary to STEMI. The in-hospital prognostic value of the combined estimates of HRV and ICG is lower in the STEMI patients with diabetes mellitus as compared with the nondiabetic patients.
Increased Use of Antidepressants in Wuhan, China: a Retrospective Study From 2006 to 2012
Authors: Gao Ping , Zhang Huanian , Xu Hua , Zhang Chengliang , Liu Dong
Published: April 2018

Objective. The aim of this study was to investigate the trend of antidepressant use and analyze the daily cost of antidepressants in Wuhan, China. Material and Methods. The data on the expenditure of antidepressants in Wuhan from 2006 to 2012 were retrospectively analyzed based on the defined daily dose (DDD) method recommended by the World Health Organization. In addition, the daily cost of antidepressants was calculated for the pharmacoeconomic evaluation. Results. The overall sales of antidepressants increased by 566.7% over the 7-year period. The utilization of antidepressants increased annually from 1.067 DDDs per 1000 inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven by an increase in the use of selective serotonin reuptake inhibitors (SSRIs), which accounted for about 60% of antidepressant use. Notably, the use of traditional Chinese patent medicines (TCMs) approved to treat depression in China in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305 in 2012. The daily drug cost analysis indicated that selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low-cost advantage. Conclusions. Antidepressants were increasingly used over the study period. Among them, SSRIs followed by SNRIs were the most commonly used. After the approval for the treatment of depression, TCMs were generally accepted by physicians and patients. The low-cost advantage allowed TCAs to be used in the antidepressant therapy.
Degenerative Aortic Stenosis, Dyslipidemia and Possibilities of Medical Treatment
Authors: Kleinauskienė Rita , Jonkaitienė Regina
Published: April 2018

Degenerative aortic stenosis (DAS) is the most frequently diagnosed heart valve disease in Europe and North America. DAS is a chronic progressive disease which resembles development of atherosclerosis. Endothelial dysfunction, lipid infiltration, calcification and ossification are evidenced in both diseases. The same risk factors such as older age, male sex, smoking, and elevated levels of lipids are identified. The effect of smoking, visceral obesity, metabolic syndrome, hypercholesterolemia, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), adiponectin and apolipoprotein(a) on development of DAS are being studied. The search for genetic ties between disorders of lipid metabolism and DAS has been started. DAS is characterized by a long symptom-free period which can last for several decades. Aortic valve replacement surgery is necessary when the symptoms occur. The lipid-lowering therapy effect on stopping or at least slowing down the progression of DAS was studied. However, the results of the conducted clinical trials are controversial. In addition, calcium homeostasis, bone metabolism and calcinosis-reducing medication are being studied. Although prospective randomized clinical trials have not demonstrated any positive effect of statins used for slowing progression of the disease, statins are still recommended for patients with dyslipidemia. Recent study has suggested that a specific modification of treatment, based on severity of disease, may have a beneficial effect in patients with aortic sclerosis and mild DAS. New clinical studies analyzing new treatment possibilities which could correct the natural course of the disease and reduce the need for aortic valve replacement by surgery or transcatheter treatment interventions are needed.
Characterization of Austenite Microstructure from Quenched Martensite Using Conventional Metallographic Techniques and a Crystallographic Reconstruction Procedure
Authors: Sanz Lorena , López Beatriz , Pereda Beatriz
Published: April 2018

Recently, procedures for recovering austenite fcc crystallographic information from EBSD (Electron Back-Scatter Diffraction) data recorded from martensite or other bcc transformation products have been proposed. Due to the difficulties in revealing prior austenite grain boundaries using available etching techniques, these reconstruction methods appear as promising tools for understanding austenite hot deformation behavior in low carbon steels. In a previous work, the accuracy of an in-house developed reconstruction code was validated using an Fe-30Ni alloy. Validation of this method in low carbon steels is more difficult due to the loss of austenitic orientation information. In addition, it is not known how the results of conventional metallography correlate with those of the reconstruction or which scan parameters or post-processing treatments are necessary for obtaining comparable results. To study this, two martensitic specimens obtained from water quenched recrystallized and deformed austenite were characterized in this study, using both conventional metallographic techniques and the above mentioned reconstruction procedure applied to EBSD scans acquired using different parameter values. The comparability of austenite grain size and morphology was analyzed as a function of the post-processing treatment. The results show that in order to obtain comparable results, it is critical to analyze the coherence of the twins present in the microstructure.
Effects of Cryogenic Treatment after Annealing of Ti-6Al-4V Alloy Sheet on Its Formability at Room Temperature
Authors: Hu Zhiqing , Zheng Huihui , Liu Guojun , Wu Hongwei
Published: April 2018

In this article, the effects of cryogenic treatment after annealing on the formability of Ti-6Al-4V alloy sheet were experimentally studied. The Ti-6Al-4V titanium alloy was treated by cryogenic treatment after annealing (ACT). Tensile tests were carried out using a universal machine at room temperature. The microstructure evolution of Ti-6Al-4V subjected to ACT was also investigated using an optical microscope (OM). Both the shearing performance and drawing formability were analyzed by punch shearing tests and deep drawing tests, respectively. Results showed that after ACT, the tendency of the β phase can be apparently changing into stable β’ and α’ phases. The elastic modulus is lower than that of the untreated material. It was found that both the yield strength and tensile strength are declined slightly, whereas the ductility is increased significantly. The shear strength in punch shearing is decreased at room temperature and cryogenic temperature. The ratio of smooth zone on the section after ACT3 is much larger than the others. The rollover diameters are not obviously greater than those of the untreated. Additionally, the height of the burr shows a decreasing trend after ACT. During deep drawing, drawing depth is deeper than that of the untreated material, the drawing load after ACT is reduced, and the decreasing tendency of the drawing load slows down. It is noted that the micro-cracks occur at the bottom of the sample.
Flexible Tactile Sensor Array Based on Aligned MWNTs-PU Composited Sub-Microfibers
Authors: Liu Weiting , Cheng Xiaoying , Ruan Xiaodong , Fu Xin
Published: April 2018

This present paper describes a novel method to fabricate tactile sensor arrays by producing aligned multi-walled carbon nanotubes (MWNTs)-polyurethane (PU) composite sub-microfiber (SMF) arrays with the electrospinning technique. The proposed sensor was designed to be used as the artificial skin for a tactile sensation system. Although thin fibers in micro- and nanoscale have many good mechanical characteristics and could enhance the alignment of MWNTs inside, the high impedance as a consequence of a small section handicaps its application. In this paper, unidirectional composite SMFs were fabricated orthogonally to the parallel electrodes through a low-cost method to serve as sensitive elements (SEs), and the impedances of SEs were measured to investigate the changes with deformation caused by applied force. The particular piezoresistive mechanism of MWNTs disturbed in SMF was analyzed. The static and dynamic test results of the fabricated tactile sensor were also presented to validate the performance of the proposed design.
Design, Synthesis, and Docking Studies of New Torin2 Analogs as Potential ATR/mTOR Kinase Inhibitors
Authors: Shaik Althaf , Bhakuni Rashmi , Kirubakaran Sivapriya
Published: April 2018

Targeting DNA damage and response (DDR) pathway has become an attractive approach in cancer therapy. The key mediators involved in this pathway are ataxia telangiectasia-mutated kinase (ATM) and ataxia telangiectasia-mutated, Rad3-related kinase (ATR). These kinases induce cell cycle arrest in response to chemo- and radio-therapy and facilitate DNA repair via their major downstream targets. Targeting ATP-binding site of these kinases is currently under study. Torin2 is a second generation ATP competitive mTOR kinase inhibitor (EC50 = 250 pmol/L) with better pharmacokinetic profile. Torin2 also exhibits potent biochemical and cellular activity against ATM (EC50 = 28 nmol/L) and ATR (EC50 = 35 nmol/L) kinases. In this study, eight new Torin2 analogs were designed and synthesized through multistep synthesis. All the synthesized compounds were characterized by NMR and mass analysis. The newly synthesized analogs were evaluated for their anti-cancer activity via CellTiter-Glo® assay. Additionally, compounds 13 and 14 also showed significant inhibition for ATR and mTOR substrates, i.e., p-Chk1 Ser 317 and p70 S6K Thr 389, respectively. Compounds 13 and 14 displayed promising anti-cancer activity with HCT-116 cell lines in the preliminary study. Further, a comparative model of ATR kinase was generated using the SWISS-MODEL server and validated using PROCHECK, ProSA analysis. Synthesized compounds were docked into the ATP-binding site to understand the binding modes and for the rational design of new inhibitors.
Assessing the Effects of Alloxydim Phototransformation Products by QSAR Models and a Phytotoxicity Study
Authors: Villaverde Juan J. , Santín-Montanyá Inés , Sevilla-Morán Beatriz , Alonso-Prados José L. , Sandín-España Pilar
Published: April 2018

Once applied, an herbicide first makes contact with leaves and soil. It is known that photolysis can be one of the most important processes of dissipation of herbicides in the field. However, degradation does not guarantee detoxification and can give rise to byproducts that could be more toxic and/or persistent than the active substance. In this work, the photodegradation of alloxydim herbicide in soil and leaf cuticle surrogates was studied and a detailed study on the phytotoxicity of the main byproduct on sugar beet, tomato, and rotational crops was performed. Quantitative structure–activity relationship (QSAR) models were used to obtain a first approximation of the possible ecotoxicological and environmental implications of the alloxydim and its degradation product. The results show that alloxydim is rapidly degraded on carnauba and sandy loam soil surfaces, two difficult matrices to analyze and not previously studied with alloxydim. Two transformation products that formed in both matrices were identified: alloxydim Z-isomer and imine derivative (mixture of two tautomers). The phytotoxicity of alloxydim and the major byproduct shows that tomato possesses high sensitivity to the imine byproduct, while wheat crops are inhibited by the parent compound. This paper demonstrates the need to further investigate the behavior of herbicide degradation products on target and nontarget species to determine the adequate use of herbicidal products to maximize productivity in the context of sustainable agriculture.
Estimation of the Toxicity of Different Substituted Aromatic Compounds to the Aquatic Ciliate Tetrahymena pyriformis by QSAR Approach
Authors: Luan Feng , Wang Ting , Tang Lili , Zhang Shuang , Cordeiro M. Natália Dias Soeiro
Published: April 2018

Nowadays, quantitative structure–activity relationship (QSAR) methods have been widely performed to predict the toxicity of compounds to organisms due to their simplicity, ease of implementation, and low hazards. In this study, to estimate the toxicities of substituted aromatic compounds to Tetrahymena pyriformis, the QSAR models were established by the multiple linear regression (MLR) and radial basis function neural network (RBFNN). Unlike other QSAR studies, according to the difference of functional groups (−NO2, −X), the whole dataset was divided into three groups and further modeled separately. The statistical characteristics for the models are obtained as the following: MLR: n = 36, R2 = 0.829, RMS (root mean square) = 0.192, RBFNN: n = 36, R2 = 0.843, RMS = 0.167 for Group 1; MLR: n = 60, R2 = 0.803, RMS = 0.222, RBFNN: n = 60, R2 = 0.821, RMS = 0.193 for Group 2; MLR: n = 31 R2 = 0.852, RMS = 0.192; RBFNN: n = 31, R2 = 0.885, RMS = 0.163 for Group 3, respectively. The results were within the acceptable range, and the models were found to be statistically robust with high external predictivity. Moreover, the models also gave some insight on those characteristics of the structures that most affect the toxicity.
A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats
Authors: Feng Shan , He Xin , Zhong Peiru , Zhao Jinyi , Huang Cong , Hu Zhuohan
Published: April 2018

Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix Angelicae dahuricae (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration–time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05). Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment.
The Effect of PUFA-Rich Plant Oils and Bioactive Compounds Supplementation in Pig Diet on Color Parameters and Myoglobin Status in Long-Frozen Pork Meat
Authors: Pogorzelska-Nowicka Ewelina , Godziszewska Jolanta , Horbańczuk Jarosław O. , Atanasov Atanas G. , Wierzbicka Agnieszka
Published: April 2018

The study evaluated the effect of pig diet supplementation with rapeseed or linseed oil, and vitamin E or selenium, or both vitamin E and selenium on color parameters and myoglobin content of pork Semimembranosus muscle after long-term freezing storage during nine months. The influence of the type of the bioactive compounds added to pig diet on the content of myoglobin or oxymyoglobin, metmyoglobin and deoksymyoglobin in Semimembranosus m. was also assessed. The results indicate that the presence of oils rich in polyunsaturated fatty acids (PUFA) in pig diet improves the color of pork meat. Supplementation of dietary plant oils or dietary oils with antioxidants tended to increase significantly the concentration of oxymyoglobin and decrease the concentration of metmyoglobin in meat compared to the control group. The highest content of oxymyoglobin was observed in meat obtained from pigs fed diets with linseed oil. The best color scores (highest a* parameter) was noted for rapeseed oil group (with no addition of antioxidants). In conclusion, the addition of antioxidants to pigs’ forage supplemented with PUFA-rich oils is not recommended in order to improve color of long-term frozen pork.
Synthesis and Fluorescence Properties of Structurally Characterized Heterobimetalic Cu(II)–Na(I) Bis(salamo)-Based Complex Bearing Square Planar, Square Pyramid and Triangular Prism Geometries of Metal Centers
Authors: Dong Xiu-Yan , Zhao Qing , Wei Zhi-Li , Mu Hao-Ran , Zhang Han , Dong Wen-Kui
Published: April 2018

A novel heterotrinuclear complex [Cu2(L)Na(µ-NO3)]∙CH3OH∙CHCl3 derived from a symmetric bis(salamo)-type tetraoxime H4L having a naphthalenediol unit, was prepared and structurally characterized via means of elemental analyses, UV-Vis, FT-IR, fluorescent spectra and single-crystal X-ray diffraction. The heterobimetallic Cu(II)–Na(I) complex was acquired via the reaction of H4L with 2 equivalents of Cu(NO3)2·2H2O and 1 equivalent of NaOAc. Clearly, the heterotrinuclear Cu(II)–Na(I) complex has a 1:2:1 ligand-to-metal (Cu(II) and Na(I)) ratio. X-ray diffraction results exhibited the different geometric behaviors of the Na(I) and Cu(II) atoms in the heterotrinuclear complex; the both Cu(II) atoms are sited in the N2O2 coordination environments of fully deprotonated (L)4− unit. One Cu(II) atom (Cu1) is five-coordinated and possesses a geometry of slightly distorted square pyramid, while another Cu(II) atom (Cu2) is four-coordination possessing a square planar coordination geometry. Moreover, the Na(I) atom is in the O6 cavity and adopts seven-coordination with a geometry of slightly distorted single triangular prism. In addition, there are abundant supramolecular interactions in the Cu(II)–Na(I) complex. The fluorescence spectra showed the Cu(II)–Na(I) complex possesses a significant fluorescent quenching and exhibited a hypsochromic-shift compared with the ligand H4L.
Poly(urethane-norbornene) Aerogels via Ring Opening Metathesis Polymerization of Dendritic Urethane-Norbornene Monomers: Structure-Property Relationships as a Function of an Aliphatic Versus an Aromatic Core and the Number of Peripheral Norbornene Moieties
Authors: Kanellou Aspasia , Anyfantis George C. , Chriti Despoina , Raptopoulos Grigorios , Pitsikalis Marinos , Paraskevopoulou Patrina
Published: April 2018

We report the synthesis and characterization of synthetic polymer aerogels based on dendritic-type urethane-norbornene monomers. The core of those monomers is based either on an aromatic/rigid (TIPM/Desmodur RE), or an aliphatic/flexible (Desmodur N3300) triisocyanate. The terminal norbornene groups (three at the tip of each of the three branches) were polymerized via ROMP using the inexpensive 1st generation Grubbs catalyst. The polymerization/gelation conditions were optimized by varying the amount of the catalyst. The resulting wet-gels were dried either from pentane under ambient pressure at 50 °C, or from t-butanol via freeze-drying, or by using supercritical fluid (SCF) CO2. Monomers were characterized with high resolution mass spectrometry (HRMS), 1H- and solid-state 13C-NMR. Aerogels were characterized with ATR-FTIR and solid-state 13C-NMR. The porous network was probed with N2-sorption and SEM. The thermal stability of monomers and aerogels was studied with TGA, which also provides evidence for the number of norbornene groups that reacted via ROMP. At low densities (<0.1 g cm−3) all aerogels were highly porous (porosity > 90%), mostly macroporous materials; aerogels based on the aliphatic/flexible core were fragile, whereas aerogels containing the aromatic/rigid core were plastic, and at even lower densities (0.03 g cm−3) foamy. At higher densities (0.2–0.7 g cm−3) all materials were stiff, strong, and hard. At low monomer concentrations all aerogels consisted of discrete primary particles that formed spherical secondary aggregates. At higher monomer concentrations the structure consisted of fused particles with the size of the previous secondary aggregates, due to the low solubility of the developing polymer, which phase-separated and formed a primary particle network. Same-size fused aggregates were observed for both aliphatic and aromatic triisocyanate-derived aerogels, leading to the conclusion that it is not the aliphatic or aromatic core that determines phase separation, but rather the solubility of the polymeric backbone (polynorbornene) that is in both cases the same. The material properties were compared to those of analogous aerogels bearing only one norbornene moiety at the tip of each branch deriving from the same cores.
Nanotechnological Strategies for Protein Delivery
Authors: Villegas María Rocío , Baeza Alejandro , Vallet-Regí María
Published: April 2018

The use of therapeutic proteins plays a fundamental role in the treatment of numerous diseases. The low physico-chemical stability of proteins in physiological conditions put their function at risk in the human body until they reach their target. Moreover, several proteins are unable to cross the cell membrane. All these facts strongly hinder their therapeutic effect. Nanomedicine has emerged as a powerful tool which can provide solutions to solve these limitations and improve the efficacy of treatments based on protein administration. This review discusses the advantages and limitations of different types of strategies employed for protein delivery, such as PEGylation, transport within liposomes or inorganic nanoparticles or their in situ encapsulation.
Grains Contribute Shortfall Nutrients and Nutrient Density to Older US Adults: Data from the National Health and Nutrition Examination Survey, 2011–2014
Authors: Papanikolaou Yanni , Fulgoni Victor L.
Published: April 2018

Previous data demonstrate grain foods contribute shortfall nutrients to the diet of U.S. adults. The 2015–2020 Dietary Guidelines for Americans have identified several shortfall nutrients in the U.S. population, including fiber, folate, and iron (women only). Intake of some shortfall nutrients can be even lower in older adults. The present analyses determined the contribution of grain foods for energy and nutrients in older U.S. adults and ranked to all other food sources in the American diet. Analyses of grain food sources were conducted using a 24-hour recall in adults (≥51 years old; n = 4522) using data from the National Health and Nutrition Examination Survey, 2011–2014. All grains provided 278 kcal/day or 14% of all energy in the total diet, ranking as the 4th largest contributor of energy compared to 15 main food groups. All grain foods ranked 1st for thiamin (33%) and niacin (23%) intake relative to 15 main food groups. The grain foods category ranked 2nd highest of 15 main food groups for daily dietary fiber (23%), iron (38%), folate (40%), and magnesium (15%) and was the 3rd largest food group contributor for daily calcium intake (13%). When considering nutrients to limit as outlined by dietary guidance, main group of grains contributed 6% total fat, 5% saturated fat, 14% sodium and 9% added sugar. Breads, rolls and tortillas provided 150 kcal/day or 8% of all energy in the total diet, ranking as the 2nd largest contributor of energy compared to 46 food subcategories. Breads, rolls and tortillas ranked 1st of 46 foods for daily thiamin (16%) and niacin (10%) intake and 2nd for dietary fiber (12%), iron (12%), folate (13%), and magnesium (7%). Breads, rolls and tortillas ranked 3rd largest food group contributor for daily calcium (5%) intake. Ready-to-eat cereals provided 47 kcal/day or 2% of all energy in the total diet, ranking as the 20th largest contributor of energy compared to 46 food subcategories. All ready-to-eat cereals ranked 1st for daily iron (19%), 1st for folate (21%), 5th for dietary fiber (7%), 3rd for niacin (9%), 8th for magnesium (4%), and 13th for calcium (2%) intake. Given all grain foods and specific subcategories of grain foods provided a greater percentage of several underconsumed nutrients than calories (including dietary fiber, iron, and folate), grain foods provide nutrient density in the American diet of the older adult.
Polymer–Surfactant System Based Amorphous Solid Dispersion: Precipitation Inhibition and Bioavailability Enhancement of Itraconazole
Authors: Feng Disang , Peng Tingting , Huang Zhengwei , Singh Vikramjeet , Shi Yin , Wen Ting , Lu Ming , Quan Guilan , Pan Xin , Wu Chuanbin
Published: April 2018

The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or thermodynamic crystal growth. To evaluate the combined effect of polymers and surfactants on maintaining the supersaturated state of itraconazole (ITZ), various surfactants were integrated with enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMC AS) to develop polymer–surfactant based solid dispersion. The supersaturation stability was investigated by in vitro supersaturation dissolution test and nucleation induction time measurement. Compared to the ASD prepared with HPMC AS alone, the addition of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) exhibited a synergistic effect on precipitation inhibition. The results indicated that the TPGS not only significantly reduced the degree of supersaturation which is the driving force for precipitation, but also provided steric hindrance to delay crystal growth by absorbing onto the surface of small particles. Subsequently, the formulations were evaluated in vivo in beagle dogs. Compared with commercial product Sporanox®, the formulation prepared with HPMC AS/TPGS exhibited a 1.8-fold increase in the AUC (0–24 h) of ITZ and a 1.43-fold increase of hydroxyitraconazole (OH-ITZ) in the plasma. Similarly, the extent of absorption was increased by more than 40% when compared to the formulation prepared with HPMC AS alone. The results of this study demonstrated that the ASD based on polymer–surfactant system could obviously inhibit drug precipitation in vitro and in vivo, which provides a new access for the development of ASD for poorly water-soluble drug.
Experiences of Pharmacy Trainees from an Interprofessional Immersion Training
Authors: Boland Daubney , White Traci , Adams Eve
Published: April 2018

Interprofessional education is essential in that it helps healthcare disciplines better utilize each other and provide team-based collaboration that improves patient care. Many pharmacy training programs struggle to implement interprofessional education. This purpose of the study was to examine the effect of a 30-h interprofessional training that included pharmacy students to determine if the training helped these students build valuable knowledge and skills while working alongside other health care professions. The interprofessional training included graduate-level trainees from pharmacy, behavioral health, nursing, and family medicine programs where the trainees worked within teams to build interprofessional education competencies based on the Interprofessional Education Collaborative core competencies. Sixteen pharmacy trainees participated in the training and completed pre- and post-test measures. Data were collected over a two-year period with participants completing the Team Skills Scale and the Interprofessional Attitudes Scale. Paired sample t-tests indicated that, after this training, pharmacy trainees showed significant increases in feeling better able to work in healthcare teams and valuing interprofessional practice.