bluuebunny/crossref_metadata_2025 huggingface dataset:
2D Phosphorene: Epitaxial Growth and Interface Engineering for Electronic Devices
Authors: Zhang Jia Lin , Han Cheng , Hu Zehua , Wang Li , Liu Lei , Wee Andrew T. S. , Chen Wei
Published: August 2018

Black phosphorus (BP), first synthesized in 1914 and rediscovered as a new member of the family of 2D materials in 2014, combines many extraordinary properties of graphene and transition‐metal dichalcogenides, such as high charge‐carrier mobility, and a tunable direct bandgap. In addition, it displays other distinguishing properties, e.g., ambipolar transport and highly anisotropic properties. The successful application of BP in electronic and optoelectronic devices has stimulated significant research interest in other allotropes and alloys of 2D phosphorene, a class of 2D materials consisting of elemental phosphorus. As an atomically thin sheet, the various interfaces presented in 2D phosphorene (substrate/phosphorene, electrode/phosphorene, dielectric/phosphorene, atmosphere/phosphorene) play dominant roles in its bottom‐up synthesis, and determine several key characteristics for the devices, such as carrier injection, carrier transport, carrier concentration, and device stability. The rational design/engineering of interfaces provides an effective way to manipulate the growth of 2D phosphorene, and modulate its electronic and optoelectronic properties to realize high‐performance multifunctional devices. Here, recent progress of the interface engineering of 2D phosphorene is highlighted, including the epitaxial growth of single‐layer blue phosphorus on different substrates, surface functionalization of BP for high‐performance complementary devices, and the investigation of the BP degradation mechanism in ambient air.
Photosynthetic Bioelectronic Sensors for Touch Perception, UV‐Detection, and Nanopower Generation: Toward Self‐Powered E‐Skins
Authors: Ravi Sai Kishore , Wu Tingfeng , Udayagiri Vishnu Saran , Vu Xuan Minh , Wang Yanan , Jones Michael R. , Tan Swee Ching
Published: August 2018

Energy self‐sufficiency is an inspirational design feature of biological systems that fulfills sensory functions. Plants such as the “touch‐me‐not” and “Venus flytrap” not only sustain life by photosynthesis, but also execute specialized sensory responses to touch. Photosynthesis enables these organisms to sustainably harvest and expend energy, powering their sensory abilities. Photosynthesis therefore provides a promising model for self‐powered sensory devices like electronic skins (e‐skins). While the natural sensory abilities of human skin have been emulated in man‐made materials for advanced prosthetics and soft‐robotics, no previous e‐skin has incorporated phototransduction and photosensory functions that could extend the sensory abilities of human skin. A proof‐of‐concept bioelectronic device integrated with natural photosynthetic pigment‐proteins is presented that shows the ability to sense not only touch stimuli (down to 3000 Pa), but also low‐intensity ultraviolet radiation (down to 0.01 mW cm‐2) and generate an electrical power of ≈260 nW cm‐2. The scalability of this device is demonstrated through the fabrication of flexible, multipixel, bioelectronic sensors capable of touch registration and tracking. The polysensory abilities, energy self‐sufficiency, and additional nanopower generation exhibited by this bioelectronic system make it particularly promising for applications like smart e‐skins and wearable sensors, where the photogenerated power can enable remote data transmission.
Long‐Life Lithium–Sulfur Batteries with a Bifunctional Cathode Substrate Configured with Boron Carbide Nanowires
Authors: Luo Liu , Chung Sheng‐Heng , Yaghoobnejad Asl Hooman , Manthiram Arumugam
Published: August 2018

Developing high‐energy‐density lithium–sulfur (Li–S) batteries relies on the design of electrode substrates that can host a high sulfur loading and still attain high electrochemical utilization. Herein, a new bifunctional cathode substrate configured with boron‐carbide nanowires in situ grown on carbon nanofibers (B4C@CNF) is established through a facile catalyst‐assisted process. The B4C nanowires acting as chemical‐anchoring centers provide strong polysulfide adsorptivity, as validated by experimental data and first‐principle calculations. Meanwhile, the catalytic effect of B4C also accelerates the redox kinetics of polysulfide conversion, contributing to enhanced rate capability. As a result, a remarkable capacity retention of 80% after 500 cycles as well as stable cyclability at 4C rate is accomplished with the cells employing B4C@CNF as a cathode substrate for sulfur. Moreover, the B4C@CNF substrate enables the cathode to achieve both high sulfur content (70 wt%) and sulfur loading (10.3 mg cm−2), delivering a superb areal capacity of 9 mAh cm−2. Additionally, Li–S pouch cells fabricated with the B4C@CNF substrate are able to host a high sulfur mass of 200 mg per cathode and deliver a high discharge capacity of 125 mAh after 50 cycles.
Insights into Mechanochemical Reactions at Targetable and Stable, Sub‐ambient Temperatures
Authors: Andersen Joel , Mack James
Published: August 2018

We provide insights into the effects of stable and verifiable, low‐temperature conditions on mechanochemical reactions. These are made possible by modifications made to a SPEX 8000 m Mixer/mill allowing reliable fine control of low‐temperature mechanochemical reactions. Using the reduction of 4‐tert‐butylcyclohexanone as a model system we find the diastereomeric product distribution bore a strong dependence on the selected temperature. The same reduction in methanol at room temperature shows similar stereoselectivity trends. In both cases decreasing temperature favors increases in selectivity, although the effect is more pronounced in the solvent‐free mechanochemical conditions. These results indicate that the cooled jar provides a heatsink to mitigate the exothermic character of the reaction. Stereoselectivity also showed a dependence on operating frequency, although the nature of this dependence remains unclear. Applications of our reactor extend far beyond what is presented herein.
RNA Structure and Cellular Applications of Fluorescent Light‐Up Aptamers
Authors: Neubacher Saskia , Hennig Sven
Published: August 2018

The 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

An 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

Heterometallic 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

Hydrogen 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

Rice 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

The 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

Targeting 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

Advancing 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

Electrochemical 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

This 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

To 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

In 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

Constructing 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

Rat 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.
Follow 5 success strategies to advance your career
Authors: McCarthy Claudine
Published: August 2018

PHILADELPHIA — If you aspire to move up the ranks in your career, you need a plan to get to the position you seek.
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

In 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

The 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

By 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.
Adjunctive levetiracetam in the treatment of Chinese and Japanese adults with generalized tonic–clonic seizures: A double‐blind, randomized, placebo‐controlled trial
Authors: Wu Liwen , Yagi Kazuichi , Hong Zhen , Liao Weiping , Wang Xuefeng , Zhou Dong , Inoue Yushi , Ohtsuka Yoko , Sasagawa Mutsuo , Terada Kiyohito , Du Xinlu , Muramoto Yoshihiro , Sano Tomonobu
Published: August 2018

Objective

To assess the efficacy, safety, and tolerability of adjunctive levetiracetam (LEV) in Chinese and Japanese adults with generalized tonic–clonic (GTC) seizures (N01159; NCT01228747).

Methods

This double‐blind, randomized, placebo‐controlled, multicenter phase III trial comprised: 4‐week retrospective and 4‐week prospective baseline, 12‐week dose‐adjustment, and 16‐week evaluation periods. Chinese and Japanese patients ≥16 years old with idiopathic generalized, symptomatic generalized, or undetermined epilepsy with GTC seizures received a single‐blind placebo during the prospective baseline, and then were randomized 1:1 to placebo or LEV 1,000 mg/day administered twice daily. Patients reporting GTC seizures up to week 8 had the LEV dosage increased to 3,000 mg/day. The primary efficacy variable was percent reduction from combined baseline in GTC seizures/week during the 28‐week treatment period.

Results

Overall, 251 patients were randomized (208 from China; 43 from Japan); 141 (56.2%) completed the 28‐week treatment period. Least‐squares mean percent reduction from combined baseline in GTC seizures/week (treatment period) was placebo 12.6% versus LEV 68.8% (95% confidence interval, 44.0–68.2; p < 0.0001). GTC seizure frequency reduction occurred in both patients with idiopathic and symptomatic generalized epilepsy. The 50% responder rate (treatment period) was placebo 28.4% versus LEV 77.8%. Freedom from GTC seizures (evaluation period) was placebo 3.1% versus LEV 29.6%. Incidence of treatment‐emergent adverse events (TEAEs; treatment period) was placebo 52.0% versus LEV 57.1%; most frequently nasopharyngitis, protein in urine, decreased platelet count, and pyrexia. Incidence of TEAEs leading to discontinuation was 4.8% versus 3.2%; incidence of serious TEAEs was 3.2% versus 0.8% for placebo and LEV, respectively; 3 patients taking placebo died versus none taking LEV.

Significance

In this trial, adjunctive LEV 1,000–3,000 mg/day was effective in reducing GTC seizure frequency in Chinese and Japanese patients ≥16 years old with GTC seizures. Seizure reduction occurred in both patients with idiopathic and symptomatic generalized epilepsy. LEV was well tolerated in this population.
Introducing new design spectra derived from Italian recorded ground motions 1972 to 2017
Authors: Calvi G. Michele , Rodrigues Daniela , Silva Vitor
Published: August 2018

The shape of design spectra, traditionally based on regions characterized by constant displacement, constant velocity, and constant acceleration, has been discussed from a conceptual point of view by Calvi (2018). In the same study, a formulation for the definition of the design spectra relying on four parameters was proposed. Predictive models are proposed herein to calculate these four parameters, conditional on magnitude and distance. These models were developed using a large number of recorded ground motions in Italy, and they allow defining combined spectral acceleration versus spectral displacement plots. Such design spectra are shown to reasonably interpolate the experimental data, resulting in acceleration and displacement demand that approximate the response spectra resulting from +1σ results obtained from recorded ground motions.

While it is recognized that numerous additional parameter should be considered (eg, focal depth and fault distance, site amplification), it is also concluded that this approach to define the seismic demand is promising toward a rationalization of seismic design. A thorough application of the approach developed and preliminary tested in this work may result in a re‐visitation of seismic design approaches and, ultimately, in a more efficient use of the available resources.
After 2018 Conference, Modeling Guidance From EPA Still Unclear
Authors: Hoffnagle Gale F.
Published: August 2018

This guidance continues to evolve.
Adverse pathologic features in T1/2 oral squamous cell carcinoma classified by the American Joint Committee on Cancer eighth edition and implications for treatment
Authors: Subramaniam Narayana , Murthy Samskruthi , Balasubramanian Deepak , Low Tsu‐Hui (Hubert) , Vidhyadharan Sivakumar , Clark Jonathan R. , Thankappan Krishnakumar , Iyer Subramania
Published: August 2018

Background

The American Joint Committee on Cancer (AJCC) eighth edition has incorporated depth of invasion into TNM classification of oral cavity squamous cell carcinoma (SCC) due to the prognostic impact on recurrence and survival. After reclassifying our patients with T1 to T2 oral cavity SCC according to these recommendations, we intended to study the effect of adverse pathological features (perineural invasion [PNI], lymphovascular invasion, and differentiation) on overall survival (OS).

Methods

We conducted a retrospective analysis of 442 patients with T1 to T2 oral cavity SCC. Univariate and multivariate analysis was performed for impact of adverse pathological features on OS.

Results

For the newly reclassified T1 to T2 oral cavity tumors, on multivariate analysis, the prognostically relevant parameters were PNI (P = .032) and differentiation (P = .009). Increasing adverse pathological features resulted in worse survival (P = .005).

Conclusion

Incorporation of PNI and differentiation better reflect prognostic outcome in oral cavity tumors classified as T1 to T2 as per the new AJCC eighth edition. Increasing adverse pathological features resulted in worse survival.
Bile Microinfarcts in Cholestasis Are Initiated by Rupture of the Apical Hepatocyte Membrane and Cause Shunting of Bile to Sinusoidal Blood
Authors: Ghallab Ahmed , Hofmann Ute , Sezgin Selahaddin , Vartak Nachiket , Hassan Reham , Zaza Ayham , Godoy Patricio , Schneider Kai Markus , Guenther Georgia , Ahmed Yasser A. , Abbas Aya A. , Keitel Verena , Kuepfer Lars , Dooley Steven , Lammert Frank , Trautwein Christian , Spiteller Michael , Drasdo Dirk , Hofmann Alan F. , Jansen Peter L.M. , Hengstler Jan G. , Reif Raymond
Published: August 2018

Bile duct ligation (BDL) is an experimental procedure that mimics obstructive cholestatic disease. One of the early consequences of BDL in rodents is the appearance of so‐called bile infarcts that correspond to Charcot‐Gombault necrosis in human cholestasis. The mechanisms causing bile infarcts and their pathophysiological relevance are unclear. Therefore, intravital two photon–based imaging of BDL mice was performed with fluorescent bile salts (BS) and non‐BS organic anion analogues. Key findings were followed up by matrix‐assisted laser desorption ionization imaging, clinical chemistry, immunostaining, and gene expression analyses. In the acute phase, 1‐3 days after BDL, BS concentrations in bile increased and single‐cell bile microinfarcts occurred in dispersed hepatocytes throughout the liver caused by the rupture of the apical hepatocyte membrane. This rupture occurred after loss of mitochondrial membrane potential, followed by entry of bile, cell death, and a “domino effect” of further death events of neighboring hepatocytes. Bile infarcts provided a trans‐epithelial shunt between bile canaliculi and sinusoids by which bile constituents leaked into blood. In the chronic phase, ≥21 days after BDL, uptake of BS tracers at the sinusoidal hepatocyte membrane was reduced. This contributes to elevated concentrations of BS in blood and decreased concentrations in the biliary tract. Conclusion:
Bile microinfarcts occur in the acute phase after BDL in a limited number of dispersed hepatocytes followed by larger infarcts involving neighboring hepatocytes, and they allow leakage of bile from the BS‐overloaded biliary tract into blood, thereby protecting the liver from BS toxicity; in the chronic phase after BDL, reduced sinusoidal BS uptake is a dominant protective factor, and the kidney contributes to the elimination of BS until cholemic nephropathy sets in.
Mindfulness, selfcompassion, and depressive symptoms in chronic pain: The role of pain acceptance
Authors: Carvalho Sérgio A. , Gillanders David , Palmeira Lara , Pinto‐Gouveia José , Castilho Paula
Published: August 2018

Objective(S)

The aim of this study was to test a theory driven model in which pain acceptance (both pain willingness [PW] and activity engagement [AE]) mediates the relationships of mindfulness and selfcompassion with depressive symptoms, while controlling for pain intensity.

Methods

A path analysis was conducted using AMOS software to test a meditational model in a sample of women with chronic musculoskeletal pain (N = 231).

Results

Participants with higher levels of mindful awareness and selfcompassion presented lower levels of pain intensity and depressive symptoms, and higher levels of AE. PW did not significantly correlate with any variable in study. The mediation analysis showed that AE mediated the relationship between selfcompassion and depressive symptoms, independently from pain intensity.

Conclusions

These findings seem to corroborate the hypothesis that selfcompassion is rooted in a motivational system, as it seems to correlate with less depressive symptoms through increasing the engagement with valued actions despite experiencing pain.
ChemFrag: Chemically meaningful annotation of fragment ion mass spectra
Authors: Schüler Jördis‐Ann , Neumann Steffen , Müller‐Hannemann Matthias , Brandt Wolfgang
Published: August 2018

Identification and structural determination of small molecules by mass spectrometry is an important step in chemistry and biochemistry. However, the chemically realistic annotation of a fragment ion spectrum can be a difficult challenge. We developed ChemFrag, for the detection of fragmentation pathways and the annotation of fragment ions with chemically reasonable structures. ChemFrag combines a quantum chemical with a rule‐based approach. For different doping substances as test instances, ChemFrag correctly annotates fragment ions. In most cases, the predicted fragments are chemically more realistic than those from purely combinatorial approaches, or approaches based on machine learning. The annotation generated by ChemFrag often coincides with spectra that have been manually annotated by experts. This is a major advance in peak annotation and allows a more precise automatic interpretation of mass spectra.
Effects of lily/maize intercropping on rhizosphere microbial community and yield of Lilium davidii var. unicolor
Authors: Zhou Lijing , Wang Yajun , Xie Zhongkui , Zhang Yubao , Malhi Sukhdev S. , Guo Zhihong , Qiu Yang , Wang Le
Published: August 2018

Continuous cropping of lily (Lilium davidii var. unicolor) or any other crop seriously affects yield and quality. In this study, we compared continuous cropping with lily/maize intercropping. We also examined the lily rhizosphere microbes community in both sole lily cropping and lily/maize intercropping systems, by the llumina Miseq platform. Here we refer to data of recent years field experimentation of a lily/maize intercrop system in different planting configurations in the Gaolan Ecological and Agricultural Research Station. Treatments included sole crops of lily and maize, an intercrop consisting of strips of four lily rows alternating with one maize rows. The land equivalent ratio (LER) of intercrops was 1.294. The results showed that compared to sole cropping, the yield of lily in the first year of planting increased when lily was intercropped with maize. The species annotation of the high‐throughput sequencing experiment showed that there was no difference in the diversity of the lily rhizosphere soil microbes on phylum taxonomic level, but the relative abundance of some genus changed obviously. The relative abundance of harmful fungus Fusarium spp. and, Funneliformis spp., decreased, and the relative abundance of beneficial bacteria Sphingomonas spp. and, Nitrospira spp., increased. In addition, we found that Lecanicillium spp., appeared only in the intercropping lily rhizosphere soil and sole cropping maize rhizosphere soil. In conclusion, the findings indicated that lily/maize intercropping could change soil microenvironment, and affect the diversity and structure of microorganism community in lily rhizosphere, with further beneficial effect on the yield of lily.
Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored Multilayer Interactions
Authors: Geryak Ren , Quigley Elizabeth , Kim Sunghan , Korolovych Volodymyr F. , Calabrese Rossella , Kaplan David L. , Tsukruk Vladimir V.
Published: August 2018

Microencapsulation techniques represent a critical step in realizing highly controlled transport of functional materials in multiphase systems. The first demonstration of microcapsules prepared from minimally grafted silk ionomers (silk fibroin modified with cationic/anionic charge groups) are presented here. These tailored biomacromolecules have shown significantly increased biocompatibility over traditional polyelectrolytes and heavily grafted silk ionomers, but the low grafting density had previously limited attempts to fabricate stable microcapsules. In addition, the first microcapsules from polyethylene‐glycol‐grafted silk ionomers are fabricated and the corresponding impact on microcapsule behavior is demonstrated. The materials are shown to exhibit pH‐responsive properties, with the microcapsules demonstrating an approx. tenfold decrease in stiffness and an approx. threefold change in diffusion coefficient when moving from acidic to basic buffer. Finally, the effect of assembly conditions of the microcapsules are shown to play a large role in determining final properties, with microcapsules prepared in acidic buffers showing lower roughness, stiffness, and an inversion in transport behavior (i.e., permeability decreases at higher pH).
Mechanochemical Activation of Fluorogenic CuAAC “Click” Reactions for Stress‐Sensing Applications
Authors: Michael Philipp , Biewend Michel , Binder Wolfgang H.
Published: August 2018

Strategies for visualizing stress within polymeric materials are of growing interest during the past decade. In this paper, stress‐sensing materials, triggered by a mechanoresponsive catalytic system based on latent copper(I)bis(N‐heterocyclic carbene) mechanophores, are reported, which can be activated by compression force to trigger a fluorogenic copper(I)‐catalyzed alkyne/azide “click” cycloaddition reaction, activating a fluorescent dye useful for stress‐sensing applications in bulk polymeric materials. The focus is placed on the polymeric architecture, which is responsible for an efficient stress transmission, revealing the greatest activation for network‐based mechanocatalysts, observing “click” conversions up to 44%, while chain‐extended and linear mechanocatalysts activate either in a less efficient manner or are not completely latent in the initial state. The developed catalysts enable “irreversible” mechanochromic systems for stress‐sensing devices.
A multigroup SEIR epidemic model with age‐dependent latency and relapse
Authors: Liu Lili , Feng Xiaomei
Published: August 2018

Different multigroup epidemic models have been proposed, but few models include the latent class that becomes infectious at different rates and the fact that the removed class may relapse into an infectious class at different rates. In this paper, a multigroup SEIR epidemic model is constructed to study the transmission dynamics of infectious diseases with age‐dependent latency and relapse. The model is realistic for some infectious diseases, such as TB and herpes virus. The sharp threshold condition, which corresponds to the well‐known basic reproduction number
, is derived, and it determines the global stability of each equilibrium. In particular, if
, then the disease‐free equilibrium is globally asymptotically stable, whereas if  
, the endemic equilibrium exists uniquely and is globally asymptotically stable. We utilize appropriate Lyapunov functionals, graph‐theoretical results, and the LaSalle's invariance principle to prove these results. Two specific examples and their corresponding numerical simulations are provided to explain the obtained results.
Application of the finite element submodeling technique in a single point contact and wear problem
Authors: Curreli Cristina , Di Puccio Francesca , Mattei Lorenza
Published: August 2018

Finite element simulation is a powerful tool to study and predict the wear behavior of different mechanical systems. However, the high computational cost required to obtain accurate numerical solutions is a crucial aspect especially for large and complex models. The present study proposes a possible solution to overcome this limitation by exploiting the potentiality of the submodeling technique, whose application to wear problem is still rare in the literature. A global‐local approach for wear analysis is presented and validated for a simple pin‐on‐disk wear test. In a preliminary step, different submodeling techniques were implemented and compared. They differed for the quantity (nodal forces and/or displacements) transferred from the global model to the local one. Numerical models have been developed in Ansys® mechanical APDL using its new wear simulation and mesh smoothing routines. Results suggest that the proposed strategy can significantly reduce the computational cost of finite element wear models. Some interesting points on the use of submodeling in contact problems are also discussed.