bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of g‐C3N4 nanofiller as filler on mechanical properties of multidirectional glass fiber epoxy hybrid composites
Authors: Naidu P. Pratap , Raghavendra Gujjala , Ojha Shakuntala , Paplal Banoth
Published: August 2019

An experimental study was carried out to investigate the flexural strength of glass‐fiber‐reinforced (multidirectional woven glass fiber) epoxy hybrid composites filled with different proportions (1, 1.5, 2, 2.5, and 3%) of graphitic carbon nitride (g‐C3N4) filler. g‐C3N4 powder filled glass epoxy composites were fabricated in conventional hand lay‐up method. Results showed an increase in flexural strength of g‐C3N4 particles content by 2% and beyond which the strength decreased. With the addition of 2 wt % of g‐C3N4 in glass‐fiber‐reinforced epoxy composites, the tensile strength increased by 11% and the flexural strength increased by 13%. The eroded surface of the specimen was observed under scanning electron microscope and the results are reported. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48413.
Captive breeding of Margaritifera auricularia (Spengler, 1793) and its conservation importance
Authors: Nakamura Keiko , Elbaile Eva , Salinas Carlos , Mesquita‐Joanes Francesc , Sousa Ronaldo , Guerrero‐Campo Joaquín , Ruiz‐Zarzuela Imanol , de Blas Ignacio
Published: August 2019

Margaritifera auricularia is one of the most endangered freshwater mussels (Bivalvia, Unionida) in the world. Since 2013, the abundance of this species in the Ebro River basin (Spain) has sharply declined, driving the species to the verge of regional extinction. Therefore, any management measures that might facilitate the recovery of this species would be essential for its conservation.

During 2014–2016, captive breeding of M. auricularia allowed the production of >106 juveniles, out of which 95% were released into the natural environment, and 5% were grown in the laboratory under controlled conditions. The aim of this experimental work was to establish the best culture conditions for the survival and growth of M. auricularia juveniles in the laboratory.

The experiment was divided into two phases: phase I, in which juveniles recently detached from fish gills were cultured in detritus boxes until they reached a shell length of 1 mm; and phase II, in which these specimens were transferred to larger aquaria to grow up to 3–4 mm.

The best experimental conditions for juvenile survival and growth corresponded to treatments in glass containers at a density of 0.2 ind. L−1, using river water, with added substrate and detritus, enriched with phytoplankton, and avoiding extra aeration. The highest survival and growth rates attained, respectively, values of c. 60% at 100 days and 2.56 mm in shell length at 30–32 weeks.

This is the first study to report on the long‐term survival and growth of juvenile M. auricularia in the laboratory, providing essential information in order to implement future conservation measures addressed at reinforcing the natural populations of this highly threatened species in European water bodies.
Interrelationship Between Cognitive Control, Anxiety, and Restricted and Repetitive Behaviors in Children with 22q11.2 Deletion Syndrome
Authors: Uljarević Mirko , McCabe Kathryn L. , Angkustsiri Kathleen , Simon Tony J. , Hardan Antonio Y.
Published: August 2019

Restricted and repetitive behaviors (RRB) are common in individuals with 22q11.2 microdeletion syndrome (22q11.2DS), yet the underlying mechanisms of these behaviors remain poorly characterized. In the present pilot investigation, we aimed to further our understanding of RRB in 22q11.2DS by exploring their relationship with cognitive control and anxiety as well as with sex, chronological age, and full‐scale IQ. Parents of 38 children with 22q11.2DS (17 females;Mage= 11.15 years,SD= 2.46) completed the Social Communication Questionnaire as a measure of RRB and social and communication (SC) problems and the Behavioral Assessment System for Children‐2 as a measure of anxiety and cognitive control. Higher RRB scores were significantly associated with higher anxiety levels (r= 0.44,P= 0.006), more impairments in cognitive control (r= 0.56,P < 0.001), and higher SC scores (r= 0.43,P= 0.011). In the first step of the hierarchical regression model, anxiety accounted for 24.5% of variance (F= 10.05,P= 0.003); cognitive control accounted for an additional 18.1% of variance (Fchange= 11.15,P < 0.001) in the second step; SC score accounted for only 0.8% of additional variance in the third step (Fchange= 0.40,P= 0.53). The final model explained 43.4% of variance (F= 7.42,P= 0.001), with cognitive control as a unique independent predictor of RRB score (t= 2.52,P= 0.01). The current study provides the first exploration of the cognitive control—anxiety—RRB link in individuals with 22q11.2DS and points to cognitive control as a potentially viable target for treatments aimed at reducing RRB.Autism Res2019, 12: 1737–1744. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

People with 22q11.2 deletion syndrome show high levels of repetitive behaviors, however, the previous research has not explored why people with this syndrome exhibit high rates of repetitive behaviors. Understanding the reasons for the high levels of repetitive behaviors is important given that these behaviors can be highly impairing. Our study found that repetitive behaviors were associated with impaired ability to self‐regulate and high levels of anxiety. These findings need to be further replicated; however, they are important as they suggest potentially promising ways of reducing these behaviors.
Construction of a fusion anti‐caries DNA vaccine in transgenic tomato plants for PAcA gene and cholera toxin B subunit
Authors: Bai Guohui , Tian Yuan , Wu Jiayuan , Gu Yu , Chen Zhu , Zeng Fengjiao , Liu Jianguo
Published: August 2019

Chronic bacterial infections in the oral cavity influence the development of dental caries. Mutans streptococci are the major pathogenic cause of dental caries. The World Health Organization (WHO) ranks dental caries, cancer, and cardiovascular diseases as the three major global diseases that need urgent preventative and curative measures. However, substantial evidence suggests that traditional prevention and treatment strategies are inefficient in reducing the prevalence of dental caries. For protection against caries, it is important to develop effective vaccines that induce anticolonizing immunity against Streptococcus mutans infections. In the present investigation, we constructed a fusion anti‐caries DNA vaccine (PAcA‐ctxB) through fusing A region of cell surface protein PAc (PAcA) coding gene of mutans streptococci with cholera toxin B subunit coding gene (CTB). Afterward, the plasmids were integrated into tomato genomes through agrobacterium‐mediated plant transformation technology. The presence of transgenes in the tomato genome was confirmed by PCR, β‐glucuronidase gene (GUS), and western blot. The expression of genes was confirmed at transcription and protein level. Altogether, the results presented herein showed that transgenic tomatoes may provide a useful system for the production of human caries antigen.
Grundlagen mathematischer Theorie adaptiver Tragwerke
Authors: Wilhelm Viktor
Published: August 2019

Adaptive Tragwerke sind mit Verschiebungen und Kräfteumlagerungen in der Zeit verbunden. Als Ziel der Adaption bzw. der Kräfteumlagerungen wird in der einschlägigen Literatur die gleichmäßige volle Ausnutzung des Materials definiert. Die gleichmäßige volle Ausnutzung des Konstruktionsmaterials wird seinerseits mit der Effektivität des Leichtbaus verknüpft.

Im vorliegenden Aufsatz analysiert der Autor zunächst aus Sicht der Baustatik den Adaptivitätsmechanismus anhand des aus der Literatur bekannten selbstanpassenden Tragwerks: Stuttgarter Träger. Durch den Adaptivitätsmechanismus, bestehend aus Sensoren und Aktuatoren, manipulieren die Erfinder des Stuttgarter Trägers die inneren und äußeren Kräfte anhand eines Modells (Computermodell und gebautes Miniaturmodell).

Im Anschluss werden Grundlagen der linearen Theorie der Kräfteumlagerungen in Tragwerkssystemen aufgezeigt. In diesen Systemen wird die Steuerung der Kräfteumlagerungen dem Material selbst überlassen.
Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
Authors: Fei Qian , Du Ming‐Yu , Qian Lu‐Xi , Chen Han‐Bo , Chen Jie , Zhu Hong‐Ming , Tian Xiao‐Kang , Jiang Ning , Gu Jia‐Jia , He Xia , Yin Li
Published: August 2019

An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR‐449b‐3p was downregulated in NPC specimens (P < .001) and cells (P < .05). Cytological and animal experiments provided evidence that miR‐449b‐3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR‐449b‐3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR‐449b‐3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR‐449b‐3p by inducing NF‐κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR‐449b‐3p/ADAM17/NF‐κB feedback loop could be a target for the clinical treatment of NPC.
Quantification and Statistical Analysis of Errors Related to the Approximate Description of Active Site Models in Metal‐Exchanged Zeolites
Authors: Thirumalai Hari , Rimer Jeffrey D. , Grabow Lars C.
Published: August 2019

Metal‐exchanged zeolites are complex catalytic systems with great potential for applications in hydrocarbon conversion processes. The numerous combinations of zeotypes and metal‐based Lewis acid motifs create a vast material space that can only be effectively navigated with robust structure‐function relationships. Exhaustive modeling of extraframework metal sites in all crystallographically distinct framework positions is not practical; thus, we quantified the uncertainties arising from the use of simplified active site representations using the C−H bond activation in methane as a probe reaction. Density functional theory calculations and statistical analysis of associated error ensembles suggest that the Lewis acid identity primarily determines the reactivity of the zeolite towards methane activation, with other factors such as zeolite model characteristics deemed secondary. The error ensemble distributions were used to predict the relative probability of creating active C−H bond scission fragments in metal‐exchanged zeolites, and thus can be used to efficiently screen various metal‐exchange candidates in their efficacy towards hydrocarbon conversion.
Performance Map for the Design of Liquid‐Liquid Extraction Columns
Authors: Weber Benedikt , Meyer Christian , Jupke Andreas
Published: August 2019

For the fast approximation of liquid‐liquid extraction column designs via HETS (height equivalent of a theoretical stage) values and flooding points, a population balance model was developed. The model requires only one pilot‐scale column experiment to fit a coalescence parameter. The comparison of experimental data with simulations shows good agreement for a stirred extraction column. With the model, the operation domain of the column is simulated and visualized in a performance map, showing the holdup, the distance to the flooding point and HETS values.
Analytical attractive functions and their derivatives in bulk and nanoconfined pores
Authors: Zhang Kaiqiang , Jia Na , Zeng Fanhua
Published: August 2019

In this paper, two new analytical attractive (alpha) functions and their derivatives in bulk and nanoconfined pores are developed based on the virial equation of state (EOS) and statistical thermodynamics and are evaluated at different conditions for the first time. A cubic EOS is modified to nanometer scale and applied to predict the thermodynamic and phase properties in bulk and nanoconfined pores coupled with the new analytical alpha functions. The nanoscale‐extended EOS coupled with the analytical alpha functions are validated to be accurate by means of the experimental data for the thermodynamic and phase calculations. The alpha functions and dimensionless attractive term A for the O2, Ar, CO2, N2, and C1‐C10 are always positive and monotonically decrease with the temperature increases at T ≤ 2000 K in the bulk phase, whereas the second virial coefficients (B2) are always negative and increase with the temperature increases. Moreover, the alpha functions, A, and B2 for all of components remain constant with the decreasing pore radius until rp = 50 nm, the former two of which decrease while the latter one increases by further reducing the pore radius. It should be noted that the intermolecular attractive force (ie, A) is a function of the pressure, which is gradually increased at P ≤ 10 MPa though drastically increases afterwards. Also, the enhanced confinement effects lead the same‐component intermolecular attractive forces to be smaller. The analytical formulations in the SRK type slightly outperform in the gaseous or light component cases, while those in the PR type are better for the heavy component cases in terms of the thermodynamic property calculations, both of which are compatible with the modified EOS and analytical alpha functions.
An Iron Quaterpyridine Complex as Precursor for the Electrocatalytic Reduction of CO2 to Methane
Authors: Cometto Claudio , Chen Lingjing , Mendoza Daniela , Lassalle‐Kaiser Benedikt , Lau Tai‐Chu , Robert Marc
Published: August 2019

A Fe quaterpyridine complex was used as a molecular precursor for the electrochemical reduction of CO2 to CH4 in acetonitrile in the presence of triethanolamine. CH4 was produced with a faradaic yield of approximately 2.1 % at 25 °C and 1 atm pressure of CO2 as reactant. Controlled potential electrolysis coupled to ex situ X‐ray photoelectron spectroscopy and X‐ray absorption spectroscopy of the electrode surface revealed the formation of metallic iron covered by iron oxides as species responsible for catalysis.
Performance evaluation of a priority‐based resource allocation scheme for multiclass services in IoT
Authors: Alqahtani Salman A.
Published: August 2019

Recently, the deployment of novel smart network concepts, such as the Internet of things (IoT) or machine‐to‐machine communication, has gained more attention owing to its role in providing communication among various smart devices. The IoT involves a set of IoT devices (IoTDs) such as actuators and sensors that communicate with IoT applications via IoT gateways without human intervention. The IoTDs have different traffic types with various delay requirements, and we can classify them into two main groups: critical and massive IoTDs. The fundamental promising technology in the IoT is the advanced long‐term evolution (LTE‐A). In the future, the number of IoTDs attempting to access an LTE‐A network in a short period will increase rapidly and, thus, significantly reduce the performance of the LTE‐A network and affect the QoS required by variant IoT traffic. Therefore, efficient resource allocation is required.

In this paper, we propose a priority‐based allocation scheme for multiclass service in IoT to efficiently share resources between critical and massive IoTD traffic based on their specific characteristics while protecting the critical IoTDs, which have a higher priority over the massive IoTDs. The performance of the proposed scheme is analyzed using the Geo/G/1 queuing system focusing on QoS guarantees and resource utilization of both critical and massive IoTDs. The distribution of service time of the proposed system is determined and, thus, the average waiting and service times are derived. The results indicate that the performance of the massive IoTDs depends on the data traffic characteristics of the critical IoTDs. Furthermore, the results emphasize the importance of the system delay analysis and demonstrate its effects on IoT configurations.
Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors
Authors: Dickson Brendan C. , Chung Catherine T.‐S. , Hurlbut David J. , Marrano Paula , Shago Mary , Sung Yun‐Shao , Swanson David , Zhang Lei , Antonescu Cristina R.
Published: August 2019

Alveolar soft part sarcoma (ASPS) is a rare malignancy that, since its initial description, remains a neoplasm of uncertain histogenesis. The disease‐defining molecular event characterizing the diagnosis of ASPS is the ASPSCR1‐TFE3 fusion gene. Following identification of an index case of ASPS with a novel TFE3 fusion partner, we performed a retrospective review to determine whether this represents an isolated event. We identified two additional cases, for a total of three cases lacking ASPSCR1 partners. The average patient age was 46 years (range, 17‐65); two patients were female. The sites of origin included the transverse colon, foot, and dura. Each case exhibited a histomorphology typical of ASPS, and immunohistochemistry was positive for TFE3 in all cases. Routine molecular testing of the index patient demonstrated a HNRNPH3‐TFE3 gene fusion; the remaining cases were found to have DVL2‐TFE3 or PRCC‐TFE3 fusion products. The latter two fusions have previously been identified in renal cell carcinoma; to our knowledge, this is the first report of a HNRNPH3‐TFE3 gene fusion. These findings highlight a heretofore underrecognized genetic diversity in ASPS, which appears to more broadly molecularly overlap with that of translocation‐associated renal cell carcinoma and PEComa. These results have immediate implications in the diagnosis of ASPS since assays reliant upon ASPSCR1 may yield a false negative result. While these findings further understanding of the molecular pathogenesis of ASPS, issues related to the histogenesis of this unusual neoplasm remain unresolved.
Eine Systematik für die Einteilung des Baugrunds in Homogenbereiche
Authors: Kayser Jan
Published: August 2019

Für die vertragsgerechte Beschreibung des Baugrunds wurde mit Herausgabe des VOB‐Gesamtbands 2015 ein Klassifikationssystem auf der Grundlage von Homogenbereichen eingeführt. Als Handlungshilfe zur Anwendung der Homogenbereiche hat die Bundesanstalt für Wasserbau das Merkblatt Einteilung des Baugrunds in Homogenbereiche nach VOB/C (MEH) erarbeitet. Dem MEH liegt eine Systematik zur Einteilung des Baugrunds auf der Grundlage von Leitparametern zugrunde. Für die Leitparameter werden Einteilungsgrenzen angegeben, die als Orientierung für die Einteilung des Baugrunds in Homogenbereiche verwendet werden können. Ergänzend werden Vorschläge für die Darstellung der Schichteigenschaften und der Homogenbereiche gemacht. Auch werden Hinweise für den Umgang mit heterogenen Baugrundschichten und für einige spezielle Kennwerte gegeben.
Response surface modeling of CO2dynamic storage efficiency factor in high permeability thick sandstones
Authors: Zulqarnain Muhammad , Zeidouni Mehdi , Hughes Richard G.
Published: August 2019

In order to utilize as much of the pore space for CO2storage in high permeability thick saline aquifers, it is vital to investigate the interactions of injected CO2with formation brine and rock. In order to quantify the displacement process, we investigate the dynamic storage efficiency factor (DSEF) for saline aquifers where pressure increase is minimal during the injection phase. Dimensionless numbers are derived from basic governing equations, constitutive equations, initial and boundary conditions using the inspection analysis. Then using the Hammersley sequence sampling, 178 numerical experiments are designed, and a compositional reservoir simulator is used to perform these simulations. In the next step, response surface regression analysis is used to establish a relationship between DSEF obtained from the numerical simulations and the corresponding dimensionless numbers. The simulation results show that for the studied conditions the underground dynamics is mostly influenced by the gravity number, followed by effective aspect ratio and dip numbers. The results from the response surface regression analysis are used to develop a correlation, which can be used to estimate the dynamic CO2storage capacity of relevant zones. This study provides quantitative measures for the different competing mechanisms involved in underground displacement of fluids in CO2geological storage, which can serve as a useful tool during planning phase of storage projects. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
A systematic literature review based on different fuel injection strategies used in scramjet combustors
Authors: Gugulothu Santhosh K.
Published: August 2019

A supersonic combustion ramjet engine is an air‐breathing propulsive system aimed at futuristic hypersonic vehicles. The profound advantages observed in the area of defence applications has attracted researchers' attention towards improving the fluid flow dynamics of scramjet engines. The present effort summarizes the fundamental problems and latest advances in fuel injection techniques. Improvements and application of modern fuel injection technologies have a profound impact on the scramjet engine, increasing capacity in terms of flight speed, efficiency in fuel mixing, and combustion. The fuel injection system has a direct impact on the engine's combustion processes, determining the scramjet engine's thrust power and its flight speed. A systematic database including brief descriptions of mixing enhancement mechanisms was analyzed numerically and experimentally, identifying the needed and existing fuel injection strategies. The numerical and computational analysis directly related to the experimental investigations is also included.
Optimal design of snow stake networks to estimate snow depth in an alpine mountain range
Authors: Collados‐Lara Antonio‐Juan , Pardo‐Igúzquiza Eulogio , Pulido‐Velazquez David
Published: August 2019

Monitoring and estimation of snow depth in alpine catchments is needed for a proper assessment of management alternatives for water supply in these water resources systems. The distribution of snowpack thickness is usually approached by using field data that come from snow samples collected at a given number of locations that constitute the monitoring network. Optimal design of this network is required to obtain the best possible estimates. Assuming that there is an existing monitoring network, its optimization may imply the selection of an optimal network as a subset of the existing one (if there are no funds to maintain them) or enlarging the existing network by one or more stations (optimal augmentation problem). We propose an optimization procedure that minimizes the total variance in the estimate of snowpack thickness. The novelty of this work is to treat, for the first time, the problem of snow observation network optimization for an entire mountain range rather than for small catchments as done in the previous studies. Taking into account the reduced data available, which is a common problem in many mountain ranges, the importance of a proper design of these observation networks is even larger. Snowpack thickness is estimated by combining regression models to approach the effect of the explanatory variables and kriging techniques to consider the influence of the stakes location. We solve the optimization problems under different hypotheses, studying the impacts of augmentation and reduction, both, one by one and in pairs. We also analyse the sensitivity of results to nonsnow measurements deduced from satellite information. Finally, we design a new optimal network by combining the reduction and augmentation methods. The methodology has been applied to the Sierra Nevada mountain range (southern Spain), where very limited resources are employed to monitor snowfall and where an optimal snow network design could prove critical. An optimal snow observation network is defined by relocating some observation points. It would reduce the estimation variance by around 600 cm2 (15%).
Detection and classification of microcalcification from digital mammograms with firefly algorithm, extreme learning machine and non‐linear regression models: A comparison
Authors: Sannasi Chakravarthy S. R. , Rajaguru Harikumar
Published: August 2019

In this study, abnormalities in medical images are analysed using three classifiers, and the results are compared. Breast cancer remains a major public health problem among women worldwide. Recently, many algorithms have evolved for the investigation of breast cancer diagnosis through medical imaging. A computer‐aided microcalcification detection method is proposed to categorise the nature of breast cancer as either benign or malignant from input mammogram images. The standard mammogram image corpus, the Mammogram Image Analysis Society database is utilised, and feature extraction is performed using five different wavelet families at level 4 and level 6 decomposition. The work is accomplished through firefly algorithm (FA), extreme learning machine (ELM) and least‐square‐based non‐linear regression (LSNLR) classifiers. The performance of the classifiers is compared by benchmark metrics, such as total error rate, specificity, sensitivity, area under the receiver operating characteristic curve, precision, F1 score and the Matthews correlation coefficient. As validation of the classifier results, a kappa analysis is included to determine the agreement among classifiers. The LSNLR classifier attains a 3% to 7% improvement in average accuracy compared with the average classification accuracy of the FA (86.75%) and ELM (90.836%) classifiers.
Injectable pegylated niclosamide (polyethylene glycol‐modified niclosamide) for cancer therapy
Authors: Ma Rui , Ma Zhen‐Gang , Gao Jin‐Lai , Tai Yu , Li Lan‐Jun , Zhu Hai‐Bin , Li Li , Dong De‐Li , Sun Zhi‐Jie
Published: August 2019

Niclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β‐catenin, mTORC1, signal transducer and activator of transcription 3, NF‐κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol‐modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000‐Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000‐Nic was significantly increased. Niclosamide could be released from mPEG5000‐Nic nanoparticles in PBS solution. mPEG5000‐Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000‐Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000‐Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000‐Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5‐fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.
Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy
Authors: Jia Xiangyu
Published: August 2019

The IPolQ‐Mod charges, which are the average of two charge sets fitted in vacuum state and condensed phase, take account of polarization effect implicitly in the solvation free energy calculation. However, the performance of the IPolQ‐Mod charges sensitively depends on the QM levels used to generate the electrostatic potential from which the charges are fitted. In addition, the forces on atoms are not accurate theoretically in the molecular dynamics (MD) simulation as the solvent only feels the electrostatic potential of a half‐polarized density of the solute according to the derivation of the IPolQ‐Mod charges. To study these issues in detail, the IPolQ‐Mod charges are combined with the reference potential (RP) strategy to predict the solvation free energies in the present study. It is found that the thermodynamic perturbation (TP) corrections utilizing total energy difference and interaction energy difference are almost the same and free of bias. The solvation free energies estimated by the RP method match very well with those obtained by applying IPolQ‐Mod charges into MD simulation directly. By means of the RP strategy, the performances of the IPolQ‐Mod charges with the change of the strength of the exact HF exchange in several DFT functionals are determined effectively. Although the “optimal” strengths are found in B3LYP and LC‐ωPBE, the improvements over the default strength are not too much. In addition to the IPolQ‐Mod charges, other charge models like bond charge correction (BCC) charges could also be combined with the RP strategy to study the thermodynamic properties like solvation free energy. © 2019 Wiley Periodicals, Inc.
Development and temperature gradient online monitoring of a vehicular rotary solid‐state bioreactor: a novel device for large‐scale preparation of Aspergillus niger spore inoculum
Authors: Zhang Xiaoran , Jiang Wenxia
Published: August 2019

BACKGROUND

Mechanical cultivation of Aspergillus niger spores at industrial scales as the fermentationinoculum in citric acid plants is difficult to achieve: in solid‐state cultivation, intense mechanical agitation or continuous mixing to reduce damage to the filamentous microbes is not feasible, but inadequate mixing or static cultivation would cause serious inner‐bed temperature gradients. It is therefore necessary to develop novel bioreactors coordinating the conflict between microbe protection and heat transfer, by globally investigating the inner‐bed temperature profile, an investigation that has not been reported upon previously.

RESULTS

A novel vehicular rotary solid‐state bioreactor was developed combining the characteristics of both a vertical packed bed and a horizontal rotating drum. Moderate and intermittent rotary mixing based on the characteristic posture‐shifting function ensured high spore yields of 3.1 × 1012 per batch (22‐cm‐thick bed, using a rich medium) and 1.3 × 1012 per batch (15‐cm‐thick bed, using a poor medium and two‐stage temperature control strategy). The two‐stage temperature control strategy effectively depressed the upper limit of bed temperature under 37.0 °C. A 16‐point temperature measuring system provided online 4D data of the culture bed including time, temperature, radius and height, globally displaying the inner‐bed temperature gradients. A cylindrical air distributor benefits inner bed radial air flow distribution, but did not affect the spore yield and average moisture content of the solid culture.

CONCLUSIONS

The novel devices and methods realized large‐scale production of A. niger spores by coordinating moderate mixing and inner bed temperature field monitoring and control; they also possessed application value for other filamentous microbes. © 2019 Society of Chemical Industry
An Efficient Approach for the Synthesis of 1,2,3‐Triazole Moiety to Generate Uracil Molecular Architectures Through Cu‐Catalyzed Azide–Alkyne Cycloaddition
Authors: Mohamed Asmaa H.
Published: August 2019

A simple and efficient pathway to tether conjugates of monosaccharides or aromatic moieties to uracil establishing a 1,2,3‐triazole linker via click chemistry was reported. The reaction of arylimines of 5‐amino uracil with propargyl bromide in a basic medium gave a di‐propargylated uracil. The latter compound was converted into molecular architectures containing bis‐1,2,3‐triazole rings through Cu‐catalyzed 1,3‐cycloaddition reaction with different azides. The same arylimine of 5‐amino uracil yielded different products under reflux with propargyl bromide in acetonitril with the majority to 6‐propargylated‐5‐amino uracil.
Dynamic Network Analysis of Negative Emotions and DSM‐5 Posttraumatic Stress Disorder Symptom Clusters During Conflict
Authors: Greene Talya , Gelkopf Marc , Fried Eiko I. , Robinaugh Donald J. , Lapid Pickman Liron
Published: August 2019

Investigating dynamic associations between specific negative emotions and PTSD symptom clusters may provide novel insights into the ways in which PTSD symptoms interact with, emerge from, or are reinforced by negative emotions. The present study estimated the associations among negative emotions and the four DSM‐5 PTSD symptom clusters (intrusions, avoidance, negative alterations in cognitions and mood [NACM], and arousal) in a sample of Israeli civilians (n = 96) during the Israel–Gaza War of July–August 2014. Data were collected using experience sampling methodology, with participants queried via smartphone about PTSD symptoms and negative emotions twice a day for 30 days. We used a multilevel vector auto‐regression model to estimate temporal and contemporaneous temporal networks. Contrary to our hypothesis, in the temporal network, PTSD symptom clusters were more predictive of negative emotions than vice versa, with arousal emerging as the strongest predictor that negative emotions would be reported at the next measurement point; fear and sadness were also strong predictors of PTSD symptom clusters. In the contemporaneous network, negative emotions exhibited the strongest associations with the NACM and arousal PTSD symptom clusters. The negative emotions of sadness, stress, fear, and loneliness had the strongest associations to the PTSD symptom clusters. Our findings suggest that arousal has strong associations to both PTSD symptoms and negative emotions during ongoing trauma and highlights the potentially relevant role of arousal for future investigations in primary or early interventions.
Evaluation of a membrane hybridization array for detection of Mycobacterium tuberculosis complex and resistance to isoniazid and rifampin in sputum specimens, mycobacterial liquid cultures, and clinical isolates
Authors: Chen Chao‐Ju , Yang Yuan‐Chieh , Huang Hsin‐Hui , Chang Tsung Chain , Lu Po‐Liang
Published: August 2019

The gold standard of antituberculosis susceptibility testing is based on culture method which takes weeks. Rapid detection of resistance to isoniazid (INH) and rifampin (RIF) to avoid inappropriate regimens and to prevent transmission of resistant strains are important. A membrane array (BluePoint MTBDR) was developed to identify Mycobacterium tuberculosis complex (MTBC) and the genetic mutations responsible for resistance to RIF and INH. We aimed to evaluate the performance of this array for diagnosing drug‐resistant MTBC. A total of 261 acid‐fast bacilli positive sputum specimens, 1025 positive mycobacteria growth indicator tube (MGIT) cultures and 544 clinical isolates were analyzed. Antituberculosis susceptibility testing was the gold standard and was performed on MTBC isolated from positive MGIT cultures and on 544 clinical isolates. The sensitivity and specificity of the array to detect MTBC were 62.2% and 88.1% for sputum specimens, 100% and 97.9% for MGIT cultures. For detection of drug‐resistant MTBC in positive MGIT tubes, the sensitivities of the array were 100% for RIF and 97.1% for INH, while the specificities were 99.7% and 100%, respectively. Interestingly, we noticed four genotypically RIF‐resistant but phenotypically RIF‐susceptible isolates and eight genotypically INH resistant but phenotypically INH‐susceptible isolates. Comparing with conventional culture methods for species identification and drug susceptibility testing, the BluePoint MTBDR assay demonstrated to be a rapid test with high sensitivity and specificity to identify MTBC and to detect isoniazid and rifampin resistance when it is applied to broth culture specimens and clinical isolates.
Antitumor effect of insulin‐like growth factor‐1 receptor inhibition in head and neck squamous cell carcinoma
Authors: Lehman Christine E. , Khalil Ashraf A. , Axelrod Mark J. , Dougherty Michael I. , Schoeff Stephen S. , Taniguchi Linnea E. , Mendez Rolando E. , David Abel P. , McGarey Patrick O. , Hubbard Matthew A. , Donaldson Lane , Frierson Henry F. , Stelow Edward B. , Bekiranov Stefan , Wulfkuhle Julia D. , Petricoin Emanuel F. , Gioeli Daniel G. , Jameson Mark J.
Published: August 2019

Objectives

The insulin‐like growth factor‐1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R‐TKIs, OSI‐906 and BMS‐754807, were evaluated in HNSCC cell lines in vitro.

Methods

Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression‐specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R‐TKIs.

Results

For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5‐year survival (P = 0.029). Both BMS‐754807 and OSI‐906 caused dose‐dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS‐754807 was more potent than OSI‐906. Both drugs reduced HNSCC cell viability; only OSI‐906 was able to eliminate all viable cells at 10 μM. The two drugs similarly inhibited clonogenic cell survival. At 1 μM, only BMS‐754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor‐3 (HER3), Src, paxillin, and ezrin phosphorylation.

Conclusion

OSI‐906 and BMS‐754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC.

Level of Evidence

NA Laryngoscope, 130:1470–1478, 2020
3D Printing of Silk Protein Structures by Aqueous Solvent‐Directed Molecular Assembly
Authors: Mu Xuan , Wang Yu , Guo Chengchen , Li Yamin , Ling Shengjie , Huang Wenwen , Cebe Peggy , Hsu Huan‐Hsuan , De Ferrari Fabio , Jiang Xiaocheng , Xu Qiaobing , Balduini Alessandra , Omenetto Fiorenzo G. , Kaplan David L.
Published: August 2019

Hierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural strategy into advanced digital manufacturing like three‐dimensional (3D) printing remains a technical challenge. This work presents a 3D printing technique with silk fibroin to address this challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and robust mechanical features. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. The manufacturing capability is exemplified by the single‐step construction of perfusable microfluidic chips which eliminates the use of supporting or sacrificial materials. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds. This work also provides insights into the recapitulation of solvent‐directed hierarchical molecular assembly for artificial manufacturing.
Redox Polymer–Based Nano‐Objects via Polymerization‐Induced Self‐Assembly
Authors: Boujioui Fadoi , Zhuge Flanco , Gohy Jean‐François
Published: August 2019

Poly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl‐methacrylate) (PTMA) redox polymer–based nano‐objects are synthesized by polymerization‐induced self‐assembly with poly[oligo(ethylene glycol) methyl ether methacrylate] and poly[(4‐methacryloyloxy)‐2,2,6,6‐tetramethylpiperidinium chloride] as hydrophilic macro‐chain transfer agents. These hydrophilic blocks are used in order to stabilize hydrophobic PTMA blocks in aqueous medium. The accordingly obtained spherical nano‐objects are observed via transmission electron microscopy analysis. Cyclic voltammetry measurements indicate that the nature and the length of coronal blocks influence the redox process of the PTMA core blocks. Moreover, these electroactive nano‐objects display low viscosities with a shear‐thinning behavior, making them suitable as cathode‐active materials for aqueous flow‐assisted electrochemical systems.
Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly
Authors: Bayram Cem , Jiang Xinyue , Gultekinoglu Merve , Ozturk Sukru , Ulubayram Kezban , Edirisinghe Mohan
Published: August 2019

The control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.
Cortical network fingerprints predict deep brain stimulation outcome in dystonia
Authors: Gonzalez‐Escamilla Gabriel , Muthuraman Muthuraman , Reich Martin M. , Koirala Nabin , Riedel Christian , Glaser Martin , Lange Florian , Deuschl Günther , Volkmann Jens , Groppa Sergiu
Published: August 2019

Background

Deep brain stimulation (DBS) is an effective evidence‐based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns.

Methods

From a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior‐outcome group or moderate‐outcome group, depending on whether they had above or below 70% motor improvement, respectively. Fifty‐one patients met MRI‐quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray‐matter fingerprints.

Results

The moderate‐outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88% of accuracy using individual gray‐matter atrophy patterns to predict DBS outcomes.

Conclusions

The analysis of cortical integrity, informed by group‐level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions
Authors: Fasano Alfonso , Helmich Rick C.
Published: August 2019

DBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as “tolerance.” Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on “eminence rather than evidence.” The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different—not mutually exclusive—factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease‐related factors (tremor etiology and progression); surgery‐related factors (electrode location, microlesional effect and placebo); and stimulation‐related factors (not optimized stimulation, stimulation‐induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society
Feedback control variables to restrain the Babesiosis disease
Authors: Dang Quang A. , Hoang Manh T. , Trejos Deccy Y. , Valverde Jose C.
Published: August 2019

In this paper, we complete the study of the dynamics of a recognized continuous‐time model for the Babesiosis disease. The local and global asymptotic stability of the endemic state are established theoretically and experimentally. In addition, to restrain the disease in the original model when the endemic state exists, we propose and study the continuous model with feedback controls. The global stability of the boundary‐equilibrium point of this model is analyzed by means of rigorous mathematical methods. As an important consequence of this result, we propose a strategy to select feedback control variables in order to restrain the disease in the original model. This strategy allows us to make the disease vanish completely. In other words, the feedback controls are specially effective for restraining disease in the model. The validity of the established theoretical result is supported by a set of numerical simulations.