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Glycosylation engineering of therapeutic IgG antibodies： challenges for the safety, functionality and efficacy

Protein & Cell 2018年第1期9卷 47-62页

作者： Yusuke Mimura Toshihiko Katoh Radka Saldova Roisin O'Flaherty Tomonori Izumi Yuka Mimura-Kimura Toshiaki Utsunomiya Yoichi Mizukami Kenji Yamamoto Tsuneo Matsumoto Pauline M. Rudd Department of Clinical research NHO Yamaguchi-Ube Medical Center 685 Higashi-Kiwa Ube 755-0241 Japan Laboratory of Molecular Biology and Bioresponse Division of Integrated Life Science Graduate School of Biostudies KyotoUniversity Kitashirakawa Oiwake-Cho Sakyo-Ku Kyoto 606-8502 Japan NIBRT Glycoscience Group National Institute for Bioprocessing Research and Training Mount Merrion Blackrock Dublin 4Ireland Center for Regenerative Medicine Yamaguchi University Graduate School of Medicine 1-1-1 Minami Kogushi Ube 755-8505 Japan Center for Gene research Yamaguchi University 1-1-1 Minami-Kogushi Ube 755-8505 Japan research Institute for Bioresources and Biotechnology Ishikawa Prefectural University 1-308 Suematsu Nonoichi Ishikawa 921-8836 Japan

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary *** oligosaccharide attached to Asn297 of the Fc is essen- tial for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that gen- erate structural heterogeneity （glycoforms） exhibit unique biological activities. Hence, efficient and quan- titative glycan analysis techniques have been increas- ingly important for the development and quality control of therapeutic antibodies, and g｜ycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosy- lation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibili- ties for the design of novel antibody therapeutics. Fur- thermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosyn- thases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next- generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety,functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.

关键词： chemoenzymatic glycoengineering crysta structure endoglycosidase fucose glycosylation,intravenous immunoglobulin sialic acid transglycosylation,ultra performance liquid chromatography

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Formation of Extended Covalently Bonded Ni Porphyrin Networks on the Au（lll） Surface

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Nano research 2011年第4期4卷 376-384页

作者： Sergey A. Krasnikov Catherine M. Doyle Natalia N. Sergeeva Alexei B. Preobrajenski Nikolay A.Vinogradov Yulia N. Sergeeva Alexei A. Zakharov Mathias O. Senge Attilio A. Cafolla School of Physical sciences Dublin City University Glasnevin Dublin 9 Ireland Centre tbr research on Adaptive Nanostructures and Nanodevices （CRANN） School of Physics Trinity College Dublin Dublin 2 Ireland SFI Tetrapyrrole Laboratory School of Chemistry Trinity College Dublin Dublin 2 Ireland MAX-Lab Lund University Box 118 22100 Lund Sweden

The growth and ordering of {5,10,15,20-tetrakis（4-bromophenyl）porphyrinato}nickel（II）（NiTBrPP） molecules on the Au（111） surface have been investigated using scanning tunnelling microscopy, X-ray absorption, core-level photoemission, and microbeam low-energy electron diffraction. When deposited onto the substrate at room temperature, the NiTBrPP forms a well-ordered close-packed molecular layer in which the molecules have a flat orientation with the porphyrin macrocycle plane lying parallel to the substrate. Annealing of the NiTBrPP layer on the Au（111） surface at 525 K leads to dissociation of bromine from the porphyrin followed by the formation of covalent bonds between the phenyl substituents of the porphyrin. This results in the formation of continuous covalently bonded porphyrin networks, which are stable up to 800 K and can be recovered after exposure to ambient conditions. By controlling the experimental conditions, a robust, extended porphyrin network can be prepared on the Au（111） surface that has many potential applications such as protective coatings, in sensing or as a host structure for molecules and clusters.

关键词： Porphyrins covalently bonded networks scanning tunnelling microscopy X-ray photoemission spectroscopy near-edge X-ray absorption fine structure Au(111)

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Unifying concepts in methanogenic,aerobic,and anammox sludge granulation

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Environmental science and Ecotechnology 2024年第1期17卷 17-30页

作者： Simon Mills Anna Christine Trego Marco Prevedello Jo De Vrieze Vincent O’Flaherty Piet N.L.Lens Gavin Collins Microbial Communities Laboratory School of Biological and Chemical SciencesNational University of Ireland GalwayUniversity RoadGalwayH91 TK33Ireland Microbial Ecology Laboratory School of Biological and Chemical sciences University of GalwayUniversity RoadGalwayH91 TK33Ireland Center for Microbial Ecology and Technology(CMET) Ghent UniversityCoupure Links 653B-9000GentBelgium University of Galway University RoadGalwayH91 TK33Ireland

The retention of dense and well-functioning microbial biomass is crucial for effective pollutant removal in several biological wastewater treatment *** solids retention is often achieved through aggregation of microbial communities into dense,spherical aggregates known as granules,which were initially discovered in the *** granules have since been widely applied in upflow anaerobic digesters for waste-to-energy ***,granular biomass has been applied in aerobic wastewater treatment and anaerobic ammonium oxidation(anammox)*** mechanisms underpinning the formation of methanogenic,aerobic,and anammox granules are the subject of ongoing *** each granule type has been extensively studied in isolation,there has been a lack of comparative studies among these granulation *** is likely that there are some unifying concepts that are shared by all three sludge *** these unifying concepts could allow a unified theory of granulation to be ***,we review the granulation mechanisms of methanogenic,aerobic,and anammox granular sludge,highlighting several common concepts,such as the role of extracellular polymeric substances,cations,and operational parameters like upflow velocity and shear *** have then identified some unique features of each granule type,such as different internal structures,microbial compositions,and quorum sensing ***,we propose that future research should prioritize aspects of microbial ecology,such as community assembly or interspecies interactions in individual granules during their formation and growth.

关键词： Granule Granulation Anaerobic digestion Anammox Aerobic granule

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Wavelength stability in a hybrid photonic crystal laser through controlled nonlinear absorptive heating in the reflector

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Light(science & Applications) 2018年第1期7卷 654-660页

作者： Andrei P.Bakoz Alexandros A.Liles Alfredo A.Gonzalez-Fernandez Tatiana Habruseva Changyu Hu Evgeny A.Viktorov Stephen P.Hegarty Liam O’Faolain Centre for Advanced Photonics and Process Analysis&Department of Physical sciences Cork Institute of TechnologyCork T12P928Ireland Tyndall National Institute University College CorkLee MaltingsDyke ParadeCork T12R5CPIreland School of Physics&Astronomy University of St AndrewsNorth HaughSt Andrews KY169SSUK National research University of Information Technologies Mechanics and OpticsSaint Petersburg 199034Russia IMEC Department of Information Technology(INTEC)Photonics Research GroupGhent UniversityTechnologiepark-Zwijnaarde 159052 GhentBelgium National Institute of Astrophysics Optics and Electronics72840 TonantzintlaMexico

The need for miniaturized,fully integrated semiconductor lasers has stimulated significant research efforts into realizing unconventional configurations that can meet the performance requirements of a large spectrum of applications,ranging from communication systems to *** demonstrate a hybrid,silicon photonicscompatible photonic crystal(PhC)laser architecture that can be used to implement cost-effective,high-capacity light sources,with high side-mode suppression ratio and milliwatt output output *** emitted wavelength is set and controlled by a silicon PhC cavity-based reflective filter with the gain provided by a Ⅲ–Ⅴ-based reflective semiconductor optical amplifier(RSOA).The high power density in the laser cavity results in a significant enhancement of the nonlinear absorption in silicon in the high Q-factor PhC *** heat generated in this manner creates a tuning effect in the wavelength-selective element,which can be used to offset external temperature fluctuations without the use of active *** approach is fully compatible with existing fabrication and integration technologies,providing a practical route to integrated lasing in wavelength-sensitive schemes.

关键词： amplifier tuning nonlinear

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Development of a facile block copolymer method for creating hard mask patterns integrated into semiconductor manufacturing

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Nano research 2016年第10期9卷 3116-3128页

作者： Tandra Ghoshal Matthew T. Shaw Justin D. Holmes Michael A. Morris Department of Chemistry and Tyndall National Institute University College Cork Cork Ireland AMBER Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) Trinity College Dublin Dublin Ireland Intel ireland Ltd. Collinstown Industrial Estate Co. Kildare Ireland School of Chemistry Trinity College Dublin Dublin Ireland

Our goal is to develop a facile process to create patterns of inorganic oxides and metals on a substrate that can act as hard masks. These materials should have high etch contrast （compared to silicon） and so allow high-aspect-ratio, high- fidelity pattern transfer whilst being readily integrable in modem semiconductor fabrication （FAB friendly）. Here, we show that ultra-small-dimension hard masks can be used to develop large areas of densely packed vertically and horizontally orientated Si nanowire arrays. The inorganic and metal hard masks （Ni, NiO, and ZnO） of different morphologies and dimensions were formed using microphase- separated polystyrene-b-poly（ethylene oxide）（PS-b-PEO） block copolymer （BCP） thin films by varying the BCP molecular weight, annealing temperature, and annealing solvent（s）. The self-assembled polymer patterns were solvent-processed, and metal ions were included into chosen domains via a selective inclusion method. Inorganic oxide nanopatterns were subsequently developed using standard techniques. High-resolution transmission electron microscopy studies show that high-aspect-ratio pattern transfer could be affected by standard plasma etch techniques. The masking ability of the different materials was compared in order to create the highest quality uniform and smooth sidewall profiles of the Si nanowire arrays. Notably good performance of the metal mask was seen, and this could impact the use of these materials at small dimensions where conventional methods are severely limited.

关键词： block copolymer self-assembly hard mask silicon nanowires

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Fe Nanoclusters on the Ge（001） Surface Studied by Scanning Tunneling Microscopy, Density Functional Theory Calculations and X-Ray Magnetic Circular Dichroism

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Nano research 2011年第10期4卷 971-978页

作者： Olaf LUbben Sergey A. Krasnikov Alexei B. Preobrajenski Barry E. Murphy Igor V. Shvets Centre for research on Adaptive Nanostructures and Nanodevices （CRANN） School of Physics Trinity College Dublin Dublin 2 Ireland MAX-lab Lund University Box 118. 22100 Lund Sweden

The growth of Fe nanoclusters oN the Ge（001） surface has been studied using low-temperature scanning tunneling microscopy （STM） and density functional theory （DFT） calculations. STM results indicate that Fe nucleates on the Ge（001） surface, forming well-ordered nanoclusters of uniform size. Depending on the preparation conditions, two types of nanoclusters were observed having either four or sixteen Fe atoms within a nanocluster. The results were confirmed by DFT calculations. Annealing the nanoclusters at 420 K leads to the formation of nanorow structures, due to cluster mobility at such temperature. The Fe nanoclusters and nanorow structures formed on the Ge（001） surface show a superparamagnetic behaviour as measured by X-ray magnetic circular dichroism.

关键词： Ge(001) iron nanoclusters self-assembly scanning tunnelling microscopy X-ray magnetic circular dichroism density functional theory calculations

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Origin and molecular characterization of the human-infecting H6N1 infl uenza virus in Taiwan

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Protein & Cell 2013年第11期4卷 846-853页

作者： Weifeng Shi Yi Shi Ying Wu Di Liu George F.Gao School of Medical sciences Taishan Medical CollegeTaian 271016China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Beijing Institutes of Life sciences Chinese Academy of SciencesBeijing 100101China Network Information Center Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Offi ce of Director-General Chinese Center for Disease Control and Prevention(China CDC)Beijing 102206China

In June 2013,the fi rst human H6N1 infl uenza virus infec-tion was confirmed in ***,the origin and molecular characterization of this virus,A/Taiwan/2/2013(H6N1),have not been well studied thus *** the present report,we performed phylogenetic and coalescent analy-ses of this virus and compared its molecular profi le/char-acteristics with other closely related *** characterization of H6N1 revealed that it is a typical avian infl uenza virus of low pathogenicity,which might not rep-licate and propagate well in the upper airway in *** analysis revealed that the virus clusters with A/chicken/Taiwan/A2837/2013(H6N1)in seven genes,except *** the PB1 gene,A/Taiwan/2/2013 was clus-tered with a different H6N1 lineage from A/chicken/Taiwan/A2837/*** a previous study demonstrated that the PB2,PA,and M genes of A/Taiwan/2/2013 might be derived from the H5N2 viruses,coalescent analyses revealed that these H5N2 viruses were derived from more recent strains than that of the ancestor of A/Taiwan/2/***,we propose that A/Taiwan/2/2013 is a reassor-tant from different H6N1 lineages circulating in chickens in ***,compared to avian isolates,a sin-gle P186L(H3 numbering)substitution in the hemaggluti-nin H6 of the human isolate might increase the mammali-an receptor binding and,hence,this strain’s pathogenicity in ***,human infection with this virus seems an accidental event and is unlikely to cause an infl uenza ***,its co-circulation and potential reas-sortment with other infl uenza subtypes are still worthy of attention.

关键词： molecular characterization phylogenetic analysis coalescent analysis H6N1 infl uenza virus Taiwan

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Effect of electron injection in copper-contacted graphene nanoribbons

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Nano research 2016年第9期9卷 2735-2746页

作者： Konstantin A.Simonov Nikolay A.Vinogradov Alexander S.Vinogradov Alexander V.Generalov Gleb I.Svirskiy Attilio A.Cafolla Nils Martensson Alexei B. Preobrajenski Department of Physics and Astronomy Uppsala UniversityUppsala Box 51675120Sweden MAX Ⅳ Laboratory Lund UniversityLund Box 11822100Sweden V.A.Fock Institute of Physics St.Petersburg State UniversitySt.Petersburg 198504Russia School of Physical sciences Dublin City UniversityDublin 9Ireland

For practical electronic device applications of graphene nanoribbons (GNRs), it is essential to have abrupt and well-defined contacts between the ribbon and the adjacent metal lead. By analogy with graphene, these contacts can induce electron or hole doping, which may significantly affect the I/V characteristics of the device. Cu is among the most popular metals of choice for contact materials. In this study, we investigate the effect of in situ intercalation of Cu on the electronic structure of atomically precise, spatially aligned armchair GNRs of width N = 7 (7-AGNRs) fabricated via a bottom-up method on the Au(788) surface. Scanning tunneling microscopy data reveal that the complete intercalation of about one monolayer of Cu under 7-AGNRs can be facilitated by gentle annealing of the sample at 80 °C. Angle-resolved photoemission spectroscopy (ARPES) data clearly reflect the one-dimensional character of the 7-AGNR band dispersion before and after intercalation. Moreover, ARPES and core-level photoemission results show that intercalation of Cu leads to significant electron injection into the nanoribbons, which causes a pronounced downshift of the valence and conduction bands of the GNR with respect to the Fermi energy (ΔE ~ 0.5 eV). As demonstrated by ARPES and X-ray absorption spectroscopy measurements, the effect of Cu intercalation is restricted to n-doping only, without considerable modification of the band structure of the GNRs. Post-annealing of the 7-AGNRs/Cu/Au(788) system at 200 °C activates the diffusion of Cu into Au and the formation of a Cu-rich surface Au layer. Alloying of intercalated Cu leads to the recovery of the initial position of GNR-related bands with respect to the Fermi energy (E F), thus, proving the tunability of the induced n-doping.

关键词： graphene nanoribbons bottom-up method copper intercalation charge injection angle-resolved photoemission spectroscopy (ARPES) scanning tunneling microscopy

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40 Gb/s NRZ-DQPSK data wavelength conversion with amplitude regeneration using four-wave mixing in a quantum dash semiconductor optical amplifier

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Frontiers of Optoelectronics 2016年第3期9卷 341-345页

作者： Michael J. CONNELLY Lukasz KRZCZANOWICZ Pascal MOREL Ammar SHARAIHA Francois LELARGE Romain BRENOT Siddharth JOSHI Sophie BARBET Optical Communications research Group Department of Electronic and Computer Engineering University of Limerick Limerick Ireland Lab-STICC UMR CNRS 6285 Ecole Nationale d'Ingenieurs de Brest CS 73862 29238 Brest Cedex 3 France Alcatel Thales III-V Laboratory Route Departementale 128 91767 Palaiseau France

Differential quadrature phase shift keying （DQPSK） modulation is attractive in high-speed optical communications because of its resistance to fiber non-linearities and more efficient use of fiber bandwidth compared to conventional intensity modulation schemes. Because of its wavelength conversion ability and phase preservation, semiconductor optical amplifier （SOA） four- wave mixing （FWM） has attracted much attention. We experimentally study wavelength conversion of 40 Gbit/s （20 Gbaud） non-return-to-zero （NRZ）-DQPSK data using FWM in a quantum dash SOA with 20 dB gain and 5 dBm output saturation power. Q factor improvement and eye diagram reshaping is shown for up to 3 nm pump-probe detuning and is superior to that reported for a higher gain bulk SOA.

关键词： differential quadrature phase shift keying (DQPSK) phase modulation quantum-dash semiconductor optical amplifier (SOA) four-wave mixing (FWM) wavelength conversion

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Dynamic epi-transcriptomic landscape mapping with disease progression in estrogen receptor-positive breast cancer

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Cancer Communications 2023年第5期43卷 615-619页

作者： Stephen Keelan Mihaela Ola Sara Charmsaz Sinéad Cocchiglia Daniela Ottaviani Seán Hickey Siobhan Purcell Fiona Bane Aisling Hegarty Ben Doherty Katherine Sheehan Lance Hudson Nicola Cosgrove Benjamin Roux Muriel Laine Geoffrey Greene Damir Varešlija Arnold Konrad Hill Leonie Young Endocrine Oncology research Group Department of SurgeryRoyal College of Surgeons in IrelandUniversity of Medicine and Health SciencesDublinIreland Department of Surgery Beaumont HospitalDublinIreland Department of Pathology Beaumont HospitalDublinIreland Ben May Department for Cancer research Department of Biochemistry and Molecular BiologyThe University of ChicagoChicagoILUSA The School of Pharmacy and Biomolecular sciences The Royal College of Surgeons University of Medicine and Health SciencesDublinIreland Beaumont Royal College of Surgeons in ireland Cancer Centre Beaumont HospitalDublinIreland

Dear Editor,The molecular determinants that drive breast cancer progression to metastasis are complex and partly controlled by nucleic acid epi-modifications[1].Although DNA-methyl modifications in breast cancer metastasis have been well described,there is limited understanding of the role of RNA methylation in advanced disease[2].This study aimed to provide an understanding on the role of the epitranscriptome in estrogen receptor-positive(ER+)breast cancer progression to metastasis.

关键词： breast metastasis cancer

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