bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Structure and Cellular Applications of Fluorescent Light‐Up Aptamers
Authors: Neubacher Saskia , Hennig Sven 
Published: August 2018

AbstractThe cellular functions of RNA are not limited to their role as blueprints for protein synthesis. In particular, noncoding RNA, such as, snRNAs, lncRNAs, miRNAs, play important roles. With increasing numbers of RNAs being identified, it is well known that the transcriptome outnumbers the proteome by far. This emphasizes the great importance of functional RNA characterization and the need to further develop tools for these investigations, many of which are still in their infancy. Fluorescent light‐up aptamers (FLAPs) are RNA sequences that can bind nontoxic, cell‐permeable small‐molecule fluorogens and enhance their fluorescence over many orders of magnitude upon binding. FLAPs can be encoded on the DNA level using standard molecular biology tools and are subsequently transcribed into RNA by the cellular machinery, so that they can be used as fluorescent RNA tags (FLAP‐tags). In this Minireview, we give a brief overview of the fluorogens that have been developed and their binding RNA aptamers, with a special focus on published crystal structures. A summary of current and future cellular FLAP applications with an emphasis on the study of RNA–RNA and RNA–protein interactions using split‐FLAP and Förster resonance energy transfer (FRET) systems is given.
Selective Boryl‐Anion Migration in a Vinyl sp2−sp3 Diborane Induced by Soft Borane Lewis Acids
Authors: Fasano Valerio , Cid Jessica , Procter Richard J. , Ross Emily , Ingleson Michael J. 
Published: August 2018

AbstractAn intramolecular 1,2‐boryl‐anion migration from boron to carbon has been achieved by selective activation of the π system in [(vinyl)B2Pin2)]− using “soft” BR3 electrophiles (BR3=BPh3 or 9‐aryl‐BBN). The soft character is key to ensure 1,2‐migration proceeds instead of oxygen coordination/B−O activation. The BR3‐induced 1,2‐boryl‐anion migration represents a triple borylation of a vinyl Grignard reagent using only B2Pin2 and BR3 and forms differentially protected 1,1,2‐triborylated alkanes. Notably, by increasing the steric bulk at the β position of the vinyl Grignard reagent used to activate B2Pin2, 1,2‐boryl‐anion migration can be suppressed in favor of intermolecular {BPin}− transfer to BPh3, thus enabling simple access to unsymmetrical sp2−sp3 diboranes.
Sequential Transformation of Zirconium(IV)‐MOFs into Heterobimetallic MOFs Bearing Magnetic Anisotropic Cobalt(II) Centers
Authors: Yuan Shuai , Qin Jun‐Sheng , Su Jian , Li Bao , Li Jialuo , Chen Wenmiao , Drake Hannah F. , Zhang Peng , Yuan Daqiang , Zuo Jinglin , Zhou Hong‐Cai 
Published: August 2018

AbstractHeterometallic metal–organic frameworks (MOFs) allow the precise placement of various metals at atomic precision within a porous framework. This new level of control by MOFs promises fascinating advances in basic science and application. However, the rational design and synthesis of heterometallic MOFs remains a challenge due to the complexity of the heterometallic systems. Herein, we show that bimetallic MOFs with MX2(INA)4 moieties (INA=isonicotinate; M=Co2+ or Fe2+; X=OH−, Cl−, Br−, I−, NCS−, or NCSe−) can be generated by the sequential modification of a Zr‐based MOF. This multi‐step modification not only replaced the linear organic linker with a square planar MX2(INA)4 unit, but also altered the symmetry, unit cell, and topology of the parent structure. Single‐crystal to single‐crystal transformation is realized so that snapshots for transition process were captured by successive single‐crystal X‐ray diffraction. Furthermore, the installation of Co(NCS)2(INA)4 endows field‐induced slow magnetic relaxation property to the diamagnetic Zr‐MOF.
Colorimetric Carbonyl Sulfide (COS)/Hydrogen Sulfide (H2S) Donation from γ‐Ketothiocarbamate Donor Motifs
Authors: Zhao Yu , Steiger Andrea K. , Pluth Michael D. 
Published: August 2018

AbstractHydrogen sulfide (H2S) is a biologically active molecule that exhibits protective effects in a variety of physiological and pathological processes. Although several H2S‐related biological effects have been discovered by using H2S donors, knowing how much H2S has been released from donors under different conditions remains challenging. Now, a series of γ‐ketothiocarbamate (γ‐KetoTCM) compounds that provide the first examples of colorimetric H2S donors and enable direct quantification of H2S release, were reported. These compounds are activated through a pH‐dependent deprotonation/β‐elimination sequence to release carbonyl sulfide (COS), which is quickly converted into H2S by carbonic anhydrase. The p‐nitroaniline released upon donor activation provides an optical readout that correlates directly to COS/H2S release, thus enabling colorimetric measurement of H2S donation.
Rice‐Endosperm and Rice‐Bran Proteins: A Review
Authors: Al‐Doury Mohammed K. W. , Hettiarachchy Navam S. , Horax Ronny 
Published: August 2018

AbstractRice protein is the most preferred protein among all other cereal proteins in terms of its amino acid structure, and it contains the second highest content of lysine, the limiting amino acid in cereals. Processing rough rice into edible rice yields different by‐products including rice bran. Rice‐endosperm and rice‐bran proteins are known to be hypoallergenic, nutritious, and healthful, which gives them high potential in the food‐ingredient industry, especially in gluten‐free preparations and in infant formulas. Multiple methods can be used for the extraction of rice‐endosperm and rice‐bran proteins, including chemical and enzymatic extraction methods. The functional properties, including emulsification, foaming, gelation, and water and oil absorption, of rice‐endosperm and rice‐bran proteins require enhancement before utilizing them in food applications because of their low solubilities, which affects the other functionalities. Enhancement methods include manipulating pH and salt concentration of extracting solvents and selecting specific extraction procedures. Rice‐endosperm and rice‐bran peptides are known to exhibit different bioactivities. These peptides can be generated by different hydrolysis approaches, including the enzymatic, chemical, or microbial assays. Some of the confirmed bioactivities of rice‐endosperm and rice‐bran peptides are the antioxidant, antihypertensive, anticancer, anti‐inflammatory, and antimicrobial activities. These bioactivities increase the potential of rice‐endosperm and rice‐bran proteins to be utilized in food applications, as natural preservatives, or in pharmaceutical applications.
Overcoming resistance in non‐small‐cell lung cancer: A practical lesson for the medicinal chemist
Authors: Ribaudo Giovanni , Zanforlin Enrico , Zagotto Giuseppe 
Published: August 2018

AbstractThe introduction of tyrosine kinase inhibitors (TKIs) in the clinical management of oncological patients spread the light on the use of selective, rationally designed small molecules for the treatment of cancer. First‐generation TKIs bared high response against these malignancies, although the unavoidable shadow of resistance limits their long‐term efficacy. Non‐small‐cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, and it is the first cause of cancer deaths worldwide for men and women. Traditional chemotherapy is marginally effective against this form, and erlotinib and gefitinib were introduced as first‐line treatments based on the observation that the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), is mutated in several cases and, thus, represents a druggable target. EGFR‐mutant and anaplastic lymphoma kinase (ALK)‐positive patients are more responsive to these treatments, even if secondary mutations causing resistance soon emerged. The efforts of medicinal chemists are currently oriented toward the development of new generations of TKIs overcoming these obstacles. We here overview the novel strategies from the point of view of the medicinal chemist: the rational structure‐based drug design that led to the development of irreversible and non‐ATP‐competitive inhibitors. Such improvements parallel the novel therapeutic strategies adopted in the clinic, which are also discussed.
Epitope‐specific affinity maturation improved stability of potent protease inhibitory antibodies
Authors: Lopez Tyler , Chuan Chen , Ramirez Aaron , Chen Kuan‐Hui E. , Lorenson Mary Y. , Benitez Chris , Mustafa Zahid , Pham Henry , Sanchez Ramon , Walker Ameae M. , Ge Xin 
Published: August 2018

AbstractTargeting effectual epitopes is essential for therapeutic antibodies to accomplish their desired biological functions. This study developed a competitive dual color fluorescence‐activated cell sorting (FACS) to maturate a matrix metalloprotease 14 (MMP‐14) inhibitory antibody. Epitope‐specific screening was achieved by selection on MMP‐14 during competition with N‐terminal domain of tissue inhibitor of metalloproteinase‐2 (TIMP‐2) (nTIMP‐2), a native inhibitor of MMP‐14 binding strongly to its catalytic cleft. 3A2 variants with high potency, selectivity, and improved affinity and proteolytic stability were isolated from a random mutagenesis library. Binding kinetics indicated that the affinity improvements were mainly from slower dissociation rates. In vitro degradation tests suggested the isolated variants had half lives 6–11‐fold longer than the wt. Inhibition kinetics suggested they were competitive inhibitors which showed excellent selectivity toward MMP‐14 over highly homologous MMP‐9. Alanine scanning revealed that they bound to the vicinity of MMP‐14 catalytic cleft especially residues F204 and F260, suggesting that the desired epitope was maintained during maturation. When converted to immunoglobulin G, B3 showed 5.0 nM binding affinity and 6.5 nM inhibition potency with in vivo half‐life of 4.6 days in mice. In addition to protease inhibitory antibodies, the competitive FACS described here can be applied for discovery and engineering biosimilars, and in general for other circumstances where epitope‐specific modulation is needed.
High‐throughput combinatorial screening reveals interactions between signaling molecules that regulate adult neural stem cell fate
Authors: Muckom Riya , McFarland Sean , Yang Chun , Perea Brian , Gentes Megan , Murugappan Abirami , Tran Eric , Dordick Jonathan S. , Clark Douglas S. , Schaffer David V. 
Published: August 2018

AbstractAdvancing our knowledge of how neural stem cell (NSC) behavior in the adult hippocampus is regulated has implications for elucidating basic mechanisms of learning and memory as well as for neurodegenerative disease therapy. To date, numerous biochemical cues from the endogenous hippocampal NSC niche have been identified as modulators of NSC quiescence, proliferation, and differentiation; however, the complex repertoire of signaling factors within stem cell niches raises the question of how cues act in combination with one another to influence NSC physiology. To help overcome experimental bottlenecks in studying this question, we adapted a high‐throughput microculture system, with over 500 distinct microenvironments, to conduct a systematic combinatorial screen of key signaling cues and collect high‐content phenotype data on endpoint NSC populations. This novel application of the platform consumed only 0.2% of reagent volumes used in conventional 96‐well plates, and resulted in the discovery of numerous statistically significant interactions among key endogenous signals. Antagonistic relationships between fibroblast growth factor 2, transforming growth factor β (TGF‐β), and Wnt‐3a were found to impact NSC proliferation and differentiation, whereas a synergistic relationship between Wnt‐3a and Ephrin‐B2 on neuronal differentiation and maturation was found. Furthermore, TGF‐β and bone morphogenetic protein 4 combined with Wnt‐3a and Ephrin‐B2 resulted in a coordinated effect on neuronal differentiation and maturation. Overall, this study offers candidates for further elucidation of significant mechanisms guiding NSC fate choice and contributes strategies for enhancing control over stem cell‐based therapies for neurodegenerative diseases.
Sharp‐Tipped Zinc Nanowires as an Efficient Electrocatalyst for Carbon Dioxide Reduction
Authors: Li Yu Hang , Liu Peng Fei , Li Chunzhong , Yang Hua Gui 
Published: August 2018

AbstractElectrochemical carbon dioxide reduction is a key reaction for carbon dioxide conversion to valuable fuels and chemicals. Due to the intrinsic stability of the carbon dioxide molecule, a catalyst is required to minimize the energy input and improve the reaction rates. Although the developed catalysts still suffer from low catalytic activity, selectivity, and stability, these could be enhanced by the involvement of sharp tip structure. Here, we report a nanowire‐like zinc electrocatalyst with sharp tips for carbon dioxide reduction. The catalyst achieves a geometry current density of −40 mA cm−2 at a potential of −0.95 V versus reversible hydrogen electrode over 35 hours with a stable carbon monoxide Faradaic efficiency of 98±2 %. The carbon monoxide partial current density surpasses by 60 % of that of the best reported zinc catalyst.
Catalytic Arylhydroxylation of Dehydroalanine in Continuous Flow for Simple Access to Unnatural Amino Acids
Authors: Khan R. Kashif M. , Zhao Yang , Scully Tal D. , Buchwald Stephen L. 
Published: August 2018

AbstractThis report discloses the first example of catalytic arylhydroxylation of dehydroalanine with aryldiazonium salts. Aryldiazonium salts, which are generated from aniline precursors under partially aqueous conditions in continuous flow, efficiently reacted with dehydroalanine in the presence of 10–15 mol % ferrocene to furnish α‐hydroxyarylalanine derivatives (up to 82 % yield). The reactions proceeded with regioselectivity, broad functional group tolerance, and without polymerization of the dehydroalanine. Furthermore, the products were used to access α‐unnatural amino acids, important targets with application in drug development.
Exploring Factors for the Design of Nanoparticles as Drug Delivery Vectors
Authors: Castillo Paula M. , Jimenez‐Ruiz Aila , Carnerero Jose M. , Prado‐Gotor Rafael 
Published: August 2018

AbstractTo achieve optimal results when employing nanoparticles in biomedical fields, choosing the right type of nanoparticle and determining the correct procedure for drug loading are key factors. Each type of nanoparticle presents a determined set of characteristics that are, in some cases, unique. In general, their surface charge, geometry or hydrophilic character may be limiting factors, depending on what their intended application is. Once synthesized, additional factors, such as their interaction with biological systems and liberation mechanisms into the target cells, also need to be taken into account. Multiple advantages arise from the use of nanoparticles, such as the capability to solubilize hydrophobic compounds and an increased bioavailability. Those advantages justify the extensive and delicate study that should be undertaken in order to use them as drug delivery agents. One of the most important factors for the design of a drug delivery system with nanoparticles is achieving a high drug‐to‐nanoparticle ratio. In this Minireview, all of these key factors, both physicochemical and biological, are described, and special emphasis is placed on loading methods employed to introduce drugs into nanoparticles.
Group protection and LAN service scheme utilizing flexible modularization and high efficiency for metro‐access network
Authors: Chen Yuanyuan , Gan Chaoqin , Li Xingfeng , Hua Jian 
Published: August 2018

SummaryIn this paper, a reliable scheme based on star topology is proposed by introducing group protection. Depending on interconnecting fibers, all optical network units (ONUs) are divided into some groups and each group contains 2 ONUs. Through these groups, the network can not only realize efficient transmission of local area network service between adjacent ONUs but also provide mutual protection for ONUs in a group when distribution fibers happen to faults. By using the backup pathway, the network can further provide protections for feeder fibers when they fall in faults. With the help of the optical tunable receiver in ONU, dynamic bandwidth allocation algorithm is also supported to realize flexible bandwidth allocation in 1 group. By the subtly design, the network can realize passivity (there are no active devices in remote nodes), modularization, and scalability. By utilizing amplitude modulation, differential phase shift keying modulation and reflective semiconductor optical amplifier technology, wavelength triple reuse is also achieved. Finally, the results of simulation and performance analysis demonstrate the feasibility of the architecture.
Quantitative analysis of multilayer switching networks providing multiple internal routes
Authors: Stergiou Eleftherios , Garofalakis John 
Published: August 2018

SummaryConstructing capable and scalable parallel computers or connecting contemporary networks efficiently makes multistage switching networks essential and significant devices. This is why they remain an interesting field of research and are being continually improved. This paper introduces a new idea—a new architecture—to ameliorate the behaviour of the networks' connection points. The proposed novel construction accommodates multiple internal paths and a fan‐out at the end. Via this study, basic features of this introduced fabric (such as cost, reliability, and performance measures) are presented in a quantitative manner. Moreover, some comparisons—especially in terms of complexity, cost, and reliability—with other similar modern constructions that also enclose multiple internal routes are shown. This study reveals that the proposed multistage system improves performance metrics, fault tolerance, and reliability and indicates that due to its properties, this innovative device can be used in the commercial sector.
Both maternal care received and genotype influence stress‐related phenotype in female rats
Authors: Pan Pauline , Lawson Daeria O. , Dudin Aya , Vasquez Oscar E. , Sokolowski Marla B. , Fleming Alison S. , McGowan Patrick O. 
Published: August 2018

AbstractRat dams differ naturally in the level of maternal care they provide to their offspring within the same litter. We explored possible mechanisms of differential maternal care focused on genetic variation. We examined single nucleotide polymorphisms in the glucocorticoid receptor, FK506‐binding protein, and serotonin transporter genes in two separate cohorts, and the relationship between differential maternal care received, genotype, and offspring phenotype. Allelic variation in all three genes was significantly associated with levels of maternal care received by offspring and behavioral and endocrine stress responses in adulthood. Differences in pup behavior were also associated with allelic variation in these genes. Together, these results indicate that the dam/pup interaction is dynamic and implicate the genotype of the offspring in influencing the level of maternal care received. They further suggest that some genotypes may have a dampening effect on the impact of maternal care on stress‐related phenotypes in adulthood.
Electric fields induced inside numerical human model standing on ground plane with elevated arms in uniform electric field at power frequency
Authors: Tarao Hiroo , Takei Amane , Hayashi Noriyuki , Isaka Katsuo 
Published: August 2018

AbstractIn the ICNIRP guidelines on the protection of human exposure to low frequency electric and magnetic fields, the reference levels are given based on the maximum value of induced electric fields (EF’s) inside a numerical human model that stands erect on ground plane with both hands down by its sides. In this contribution, numerical results on the induced EF’s inside a numerical human model standing with elevated arms in a 50 Hz uniform EF, are illustrated. The effect of the arm elevation angle on the maximum EF is discussed. It is found that, when both arms are raised overhead, the maximum values of the induced EF in the nervous system tissues increase by 20–35% compared with those obtained when both hands are down by its sides, which falls within the reduction factor of 2.4.
Global patterns of STR sequence variation: Sequencing the CEPH human genome diversity panel for 58 forensic STRs using the Illumina ForenSeq DNA Signature Prep Kit
Authors: Phillips Christopher , Devesse Laurence , Ballard David , van Weert Leanne , de la Puente Maria , Melis Stefania , Álvarez Iglesias Vanessa , Freire‐Aradas Ana , Oldroyd Nicola , Holt Cydne , Syndercombe Court Denise , Carracedo Ángel , Lareu Maria Victoria 
Published: August 2018

AbstractThe 944 individuals of the CEPH human genome diversity panel (HGDP–CEPH), a standard sample set of 51 globally distributed populations, were sequenced using the Illumina ForenSeq™ DNA Signature Prep Kit. The ForenSeq™ system is a single multiplex for the MiSeq/FGx™ massively parallel sequencing instrument, comprising: amelogenin, 27 autosomal STRs, 24 Y‐STRs, 7 X‐STRs, and 94 SNPforID+Kiddlab autosomal ID‐SNPs (plus optionally detected ancestry and phenotyping SNP sets). We report in detail the patterns of sequence variation observed in the repeat regions of the 58 forensic STR loci typed by the ForenSeq™ system. Sequence alleles were characterized and repeat region structures annotated by aligning the ForenSeq™ sequence output to the latest GRCh38 human reference sequence, necessitating the reversal and re‐alignment of STR allele sequences reported by the Forenseq™ system in 20 of 58 STRs (plus the reverse alleles in two Y‐STRs with duplicated‐inverted repeat regions). Individual population sample sizes of the HGDP–CEPH panel do not allow reliable inferences to be made about levels of genetic variability in low frequency STR alleles‐where particular sequence variants are found in only a few individuals; but we assessed the occurrence of both population‐specific sequence variants and singleton observations; finding each of these in a sizeable proportion of HGDP–CEPH samples, with consequences for planning the co‐ordinated compilation of sequence variation on a much larger scale than was required before by forensic laboratories now adopting massively parallel sequencing.
Authors’ Reply to the Commentary in the journal of Electrophoresis regarding “The effect of simulated space radiation on the N‐glycosylation of human immunoglobulin G1” by J.J. Bevelacqua and S.M.J. Mortazavi
Authors: Guttman Andras , Szilasi Szabolcs , Donczo Boglarka , Szarka Mate 
Published: August 2018

AbstractBy reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as “The effect of simulated space radiation on the N‐glycosylation of human immunoglobulin G1”[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists. First, we should clarify that complete space radiation description was not the goal of this paper. In this short communication we only intended to show the effect of simulated space radiation on the conserved N‐glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers. Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N‐linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel. Radioadaptation was never an issue in our study for the reasons mentioned above.