bluuebunny/crossref_metadata_2025 huggingface dataset:
Three cell deaths and a funeral: macrophage clearance of cells undergoing distinct modes of cell death
Authors: Klöditz Katharina , Fadeel Bengt
Published: February 2019

Macrophage clearance of apoptotic cells has been extensively investigated, but less is known regarding the clearance of cells dying by other forms of programmed cell death, e.g., necroptosis or ferroptosis. Here, we established a model of three different cell deaths using the same cell line and the occurrence of distinct cell death modalities was verified by using the specific inhibitors, zVAD-fmk, necrostatin-1, and ferrostatin-1, respectively. Cell death was characterized by using transmission electron microscopy (TEM), the gold standard for the demarcation of different cell death modalities. Moreover, using annexin V as a probe, we could detect surface exposure of phosphatidylserine (PS) in all three types of cell death, and this was confirmed by using specific anti-PS antibodies. We then co-cultured the cells with human monocyte-derived macrophages and found that cells dying by all three death modalities were engulfed by macrophages. Macrophage clearance of apoptotic cells was more efficient when compared to necroptotic and ferroptotic cells with multiple internalized target cells per macrophage, as shown by TEM. We propose that clearance of dying cells also should be taken into account in the classification of different cell death modalities.
Oxytocin pathway gene networks in the human brain
Authors: Quintana Daniel S. , Rokicki Jaroslav , van der Meer Dennis , Alnæs Dag , Kaufmann Tobias , Córdova-Palomera Aldo , Dieset Ingrid , Andreassen Ole A. , Westlye Lars T.
Published: February 2019

Oxytocin is a neuropeptide involved in animal and human reproductive and social behavior. Three oxytocin signaling genes have been frequently implicated in human social behavior: OXT (structural gene for oxytocin), OXTR (oxytocin receptor), and CD38 (oxytocin secretion). Here, we characterized the distribution of OXT, OXTR, and CD38 mRNA across the human brain by creating voxel-by-voxel volumetric expression maps, and identified putative gene pathway interactions by comparing gene expression patterns across 20,737 genes. Expression of the three selected oxytocin pathway genes was enriched in subcortical and olfactory regions and there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with the processing of anticipatory, appetitive, and aversive cognitive states. The oxytocin signaling system may interact with dopaminergic and muscarinic acetylcholine signaling to modulate cognitive state processes involved in complex human behaviors.
BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis
Authors: Kim Najin , Kim Sungdae , Nahm Minyeop , Kopke Danielle , Kim Joohyung , Cho Eunsang , Lee Min-Jung , Lee Mihye , Kim Seung Hyun , Broadie Kendal , Lee Seungbok
Published: February 2019

Retrograde BMPtrans-synaptic signaling is essential for synaptic development. Despite the importance of endocytosis-regulated BMP receptor (BMPR) control of this developmental signaling, the mechanism remains unknown. Here, we provide evidence that Abelson interactor (Abi), a substrate for Abl kinase and component of the SCAR/WAVE complex, links Abl and Rac1 GTPase signaling to BMPR macropinocytosis to restrain BMP-mediated synaptic development. We find that Abi acts downstream of Abl and Rac1, and that BMP ligand Glass bottom boat (Gbb) induces macropinocytosis dependent on Rac1/SCAR signaling, Abl-mediated Abi phosphorylation, and BMPR activation. Macropinocytosis acts as the major internalization route for BMPRs at the synapse in a process driven by Gbb activation and resulting in receptor degradation. Key regulators of macropinocytosis (Rabankyrin and CtBP) control BMPR trafficking to limit BMPtrans-synaptic signaling. We conclude that BMP-induced macropinocytosis acts as a BMPR homeostatic mechanism to regulate BMP-mediated synaptic development.
Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions
Authors: Gutierrez-Arcelus Maria , Teslovich Nikola , Mola Alex R. , Polidoro Rafael B. , Nathan Aparna , Kim Hyun , Hannes Susan , Slowikowski Kamil , Watts Gerald F. M. , Korsunsky Ilya , Brenner Michael B. , Raychaudhuri Soumya , Brennan Patrick J.
Published: February 2019

How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function.
Block copolymer derived uniform mesopores enable ultrafast electron and ion transport at high mass loadings
Authors: Liu Tianyu , Zhou Zhengping , Guo Yichen , Guo Dong , Liu Guoliang
Published: February 2019

High mass loading and fast charge transport are two crucial but often mutually exclusive characteristics of pseudocapacitors. On conventional carbon supports, high mass loadings inevitably lead to sluggish electron conduction and ion diffusion due to thick pseudocapacitive layers and clogged pores. Here we present a design principle of carbon supports, utilizing self-assembly and microphase-separation of block copolymers. We synthesize porous carbon fibers (PCFs) with uniform mesopores of 11.7 nm, which are partially filled with MnO2 of <2 nm in thickness. The uniform mesopores and ultrathin MnO2 enable fast electron/ion transport comparable to electrical-double-layer-capacitive carbons. At mass loadings approaching 7 mg cm−2, the gravimetric and areal capacitances of MnO2 (~50% of total mass) reach 1148 F g−1 and 3141 mF cm−2, respectively. Our MnO2-coated PCFs outperform other MnO2-based electrodes at similar loadings, highlighting the great promise of block copolymers for designing PCF supports for electrochemical applications.
Porous hypercrosslinked polymer-TiO2-graphene composite photocatalysts for visible-light-driven CO2 conversion
Authors: Wang Shaolei , Xu Min , Peng Tianyou , Zhang Chengxin , Li Tao , Hussain Irshad , Wang Jingyu , Tan Bien
Published: February 2019

Significant efforts have been devoted to develop efficient visible-light-driven photocatalysts for the conversion of CO2to chemical fuels. The photocatalytic efficiency for this transformation largely depends on CO2adsorption and diffusion. However, the CO2adsorption on the surface of photocatalysts is generally low due to their low specific surface area and the lack of matched pores. Here we report a well-defined porous hypercrosslinked polymer-TiO2-graphene composite structure with relatively high surface area i.e., 988 m2 g−1and CO2uptake capacity i.e., 12.87 wt%. This composite shows high photocatalytic performance especially for CH4production, i.e., 27.62 μmol g−1 h−1, under mild reaction conditions without the use of sacrificial reagents or precious metal co-catalysts. The enhanced CO2reactivity can be ascribed to their improved CO2adsorption and diffusion, visible-light absorption, and photo-generated charge separation efficiency. This strategy provides new insights into the combination of microporous organic polymers with photocatalysts for solar-to-fuel conversion.
Quantum risk analysis
Authors: Woerner Stefan , Egger Daniel J.
Published: February 2019

We present a quantum algorithm that analyzes risk more efficiently than Monte Carlo simulations traditionally used on classical computers. We employ quantum amplitude estimation to price securities and evaluate risk measures such as Value at Risk and Conditional Value at Risk on a gate-based quantum computer. Additionally, we show how to implement this algorithm and how to trade-off the convergence rate of the algorithm and the circuit depth. The shortest possible circuit depth—growing polynomially in the number of qubits representing the uncertainty—leads to a convergence rate of O(M−2/3), where M is the number of samples. This is already faster than classical Monte Carlo simulations which converge at a rate of O(M−1/2). If we allow the circuit depth to grow faster, but still polynomially, the convergence rate quickly approaches the optimum of O(M−1). Thus, for slowly increasing circuit depths our algorithm provides a near quadratic speed-up compared to Monte Carlo methods. We demonstrate our algorithm using two toy models. In the first model we use real hardware, such as the IBM Q Experience, to price a Treasury-bill (T-bill) faced by a possible interest rate increase. In the second model, we simulate our algorithm to illustrate how a quantum computer can determine financial risk for a two-asset portfolio made up of government debt with different maturity dates. Both models confirm the improved convergence rate over Monte Carlo methods. Using simulations, we also evaluate the impact of cross-talk and energy relaxation errors.
Effects of a contoured foot orthosis and flat insole on plantar pressure and tibial acceleration while walking in defence boots
Authors: Bonanno Daniel R. , Ledchumanasarma Ketharasarma , Landorf Karl B. , Munteanu Shannon E. , Murley George S. , Menz Hylton B.
Published: February 2019

This study investigated the effects of a contoured, prefabricated foot orthosis and a flat insole on plantar pressure and tibial acceleration while walking in defence boots. Twenty-eight adults walked along an 8-metre walkway in a: (i) defence boot (control condition), (ii) defence boot with a flat insole, and (iii) defence boot with a contoured foot orthosis. Plantar pressure data were collected using the pedar-X in-shoe system and tibial accelerations were measured with an accelerometer. In relation to plantar pressure under the rearfoot, the contoured foot orthosis, compared to the defence boot, decreased peak pressure and maximum force, and increased contact area. Under the medial midfoot, the contoured foot orthosis and flat insole increased peak pressure, maximum force and contact area. Under the medial forefoot, the contoured foot orthosis and flat insole increased maximum force. Under the lateral forefoot, the contoured foot orthosis and flat insole increased contact area, with the flat insole also increasing maximum force. In relation to tibial acceleration, the contoured foot orthosis, compared to the defence boot, decreased tibial peak positive acceleration. These findings provide novel biomechanical evidence for the effects of contoured foot orthoses in defence boots.
Automated Tracking of Biopolymer Growth and Network Deformation with TSOAX
Authors: Xu Ting , Langouras Christos , Koudehi Maral Adeli , Vos Bart E. , Wang Ning , Koenderink Gijsje H. , Huang Xiaolei , Vavylonis Dimitrios
Published: February 2019

Studies of how individual semi-flexible biopolymers and their network assemblies change over time reveal dynamical and mechanical properties important to the understanding of their function in tissues and living cells. Automatic tracking of biopolymer networks from fluorescence microscopy time-lapse sequences facilitates such quantitative studies. We present an open source software tool that combines a global and local correspondence algorithm to track biopolymer networks in 2D and 3D, using stretching open active contours. We demonstrate its application in fully automated tracking of elongating and intersecting actin filaments, detection of loop formation and constriction of tilted contractile rings in live cells, and tracking of network deformation under shear deformation.
The in vivo specificity of synaptic Gβ and Gγ subunits to the α2a adrenergic receptor at CNS synapses
Authors: Yim Yun Young , Betke Katherine M. , McDonald W. Hayes , Gilsbach Ralf , Chen Yunjia , Hyde Karren , Wang Qin , Hein Lutz , Hamm Heidi E.
Published: February 2019

G proteins are major transducers of signals from G-protein coupled receptors (GPCRs). They are made up of α, β, and γ subunits, with 16 Gα, 5 Gβ and 12 Gγ subunits. Though much is known about the specificity of Gα subunits, the specificity of Gβγs activated by a given GPCR and that activate each effector in vivo is not known. Here, we examined the in vivo Gβγ specificity of presynaptic α2a-adrenergic receptors (α2aARs) in both adrenergic (auto-α2aARs) and non-adrenergic neurons (hetero-α2aARs) for the first time. With a quantitative MRM proteomic analysis of neuronal Gβ and Gγ subunits, and co-immunoprecipitation of tagged α2aARs from mouse models including transgenic FLAG-α2aARs and knock-in HA-α2aARs, we investigated the in vivo specificity of Gβ and Gγ subunits to auto-α2aARs and hetero-α2aARs activated with epinephrine to understand the role of Gβγ specificity in diverse physiological functions such as anesthetic sparing, and working memory enhancement. We detected Gβ2, Gγ2, Gγ3, and Gγ4 with activated auto α2aARs, whereas we found Gβ4 and Gγ12 preferentially interacted with activated hetero-α2aARs. Further understanding of in vivo Gβγ specificity to various GPCRs offers new insights into the multiplicity of genes for Gβ and Gγ, and the mechanisms underlying GPCR signaling through Gβγ subunits.
Unexpected stray attractors in confined leader-follower dynamics driven by cone-of-vision interactions
Authors: Al-Sayegh Amara A. , Najem Sara A. , Klushin Leonid , Touma Jihad R.
Published: February 2019

Experiments with groups of fish inside a circular tank have provided valuable insights into the nature of leadership in social groups. Sophisticated mathematical models were constructed with a view to recovering observed schooling and leadership behavior in such experiments. Here, and with the help of variations on a promising class of such models, we explore a dual set of social concerns, namely the likelihood of permanent evasion from a cohesive group by a controlled individual in confinement. Our minimal model reduces to a leader-follower configuration, with cone-of-vision driven interactions inside a circular domain. We show that the resulting dynamical system sustains a rich supply of non-aligned, straying “follower” states, the dynamics on which displays (chaotic) intermittency between boundary following behavior and infrequent long flights. We map these states in configuration space and explore transitions between them. We demonstrate robustness of observed behavior by considering model variations, as well as alternate leader control trajectory. While it is too early to draw the implications of leader-follower dynamics to collective behavior, we do confirm that a model stray fish relates to a self-organized school bouncing back and forth along the diameter very much like a follower responds to a point leader in our model. We further draw the implications of our results to the study of dynamical systems with discontinuities, robotics, and the study of human behavior in the face of normative control and confinement.
Networks of ribosome flow models for modeling and analyzing intracellular traffic
Authors: Nanikashvili Itzik , Zarai Yoram , Ovseevich Alexander , Tuller Tamir , Margaliot Michael
Published: February 2019

The ribosome flow model with input and output (RFMIO) is a deterministic dynamical system that has been used to study the flow of ribosomes during mRNA translation. The input of the RFMIO controls its initiation rate and the output represents the ribosome exit rate (and thus the protein production rate) at the 3′ end of the mRNA molecule. The RFMIO and its variants encapsulate important properties that are relevant to modeling ribosome flow such as the possible evolution of “traffic jams” and non-homogeneous elongation rates along the mRNA molecule, and can also be used for studying additional intracellular processes such as transcription, transport, and more. Here we consider networks of interconnected RFMIOs as a fundamental tool for modeling, analyzing and re-engineering the complex mechanisms of protein production. In these networks, the output of each RFMIO may be divided, using connection weights, between several inputs of other RFMIOs. We show that under quite general feedback connections the network has two important properties: (1) it admits a unique steady-state and every trajectory converges to this steady-state; and (2) the problem of how to determine the connection weights so that the network steady-state output is maximized is a convex optimization problem. These mathematical properties make these networks highly suitable as models of various phenomena: property (1) means that the behavior is predictable and ordered, and property (2) means that determining the optimal weights is numerically tractable even for large-scale networks. For the specific case of a feed-forward network of RFMIOs we prove an additional useful property, namely, that there exists a spectral representation for the network steady-state, and thus it can be determined without any numerical simulations of the dynamics. We describe the implications of these results to several fundamental biological phenomena and biotechnological objectives.
Annual rhythms of temporal niche partitioning in the Sparidae family are correlated to different environmental variables
Authors: Sbragaglia Valerio , Nuñez Jesús D. , Dominoni Davide , Coco Salvatore , Fanelli Emanuela , Azzurro Ernesto , Marini Simone , Nogueras Marc , Ponti Massimo , del Rio Fernandez Joaquin , Aguzzi Jacopo
Published: February 2019

The seasonal timing of recurring biological processes is essential for organisms living in temperate regions. While ample knowledge of these processes exists for terrestrial environments, seasonal timing in the marine environment is relatively understudied. Here, we characterized the annual rhythm of habitat use in six fish species belonging to the Sparidae family, highlighting the main environmental variables that correlate to such rhythms. The study was conducted at a coastal artificial reef through a cabled observatory system, which allowed gathering underwater time-lapse images every 30 minutes consecutively over 3 years. Rhythms of fish counts had a significant annual periodicity in four out of the six studied species. Species-specific temporal patterns were found, demonstrating a clear annual temporal niche partitioning within the studied family. Temperature was the most important environmental variable correlated with fish counts in the proximity of the artificial reef, while daily photoperiod and salinity were not important. In a scenario of human-induced rapid environmental change, tracking phenological shifts may provide key indications about the effects of climate change at both species and ecosystem level. Our study reinforces the efficacy of underwater cabled video-observatories as a reliable tool for long-term monitoring of phenological events.
Tropical South Atlantic influence on Northeastern Brazil precipitation and ITCZ displacement during the past 2300 years
Authors: Utida Giselle , Cruz Francisco W. , Etourneau Johan , Bouloubassi Ioanna , Schefuß Enno , Vuille Mathias , Novello Valdir F. , Prado Luciana F. , Sifeddine Abdelfettah , Klein Vincent , Zular André , Viana João C. C. , Turcq Bruno
Published: February 2019

Recent paleoclimatic studies suggest that changes in the tropical rainbelt across the Atlantic Ocean during the past two millennia are linked to a latitudinal shift of the Intertropical Convergence Zone (ITCZ) driven by the Northern Hemisphere (NH) climate. However, little is known regarding other potential drivers that can affect tropical Atlantic rainfall, mainly due to the scarcity of adequate and high-resolution records. In this study, we fill this gap by reconstructing precipitation changes in Northeastern Brazil during the last 2,300 years from a high-resolution lake record of hydrogen isotope compositions of plant waxes. We find that regional precipitation along the coastal area of South America was not solely governed by north-south displacements of the ITCZ due to changes in NH climate, but also by the contraction and expansion of the tropical rainbelt due to variations in sea surface temperature and southeast trade winds in the tropical South Atlantic Basin.
The impact of long-term organic farming on soil-derived greenhouse gas emissions
Authors: Skinner Colin , Gattinger Andreas , Krauss Maike , Krause Hans-Martin , Mayer Jochen , van der Heijden Marcel G. A. , Mäder Paul
Published: February 2019

Agricultural practices contribute considerably to emissions of greenhouse gases. So far, knowledge on the impact of organic compared to non-organic farming on soil-derived nitrous oxide (N2O) and methane (CH4) emissions is limited. We investigated N2O and CH4 fluxes with manual chambers during 571 days in a grass-clover– silage maize – green manure cropping sequence in the long-term field trial “DOK” in Switzerland. We compared two organic farming systems – biodynamic (BIODYN) and bioorganic (BIOORG) – with two non-organic systems – solely mineral fertilisation (CONMIN) and mixed farming including farmyard manure (CONFYM) – all reflecting Swiss farming practices–together with an unfertilised control (NOFERT). We observed a 40.2% reduction of N2O emissions per hectare for organic compared to non-organic systems. In contrast to current knowledge, yield-scaled cumulated N2O emissions under silage maize were similar between organic and non-organic systems. Cumulated on area scale we recorded under silage maize a modest CH4 uptake for BIODYN and CONMIN and high CH4 emissions for CONFYM. We found that, in addition to N input, quality properties such as pH, soil organic carbon and microbial biomass significantly affected N2O emissions. This study showed that organic farming systems can be a viable measure contributing to greenhouse gas mitigation in the agricultural sector.
Observational constraint of in-cloud supersaturation for simulations of aerosol rainout in atmospheric models
Authors: Moteki Nobuhiro , Mori Tatsuhiro , Matsui Hitoshi , Ohata Sho
Published: February 2019

Quantitative simulation of an aerosol’s lifecycle by regional-scale and global-scale atmospheric models is mandatory for unbiased analysis and prediction of aerosol radiative forcing and climate change. Globally, aerosol deposition is dominated by the rainout process, which is mostly triggered by activation of aerosols to liquid droplets in supersaturated domains of precipitating clouds. However, the actual environmental supersaturation value that aerosols experience in precipitating clouds is difficult for models to predict, and it has never been constrained by observations; as a result, there is large uncertainty in atmospheric aerosol simulations. Here, by a particle-tracer analysis of 37 rainfall events in East Asia, near the largest source region of anthropogenic aerosols in the northern hemisphere, we observed that the environmental supersaturation actually experienced by the removed aerosols in precipitating clouds averaged 0.08 ± 0.03% and ranged from 0.03 to 0.2%. Simulations by a mixing-state-resolved global aerosol model showed that the simulated long-range transport efficiency and global atmospheric burden of black carbon aerosols can be changed by a factor of two or three as a result of a change in the environmental supersaturation in precipitating clouds within just 0.08 ± 0.03%. This result is attributable to the fact that the sensitivity of an aerosol’s rainout efficiency to environmental supersaturation is higher for the less-aged black carbon concentrated near source regions. Our results suggest that observational constraints of environmental supersaturation in precipitating clouds, particularly near source regions, are of fundamental importance for accurate simulation of the atmospheric burden of black carbon and other aerosols.
Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing
Authors: Ono Ryuichi , Yasuhiko Yukuto , Aisaki Ken-ichi , Kitajima Satoshi , Kanno Jun , Hirabayashi Yoko
Published: February 2019

The CRISPR-Cas9 system has been successfully applied in many organisms as a powerful genome-editing tool. Undoubtedly, it will soon be applied to human genome editing, including gene therapy. We have previously reported that unintentional DNA sequences derived from retrotransposons, genomic DNA, mRNA and vectors are captured at double-strand breaks (DSBs) sites when DSBs are introduced by the CRISPR-Cas9 system. Therefore, it is possible that unintentional insertions associated with DSB repair represent a potential risk for human genome editing gene therapies. To address this possibility, comprehensive sequencing of DSB sites was performed. Here, we report that exosome-mediated horizontal gene transfer occurs in DSB repair during genome editing. Exosomes are present in all fluids from living animals, including seawater and breathing mammals, suggesting that exosome-mediated horizontal gene transfer is the driving force behind mammalian genome evolution. The findings of this study highlight an emerging new risk for this leading-edge technology.
Mechanistic insights into the evolution of DUF26-containing proteins in land plants
Authors: Vaattovaara Aleksia , Brandt Benjamin , Rajaraman Sitaram , Safronov Omid , Veidenberg Andres , Luklová Markéta , Kangasjärvi Jaakko , Löytynoja Ari , Hothorn Michael , Salojärvi Jarkko , Wrzaczek Michael
Published: February 2019

Large protein families are a prominent feature of plant genomes and their size variation is a key element for adaptation. However, gene and genome duplications pose difficulties for functional characterization and translational research. Here we infer the evolutionary history of the DOMAIN OF UNKNOWN FUNCTION (DUF) 26-containing proteins. The DUF26 emerged in secreted proteins. Domain duplications and rearrangements led to the appearance of CYSTEINE-RICH RECEPTOR-LIKE PROTEIN KINASES (CRKs) and PLASMODESMATA-LOCALIZED PROTEINS (PDLPs). The DUF26 is land plant-specific but structural analyses of PDLP ectodomains revealed strong similarity to fungal lectins and thus may constitute a group of plant carbohydrate-binding proteins. CRKs expanded through tandem duplications and preferential retention of duplicates following whole genome duplications, whereas PDLPs evolved according to the dosage balance hypothesis. We propose that new gene families mainly expand through small-scale duplications, while fractionation and genetic drift after whole genome multiplications drive families towards dosage balance.
The Medicinal Chemistry of RNase H-activating Antisense Oligonucleotides
Authors: Seth Punit P. , Swayze Eric E.
Published: February 2019

This review focuses on the properties that an RNase H-activating antisense oligonucleotide (ASO) drug must have to function effectively in animals, as well as on medicinal chemistry strategies to achieve these properties. The biochemistry and structural requirements for activating RNase H are briefly summarized, as well as chemical modifications that can effect activation of RNase H when an ASO is bound to target RNA. The key modifications available to the medicinal chemist to engineer desired properties of the ASO are briefly reviewed, as are ASO design strategies to achieve optimal activity in animal systems. Lastly, the interactions of ASOs with proteins and strategies to control these interactions to improve the profile of ASOs are discussed.
Large-scale Automated Synthesis of Therapeutic Oligonucleotides: A Status Update
Authors: Sanghvi Yogesh S.
Published: February 2019

An increasing number of therapeutic oligonucleotides are entering human clinical trials, leading to multiple marketed drugs. Thus, large-scale automated synthesis of these products has become a high priority for process chemists. This chapter summarizes the advances in the large-scale solid-support synthesis of oligonucleotides using conventional phosphoramidite chemistry. An overview of the most prevalent modifications currently utilized for the assembly of modified oligonucleotides along with a four-step automated process is presented. A brief description of the post-synthesis processes is also included with protocols for characterization of drug substance. A glimpse of possible future technologies that may tackle the economic and ecological challenges of the 21st century when oligonucleotides will be required in metric-tonne quantity is also discussed.
The influence of nitrogen position on charge carrier mobility in enantiopure aza[6]helicene crystals
Authors: Salerno Francesco , Rice Beth , Schmidt Julia A. , Fuchter Matthew J. , Nelson Jenny , Jelfs Kim E.
Published: February 2019

A computational study exploring the influence of the nitrogen position on charge carrier mobility in enantiopure aza[6]helicene crystals
Role of antibody heavy and light chain interface residues in affinity maturation of binding to HIV envelope glycoprotein
Authors: Cisneros Alberto , Nargi Rachel Stecker , Parrish Erica Hammaker , Haliburton Christian Marie , Meiler Jens , Crowe Jr. James E.
Published: February 2019

Optimization of the heavy chain/light chain interface could serve as an important tool for maximizing antibody/antigen binding affinity without altering antigen contact residues.
Ionic conductivity and counterion condensation in nanoconfined polycation and polyanion brushes prepared from block copolymer templates
Authors: Arges Christopher G. , Li Ke , Zhang Le , Kambe Yu , Wu Guang-Peng , Lwoya Baraka , Albert Julie N. L. , Nealey Paul F. , Kumar Revati
Published: February 2019

Counterion condensation sensed in nano-confined and non-confined polymer electrolyte brushes with 2D force mapping AFM.
Browning control of fresh-cut Chinese yam by edible coatings enriched with an inclusion complex containing star anise essential oil
Authors: Zhang Guangjie , Gu Lingbiao , Lu Zhifang , Yuan Chao , Sun Yonghai
Published: February 2019

The encapsulation of hydroxypropyl-β-cyclodextrin improved the inhibitory effect of star anise essential oil on the browning of fresh-cut Chinese yam.
Designing photolabile ruthenium polypyridyl crosslinkers for hydrogel formation and multiplexed, visible-light degradation
Authors: Rapp Teresa L. , Wang Yanfei , Delessio Maegan A. , Gau Michael R. , Dmochowski Ivan J.
Published: February 2019

Multiplexed visible-light photolysis: two ruthenium crosslinkers were used to generate a PEG based hydrogel that can be degraded selectively with orange and blue light.
Support morphology-dependent alloying behaviour and interfacial effects of bimetallic Ni–Cu/CeO2 catalysts
Authors: Liu Yanan , McCue Alan J. , Yang Pengfei , He Yufei , Zheng Lirong , Cao Xingzhong , Man Yi , Feng Junting , Anderson James A. , Li Dianqing
Published: February 2019

The dependence of alloying behavior and interfacial effects on the support morphology is revealed, in which homogeneous Ni–Cu nanoalloys were induced by polyhedron ceria.
A high-temperature multiaxial precision time-delayed dielectric switch crystal triggered by linear/propeller/ball three-form motion
Authors: Wang Qing , Zhang Yu-Wei , Zhang Wan-Ying , Shi Ping-Ping , Ye Qiong , Fu Da-Wei
Published: February 2019

The new crystal motor with extraordinary thermal hysteresis turns out to be a multiaxial precision time-delayed dielectric switch.
Fast self-assembly of polystyrene-b-poly(fluoro methacrylate) into sub-5 nm microdomains for nanopatterning applications
Authors: Li Xuemiao , Li Jie , Wang Chenxu , Liu Yuyun , Deng Hai
Published: February 2019

Block copolymers with perfluoroalkyl side-chains can self-assemble rapidly at moderate temperatures to yield sub-5 nm domains.
Non-reducible disulfide bond replacement implies that disulfide exchange is not required for hepcidin–ferroportin interaction
Authors: Huang Dong-Liang , Bai Jing-Si , Wu Meng , Wang Xia , Riedl Bernd , Pook Elisabeth , Alt Carsten , Erny Marion , Li Yi-Ming , Bierer Donald , Shi Jing , Fang Ge-Min
Published: February 2019

Non-reducible disulfide bond replacement was used to study the disculfide exchange between hepcidin and ferroportin, and the results indicate that the hepcidin–ferroportin interaction does not require disfulfide exchange.
Practical and selective hydroboration of aldehydes and ketones in air catalysed by an iron(ii) coordination polymer
Authors: Zhang Guoqi , Cheng Jessica , Davis Kezia , Bonifacio Mary Grace , Zajaczkowski Cynthia
Published: February 2019

The in air selective hydroboration of aldehydes and ketones with pinacolborane was catalysed by an air-stable iron(ii) coordination polymer under heterogeneous conditions.
Effects of solvents on the DACBO-catalyzed vinylogous Henry reaction of isatin with 3,5-dimethyl-4-nitroisoxazole “on-water” and in solution from QM/MM MC simulations
Authors: Yang Lian , Zhao Jianming , Yang Xin , Chen Ming , Xue Ying
Published: February 2019

QM/MM MC simulations indicate that the special hydrogen bonding effects are the main source of the rate enhancement of the title reaction on water.
Correction: Barrier kinetics of adsorption–desorption of alcohol monolayers on water under constant surface tension
Authors: Minkov Ivan L. , Arabadzhieva Dimitrinka , Salama Ibrahim E. , Mileva Elena , Slavchov Radomir I.
Published: February 2019

Correction for ‘Barrier kinetics of adsorption–desorption of alcohol monolayers on water under constant surface tension’ by Ivan L. Minkov et al., Soft Matter, 2019, DOI: 10.1039/c8sm02076k.
Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury
Authors: Chen Wei , Liu Wen-Rui , Hou Jie-Bin , Ding Jia-Rong , Peng Zhong-Jiang , Gao Song-Yan , Dong Xin , Ma Jun-Hua , Lin Qi-Shan , Lu Jian-Rao , Guo Zhi-Yong
Published: February 2019

Nephrolithiasis is one of the world’s major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.
The therapeutic effect of switching from tacrolimus to low-dose cyclosporine A in renal transplant recipients with BK virus nephropathy
Authors: Chen Xu-Tao , Li Jun , Deng Rong-Hai , Yang Shi-Cong , Chen Yan-Yang , Chen Pei-Song , Wang Ze-Yuan , Huang Yang , Wang Chang-Xi , Huang Gang
Published: February 2019

Background: There is no effective therapy for BK virus (BKV) nephropathy (BKVN). Cyclosporine A (CsA) has a lower immunosuppressive effect than tacrolimus. In vitro studies have shown that CsA inhibits BKV replication. The present study aimed to evaluate the effectiveness of switching from tacrolimus to low-dose CsA in renal transplant recipients with BKVN. Methods: Twenty-four patients diagnosed with BKVN between January 2015 and December 2016 were included. Tacrolimus was switched to low-dose CsA, and patients were followed for 24 months. Primary end points were BKV clearance in blood and graft. Secondary end points were urine specific gravity, serum creatinine, and graft loss. Results: The viremia in all patients cleared at a mean of 2.7 ± 2.0 months after switching to CsA. Urine specific gravity at 3 months after switching to CsA increased significantly compared with that at diagnosis (P=0.002). The timing and trend of urine specific gravity increase was consistent with the timing and trend of blood and urine viral load decrease. Repeated biopsies at a median of 11.2 months (range: 9.1–12.5 months) after switching to CsA showed that 8 patients (42.1%) were negative for BKV, and 11 patients (58.9%) had a decrease in BKV load (P<0.001). There was no statistical difference in the serum creatinine level between the time of diagnosis and 24 months of CsA therapy (P=0.963). The graft survival rate was 100%. Only two patients (8.3%) suffered from acute rejection. Conclusion: Switching from tacrolimus to low-dose CsA may be an effective therapy for BKVN.
Thermal energy harvesting system based on magnetocaloric materials★
Authors: Ahmim Smail , Almanza Morgan , Pasko Alexandre , Mazaleyrat Frédéric , LoBue Martino
Published: February 2019

We numerically study the design of a thermomagnetic generator aimed to convert a heat flow into electrical energy. The device uses the variation of magnetization of a magnetocaloric material (MCM) along a cyclic transformation between the hot and the cold sources. The magnetic energy is transformed into mechanical energy via the magnetic forces and eventually into electrical energy through an electromechanical transducer. Firstly, we work-out the optimal size of the cantilever in order to achieve the self-oscillation of the MCM between the two heat sources. Eventually, using finite element calculations, we compare the efficiency of a piezoelectric transducer (PZT 5a) with that of a set of coils in order to convert the mechanical into electrical energy. The piezoelectrics and the coils recover 0.025% and 0.018% respectively of the available mechanical energy (116 mJ/cm3). The possible strategies to achieve a better performance are discussed in theconclusion.
One-dimensional model describing eigenmode frequency shift during transverse excitation
Authors: Webster S. , Hardi J. , Oschwald M.
Published: February 2019

A shift in transverse eigenmode frequency was observed in an experimental combustion chamber when exposed to large amplitude acoustic oscillations during oxygen–hydrogen combustion tests. A shift in eigenmode frequency under acoustic conditions representative of combustion conditions is of critical importance when tuning acoustic absorbers or investigating injection coupled combustion instabilities. The experimentally observed frequency shift was observed both in the frequency domain and as an asymmetric amplitude response to a linear frequency ramp of an external excitation system in the time domain. The frequency shift was found to be dependent on amplitude and operating condition. A hypothesis is presented for the frequency shift based on change in speed-of-sound distributions due to flame contraction when exposed to high amplitude pressure oscillations. A one-dimensional (1D) model was created to test the hypothesis. Model parameters were based on relationships observed in experimental data. The model was found to accurately recreate the frequency shifting asymmetric response observed in test data as well as its amplitude dependence. Further development is required to investigate the influence of operating conditions and chamber design on the quantitative modeling of the frequency shift.
Aluminium grain refinement by Ti(C, N) nanoparticles additions: principles, advantages and drawbacks
Authors: Li Wanpeng , Mao Jian , Feng Jie
Published: February 2019

Ti(C, N) is a ceramic particle with high melting point, high hardness, high thermal and chemical stability. And incorporated Ti(C, N) particles is demonstrated to refine the grain and improve the mechanical properties of aluminium and its alloys. In this article, effects of the addition amount of Ti(C, N) particles on grain refinement and mechanical properties of aluminium alloy are reviewed, and the mechanisms of aluminium alloy refined by Ti(C, N) are described. In addition, due to the poor wettability of Ti(C, N) nanoparticles with aluminium alloy melt and the large specific surface area of Ti(C, N) nanoparticles, the Ti(C, N) nanoparticles are prone to aggregate in molten aluminium, which severely limits the application of Ti(C, N) in aluminium alloy. And effective approaches to improving the wettability of Ti(C, N) nanoparticles refine aluminium alloys are provided.
Carbon footprint management of unconventional natural gas development in the export scenario
Authors: Bista Sangita , Jennings Philip , Anda Martin
Published: February 2019

In Australia, exploitation of shale gas is at an early stage. Western Australia has estimated its technically recoverable gas resources at 235 trillion cubic feet (tcf). It is viewed as an exciting economic prospect and decarbonising option for transition to climate change mitigation. The central focus of this paper is to estimate the climate impacts of Australian shale gas fracking and compare with other energy sources. Electricity generation has been considered as end use of gas in export scenarios to Japan and China. Analysis has been done for resource development periods of 20 and 40 years. Carbon footprints of shale gas range from 604MtCO2e to 543 MtCO2e per annum for China and Japan export cases, respectively, for 20 years field lifetime, if 66 tcf of shale gas is exploited and used. This result is roughly equivalent to 115% of Australia's total national emissions for the year 2014. If all technically recoverable shale gas (235tcf) from the Canning Basin in the Kimberley is exploited and exported to China and Japan over 40 years, the annual emissions are double the total Australian national emissions. The result suggests that shale gas has low carbon intensity compared to coal and oil but solar PV and wind are much cleaner energy options for GHG mitigation. The solar PV and wind electricity would produce 8% and 5% of the shale gas electricity emissions, respectively. Unless accompanied by stringent regulation and compliance on the upstream resource development, stage shale gas cannot be an appropriate energy source for sustainable development as opposed to renewable energy sources.
Faziale Hauttumore: Resektion und plastische
Defektrekonstruktion – Teil 1
Authors: Häussler Daniel , Sadick Haneen , Rotter Nicole
Published: February 2019

Die Häufigkeit von Tumoren der Gesichtshaut nimmt aufgrund der steigenden
UV-Exposition und der zunehmenden Alterung der Bevölkerung zu. Gleichzeitig
steigen die Ansprüche an die Funktion und Ästhetik der rekonstruktiven Chirurgie
im Gesicht. Die In-sano-Resektion mit Sicherheitsabstand ist der entscheidende
erste Schritt eines operativen Vorgehens. Die anschließende Rekonstruktion ist
von patientenspezifischen und weiteren Faktoren abhängig.
Sonografie von Schilddrüsenknoten
Authors: Schmidt Daniela
Published: February 2019

Die Sonografie gehört zu den Standardverfahren bei der Evaluation von
Schilddrüsenknoten. Verschiedene sonografische Veränderungen sind mit einem
erhöhten Malignitätsrisiko assoziiert. Basierend hierauf wurden in den letzten
Jahren Klassifizierungssysteme entwickelt, um leichter diejenigen Knoten zu
selektieren, welche einer weiteren Abklärung bedürfen (TI-RADS: thyroid imaging
and reporting systems). Bis jetzt werden in diesen Systemen nur morphologische
Kriterien eingeschlossen. Resultate einer Farbdoppler-Sonografie als ergänzendem
Verfahren werden in diesen Klassifizierungen nicht berücksichtigt, obwohl eine
erhöhte intranoduläre Vaskularisation bei follikulären Neoplasien mit einem
erhöhten Malignitätsrisiko assoziiert ist. Aktuell werden die neuen Systeme
evaluiert und müssen gegebenenfalls für die klinische Praxis optimiert werden.
Außerdem gibt es erste Ansätze, die Dokumentation der Ultraschallergebnisse
weiter zu standardisieren, um die diagnostischen Möglichkeiten der
Ultraschalluntersuchung im Sinne der Verbesserung der Patientenversorgung zu
optimieren.
Soft Tissue Sarcoma – a Current Review of the Diagnostic and Treatment Strategies
Authors: Scheidt Sebastian , Jacobs Cornelius , Koob Sebastian , Welle Kristian , Walter Sebastian , Jakob Jens , Kehrer Michael , Schmolders Jan
Published: February 2019

Soft tissue sarcomas are a heterogeneous group of neoplasias that due to their often clinically silent appearance often remain undetected or experience delayed treatment. Especially soft tissue swelling is often misinterpreted by patients and doctors and trivialized or verified with an incorrect biopsy technique. The hereby evoked complications for the patients are serious and may be reduced by simply following the available guidelines. The treatment of soft tissue sarcomas requires a close interdisciplinary coordination between specialists in tumor orthopedics, oncology, radiology, pathology and radiotherapy. On the basis of a selective literature review, the following article points out the current evidence on the treatment and illustrates a treatment algorithm.
Recent Advances in the Application of Ring-Closing Metathesis for the Synthesis of Unsaturated Nitrogen Heterocycles
Authors: Groso Emilia , Schindler Corinna
Published: February 2019

This short review summarizes recent advances relating to the application of ring-closing olefin-olefin and carbonyl-olefin metathesis reactions towards the synthesis of unsaturated five- and six-membered nitrogen heterocycles. These developments include catalyst modifications and reaction designs that will enable access to more complex nitrogen heterocycles.

1 Introduction

2 Expansion of Ring-Closing Metathesis Methods

3 Evaluation of Catalyst Design

4 Indenylidene Catalysts

5 Unsymmetrical N-Heterocyclic Carbene Ligands

6 Carbonyl-Olefin Metathesis

7 Conclusions