bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compact Seahorse‐Shaped T Cell–Activating Antibody for Cancer Therapy
Authors: Fujii Hiroto , Tanaka Yoshikazu , Nakazawa Hikaru , Sugiyama Aruto , Manabe Noriyoshi , Shinoda Akira , Shimizu Nobutaka , Hattori Takamitsu , Hosokawa Katsuhiro , Sujino Takuma , Ito Tomoyuki , Niide Teppei , Asano Ryutaro , Kumagai Izumi , Umetsu Mitsuo 
Published: June 2018

AbstractThe vast information available on hierarchically structured proteins enables the creation of novel proteins with customized functions through the assembly of independent functional component modules. Here, a compact T cell–activating antibody is constructed from the antigen‐binding modules of variable domains. Genetic fusion of a single variable domain of the heavy chain of a heavy chain llama antibody (VHH) to the human single‐chain variable region of an antigen‐binding fragment (scFv), which is designed to be dimerized, yields a compact bispecific and bivalent antibody (BiBian) with a seahorse‐shaped structure. BiBian recognizes epidermal growth factor receptor (EGFR) on cancer cells and CD3 receptors on T cells; the two VHHs and dimerized scFv are structurally independent and positioned such that they are easily accessible to each target. BiBian adhered strongly to both cancer cells and T cells, promoted T cell activation (due to the bivalent CD3 modules), and induced dramatic cytotoxicity against tumor spheroids in vitro and in vivo. This compact structure is proposed as a fundamental format for homogeneous, highly cytotoxic, bacterially expressed antibodies.
Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy
Authors: Olesen Morten T. Jarlstad , Winther Anna K. , Fejerskov Betina , Dagnaes‐Hansen Frederik , Simonsen Ulf , Zelikin Alexander N. 
Published: June 2018

AbstractEmbolic beads, a successful tool for localized, site‐specific drug delivery, are engineered herein to contain the toolbox of enzyme‐prodrug therapy (EPT). EPT offers facile means to synthesize diverse drugs at their nominated concentrations; individually, in sequence, or in a combination. The authors investigate alginate beads as embolic bodies and screen alginate type and bead production parameters as factors to control activity of the immobilized enzymes. Engineered embolic bodies are armed with bi‐enzymatic EPT such that two enzymes perform biosynthesis of drugs with an independent control over each enzyme. Enzymatic synthesis of nitric oxide (NO) performed by embolic bodies is accomplished herein for the first time and is fine‐tuned such that flux of NO afforded by the beads matches that of healthy human endothelium. Ensuing vasodilation is illustrated ex vivo using rat mesenteric arteries. Independently, the production of SN‐38 is used to control the antiproliferative effects elicited by the beads. Bi‐enzymatic EPT engineered into embolic bodies thus affords opportunities for combination therapy and personalized treatment (adjusted combinations and concentrations of drugs) that go well beyond the state‐of‐the‐art of current embolic bodies and hold much promise for biomedical applications, specifically the treatment of hepatocellular carcinoma.
Curvature‐Induced Sorting of Lipids in Plasma Membrane Tethers
Authors: Baoukina Svetlana , Ingólfsson Helgi I. , Marrink Siewert J. , Tieleman D. Peter 
Published: June 2018

AbstractMembrane curvature controls the spatial organization and activity of cells. Lipid sorting in cell membranes can be explained by matching lipid molecular shape to regions of different curvatures. A molecular view of curvature‐induced lipid sorting is obtained using coarse‐grained molecular dynamics. A model membrane consisting of an asymmetric bilayer of multiple lipid species is simulated. Curvature is induced by pulling a tether, that is, a bilayer nanotube, from a flat membrane. Pulling is performed both from the inner and outer leaflets, corresponding to directions in and out of the cell. Redistribution of different lipid types between the tether and the bilayer is observed, leading to spatial variations in the composition of both leaflets, and, in turn, softening of the tether. Depending on the direction of pulling, the lipid distributions and the tether properties differ. Formation of a tether from the planar membrane thus induces lipid sorting without phase separation.
The Alkaline Stability of Anion Exchange Membrane for Fuel Cell Applications: The Effects of Alkaline Media
Authors: Sun Zhe , Pan Ji , Guo Jiangna , Yan Feng 
Published: June 2018

AbstractAlkaline alcohols (methanol, ethanol, propanol, and ethylene glycol) have been applied as fuels for alkaline anion exchange membrane fuel cells. However, the effects of alkaline media on the stability of anion exchange membranes (AEMs) are still elusive. Here, a series of organic cations including quaternary ammonium, imidazolium, benzimidazolium, pyridinium, phosphonium, pyrrolidinium cations, and their corresponding cationic polymers are synthesized and systematically investigated with respect to their chemical stability in various alkaline media (water, methanol, ethanol, and dimethyl sulfoxide) by quantitative 1H nuclear magnetic resonance spectroscopy and density functional theory calculations. In the case of protic solvents (water, methanol, and ethanol), the lower dielectric constant of the alkaline media, the lower is the lowest unoccupied molecular orbital (LUMO) energy of the organic cation, which leads to the lower alkaline stability of cations. However, the hydrogen bonds between the anions and protic solvents weaken the effects of low dielectric constant of the alkaline media. The aprotic solvent accelerated the SN2 degradation reaction of “naked” organic cations. The results of this study suggest that both the chemical structure of organic cations and alkaline media (fuels) applied affect the alkaline stability of AEMs.
3D Nanofabrication of High‐Resolution Multilayer Fresnel Zone Plates
Authors: Sanli Umut Tunca , Jiao Chengge , Baluktsian Margarita , Grévent Corinne , Hahn Kersten , Wang Yi , Srot Vesna , Richter Gunther , Bykova Iuliia , Weigand Markus , Schütz Gisela , Keskinbora Kahraman 
Published: June 2018

AbstractFocusing X‐rays to single nanometer dimensions is impeded by the lack of high‐quality, high‐resolution optics. Challenges in fabricating high aspect ratio 3D nanostructures limit the quality and the resolution. Multilayer zone plates target this challenge by offering virtually unlimited and freely selectable aspect ratios. Here, a full‐ceramic zone plate is fabricated via atomic layer deposition of multilayers over optical quality glass fibers and subsequent focused ion beam slicing. The quality of the multilayers is confirmed up to an aspect ratio of 500 with zones as thin as 25 nm. Focusing performance of the fabricated zone plate is tested toward the high‐energy limit of a soft X‐ray scanning transmission microscope, achieving a 15 nm half‐pitch cut‐off resolution. Sources of adverse influences are identified, and effective routes for improving the zone plate performance are elaborated, paving a clear path toward using multilayer zone plates in high‐energy X‐ray microscopy. Finally, a new fabrication concept is introduced for making zone plates with precisely tilted zones, targeting even higher resolutions.
Area Increase and Budding in Giant Vesicles Triggered by Light: Behind the Scene
Authors: Georgiev Vasil N. , Grafmüller Andrea , Bléger David , Hecht Stefan , Kunstmann Sonja , Barbirz Stefanie , Lipowsky Reinhard , Dimova Rumiana 
Published: June 2018

AbstractBiomembranes are constantly remodeled and in cells, these processes are controlled and modulated by an assortment of membrane proteins. Here, it is shown that such remodeling can also be induced by photoresponsive molecules. The morphological control of giant vesicles in the presence of a water‐soluble ortho‐tetrafluoroazobenzene photoswitch (F‐azo) is demonstrated and it is shown that the shape transformations are based on an increase in membrane area and generation of spontaneous curvature. The vesicles exhibit budding and the buds can be retracted by using light of a different wavelength. In the presence of F‐azo, the membrane area can increase by more than 5% as assessed from vesicle electrodeformation. To elucidate the underlying molecular mechanism and the partitioning of F‐azo in the membrane, molecular dynamics simulations are employed. Comparison with theoretically calculated shapes reveals that the budded shapes are governed by curvature elasticity, that the spontaneous curvature can be decomposed into a local and a nonlocal contribution, and that the local spontaneous curvature is about 1/(2.5 µm). The results show that exo‐ and endocytotic events can be controlled by light and that these photoinduced processes provide an attractive method to change membrane area and morphology.
Is high serum programmed death ligand 1 level a risk factor for poor survival in patients with gastric cancer?
Authors: Ito Masaaki , Oshima Yoko , Yajima Satoshi , Suzuki Takashi , Nanami Tatsuki , Shiratori Fumiaki , Funahashi Kimihiko , Nemoto Tetsuo , Shimada Hideaki 
Published: June 2018

AbstractBackground and AimAlthough the clinicopathological significance of the expression of programmed death ligand 1(PD‐L1) in various cancer tissues has been reported, serum PD‐L1 level has not been evaluated in patients with surgically treated gastric cancer. Therefore, we evaluated the clinicopathological characteristics and prognostic significance of preoperative serum PD‐L1 levels in patients with gastric cancer.Patients and MethodsSerum samples were obtained before surgery from 152 patients with gastric cancer, including 75 patients with stage I, 31 with stage II, 23 with stage III, and 23 with stage IV gastric cancer. The samples were analyzed using enzyme‐linked immunosorbent assay to detect soluble PD‐L1. Using the median serum PD‐L1 level of 50 pg/mL, patients were divided into two groups, namely high serum and low serum PD‐L1 level groups. Clinicopathological characteristics and prognosis were compared between these two groups using univariate and multivariate analysis.ResultsSerum PD‐L1 level was significantly associated with older age, positive cancer antigen 19‐9 (CA19‐9), C‐reactive protein levels, and albumin levels but not with tumor stage. Patients in the high serum PD‐L1 group showed significantly worse overall survival and recurrence‐free survival than those in the low serum PD‐L1 group (P < .05). Multivariate analysis showed that high serum PD‐L1 level was an independent risk factor for poor overall survival (P = .02).ConclusionHigh serum PD‐L1 level was a prognostic factor for reduced overall survival in patients with surgically treated gastric cancer.
I2/TBPB Mediated Oxidative Reaction to Construct of Imidazo[1,5‐α]pyridines under Metal‐Free Conditions
Authors: Qin Mingda , Tian Yuan , Guo Xin , Yuan Xinglong , Yang Xueying , Chen Baohua 
Published: June 2018

AbstractA new method for the synthesis of imidazo[1,5‐α]pyridines, one of the most important N‐heterocyclic compounds due to their wide application, was reported in this study. Specifically, using I2 as a non‐metal catalyst and TBPB as an oxidant can efficiently facilitate the synthesis and avoid the use of a metal catalyst. The reaction between ethyl (E)‐2‐(benzylideneamino)acetate and pyridine represents an unprecedented 1,3‐diolar cycloaddition in highly straightforward process with great value.
Overview of doctor‐staffed ambulance use in Japan: a nationwide survey and 1‐week study
Authors: Igarashi Yutaka , Yokobori Shoji , Yamana Hidetoshi , Nagakura Kosuke , Hagiwara Jun , Masuno Tomohiko , Yokota Hiroyuki 
Published: June 2018

AimIn Japan, standard prehospital care is provided by emergency medical services teams. Doctor‐staffed ambulances play a role in facilitating the immediate treatment of critically ill patients to increase the survival rates. However, little is known about their activities. We revealed the present situation of doctor‐staffed ambulances in Japan.MethodsFirst, we surveyed all the fire departments in Japan and determined whether a doctor‐staffed ambulance was present within their district boundary. Second, we surveyed hospitals that operate doctor‐staffed ambulances in their system to list their activities during a 1‐week period.ResultsOf 133 hospitals that operated a doctor‐staffed ambulance, 73 (55%) replied to our questionnaire. Only 26 (36%) of them provided 24‐h ambulance deployment. Additionally, 51 (70%) of hospitals bore the operational costs of ambulances. Within 1 week, 345 doctor‐staffed ambulances were dispatched, but 97 (28%) were cancelled. In total, 62 patients (28%) were diagnosed with cardiac arrest, 48 (19%) with trauma or burns, 36 (15%) with stroke, and 22 (9%) with acute coronary syndrome; 159 (58%) were transferred to a tertiary emergency medical center.ConclusionsDoctor‐staffed ambulances have the advantage of deployment at night and in urban areas compared to doctor‐staffed helicopters. Among the 73 hospitals that responded to the questionnaire, doctor‐staffed ambulances were dispatched almost as frequently as doctor‐staffed helicopters. However, doctor‐staffed ambulances did not receive adequate funding. Future data collection is necessary to determine the efficacy of doctor‐staffed ambulances among hospitals that operate this service.
Effect of Polysoap on the Physical and Tribological Properties of Soybean Oil‐Based Grease
Authors: Liu Zengshe , Biresaw Girma , Biswas Atanu , Cheng Huai N. 
Published: June 2018

AbstractSoybean oil (SBO)‐based grease, containing polysoaps synthesized from polymeric epoxidized soybean oil (PESO), were investigated. Greases were prepared using a mixture of lithium soap and triethanolammonium polysoap. Grease properties investigated were hardness, using the cone penetration procedure (ASTM D217); oxidation stability, using the pressurized differential scanning calorimetry (PDSC) method (ASTM D‐5483); and friction and wear, using a four‐ball tribometer (ASTM D‐2266). Penetration data showed that grease formulated in the presence of polysoap was harder than that without polysoap, and this was attributed to the cross‐linking in the polysoap structure, which was expected to provide higher resistance to deformation. The PDSC results indicated that the onset temperature of grease formulated with 3.8 and 7.3 wt% polysoap increased by 8 and 12°C, respectively, compared to grease without polysoap. The coefficient of friction of grease formulated with polysoap was much lower (0.015) than grease without polysoap (0.034).
Development and characterization of polymorphic EST‐SSR markers for Paphiopedilum henryanum (Orchidaceae)
Authors: Xu Yufeng , Jia Ruidong , Zhou Yanhui , Cheng Hao , Zhao Xin , Ge Hong 
Published: June 2018

Premise of the StudyMicrosatellite primers were developed for Paphiopedilum henryanum (Orchidaceae), a species threatened with extinction, to assess genetic diversity and population genetic structure.Methods and ResultsBased on the transcriptome data of P. henryanum, 34 novel polymorphic microsatellite expressed sequence tag–simple sequence repeat markers were developed and characterized in 33 individuals from two P. henryanum populations. The results showed the number of alleles per locus ranged from two to four, and levels of observed and expected heterozygosity per locus ranged from 0.000 to 1.000 and from 0.000 to 0.7333, respectively. Of these markers, some primers showed good amplification results in seven other Paphiopedilum species.ConclusionsThe developed microsatellite markers will be useful in exploring the genetic diversity and structure of P. henryanum. Furthermore, most loci were successfully cross‐amplified in seven other species of Paphiopedilum, indicating that they will be of great value for genetic study across this genus.
Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
Authors: Ciccia Francesco , Guggino Giuliana , Zeng Michael , Thomas Ranjeny , Ranganathan Vidya , Rahman Arifur , Alessandro Riccardo , Rizzo Aroldo , Saieva Laura , Macaluso Federica , Peralta Sergio , Di Liberto Diana , Dieli Francesco , Cipriani Paola , Giacomelli Roberto , Baeten Dominique , Haroon Nigil 
Published: June 2018

ObjectiveGut‐derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients.MethodsMNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR‐6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with ILC3, and changes in their frequency were evaluated by flow cytometry. Transcriptome analysis of circulating CX3CR1+ monocytes was also performed.ResultsDcR‐6 deficiency and CCL2 overexpression were observed in inflamed tissues from AS patients. In the gut, the proinflammatory CX3CR1+CD59+ MNP population was expanded, correlated with the presence of bacteria, and produced high levels of tumor necrosis factor–like molecule 1A (TL1A) and interleukin‐23 (IL‐23). MNPs positive for CD11b, CD11c, and major histocompatibility complex class II, predominantly expressing CX3CR1, were also expanded in the small intestines of treatment‐naive SKG relative to BALB/c mice. The frequency of gut‐derived CX3CR1+CD59+CCR9+TL1A+IL‐23+ MNPs was significantly higher in the peripheral blood and synovial fluid of AS patients than controls. CCR9+CX3CR1+CD59+ monocytes were also expanded in AS synovial and bone marrow samples. Transcriptome analysis of isolated CX3CR1+CD59+ monocytes demonstrated a specific proinflammatory profile in AS. Isolated proinflammatory CX3CR1+CD59+ MNPs from AS patients induced the expansion and activation of ILC3.ConclusionProinflammatory CX3CR1+CD59+TL1A+IL‐23+ MNPs are expanded in AS patients and display a specific proinflammatory transcriptome profile. Given the ability of these cells to support ILC3 expansion, they may promote a sustained proinflammatory status in AS.
Kinetics of Spontaneous Bimetallization between Silver and Noble Metal Nanoparticles
Authors: Hirakawa Kazutaka , Kaneko Tetsuya , Toshima Naoki 
Published: June 2018

AbstractA physical mixture of polymer‐protected Ag nanoparticles and Rh, Pd, or Pt nanoparticles spontaneously forms Ag‐core bimetallic nanoparticles. The formed nanoparticles were smaller than the parent Ag nanoparticles. In the initial process of this reaction, the surface plasmon absorption of Ag nanoparticles diminished and then almost ceased within one hour. Within several minutes, the decrease in Ag surface plasmon absorption could be analyzed by second‐order reaction. This reaction was accelerated with an increase of temperature and the energy gap in the Fermi level between Ag and the other metals. The activation energy (Ea) of this reaction could be determined. An electron transfer reaction from Ag to other metal nanoparticles was proposed as the initial interaction between these metal nanoparticles because the Fermi level of Ag is relatively high, and the electron transfer is possible in terms of energy. The Marcus plot between the rate constant and the driving force, roughly estimated from the work function of metals, and the observed Ea values reasonably explained the proposed electron transfer mechanism.
A Nontemplated Route to Macrocyclic Dibridgehead Diphosphorus Compounds: Crystallographic Characterization of a “Crossed‐Chain” Variant of in/out Stereoisomers
Authors: Kharel Sugam , Jia Tiezheng , Bhuvanesh Nattamai , Reibenspies Joseph H. , Blümel Janet , Gladysz John A. 
Published: June 2018

AbstractReactions of (O=)PH(OCH2CH3)2 and BrMg(CH2)mCH=CH2 (4.9–3.2 equiv; m=4 (a), 5 (b), 6 (c)) give the dialkylphosphine oxides (O=)PH[(CH2)mCH=CH2]2 (2 a–c; 77–81 % after workup), which are treated with NaH and then α,ω‐dibromides Br(CH2)nBr (0.49–0.32 equiv; n=8 (a′), 10 (b′), 12 (c′), 14 (d′)) to yield the bis(trialkylphosphine oxides) [H2C=CH(CH2)m]2P(=O)(CH2)n(O=)P[(CH2)mCH=CH2]2 (3 ab′, 3 bc′, 3 cd′, 3 ca′; 79–84 %). Reactions of 3 bc′ and 3 ca′ with Grubbs’ first‐generation catalyst and then H2/PtO2 afford the dibridgehead diphosphine dioxides
(4 bc′, 4 ca′; 14–19 %, n′=2m+2); 31P NMR spectra show two stereoisomeric species (ca. 70:30). Crystal structures of two isomers of the latter are obtained, out,out‐4 ca′ and a conformer of in,out‐4 ca′ that features crossed chains, such that the (O=)P vectors appear out,out. Whereas 4 bc′ resists crystallization, a byproduct derived from an alternative metathesis mode, (CH2)12P(=O)(CH2)12(O=)P(CH2)12, as well as 3 ab′ and 3 bc′, are structurally characterized. The efficiencies of other routes to dibridgehead diphosphorus compounds are compared.
Experiences on the use of a game for improving learning and assessing knowledge
Authors: Mesquida Antoni‐Lluís , Mas Antonia 
Published: June 2018

AbstractThe combination of traditional teaching methods with innovative learning tools generates a positive effect on the learning. MiProJOC is a web‐based question and answer game developed to support the delivery of interactive lessons and the assessment of the students’ learning, both as in‐class and distance education activities. MiProJOC was designed to maintain a repository of questions from different knowledge areas, to define and set different game modes, and to present the statistical results from the use of the tool. MiProJOC has been used to facilitate the learning of the software life cycle processes of the ISO/IEC/IEEE 12207 International Standard within a Software Quality course. This tool has been tested and validated by three different groups of users: students, teachers, and experts from an Information Technology center. The use of MiProJOC to consolidate theoretical concepts is quite profitable, instructive, and beneficial. The tool has achieved an increase in the student interest toward the topics studied. Students are more motivated when innovative techniques are used for the acquisition and consolidation of knowledge.