bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cell–Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis
Authors: Lu Daniel R. , McDavid Andrew N. , Kongpachith Sarah , Lingampalli Nithya , Glanville Jacob , Ju Chia‐Hsin , Gottardo Raphael , Robinson William H. 
Published: June 2018

ObjectiveRheumatoid arthritis (RA) is characterized by the activation of B cells that produce anti–citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs), but the mechanisms by which tolerance is broken in these B cells remain incompletely understood. We undertook this study to investigate whether ACPA+ and RF+ B cells break tolerance through distinct molecular mechanisms.MethodsWe developed antigen–tetramers to isolate ACPA+ and RF+ B cells and performed single‐cell RNA sequencing on 2,349 B cells from 6 RA patients and 1 healthy donor to analyze their immunoglobulin repertoires and transcriptional programs. Prominent immunoglobulins were expressed as monoclonal antibodies and tested for autoantigen reactivity.ResultsACPA+ and RF+ B cells were enriched in the peripheral blood of RA patients relative to healthy controls. Characterization of patient‐derived monoclonal antibodies confirmed ACPA and RF targeting of tetramer‐specific B cells at both antigen‐inexperienced and affinity‐matured B cell stages. ACPA+ B cells used more class‐switched isotypes and exhibited more somatic hypermutations relative to RF+ B cells, and these differences were accompanied by down‐regulation of CD72 and up‐regulation of genes that promote class‐switching and T cell–dependent responses. In contrast, RF+ B cells expressed transcriptional programs that stimulate rapid memory reactivation through multiple innate immune pathways. Coexpression analysis revealed that ACPA+ and RF+ B cell–enriched genes belong to distinct transcriptional regulatory networks.ConclusionOur findings suggest that ACPA+ and RF+ B cells are imprinted with distinct transcriptional programs, which suggests that these autoantibodies associated with increased inflammation in RA arise from 2 different molecular mechanisms.
Full‐Order Sliding‐Mode Control of Rigid Robotic Manipulators
Authors: Feng Yong , Zhou Minghao , Yu Xinghuo , Han Fengling 
Published: June 2018

AbstractThis paper proposes a full‐order sliding‐mode control for rigid robotic manipulators. The output signals of the proposed controller are continuous. Therefore, the controller can be directly applied in practice. A time‐varying gain is constructed to regulate the gain of the signum function in the sliding‐mode control so as to avoid the overestimation of the upper‐bounds of the uncertainties in the systems and reduce the waste of the control power. The chattering is attenuated by using a novel full‐order sliding manifold and establishing a novel ideal sliding motion. The proposed method is robust to the load disturbance and unmodeled parameters, especially to the unknown portion in the control matrix. Simulation results validate the proposed methods.
Temporary conductive hearing loss in early life impairs spatial memory of rats in adulthood
Authors: Zhao Han , Wang Li , Chen Liang , Zhang Jinsheng , Sun Wei , Salvi Richard J. , Huang Yi‐Na , Wang Ming , Chen Lin 
Published: June 2018

AbstractIntroductionIt is known that an interruption of acoustic input in early life will result in abnormal development of the auditory system. Here, we further show that this negative impact actually spans beyond the auditory system to the hippocampus, a system critical for spatial memory.MethodsWe induced a temporary conductive hearing loss (TCHL) in P14 rats by perforating the eardrum and allowing it to heal. The Morris water maze and Y‐maze tests were deployed to evaluate spatial memory of the rats. Electrophysiological recordings and anatomical analysis were made to evaluate functional and structural changes in the hippocampus following TCHL.ResultsThe rats with the TCHL had nearly normal hearing at P42, but had a decreased performance with the Morris water maze and Y‐maze tests compared with the control group. A functional deficit in the hippocampus of the rats with the TCHL was found as revealed by the depressed long‐term potentiation and the reduced NMDA receptor‐mediated postsynaptic current. A structural deficit in the hippocampus of those animals was also found as revealed the abnormal expression of the NMDA receptors, the decreased number of dendritic spines, the reduced postsynaptic density and the reduced level of neurogenesis.ConclusionsOur study demonstrates that even temporary auditory sensory deprivation in early life of rats results in abnormal development of the hippocampus and consequently impairs spatial memory in adulthood.
LINC00857 expression predicts and mediates the response to platinum‐based chemotherapy in muscle‐invasive bladder cancer
Authors: Dudek Aleksandra M. , van Kampen Jasmijn G. M. , Witjes J. Alfred , Kiemeney Lambertus A. L. M. , Verhaegh Gerald W. 
Published: June 2018

AbstractApproximately 20% of patients with bladder cancer are diagnosed with muscle‐invasive disease (MIBC). The treatment involves radical cystectomy, but almost 50% of patients with MIBC eventually relapse and develop metastasis. The use of platinum‐based chemotherapy in the neoadjuvant setting or for metastatic patients has been shown to improve the overall survival in a subset of patients. Unfortunately, no biomarkers are available to select patients with MIBC who will benefit from chemotherapy or to monitor the efficacy of the treatment. Recently, long noncoding RNAs (lncRNAs) were shown to regulate a variety of processes involved in the development and progression of cancer, including bladder cancer. Moreover, several lncRNAs have been shown to play a role in chemotherapy resistance. Here, we analyzed lncRNA expression associated with response to platinum‐based chemotherapy in metastatic MIBC using data from the MiTranscriptome lncRNA expression database. Expression of the lncRNA, LINC00857, was found to be upregulated in tumors from patients that did not respond to platinum‐based chemotherapy. Moreover, high expression of LINC00857 is correlated with shorter recurrence‐free and overall survival of patients with MIBC. Knockdown of LINC00857 significantly decreased cell viability of bladder cancer cell lines through the induction of apoptosis. Furthermore, LINC00857 knockdown sensitized UM‐UC‐3 and T24 bladder cancer cells to cisplatin, via the negative regulation of the LMAN1 gene. Our data indicate that LINC00857 plays an important role in the regulation of response to platinum‐based chemotherapy. LINC00857 potentially could serve as a novel prognostic and predictive biomarker and might be a therapeutic target to overcome cisplatin resistance in patients with MIBC.
Electrochemically Faceted Bamboo‐type TiO2 Nanotubes Provide Enhanced Open‐Circuit Hydrogen Evolution
Authors: Ji Lei , Zhou Xuemei , Schmuki Patrik 
Published: June 2018

AbstractIn this paper we prepare facetted “black” TiO2 nanotube arrays (NTAs) with a bamboo‐type structure which exhibits an enhanced performance for open‐circuit H2 generation without the use of any noble metal co‐catalyst. The TiO2 nanotubes were formed by applying alternating positive and negative voltages. During the electrochemical formation, not only a bamboo structure is formed but the tubes are reduced in the cathodic cycle. After a rapid annealing treatment of these tubes in air at 500 °C for 10 s, the bamboo rings (knots) provide (001) facets preferentially located at the knot, while (101) planes prevail on the smooth part of tube between knots, as shown by TEM. The short annealing time keeps Ti3+/oxygen vacancies (VO) as co‐catalytically active centers still preserved in the TiO2 NTAs. The results of intensity modulated photocurrent spectroscopy (IMPS) and open‐circuit potential decay measurements (VOC) indicate that these faceted and reduced TiO2 nanotube arrays provide an efficient separation and reaction of photo‐generated charge carriers, leading to an improved photocatalytic H2 evolution performance.
A DNA‐Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition
Authors: Favalli Nicholas , Biendl Stefan , Hartmann Marco , Piazzi Jacopo , Sladojevich Filippo , Gräslund Susanne , Brown Peter J. , Näreoja Katja , Schüler Herwig , Scheuermann Jörg , Franzini Raphael , Neri Dario 
Published: June 2018

AbstractA DNA‐encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contributed to ligand affinity. Molecules based on a 3,5‐bis(aminomethyl)benzoic acid core structure were found to bind human serum albumin with a Kd value of 6 nm, while compounds with the same substituents on an equidistant but flexible l‐lysine scaffold showed 140‐fold lower affinity. A 18 nm tankyrase‐1 binder featured l‐lysine as linking moiety, while molecules based on d‐Lysine or (2S,4S)‐amino‐l‐proline showed no detectable binding to the target. This work suggests that central scaffolds which predispose the orientation of chemical building blocks toward the protein target may enhance the screening productivity of encoded libraries.
Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins
Authors: Hiller Noemi de J. , Silva Nayane A. A. e , Faria Robson X. , Souza André Luís A. , Resende Jackson A. L. C. , Borges Farias André , Correia Romeiro Nelilma , de Luna Martins Daniela 
Published: June 2018

AbstractMolecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds.
PET Imaging of T Cells: Target Identification and Feasibility Assessment
Authors: Auberson Yves P. , Briard Emmanuelle , Rudolph Bettina , Kaupmann Klemens , Smith Paul , Oberhauser Berndt 
Published: June 2018

AbstractImaging T cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are, however, no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in T cells, and for which lead molecules were available: protein kinase C isozyme θ (PKC θ), lymphocyte‐specific protein tyrosine kinase (Lck), zeta‐chain‐associated protein kinase 70 (ZAP70), and interleukin‐2‐inducible T‐cell kinase (Itk). Ultimately, we focused on Itk and identified a tool molecule with properties suitable for in vivo imaging of T cells: (5aR)‐5,5‐difluoro‐5a‐methyl‐N‐(1‐((S)‐3‐(methylsulfonyl)phenyl)(tetrahydro‐2H‐pyran‐4‐yl)methyl)‐1H‐pyrazol‐4‐yl)‐1,4,4a,5,5a,6‐hexahydrocyclopropa[f]indazole‐3‐carboxamide (23). Although it does not have the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk‐selective PET ligands for imaging the distribution of T cells in patients.
Naphthalimide‐and Methacrylate‐Functionalized Polysiloxanes: Visible‐Light Photoinitiators, Modifiers for Polyurethane Acrylate and Photocurable Coatings
Authors: Yang Jianjing , Xiong Ying , Wang Xiaoling , Li Zhen , Tang Hongding 
Published: June 2018

AbstractEmploying “green chemistry” photopolymerization techniques, a series of multifunctionalized macrophotoinitiators (SND‐MAs) containing naphthalimide (ND), methacrylate (MA) and polysiloxane were successfully prepared. The introduction of methacrylate enhances their compatibility with acrylate monomers and resins. SND‐MAs showed very good photoinitiating properties in the presence or absence of hydrogen donors. The migration study demonstrates that SND‐MAs possess excellent migration stability. In particular, the mass fractions of the extracted SND‐MA‐I‐3 and SND‐MA‐I‐4 in the cured 1,6‐hexanediol diacrylate (HDDA) polymer are as low as 0.082 % and 0.054 %, respectively. More importantly, the use of SND‐MAs as initiators brings about desirable modifications to the cured materials, such as an improved resistance against water and ethanol as well as improved thermal stability. Moreover, the series of SND‐MA‐Is exhibit good self‐forming properties. Their self‐forming films show excellent thermal properties, hardness and hydrophobicity. Thus, SND‐MAs could be used as photoinitiators, modifiers and coatings at the same time.
Legacy effects of land use on soil nitrous oxide emissions in annual crop and perennial grassland ecosystems
Authors: Abraha Michael , Gelfand Ilya , Hamilton Stephen K. , Chen Jiquan , Robertson G. Philip 
Published: June 2018

AbstractLand use conversions into and out of agriculture may influence soil–atmosphere greenhouse gas fluxes for many years. We tested the legacy effects of land use on cumulative soil nitrous oxide (N2O) fluxes for 5 yr following conversion of 22‐yr‐old Conservation Reserve Program (CRP) grasslands and conventionally tilled agricultural fields (AGR) to continuous no‐till corn, switchgrass, and restored prairie. An unconvertedCRPfield served as a reference. We assessed the labile soil C pool of the upper 10 cm in 2009 (the conversion year) and in 2014 using short‐term soil incubations. We also measured in situ soil N2O fluxes biweekly from 2009 through 2014 using static chambers except when soils were frozen. The labile C pool was approximately twofold higher in soils previously inCRPthan in those formerly in tilled cropland. Five‐year cumulative soil N2O emissions were approximately threefold higher in the corn system on formerCRPthan on former cropland despite similar fertilization rates (~184 kg N·ha−1·yr−1). The lower cumulative emissions from corn on former cropland were similar to emissions from switchgrass that was fertilized less (~57 kg N·ha−1·yr−1), regardless of former land use, and lowest emissions were observed from the unfertilized restored prairie and reference systems. Findings support the hypothesis that soil labile carbon levels modulate the response of soil N2O emissions to nitrogen inputs, with soils higher in labile carbon but otherwise similar, in this case reflecting land use history, responding more strongly to added nitrogen.
Diurnal and seasonal coupling of conifer sap flow and vapour pressure deficit across topoclimatic gradients in a subalpine catchment
Authors: Looker Nathaniel , Martin Justin , Hoylman Zachary , Jencso Kelsey , Hu Jia 
Published: June 2018

AbstractThe hydroclimatic controls on transpiration often follow hillslope‐ or catchment‐scale topography in water‐limited ecosystems; however, rates of transpiration may deviate from these patterns due to microtopographic variation in environmental conditions or physiology. Here, we assessed the microtopographic effects on water use of five conifer species within four subcatchments in western Montana along a water availability gradient that was driven by aspect and elevation. To infer physiological processes at both diurnal and seasonal time scales, we analysed the relationship between sap velocity,Vs, and vapour pressure deficit,D, using instantaneous (half‐hourly) and aggregated (daily mean) values ofVsandD. Both within and across species, daily meanVswas more tightly coupled toDat higher elevation sites (1,720 m), whereas trees 350 m lower in elevation became decoupled fromDas snowmelt‐derived soil moisture declined. At the diurnal scale, we found that the degree of decoupling ofVsfromDduring soil moisture deficits decreased when a time lag betweenVsandDwas considered. Additionally, contrary to the common inference of plant hydraulic capacitance based onVslagging behindDat the diurnal scale, half‐hourlyVstended to leadDin three of the five conifer species we studied. Predawn and midday branch water potential measurements provided additional evidence that topography influenced plant water status. These results suggest that improved understanding of soil–vegetation–atmosphere coupling in mountainous terrain requires further inquiry into the spatial variability of plant hydraulic regulation.
A morphometric dive into fish diversity
Authors: Caillon Florian , Bonhomme Vincent , Möllmann Christian , Frelat Romain 
Published: June 2018

AbstractTrait‐based approaches are increasingly popular in ecology to describe communities and their responses to natural or anthropogenic changes. Morphology is an integrative trait that combines functional and evolutionary information. However, the objective and quantitative description of the morphological diversity is quite challenging. Modern morphometrics encompass an array of mathematical approaches that turn shapes into quantitative variables. For models with no or only a few homologous points, outline analysis (e.g., elliptical Fourier transform) converts the outline geometry into quantitative variables, which can be used in the multivariate framework. The elliptical Fourier transform here describes the shape of 85 fish species found in the North Sea. This study shows that the main component of morphological diversity in the North sea is the elongation and development of dorsal, pelvic, and caudal fins. The spatial distribution of morphological diversity decreases along a latitudinal gradient, with higher diversity in the southern part of the study area. Compared to species diversity, our results indicate that environmental conditions filter morphological traits in the northern North Sea. Outline analysis is a powerful approach to provide an objective description of fish morphology and to improve our understanding of the diversity of large marine ecosystems.
Environmentally induced development costs underlie fitness tradeoffs
Authors: Walter Greg M. , Wilkinson Melanie J. , Aguirre J. David , Blows Mark W. , Ortiz‐Barrientos Daniel 
Published: June 2018

AbstractLocal adaptation can lead to genotype‐by‐environment interactions, which can create fitness tradeoffs in alternative environments, and govern the distribution of biodiversity across geographic landscapes. Exploring the ecological circumstances that promote the evolution of fitness tradeoffs requires identifying how natural selection operates and during which ontogenetic stages natural selection is strongest. When organisms disperse to areas outside their natural range, tradeoffs might emerge when organisms struggle to reach key life history stages, or alternatively, die shortly after reaching life history stages if there are greater risks of mortality associated with costs to developing in novel environments. We used multiple populations from four ecotypes of an Australian native wildflower (Senecio pinnatifolius) in reciprocal transplants to explore how fitness tradeoffs arise across ontogeny. We then assessed whether the survival probability for plants from native and foreign populations was contingent on reaching key developmental stages. We found that fitness tradeoffs emerged as ontogeny progressed when native plants were more successful than foreign plants at reaching seedling establishment and maturity. Native and foreign plants that failed to reach seedling establishment died at the same rate, but plants from foreign populations died quicker than native plants after reaching seedling establishment, and died quicker regardless of whether they reached sexual maturity or not. Development rates were similar for native and foreign populations, but changed depending on the environment. Together, our results suggest that natural selection for environment‐specific traits early in life history created tradeoffs between contrasting environments. Plants from foreign populations were either unable to develop to seedling establishment, or they suffered increased mortality as a consequence of reaching seedling establishment. The observation of tradeoffs together with environmentally dependent changes in development rate suggest that foreign environments induce organisms to develop at a rate different from their native habitat, incurring consequences for lifetime fitness and population divergence.
A novel evaluation on fracture pressure in depleted shale gas reservoir
Authors: Zhao Kai , Yuan Junliang , Feng Yongcun , Yan Chuanliang 
Published: June 2018

AbstractFracture pressure is the key parameter both for horizontal drilling and hydraulic fracturing in the shale gas reservoir. Reservoir depletion will push for the change of the fracture pressure. Previous studies showed that fracture pressure will be decreased with reservoir depletion, which is not suitable for the anisotropic shale gas reservoir. Aiming at resolving this problem, a novel evaluation was established, which can be used to evaluate the influence on fracture pressure of the reservoir depletion, the anisotropy, and the well inclination. The results showed that the fracture pressure will be increased for the strongly anisotropic reservoir with reservoir depletion, and the fracture pressure has a tiny difference between the various anisotropic reservoirs before reservoir depleted, but a larger difference will appear after reservoir depleted, at the later depletion period, the fracture pressure is higher for the stronger anisotropic one. When the anisotropy and the depletion are both the same, the fracture pressure for the higher deviated well is lower. The method and the results can provide a theoretical basis both for the drilling and hydraulic fracturing in depleted shale gas reservoir.
Storage sites for tunnel excavation material – challenges and approach using the Gotthard and Ceneri Base Tunnels as examples
Authors: Schwalt Markus , Rabaiotti Carlo 
Published: June 2018

AbstractThe construction of the Gotthard and Ceneri Base Tunnels through the Alps resulted in large quantities of excavated material. Selecting appropriate storage sites for the excavated material is a very important step that is often determined not only by technical criteria but also by external circumstances, a fact that may lead to sites that are not optimally suitable. Managing geotechnically difficult conditions in a professional manner is a decisive prerequisite to make a success of the planning and design process. Applying profound experience furthermore permits optimizations which lead to more efficient utilization of the available storage areas while at the same time maintaining the required structural stability. Such optimizations require detailed geotechnical investigation, careful planning and design, and thorough observation during construction. Furthermore, experience and specialist knowledge of comparable structures are helpful. The Chalchofen storage site at the Gotthard and the Sigirino site at the Ceneri Base Tunnel are used as examples to present a target‐oriented approach. The observations and measurements made the projects a success. To ensure a favorable outcome of such construction projects, it is of vital importance that all the parties involved (owner, consultant and checking engineer) work together effectively and efficiently.