bluuebunny/crossref_metadata_2025 huggingface dataset:
BN‐Embedded Tetrabenzopentacene: A Pentacene Derivative with Improved Stability
Authors: Zhuang Fang‐Dong , Sun Ze‐Hao , Yao Ze‐Fan , Chen Qi‐Ran , Huang Zhen , Yang Jing‐Hui , Wang Jie‐Yu , Pei Jian
Published: May 2019

Considerable efforts have been devoted to achieving stable acene derivatives for electronic applications; however, the instability is still a major issue for such derivatives. To achieve higher stability with minimum structural change, CC units in the acenes were replaced with isoelectronic BN units to produce a novel BN‐embedded tetrabenzopentacene (BNTBP). BNTBP, with a planar structure, is highly stable to air, moisture, light, and heat. Compared with its carbon analogue tetrabenzopentacene (TBP), BN embedment lowered the highest occupied molecular orbital (HOMO) energy level of BNTBP, changed the orbital distribution, and decreased the HOMO orbital coefficients at the central carbon atoms, which stabilize BNTBP molecules upon exposure to oxygen and sunlight. The single‐crystal microribbons of BNTBP exhibited good performance in field‐effect transistors (FETs). The high stability and good mobility of BNTBP indicates that BN incorporation is an effective approach to afford stable large‐sized acenes with desired properties.
Practical Catalytic Cleavage of C(sp3)−C(sp3) Bonds in Amines
Authors: Li Wu , Liu Weiping , Leonard David K. , Rabeah Jabor , Junge Kathrin , Brückner Angelika , Beller Matthias
Published: May 2019

The selective cleavage of thermodynamically stable C(sp3)−C(sp3) single bonds is rare compared to their ubiquitous formation. Herein, we describe a general methodology for such transformations using homogeneous copper‐based catalysts in the presence of air. The utility of this novel methodology is demonstrated for Cα−Cβ bond scission in >70 amines with excellent functional group tolerance. This transformation establishes tertiary amines as a general synthon for amides and provides valuable possibilities for their scalable functionalization in, for example, natural products and bioactive molecules.
Molecular Engineering‐Based Aptamer–Drug Conjugates with Accurate Tunability of Drug Ratios for Drug Combination Targeted Cancer Therapy
Authors: Zhou Fang , Wang Peng , Peng Yongbo , Zhang Pengge , Huang Qin , Sun Weidi , He Nongyue , Fu Ting , Zhao Zilong , Fang Xiaohong , Tan Weihong
Published: May 2019

Polytherapy (or drug combination cancer therapy (DCCT)), targeting multiple mechanisms associated with tumor proliferation, can efficiently maximize therapeutic efficacy, decrease drug dosage, and reduce drug resistance. However, most DCCT strategies cannot coordinate the specific delivery of a drug combination in an accurately tuned ratio into cancer cells. To address these limitations, the present work reports the engineering of circular bivalent aptamer–drug conjugates (cb‐ApDCs). The cb‐ApDCs exhibit high stability, specific recognition, excellent cellular uptake, and esterase‐triggered release. Furthermore, the drug ratios in cb‐ApDCs can be tuned for an enhanced synergistic effect without the need for complex chemistry. Therefore, cb‐ApDCs provide a promising platform for the development of DCCT strategies for different drug combinations and ratios.
Palladium‐Catalyzed Directed meta‐Selective C−H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates
Authors: Achar Tapas Kumar , Zhang Xinglong , Mondal Rahul , Shanavas M. S. , Maiti Siddhartha , Maity Sabyasachi , Pal Nityananda , Paton Robert S. , Maiti Debabrata
Published: May 2019

Palladium(II)‐catalyzed meta‐selective C−H allylation of arenes has been developed utilizing synthetically inert unactivated acyclic internal olefins as allylic surrogates. The strong σ‐donating and π‐accepting ability of pyrimidine‐based directing group facilitates the olefin insertion by overcoming inertness of the typical unactivated internal olefins. Exclusive allyl over styrenyl product selectivity as well as E stereoselectivity were achieved with broad substrate scope, wide functional‐group tolerance, and good to excellent yields. Late‐stage functionalisations of pharmaceuticals were demonstrated. Experimental and computational studies shed light on the mechanism and point to key steric control in the palladacycle, thus determining product selectivities.
Functionalized Contorted Polycyclic Aromatic Hydrocarbons by a One‐Step Cyclopentannulation and Regioselective Triflyloxylation
Authors: Yang Xuan , Hoffmann Marvin , Rominger Frank , Kirschbaum Tobias , Dreuw Andreas , Mastalerz Michael
Published: May 2019

The oxidative cyclodehydrogenation (often named the Scholl reaction) is still a powerful synthetic tool to construct even larger polycyclic aromatic hydrocarbons (PAHs) by multiple biaryl bond formations without the necessity of prior installation of reacting functional groups. Scholl‐type reactions are usually very selective although the resulting products bear sometimes some surprises, such as the formation of five‐membered instead of six‐membered rings or the unexpected migration of aryl moieties. There are a few examples, where chlorinated byproducts were found when FeCl3 was used as reagent. To our knowledge, the direct functionalization of PAHs during Scholl‐type cyclization by triflyloxylation has not been observed. Herein we describe the synthesis of functionalized PAHs by the formation of five‐membered rings and a regioselective triflyloxylation in one step. The triflyloxylated PAHs can be used as reactants for further transformation to even larger contorted PAHs.
Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives
Authors: Turkan Fikret , Cetin Adnan , Taslimi Parham , Karaman Halide S. , Gulçin İlhami
Published: May 2019

In this study, synthesis of ethyl 2‐((4‐bromophenyl)diazenyl)‐3‐oxo‐phenylpropanoate 1 was carried out and a series of new 3H‐pyrazol‐3‐ones (P1–7) were synthesized from 1 as well as various hydrazines. The obtained yields of the synthesized compounds were moderate (40–70%) and these compounds were confirmed by spectral data. These novel pyrazoline derivatives were effective inhibitor compounds of the human carbonic anhydrase I and II isozymes (hCAs I and II) and of the acetylcholinesterase (AChE) enzyme, with Ki values in the range of 17.4–40.7 nM for hCA I, 16.1–55.2 nM for hCA II, and 48.2–84.1 nM for AChE. In silico studies were performed on the compounds inhibiting hCA I, hCA II, and AChE receptors. On the basis of the findings, the inhibition profile of the new pyrazoline compounds at the receptors was determined.
State estimation for nonlinear conformable fractional‐order systems: A healthy operating case and a faulty operating case
Authors: Jmal Assaad , Elloumi Mourad , Naifar Omar , Ben Makhlouf Abdellatif , Hammami Mohamed Ali
Published: May 2019

The issue of estimating states for classical integer‐order nonlinear systems has been widely addressed in the literature. Yet, generalization of existing results to the fractional‐order framework represents a fertile area of research. Note that, recently, a new and advantageous type of fractional derivative, the conformable derivative, was defined. So far, the general query of designing observers for conformable fractional‐order systems has not been investigated. In addition, it has been proved in the literature that some important tools for stability analysis of fractional‐order systems are valid using the conformable derivative concept, but invalid using other fractional derivative concepts. Motivated by the cited facts, this paper presents a first‐state estimation scheme for fractional‐order systems under the conformable derivative concept. A healthy operating case and a faulty operating case are treated. In this paper, a version of Barbalat's lemma, which is invalid using the well‐known Caputo derivative, is exploited to prove the convergence of the estimation errors. In order to validate the theoretical results, a numerical example is studied in the simulation section.
Payload pendulation and position control systems for an offshore container crane with adaptive‐gain sliding mode control
Authors: Ngo Quang Hieu , Nguyen Ngo Phong , Nguyen Chi Ngon , Tran Thanh Hung , Bui Van Huu
Published: May 2019

When container ports are not available for heavy ships, the offshore ship‐to‐ship transfer operation is an alternative method to an inland container terminal. This process is performed between a large container ship and a smaller ship, which is equipped with a container crane, called the mobile harbor or the ship‐mounted crane. The sea‐state condition is a crucial factor in open‐sea operations. The presence of waves, wind, and current disturbances excite the pendulum oscillations of the crane's hanging container. In this study, the problem of payload pendulation and container position for an offshore container crane using an adaptive‐gain sliding mode control (SMC) scheme is investigated. The primary control task during the loading and unloading process is to keep the container in the desired region under the harsh oceanic environment. The proposed control architecture incorporates an adaptive‐gain SMC with a compensation part and a prediction mechanism. Therein, a sliding surface is design to combine the desired sway motion of the payload with the desired trolley trajectory. Furthermore, a varying control gain is proposed in the sliding control, obtained by an adaption law that transitions the system into sliding mode. By constructing an appropriate Lyapunov function, we show that the proposed control law ensures the asymptotic stability of the ship‐mounted crane. Numerical simulations are presented to show the effectiveness and robustness of the proposed control system.
Hierarchical nonparametric survival modeling for demand forecasting with fragmented categorical covariates
Authors: Li Ta‐Hsin
Published: May 2019

This paper addresses the problem of data fragmentation when incorporating imbalanced categorical covariates in nonparametric survival models. The problem arises in an application of demand forecasting where certain categorical covariates are important explanatory factors for the diversity of survival patterns but are severely imbalanced in the sense that a large percentage of data segments defined by these covariates have very small sample sizes. Two general approaches, called the class‐based approach and the fusion‐based approach, are proposed to handle the problem. Both reply on judicious utilization of a data segment hierarchy defined by the covariates. The class‐based approach allows certain segments in the hierarchy to have their private survival functions and aggregates the others to share a common survival function. The fusion‐based approach allows all survival functions to borrow and share information from all segments based on their positions in the hierarchy. A nonparametric Bayesian estimator with Dirichlet process priors provides the data‐sharing mechanism in the fusion‐based approach. The hyperparameters in the priors are treated as fixed quantities and learned from data by taking advantage of the data segment hierarchy. The proposed methods are motivated and validated by a case study with real‐world data from an operation of software development service.
Dipeptidyl peptidase 4 inhibitors as novel agents in improving survival in diabetic patients with colorectal cancer and lung cancer: A Surveillance Epidemiology and Endpoint Research Medicare study
Authors: Bishnoi Rohit , Hong Young‐Rock , Shah Chintan , Ali Azka , Skelton William P. , Huo Jinhai , Dang Nam H. , Dang Long H.
Published: May 2019

Background

Dipeptidyl peptidase 4 (DPP4) is a cell surface protein that can act as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are used to treat diabetes.

Methods

We conducted this Surveillance Epidemiology and Endpoint Research‐Medicare database study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of diabetic patients diagnosed with colorectal (CRC) and lung cancers.

Results

Diabetic patients with CRC or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (hazard ratio [HR] of 0.89; CI: 0.82‐0.97, P = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin which is known to suppress cancer, the survival advantage was even more pronounced (HR of 0.83; CI: 0.77‐0.90, P < 0.0001). Data were then analyzed separately for two cancer types. In the CRC‐only cohort, the use of DPP4 inhibitors alone had a positive trend but did not meet statistically significant threshold (HR of 0.87; CI: 0.75‐1.00, P = 0.055), while the combined use of DPP4 inhibitors and metformin was associated with statistically significant survival advantage (HR of 0.77; CI: 0.67‐0.89, P = 0.003). Similarly, for the lung cancer cohort, use of DPP4 alone was not found to be statistically significant (HR of 0.93; CI: 0.83‐1.03, P = 0.153), whereas lung cancer patients treated with the combination of DPP4 inhibitors and metformin showed statistically significant survival advantage (HR of 0.88; CI: 0.80‐0.97, P = 0.010).

Conclusions

DPP4 inhibition in CRC and lung cancer is associated with improved OS, which possibly may be due to the effect of DPP4 inhibition on immunoregulation of cancer.
Suppression of epidermal growth factor receptor‐mediated β‐catenin nuclear accumulation enhances the anti‐tumor activity of phosphoinositide 3‐kinase inhibitor in breast cancer
Authors: Niu Jie , Wang Xiao , Liang Chao , Zhang Yi‐Dan , Liu Fan‐Ye , Li Hai‐Ying , Xie Song‐Qiang , Sun Hua , Fang Dong
Published: May 2019

Phosphoinositide 3‐kinase (PI3K) signaling is frequently deregulated in breast cancer and plays a critical role in tumor progression. However, resistance to PI3K inhibitors in breast cancer has emerged, which is due to the enhanced β‐catenin nuclear accumulation. Until now, the mechanisms underlying PI3K inhibition‐induced β‐catenin nuclear accumulation remains largely unknown. In the present study, we found inhibition of PI3K with LY294002 promoted β‐catenin nuclear accumulation in MCF‐7 and MDA‐MB‐231 breast cancer cells. Combining PI3K inhibitor LY294002 with XAV‐939, an inhibitor against β‐catenin nuclear accumulation, produced an additive anti‐proliferation effect against breast cancer cells. Subsequent experiments suggested β‐catenin nuclear accumulation induced by PI3K inhibition depended on the feedback activation of epidermal growth factor receptor (EGFR) signaling pathway in breast cancer cells. Inhibition of EGFR phosphorylation with Gefitinib enhanced anti‐proliferation effect of PI3K inhibitor LY294002 in MCF‐7 and MDA‐MB‐231 cells. Taken together, our findings may elucidate a possible mechanism explaining the poor outcome of PI3K inhibitors in breast cancer treatment.
Thermal and Sensitiveness Determination of Cubanes: Towards Cubane‐Based Fuels for Infrared Countermeasures
Authors: Dallaston Madeleine A. , Brusnahan Jason S. , Wall Craig , Williams Craig M.
Published: May 2019

As infrared seeking technology evolves, threats are better able to distinguish defensive infrared (IR) flares from true targets. Spectrally matched flares, which generally employ carbon‐based fuels, are better able to decoy some advanced missiles by more closely mimicking the IR emission of the target. Cubane is a high‐energy carbon‐based scaffold which may be suitable for use as a fuel in spectrally matched flares. The enthalpy of formation and strain energy of a series of cubanes was predicted in silico, and their thermal and impact stability examined. All were found to undergo highly exothermic decomposition in sealed cell differential scanning calorimetry, and two cubanes subsequently underwent quantitative sensitiveness testing. Despite their F of I values being in the secondary explosive range, cubane‐1,4‐dicarboxylic acid (F of I=70) and 4‐carbamoylcubane‐1‐carboxylic acid (F of I=90) were identified as potentially useful fuels for pyrotechnic infrared countermeasure flare formulations.
Silver Nanowire‐Templated Molecular Nanopatterning and Nanoparticle Assembly for Surface‐Enhanced Raman Scattering
Authors: Li Zhuoyao , Wang Guilin , Zhang Chengyu , Wei Cong , Wang Xiang , Gao Yongqian , Li Hai , Huang Xiao , Yuan Haifeng , Lu Gang
Published: May 2019

Developing simple and cost‐efficient methods for fabricating molecular patterns is of great importance in the field of nanoscience and nanotechnology. Here, a simple and convenient method was developed for fabricating nanopatterns composed of positively charged silane molecules by using silver nanowires as templates. The as‐obtained silane pattern copies the shape of the silver nanowires and is only 0.7 nm thick, which can later be used for templated assembly of small molecules and nanoparticles of opposite charges. As a proof of concept, the resultant assembly could be further used for surface‐enhanced Raman scattering.
Heck Diversification of Indole‐Based Substrates under Aqueous Conditions: From Indoles to Unprotected Halo‐tryptophans and Halo‐tryptophans in Natural Product Derivatives
Authors: Pubill‐Ulldemolins Cristina , Sharma Sunil V. , Cartmell Christopher , Zhao Jinlian , Cárdenas Paco , Goss Rebecca J. M.
Published: May 2019

The blending of synthetic chemistry with biosynthetic processes provides a powerful approach to synthesis. Biosynthetic halogenation and synthetic cross‐coupling have great potential to be used together, for small molecule generation, access to natural product analogues and as a tool for chemical biology. However, to enable enhanced generality of this approach, further synthetic tools are needed. Though considerable research has been invested in the diversification of phenylalanine and tyrosine, functionalisation of tryptophans thorough cross‐coupling has been largely neglected. Tryptophan is a key residue in many biologically active natural products and peptides; in proteins it is key to fluorescence and dominates protein folding. To this end, we have explored the Heck cross‐coupling of halo‐indoles and halo‐tryptophans in water, showing broad reaction scope. We have demonstrated the ability to use this methodology in the functionalisation of a brominated antibiotic (bromo‐pacidamycin), as well as a marine sponge metabolite, barettin.
Redox‐Induced Oxidative C−C Bond Cleavage of 2,2′‐Pyridil in Diruthenium Complexes
Authors: Khan Farheen Fatima , Sobottka Sebastian , Sarkar Biprajit , Lahiri Goutam Kumar
Published: May 2019

In the recent years, there has been an emerging research interest in the domain of C−C bond‐cleavage reactions. The present contribution deals with the redox‐mediated dioxygen activation and C−C bond cleavage in a diruthenium complex [(acac)2RuII(μ‐L1)RuII(acac)2], 1 (acac=acetylacetonate) incorporating 2,2′‐pyridil (L1) as the bridging ligand. The above process leads to a C−C‐cleaved monomeric product [(acac)2RuIII(pic−)], 2 (pic−=piconilate). Intriguingly, similar diastereomeric complexes [(acac)2RuII(μ‐L2)RuII(acac)2], meso (ΔΛ): 3 a and rac (ΔΔ/ΛΛ): 3 b, involving an analogous diimine bridge (L2=N1,N2‐diphenyl‐1,2‐di(pyridin‐2‐yl)ethane‐1,2‐diimine), were stable towards such oxidative transformations. Electrochemical and spectroelectrochemical studies, in combination, establish the potential non‐innocent feature of the 2,2′‐Pyridil (L1) and its derivative (L2) both in oxidation and reduction processes. Additionally, theoretical calculations have been employed to verify the redox states and their behavior. Furthermore, transition state (TS) calculations at the M06L/6‐31G*/LANL2DZ level of theory together with detailed kinetic studies outline a putative mechanism for the selective transformation of 1→2 involving the formation of an intermediate bearing peroxide linkage to complex 1.
Investigation of Dipicolinic Acid Isosteres for the Inhibition of Metallo‐β‐Lactamases
Authors: Chen Allie Y. , Thomas Pei W. , Cheng Zishuo , Xu Nasa Y. , Tierney David L. , Crowder Michael W. , Fast Walter , Cohen Seth M.
Published: May 2019

New Delhi metallo‐β‐lactamase‐1 (NDM‐1) poses an immediate threat to our most effective and widely prescribed drugs, the β‐lactam‐containing class of antibiotics. There are no clinically relevant inhibitors to combat NDM‐1, despite significant efforts toward their development. Inhibitors that use a carboxylic acid motif for binding the ZnII ions in the active site of NDM‐1 make up a large portion of the >500 inhibitors reported to date. New and structurally diverse scaffolds for inhibitor development are needed urgently. Herein we report the isosteric replacement of one carboxylate group of dipicolinic acid (DPA) to obtain DPA isosteres with good inhibitory activity against NDM‐1 (and related metallo‐β‐lactamases, IMP‐1 and VIM‐2). It was determined that the choice of carboxylate isostere influences both the potency of NDM‐1 inhibition and the mechanism of action. Additionally, we show that an isostere with a metal‐stripping mechanism can be re‐engineered into an inhibitor that favors ternary complex formation. This work provides a roadmap for future isosteric replacement of routinely used metal binding motifs (i.e., carboxylic acids) for the generation of new entities in NDM‐1 inhibitor design and development.
Disrupted network connectivity in pediatric brain tumor survivors is a signature of injury
Authors: Gauvreau Samantha , Lefebvre Jérémie , Bells Sonya , Laughlin Suzanne , Bouffet Eric , Mabbott Donald J.
Published: May 2019

Cognition is compromised in pediatric brain tumor survivors but the neurophysiological basis of this compromise remains unclear. We hypothesized that reduced neural synchronization across brain networks is involved. To test this, we evaluated group differences using a retrospective cohort comparison design between 24 pediatric brain tumor survivors [11.81 ± 3.27)] and 24 age matched healthy children [12.04 ± 3.28)] in functional connectivity within a cerebellar network to examine local effects of the tumor, a whole brain network to examine diffuse effects of treatment (i.e., chemotherapy and radiation), and across multiple intrinsic connectivity networks. Neural activity was recorded during magnetoencephalography scanning while participants were at rest and functional connectivity within networks was measured using the phase lag index. We corroborated our findings using a computational model representing the local tumor effects on neural synchrony. Compared to healthy children, pediatric brain tumor survivors show increased functional connectivity for theta and beta frequency bands within the cerebellar network and increased functional connectivity for the theta band within the whole brain network that again localized to the cerebellum. Computational modeling showed that increased synchrony in the theta bad is observed following local clustering as well as sparse interarea brain connectivity. We also observed increased functional connectivity for the alpha frequency band in the ventral attention network and decreased functional connectivity within the gamma frequency band in the motor network within paedatric brain tumor survivors versus healthy children. Notably, increased gamma functional connectivity within the motor network predicted decreased reaction time on behavioral tasks in pediatric brain tumor survivors. Disrupted network synchrony may be a signature of neurological injury and disease.
CROSA: Context‐aware cloud service ranking approach using online reviews based on sentiment analysis
Authors: Ben‐Abdallah Emna , Boukadi Khouloud , Lloret Jaime , Hammami Mohamed
Published: May 2019

The explosion of cloud services over the Internet has raised new challenges in cloud service selection and ranking. The existence of a great variety of offered cloud services made the users think deeply about the most appropriate services that meet their needs and at the same time are adaptable to their context. Nowadays, online reviews are used for the purpose of enhancing the effectiveness of finding useful product information, having impact on the consumers' decision‐making process. In this context, the current paper suggests a context‐aware cloud service ranking approach using online reviews and based on sentiment analysis (CROSA). Its main objective is to ease the cloud service selection. The CROSA approach analyzes sentiments associated with service measurement index (SMI)–based service properties for each alternative cloud service. Moreover, it enhances the cloud service decision‐making by supporting fuzzy sentiments through the intuitionistic fuzzy set theory and PROMETHEE II. The experimental results presented in this paper show that this approach is efficient and performing.
Surface Chemistry Directs the Tunable Assembly of TiO2 Anatase Nanocubes into Three‐Dimensional Mesocrystals
Authors: Huesmann Hannah , Schechtel Eugen , Lieberwirth Ingo , Panthöfer Martin , Tremel Wolfgang
Published: May 2019

An important step in nanocrystal self‐assembly is programming the large‐area organization of nanocrystals into superlattices with tunable packing efficiencies. Here we utilize nanoscale surface chemistry to direct the self‐assembly of TiO2 (anatase) nanocubes into distinct three‐dimensional mesocrystals. High nanocrystal solubility combined with weak electrostatic attraction induced by the pH mediated surface charge was sufficient to organize 3,4‐dihydroxyhydrocinnamic acid (DHCA) functionalized nanocubes into large superstructures with both translational and orientational order. The finding that translational and orientational order of nanocrystal superlattices can be induced by the interplay of thermal energy, steric repulsion, and ionic interactions in a nucleation and growth self‐assembly process offers insight into the importance of the initial nucleation stage in the self‐assembly process and suggests new routes for controlled self‐assembly of nanocrystals.
Improvement of the Oxidative Stability of Spray‐Dried Microencapsulated Chia Seed Oil Using Maillard Reaction Products (MRPs)
Authors: Copado Claudia N. , Diehl Bernd W. K. , Ixtaina Vanesa Y. , Tomás Mabel C.
Published: May 2019

The present work deals with the study of the physicochemical properties of microencapsulated chia seed oil by spray‐dried method, with different oil content, using Maillard reaction products (MRPs) generated from different heat treatments (0, 60, or 100°C, 30 min) of sodium caseinate‐lactose mixture as wall material. With an absorbance at 465 nm, the color and FTIR parameters are used to follow the Maillard reaction extent. The DPPH assay is applied to analyze the antioxidant activity. The microcapsules present low moisture contents (0.02–3.00% d.b.) and water activity (0.243–0.470), and high values of microencapsulation efficiency (≈99%). The color parameters of the powders show that the microcapsules present a light color with a slight tendency toward yellow. The micrographs of powders show individual spherical microcapsules with smooth surfaces in general. The powders present a high dispersibility. The lipid oxidation analyses show that the microencapsulation process is able to protect chia oil against lipid oxidation in all treatments, with the microcapsules with the highest heat treatment being the most effective in this sense. This fact is related to the highest content of the MRPs, which further protect microencapsulated chia oil.

Practical Applications: This research provides information about an alternative treatment to microencapsulate chia oil, which is very rich in omega‐3 fatty acids, to deliver these compounds for food applications. These treatments allow microencapsulating of chia seed oil with high microencapsulation efficiency and good oxidative stability to apply them in the production of omega‐3 fortified foods. The results are significant both for the scientific community and the food industry. The relevance of this study is the application of MRPs to confer spray‐dried microencapsulated chia seed oil higher protection against lipid oxidation. Besides, the obtained results contribute to the development of novel functional products for the food industry and also to satisfy a market with tendencies toward healthy eating.

Microencapsulation process as protection system of chia oil against lipid oxidation are studied.
Metal‐Free C=C Double Bond Cleavage on Enaminones for the Synthesis of α‐Ketoamides by Free‐Radical Aerobic Oxygenation
Authors: Yang Yiming , Zhong Guofeng , Fan Junfen , Liu Yunyun
Published: May 2019

The tandem oxidation of the enaminone C=C double bond as well as subsequent C‐N bond formation are realized under metal‐free conditions by thermo‐induced free radical transformation. In the presence of benzoyl peroxide (BPO) and N‐iodosuccinimide (NIS), a series of tertiary α‐ketoamides are synthesized practically under aerobic atmosphere. The 18O isotopic experiment confirms that air is the source of oxygen in the newly generated carbonyl group.
Experimental and Computational Studies on the 1,3‐Dipolar Cycloaddition between Enantiomerically Pure 2,3‐Dihydrothiazoles and Nitrones
Authors: Gracia‐Vitoria Jaime , Osante Iñaki , Cativiela Carlos , Tejero Tomás , Merino Pedro
Published: May 2019

The diastereoselective 1,3‐dipolar cycloaddition between nitrones and enantiomerically pure 2,3‐dihydrothiazoles derived from L‐cysteine, with different oxidation states at the sulfur atom has been studied experimentally and computationally. The reaction takes place with complete regioselectivity and diastereofacial selectivity. On the other hand, the exo/endo selectivity showed a clear dependence of the oxidation state at the sulfur atom. The computational calculations agree with the experimental findings.
C–N Coupling of Azoles or Imides with Carbocations Generated by Electrochemical Oxidation
Authors: Shao Xiaoqing , Tian Lifang , Wang Yahui
Published: May 2019

An approach for electrochemistry‐enabled intermolecular oxidative C–N coupling reactions of azoles and imides with 1,3,5‐cycloheptatriene and xanthenes is disclosed. The reaction proceeds via the anodic oxidation of 1,3,5‐cycloheptatriene or xanthenes to generate the tropylium ion or xanthene cations, followed by a nucleophilic attack of azoles and imides to form C–N bond.
Values and adolescents' self‐esteem: The role of value content and congruence with classmates
Authors: Benish‐Weisman Maya , Daniel Ella , McDonald Kristina L.
Published: May 2019

The study examined the relations between adolescents’ self‐esteem and two aspects of values: content and congruence with classmates. Using a large sample of Israeli adolescents (N = 1,683; Mage = 14.36, SD = 2.24, range = 11–18, 54.31% females), we found that self‐esteem related negatively to self‐enhancement values and positively to conservation values using zero order correlations. Multilevel polynomial regressions, controlling for demographic differences, found significant quadratic associations of self‐esteem with self‐enhancement, self‐transcendence, openness‐to‐change, and conservation values. Furthermore, using Response Surface Analyses, it was found that adolescents who were congruent with their classmates’ self‐enhancement and self‐transcendence values showed the highest levels of self‐esteem. The findings point to the importance of social context for the relations between values and self‐esteem among adolescents.
Kinetic model to describe the morphological evolution of filamentous fungi during their early stages of growth in the standard submerged and microparticle‐enhanced cultivations
Authors: Kowalska Anna , Boruta Tomasz , Bizukojc Marcin
Published: May 2019

Biosynthesis of metabolites and enzymes by filamentous fungi depends on their morphological form in submerged cultures. However, their early stages of growth lasting approximately 24 h, from the introduction of spores to the medium until the formation of stable morphological forms, such as clumps or pellets, have rarely been the objects of experimental and modeling studies. Microparticle‐enhanced cultivation (MPEC) has been applied only to a few fungal species, mainly Aspergilli. Therefore, the objective of this work was to formulate the kinetic model to describe the early stages of the fungal evolution in the standard cultivation and MPEC for Aspergillus terreus, Chaetomium globosum, Penicillium rubens, and Mucor racemosus. These fungi exhibit various mechanisms of agglomerates formation in submerged cultures. The experiments were performed in batch shake flasks (parameters identification) and a stirred tank bioreactor (model verification). In the balance equation for fungal cells, the mean projected area of hyphal objects measured by the digital analysis of microscopic images was used as the dependent variable. The analysis of the experimental data and model solution revealed that the effect of the microparticles (aluminum oxide at 6 g L−1) in MPEC toward the studied filamentous fungi was to the high extent species dependent. This effect was most evident in the case of spore coagulative A. terreus and noncoagulative M. racemosus.
KIT mutation in a naïve succinate dehydrogenase‐deficient gastric GIST
Authors: Brcic Iva , Kashofer Karl , Skone Daniela , Liegl‐Atzwanger Bernadette
Published: May 2019

Up to 85% of gastrointestinal stromal tumors (GIST) harbor mutually exclusive mutations in the KIT or the PDGFRA gene. Among others, known as wild type GIST, succinate dehydrogenase (SDH)‐deficient tumors develop due to genetic or epigenetic alterations in any of four SDH genes. Herein, we present a unique case of SDH‐deficient GIST with an unusual heterogeneous SDHA and SDHB staining pattern and mutations detected in the SDHA and KIT gene. A 50‐year‐old patient presented with a 5 cm large gastric tumor with a multinodular/plexiform growth pattern, mixed epithelioid and spindle cell morphology, and focal pronounced nuclear atypia with hyperchromasia and high mitotic activity. Immunohistochemically, CD117 and DOG‐1 were positive. SDHB and SDHA stains showed loss of expression in some of the nodules, whereas others presented with an unusually weak patchy positivity. Molecular analysis revealed a point mutation in exon 5 of the SDHA gene and a mutation in exon 11 of the KIT gene. We hypothesize that based on the allele frequency of SDHA and KIT mutations the tumor is best regarded as SDH‐deficient GIST in which the SDHA mutation represents the most likely driver mutation. The identified KIT mutation raises the distinct possibility that the KIT mutation is a secondary event reflecting clonal evolution. This is the first case of a treatment naïve GIST harboring a somatic SDHA and a KIT mutation, challenging the dogma that oncogenic mutations in treatment naïve GIST are mutually exclusive.
HIV‐1 Tat promotes astrocytic release of CCL2 through MMP/PAR‐1 signaling
Authors: Bozzelli P. Lorenzo , Yin Tao , Avdoshina Valeria , Mocchetti Italo , Conant Katherine E. , Maguire‐Zeiss Kathleen A.
Published: May 2019

The HIV‐1 protein Tat is continually released by HIV‐infected cells despite effective combination antiretroviral therapies (cART). Tat promotes neurotoxicity through enhanced expression of proinflammatory molecules from resident and infiltrating immune cells. These molecules include matrix metalloproteinases (MMPs), which are pathologically elevated in HIV, and are known to drive central nervous system (CNS) injury in varied disease settings. A subset of MMPs can activate G‐protein coupled protease‐activated receptor 1 (PAR‐1), a receptor that is highly expressed on astrocytes. Although PAR‐1 expression is increased in HIV‐associated neurocognitive disorder (HAND), its role in HAND pathogenesis remains understudied. Herein, we explored Tat's ability to induce expression of the PAR‐1 agonists MMP‐3 and MMP‐13. We also investigated MMP/PAR‐1‐mediated release of CCL2, a chemokine that drives CNS entry of HIV infected monocytes and remains a significant correlate of cognitive dysfunction in the era of cART. Tat exposure significantly increased the expression of MMP‐3 and MMP‐13. These PAR‐1 agonists both stimulated the release of astrocytic CCL2, and both genetic knock‐out and pharmacological inhibition of PAR‐1 reduced CCL2 release. Moreover, in HIV‐infected post‐mortem brain tissue, within‐sample analyses revealed a correlation between levels of PAR‐1‐activating MMPs, PAR‐1, and CCL2. Collectively, these findings identify MMP/PAR‐1 signaling to be involved in the release of CCL2, which may underlie Tat‐induced neuroinflammation.
Projected oropharyngeal carcinoma incidence among middle‐aged US men
Authors: Xu Li , Dahlstrom Kristina R. , Lairson David R. , Sturgis Erich M.
Published: May 2019

Background

The incidence of oropharyngeal cancer (OPC) is rapidly increasing. This study aimed to describe the temporal trends and projection of OPC incidence.

Methods

Incidence data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and trends were calculated using the joinpoint regression model.

Results

The incidence of OPC in the US population significantly increased by 1.94% (95% confidence interval [CI], 1.65%‐2.23%) per year from 2000 to 2015. OPC was projected to increase continuously over the next 30 years, with more than half of projected new OPC cases being found in non‐Hispanic white men aged 55‐69 years. By 2045, OPC will become the third most common cancer in 55‐69‐year‐old non‐Hispanic white men in the United States.

Conclusions

The incidence of OPC is expected to increase substantially in the US population, particularly among middle‐aged non‐Hispanic white men. Our projections may have implications for policy makers.
Preparation of Enantiomerically Pure Compounds Employing Anodic Oxidations of Carboxylic Acids – A Late Review of Research Done in the 1980ies
Authors: Seebach Dieter
Published: May 2019

There are widely unknown enantiopure building blocks and non‐conventional transformations described in this old work that could become useful in today's diversity‐oriented organic synthesis world. Coupling and mixed couplings of functionalized CF3‐substituted chiral radicals by Kolbe electrolysis of carboxylic acids lead to hexafluoro‐hexane‐2,5‐diol and to butyro‐ and valerolactone derivatives with functional‐group relationships that normally require components with reactivity umpolung. Oxidative decarboxylation of amino‐acid and peptide derivatives by Hofer‐Moest electrolyses provide entry into the synthetic use of chiral acyliminium‐ion intermediates. Chiral oxazoline and thioazoline building blocks (from serine, threonine, and cysteine) are accessible for substitutions and cycloadditions. The stereochemical course of oxidative CO2H replacement in serine by nucleophilically introduced groups with retention of configuration is discussed.
The effects of GSK2981710, a medium‐chain triglyceride, on cognitive function in healthy older participants: A randomised, placebo‐controlled study
Authors: O'Neill Barry V. , Dodds Chris M. , Miller Sam R. , Gupta Ashutosh , Lawrence Philip , Bullman Jonathan , Chen Chao , Dewit Odile , Kumar Subramanya , Dustagheer Mushi , Price Jeffrey , Shabbir Shaila , Nathan Pradeep J.
Published: May 2019

Objective

This double‐blind, randomised, placebo‐controlled, two‐part study assessed the impact of GSK2981710, a medium‐chain triglyceride (MCT) that liberates ketone bodies, on cognitive function, safety, and tolerability in healthy older adults.

Methods

Part 1 was a four‐period dose‐selection study (n = 8 complete). Part 2 was a two‐period crossover study (n = 80 complete) assessing the acute (Day 1) and prolonged (Day 15) effects of GSK2981710 on cognition and memory‐related neuronal activity. Safety and tolerability of MCT supplementation were monitored in both parts of the study.

Results

The most common adverse event was diarrhoea (100% and 75% of participants in Parts 1 and 2, respectively). Most adverse events were mild to moderate, and 11% participants were withdrawn due to one or more adverse events. Although GSK2981710 (30 g/day) resulted in increased peak plasma β‐hydroxybutyrate (BHB) concentrations, no significant improvements in cognitive function or memory‐related neuronal activity were observed.

Conclusion

Over a duration of 14 days, increasing plasma BHB levels with daily administration of GSK2981710 had no effects on neuronal activity or cognitive function. This result indicates that modulating plasma ketone levels with GSK2981710 may be ineffective in improving cognitive function in healthy older adults, or the lack of observed effect could be related to several factors including study population, plasma BHB concentrations, MCT composition, or treatment duration.
Characterization of transcriptomic signature of primary prostate cancer analogous to prostatic small cell neuroendocrine carcinoma
Authors: Alshalalfa Mohammed , Liu Yang , Wyatt Alexander W. , Gibb Ewan A. , Tsai Harrison K. , Erho Nicholas , Lehrer Jonathan , Takhar Mandeep , Ramnarine Varune R. , Collins Colin C. , Den Robert B. , Schaeffer Edward M. , Davicioni Elai , Lotan Tamara L. , Bismar Tarek A.
Published: May 2019

Prostatic small cell neuroendocrine carcinoma (SC/NE) is well studied in metastatic castration‐resistant prostate cancer; however, it is not well characterized in the primary setting. Herein, we used gene expression profiling of SC/NE prostate cancer (PCa) to develop a 212 gene signature to identify treatment‐naïve primary prostatic tumors that are molecularly analogous to SC/NE (SC/NE‐like PCa). The 212 gene signature was tested in several cohorts confirming similar molecular profile between prostatic SC/NE and small cell lung carcinoma. The signature was then translated into a genomic score (SCGScore) using modularized logistic regression modeling and validated in four independent cohorts achieving an average AUC >0.95. The signature was evaluated in more than 25,000 primary adenocarcinomas to characterize the biology, prognosis and potential therapeutic response of predicted SC/NE‐like tumors. Assessing SCGScore in a prospective cohort of 17,967 RP and 6,697 biopsy treatment‐naïve primary tumors from the Decipher Genomic Resource Information Database registry, approximately 1% of the patients were found to have a SC/NE‐like transcriptional profile, whereas 0.5 and 3% of GG1 and GG5 patients respectively showed to be SC/NE‐like. More than 80% of these patients are genomically high‐risk based on Decipher score. Interrogating in vitro drug sensitivity analyses, SC/NE‐like prostatic tumors showed higher response to PARP and HDAC inhibitors.
Identification of differentially expressed genes in primary Sjögren's syndrome
Authors: Zhang Lei , Xu Poshi , Wang Xiaoyu , Zhang Zongshan , Zhao Wenxin , Li Zhengmin , Yang Guangxia , Liu Panpan
Published: May 2019

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease that affects exocrine glands. To study the molecular mechanism and identify crucial genes/pathways in pSS pathogenesis, the microarray‐based whole‐genome gene expression profiles from salivary glands of patients with pSS and non‐sicca controls were retrieved. After normalization and subsequent batch effect adjustment, significance analysis of microarrays method was applied to five available datasets, and 379 differentially expressed genes (DEGs) were identified. The 300 upregulated DEGs were enriched in Gene Ontology terms of immune and inflammatory responses, including antigen processing and presentation, interferon‐mediated signaling pathway, and chemotaxis. Previously reported pSS‐associated genes, including HLA‐DRA, TAP2, PRDM1, and IFI16, were found to be significantly upregulated. The downregulated DEGs were enriched in pathways of salivary secretion, carbohydrate digestion and absorption, and starch and sucrose metabolism, implying dysfunction of salivary glands during pathogenesis. Next, a protein‐protein interaction network was constructed, and B2M, an upregulated DEG, was shown to be a hub, suggesting its potential involvement in pSS development. In summary, we found the activation of pSS‐associated genes in pathogenesis, and provide clues for salivary glands dysfunction. Experimental investigation on the identified DEGs in this study will deepen our understanding on pSS.
Thiophenols, Promising Scavengers of Peroxyl Radicals: Mechanisms and kinetics
Authors: Carreon‐Gonzalez Mirzam , Vivier‐Bunge Annik , Alvarez‐Idaboy Juan Raul
Published: May 2019

The activity of 12 thiophenols as primary antioxidants in aqueous solution has been studied using density functional theory. Twelve different substituted thiophenols were tested as peroxyl radicals scavengers. Single electron transfer (SET) and formal hydrogen transfer (FHT) were investigated. The SET mechanism was found to be the main mechanism, with rate constants that are close to the diffusion limit, which means that these thiophenolic compounds have the capacity to scavenge peroxyl radicals before they can damage biomolecules. All 12 thiophenolic compounds react faster with methylperoxyl than with hydroperoxyl radicals. In addition, it was found that pH plays an important role in the reactivity of these compounds. © 2019 Wiley Periodicals, Inc.
Molecular dynamics simulation of anticancer drug delivery from carbon nanotube using metal nanowires
Authors: Abbaspour Mohsen , Namayandeh Jorabchi Majid , Akbarzadeh Hamed , Salemi Sirous , Ebrahimi Reyhaneh
Published: May 2019

In this study, we have investigated delivery of cisplatin as the anticancer drug molecules in different carbon nanotubes (CNTs) in the gas phase using molecular dynamics simulation. We examined the shape and composition of the releasing agent by using the different nanowires and nanoclusters. We also investigated the doping effect on the drug delivery process using N‐, Si, B‐, and Fe‐doped CNTs. Different thermodynamics, structural, and dynamical properties have been studied by using the pure and different doped CNTs in this study. Our results show that the doping of the CNT has significant effect on the rate of the drug releasing process regardless of the composition of the releasing agent. © 2019 Wiley Periodicals, Inc.
p53/miR‐30a‐5p/SOX4 feedback loop mediates cellular proliferation, apoptosis, and migration of non‐small‐cell lung cancer
Authors: Quan Xiaowei , Li Xuelian , Yin Zhihua , Ren Yangwu , Zhou Baosen
Published: May 2019

Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non‐small‐cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR‐30a‐5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR‐30a‐5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR‐30a‐5p level could induce the increase of Bax protein level and decrease of Bcl‐2 protein level. In addition, chromatin immunoprecipitation assays showed that miR‐30a‐5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR‐30a‐5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR‐30a‐5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.