bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soft‐wall ion transfer channel accurately predicts sterically hindered ion channel permeability
Authors: Kim Youngsam , Song Suhwan , Kim Min‐Cheol , Sim Eunji 
Published: January 2022

AbstractWe provide a simple and systematic computational model to study ion channel permeability using density functional theory. While existing permeability models with a hard‐wall steric hindrance factor work reasonably well for large ions, they severely inhibit the permeation of small ions through channel pores. Here, by introducing a steric hindrance factor that allows pore expansion due to intrinsically soft ion transfer channel walls, the new permeability model accurately describes the effect of steric hindrance stemming from the soft and flexible ion channel wall. Most importantly, the soft‐wall ion transfer channel model works for a wide range of ionic radii from fluoride to gluconate. In addition, we show that strong local electrostatic interaction between densely charged ions such as fluoride and bicarbonate and ion channels with ion binding sites significantly promotes the permeation processes.
Lego Serious Play: Building engagement with cell biology
Authors: Garden Claire Louise Palmer 
Published: January 2022

AbstractA Lego Serious Play (LSP) ‐ based exercise was developed to support student engagement with learning consolidation at the end of a first‐year undergraduate cell biology course. The exercise was offered in addition to a regular revision session in preparation for the summative exam. Students were studying four‐year BSc (Hons) degrees in: Animal Biology, Environmental Biology, Marine and Freshwater Biology, Biological Sciences, Biomedical Sciences, Microbiology & Biotechnology in Scotland, UK. Although many students studied Human Biology at High School, in‐depth cell biology was studied for the first time by the majority of students during this course. The LSP process was adapted for use in the classroom. Core concepts were identified from the twelve‐week cell biology course as the basis for LSP build challenges and incorporated into LSP build – share – reflect cycles by students individually and then joined together by the group to explore the interconnected nature of cell biology processes. Student and lecturer evaluations were thematically analyzed to explore the impact of the technique on student engagement. Results indicate that the method supports student cognitive and affective engagement who report improved and understanding of the topic, and enjoyment and interest. In addition, behavioral engagement such as learner interaction, independence, and empowerment were revealed by the lecturer interview. Identified barriers to the adoption of LSP include perceived issues around creativity, play and exploration and scientific identity, together with a lack of evidence of efficacy. This study seeks to remedy that gap.
Disease Modeling and Model‐Based Meta‐Analyses to Define a New Direction for a Phase III Program of Gantenerumab in Alzheimer’s Disease
Authors: Retout Sylvie , Gieschke Ronald , Serafin Daniel , Weber Cornelia , Frey Nicolas , Hofmann Carsten 
Published: January 2022

Selecting the right dose is a significant challenge in designing clinical development programs, especially for slowly progressing diseases lacking predictive biomarkers of efficacy that may require long‐term treatment to assess clinical benefit. Gantenerumab, a fully human monoclonal antibody (mAb) that binds to aggregated amyloid‐beta, was tested in two 24‐month phase III studies (NCT01224106, NCT02051608) in participants with prodromal and mild Alzheimer’s disease (AD), respectively. Dosing in the first phase III study was suspended after a preplanned interim futility analysis in 2014. Subsequently, a dose–response relationship was observed in a subgroup of fast AD progressors that, together with contemporary aducanumab (another anti–amyloid‐beta mAb) data, indicated higher doses may be needed for clinical efficacy. The gantenerumab phase III studies were therefore transformed into dose‐finding, open‐label extension (OLE) trials. Two exposure–response models were developed to support dose selection via simulations for the OLEs: a pharmacokinetics (PK)/PET (positron emission tomography) model describing amyloid removal using PET data from low‐dose gantenerumab and high‐dose aducanumab, and a PK/ARIA‐E (amyloid‐related imaging abnormalities‐edema) model describing the occurrence of ARIA‐E events leveraging an existing bapineuzumab model. Multiple regimens were designed to gradually up‐titrate participants to the target dose of 1,200 mg gantenerumab every 4 weeks to mitigate the increased risk of ARIA‐E events that may be associated with higher doses of anti–amyloid‐beta antibodies. Favorable OLE data that matched well with model predictions supported the decision to continue the gantenerumab clinical development program and further apply model‐based analytical techniques to optimize the design of new phase III studies.
The relationship between boll retention and defoliation of cotton at the fruiting site level
Authors: Song Xinghu , Zhang Lijuan , Zhao Wenchao , Xu Daoqing , Eneji A. Egrinya , Zhang Xiang , Han Huanyong , Cao Longlong , Zhang Wangfeng , Lu Zhengying , Huang Xiaoli , Wang Hongzhe , Xu Dongyong , Luo Zhen , Chen Hongzhang , Zhang Lizhen , Du Mingwei , Tian Xiaoli , Li Zhaohu 
Published: January 2022

AbstractDefoliation is used to ease mechanical harvest and reduce lint staining of cotton (Gossypium hirsutum L.). Crop conditions are important determinants of its efficiency, but their effects have not been fully examined. We performed a multiple‐site field study during 2018–2020 (under 17 environmental conditions, covering three cotton regions in China) to explore the relationship between boll retention and defoliation at the fruiting site level. The hormonal defoliant, thidiazuron and boll opener, ethephon, were tank‐mixed or their combination product was used in this study. There was a positive Spearman ranking correlation between boll retention and defoliation in most experimental sites, with correlation coefficients (r) ranging from .275 to .725 at 7 d after application of harvest aids, suggesting that the leaves at fruiting sites bearing bolls dropped more easily than those at fruiting sites where abscission occurred. The positive correlation declined with the fruiting sites up the plant and away the mainstem. The differences in defoliation between fruiting sites with or without bolls were high (around 60–70%) at lower and/or inner positions, but low or negligible at upper and/or outer positions. It appears that the higher light intensity at upper and outer portions of plant may enhance leaf drop and thus reduce the dependence of defoliation on boll retention. In conclusion, a high boll retention would accelerate leaf removal, and may enhance leaf abscission on cloudy days or within more closed canopy.
Substrate and Process Engineering for Biocatalytic Synthesis and Facile Purification of Human Milk Oligosaccharides
Authors: Bai Yuanyuan , Yang Xiaohong , Yu Hai , Chen Xi 
Published: January 2022

AbstractInnovation in process development is essential for applying biocatalysis in industrial and laboratory production of organic compounds, including beneficial carbohydrates such as human milk oligosaccharides (HMOs). HMOs have attracted increasing attention for their potential application as key ingredients in products that can improve human health. To efficiently access HMOs through biocatalysis, a combined substrate and process engineering strategy is developed, namely multistep one‐pot multienzyme (MSOPME) design. The strategy allows access to a pure tagged HMO in a single reactor with a single C18‐cartridge purification process, despite the length of the target. Its efficiency is demonstrated in the high‐yielding (71–91 %) one‐pot synthesis of twenty tagged HMOs (83–155 mg), including long‐chain oligosaccharides with or without fucosylation or sialylation up to nonaoses from a lactoside without the isolation of the intermediate oligosaccharides. Gram‐scale synthesis of an important HMO derivative – tagged lacto‐N‐fucopentaose‐I (LNFP‐I) – proceeds in 84 % yield. Tag removal is carried out in high efficiency (94–97 %) without the need for column purification to produce the desired natural HMOs with a free reducing end. The method can be readily adapted for large‐scale synthesis and automation to allow quick access to HMOs, other glycans, and glycoconjugates.
Pleomorphic adenoma of the breast with cytologic atypia on cytopathology: A potential diagnostic pitfall and literature review
Authors: Boac Bernadette M. , Centeno Barbara A. 
Published: January 2022

AbstractPleomorphic adenoma of the salivary gland is a well‐established and recognized diagnosis; however, pleomorphic adenomas of the breast are rare and can be difficult to diagnose on cytology or intraoperatively. We report a case that was misdiagnosed on a fine needle aspiration and frozen section. The pitfalls, differential diagnoses, and current management are discussed.
Blood, lead and spheres: A hindered settling equation for sedimentologists based on metadata analysis
Authors: Baas Jaco H. , Baker Megan L. , Buffon Patricia , Strachan Lorna J. , Bostock Helen C. , Hodgson David , Eggenhuisen Joris T. , Spychala Yvonne T. 
Published: January 2022

AbstractA revision of the popular equation of Richardson and Zaki (1954a, Transactions of the Institute of Chemical Engineering, 32, 35–53) for the hindered settling of suspensions of non‐cohesive particles in fluids is proposed, based on 548 data sets from a broad range of scientific disciplines. The new hindered settling equation enables predictions of settling velocity for a wide range of particle sizes and densities, and liquid densities and viscosities, but with a focus on sediment particles in water. The analysis of the relationship between hindered settling velocity and particle size presented here shows that the hindered settling effect increases as the particle size decreases, for example, a 50% reduction in settling velocity is reached for 0.025 mm silt and 4 mm pebbles at particle concentrations of 13% and 25% respectively. Moreover, hindered settling starts to influence the settling behaviour of sediment particles at volumetric concentrations of merely a few per cent. For example, the particle settling velocity in flows that carry 5% silt is reduced by at least 22%. These observations suggest that hindered settling greatly increases the efficiency of natural flows to transport sediment particles, but also particulate carbon and pollutants, such as plastics, over large distances.
A calibration friendly approach to identify drugs of abuse mixtures with a portable near‐infrared analyzer
Authors: Kranenburg Ruben F. , Ramaker Henk‐Jan , Sap Sharon , van Asten Arian C. 
Published: January 2022

AbstractBoth the increasing number and diversity of illicit‐drug seizures complicate forensic drug identification. Traditionally, colorimetric tests are performed on‐site, followed by transport to a laboratory for confirmatory analysis. Higher caseloads increase laboratory workload and associated transport and chain‐of‐evidence assurance performed by police officers. Colorimetric tests are specific only for a small set of drugs. The rise of new psychoactive substances therefore introduces risks for erroneous results. Near‐infrared (NIR)‐based analyzers may overcome these encumbrances by their compound‐specific spectral selectivity and broad applicability. This work introduces a portable NIR analyzer that combines a broad wavelength range (1300–2600 nm) with a chemometric model developed specifically for forensic samples. The application requires only a limited set of reference spectra for time‐efficient model training. This calibration‐light approach thus eliminates the need of extensive training sets including mixtures. Performance was demonstrated with 520 casework samples resulting in a 99.6% true negative and 97.6% true positive rate for cocaine. Similar results were obtained for MDMA, methamphetamine, ketamine, and heroin. Additionally, 236 samples were analyzed by scanning directly through their plastic packaging. Also here, a >97% true positive rate was obtained. This allows for non‐invasive, operator‐safe chemical identification of potentially potent drugs of abuse. Our results demonstrate the applicability for multiple drug‐related substances. Ideally, the combination of this NIR approach with other portable techniques, such as Raman and IR spectroscopy and electrochemical tests, may eventually eliminate the need for subsequent laboratory analysis; therefore, saving tremendous resources in the overall forensic process of confirmatory illicit drug identification.
Immunopathology caused by impaired CD8+ T‐cell responses
Authors: Aichele Peter , Neumann‐Haefelin Christoph , Ehl Stephan , Thimme Robert , Cathomen Toni , Boerries Melanie , Hofmann Maike 
Published: January 2022

AbstractRecent findings indicate that many immunopathologies are at their roots a consequence of impaired immune responses (“too little” immunity) and not the result of primarily exaggerated immune responses (“too much” immunity). We have summarized this conceptional view as “IMPATH paradox.” In this review, we will focus on impaired immune reactions in the context of CD8+ T‐cell‐mediated immunopathologies. In particular, we will exemplify this concept in two disease models: Virus‐triggered primary hemophagocytic lymphohistiocytosis, an inflammatory syndrome caused by genetically impaired cytolytic functions of T cells, and viral hepatitis, where T‐cell exhaustion is a major underlying mechanism for impaired effector functions. In both situations, T cells fail to eliminate the source of immune stimulation, which usually serves as an important negative feedback loop curtailing immune reactions. Persistent antigen presentation by APCs and/or infected cells results in continuous stimulation causing chronic inflammation and immunopathology mediated by residual T‐cell functions. Hence, immune stimulation or reconstitution rather than immune suppression may be strategies for therapeutic interventions.
Innate lymphoid cell characterization in the rat and their correlation to gut commensal microbes
Authors: Sudworth Amanda , Segers Filip M. , Yilmaz Bahtiyar , Guslund Naomi C. , Macpherson Andrew J. , Dissen Erik , Qiao Shuo‐Wang , Inngjerdingen Marit 
Published: January 2022

AbstractInnate lymphoid cells (ILCs) are important for tissue immune homeostasis, and are thoroughly characterized in mice and humans. Here, we have performed in‐depth characterization of rat ILCs. Rat ILCs were identified based on differential expression of transcription factors and lack of lineage markers. ILC3s represented the major ILC population of the small intestine, while ILC2s were infrequent but most prominent in liver and adipose tissue. Two major subsets of group 1 ILCs were defined. Lineage–T‐bet+Eomes+ cells were identified as conventional NK cells, while lineage–T‐bet+Eomes– cells were identified as the probable rat counterpart of ILC1s based on their selective expression of the ILC marker CD200R. Rat ILC1s were particularly abundant in liver and intestinal tissues, and were functionally similar to NK cells. Single‐cell transcriptomics of spleen and liver cells confirmed the main division of NK cells and ILC1‐like cells, and demonstrated Granzyme A as an additional ILC1 marker. We further report differential distributions of NK cells and ILCs along the small and large intestines, and the association of certain bacterial taxa to frequencies of ILCs. In conclusion, we provide a framework for future studies of ILCs in diverse rat experimental models, and novel data on the potential interplay between commensals and intestinal ILCs.
SARS‐CoV‐2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs
Authors: van der Donk Lieve E.H. , Eder Julia , van Hamme John L. , Brouwer Philip J. M. , Brinkkemper Mitch , van Nuenen Ad C. , van Gils Marit J. , Sanders Rogier W. , Kootstra Neeltje A. , Bermejo‐Jambrina Marta , Geijtenbeek Teunis B. H. 
Published: January 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), an infectious disease characterized by strong induction of inflammatory cytokines, progressive lung inflammation, and potentially multiorgan dysfunction. It remains unclear how SARS‐CoV‐2 infection leads to immune activation. The Spike (S) protein of SARS‐CoV‐2 has been suggested to trigger TLR4 and thereby activate immunity. Here, we have investigated the role of TLR4 in SARS‐CoV‐2 infection and immunity. Neither exposure of isolated S protein, SARS‐CoV‐2 pseudovirus nor primary SARS‐CoV‐2 isolate induced TLR4 activation in a TLR4‐expressing cell line. Human monocyte‐derived DCs express TLR4 but not angiotensin converting enzyme 2 (ACE2), and DCs were not infected by SARS‐CoV‐2. Notably, neither S protein nor SARS‐CoV‐2 induced DC maturation or cytokines, indicating that both S protein and SARS‐CoV‐2 virus particles do not trigger extracellular TLRs including TLR4. Ectopic expression of ACE2 in DCs led to efficient infection by SARS‐CoV‐2 and, strikingly, efficient type I IFN and cytokine responses. These data strongly suggest that not extracellular TLRs but intracellular viral sensors are key players in sensing SARS‐CoV‐2. These data imply that SARS‐CoV‐2 escapes direct sensing by TLRs, which might underlie the lack of efficient immunity to SARS‐CoV‐2 early during infection.
Dithiol surface treatment towards improved charge transfer dynamic and reduced lead leakage in lead halide perovskite solar cells
Authors: Wang Qingrui , Lin Zhenhua , Su Jie , Xu Yumeng , Guo Xing , Li Yingchun , Zhang Miao , Zhang Jincheng , Chang Jingjing , Hao Yue 
Published: January 2022

AbstractWith efficiency surpassing 25%, perovskite solar cells (PSCs) have received much attention because of their excellent potential in photovoltaic field. However, there are some challenging issues still exist which need to be addressed. One issue is that the surface/interface and grain boundaries related defects and traps could work as charge recombination centers during the device operation, compromising the charge transfer as well as the device performance. Another issue is the leakage of toxic Pb, which may cause undesired contamination to water or soil and make devices not appropriate to work outdoors. Herein, the dithiol molecule was introduced to passivate surface defects and traps as well as reduce the Pb leakage. The unsaturated Pb2+ usually acting as recombination centers could coordinate with thiol group to reduce the recombination. Meanwhile, the beneficial band bend was observed, which facilitates the interface charge transfer. Crucially, we confirmed dithiol molecule could help reduce the Pb leakage. Retarded dissolution of PbI2 into water was observed for perovskite films after dithiol treatment, which eventually contributed less Pb leakage. Overall, this study proposes a universal strategy for defects passivation and reduced lead leakage, which is promising for environmental stable optoelectronic applications.image
Low‐cycle fatigue performance of high‐strength steel rebars in concrete bridge columns
Authors: Aldabagh Saif , Rodríguez Jhordy , Alam M. Shahria 
Published: January 2022

AbstractDesign codes often restrict the use of high‐strength steel (HSS) rebars in seismic applications due to their inferior low‐cycle fatigue performance when compared to conventional steel rebars. In this study, previously established low‐cycle fatigue life models of HSS rebars, namely ASTM A706 Grade 550 and ASTM A1035 Grade 690, were incorporated into a new cumulative damage model to identify conditions under which such rebars can achieve seismic performance comparable to that of benchmark ASTM A706 Grade 420 steel bars in concrete bridge columns. An ensemble of well confined flexure‐dominated circular concrete bridge columns located in high seismic regions was considered where the axial load ratio, and longitudinal and spiral reinforcement ratios were varied. The bridge columns were reinforced with ASTM A706 Grade 420, ASTM A706 Grade 550, and ASTM A1035 Grade 690 steel and numerically analyzed under different displacement ductility levels (2, 4, and 6), earthquake types (crustal and subduction), and ratio of hoop spacing to longitudinal bar diameter ratio (4 and 6). Their low‐cycle fatigue performances were compared based on the computed bar fracture and accumulated damage indices. Based on the reported observations, it is concluded that design codes are overly restrictive in not permitting the use of HSS in seismic application on the basis of inadequate low‐cycle fatigue life. As an alternative, this study proposes imposing certain limits on displacement ductility demand and ratio of hoop spacing to longitudinal bar diameter ratio to promote safe and efficient use of HSS rebars in concrete bridge columns.
Efficient deployment of multi‐UAV assisted mobile edge computing: A cost and energy perspective
Authors: Xu Fei , Zhang Zhuoya , Feng Jianqiang , Qin Zengshi , Xie Yue 
Published: January 2022

AbstractAn important issue for service providers to consider before building a mobile edge services network is the limited budget for edge server deployment. In addition, the geographic position of unmanned aerial vehicle (UAV) edge server will affect its energy consumption. Therefore, we have established a UAV‐assisted mobile edge computing (MEC) system. UAV acts as a mobile edge server to provide computing services for user equipment (UE). This system aim to minimize the total energy consumption and deployment cost required for the UAVs to complete offload tasks and hover. To optimize the total energy consumption and deployment cost of UAVs, we proposed an improved mean shift (IMS) algorithm, which jointly optimizing the location and number of UAV edge servers. Various simulation results show the effectiveness of our proposed scheme in reducing energy consumption compared to other deployment methods. Furthermore, our research is of great significance for service providers in control the trade‐off between investment cost and energy consumption.
Effects of lake‐groundwater interaction on the thermal regime of a sub‐alpine headwater stream
Authors: Roesky Benjamin , Hayashi Masaki 
Published: January 2022

AbstractStream thermal regimes are critical to the stability of freshwater habitats. There is growing concern that climate change will result in stream warming due to rising air temperatures, decreased shading in forested areas due to wildfires, and changes in streamflow. Groundwater plays an important role in controlling stream temperatures in mountain headwaters, where it makes up a considerable portion of discharge. This study investigated the controls on the thermal regime of a headwater stream, and the surrounding groundwater processes, in a catchment on the eastern slopes of the Canadian Rocky Mountains. Groundwater discharge to the headwater spring is partially sourced by a seasonal lake. Spring, stream and lake temperature, water level, discharge and chemistry data were used to build a conceptual model of the system. Meteorological data was used to set up a stream temperature model. This study presents a unique example of an indirectly lake‐headed stream, that is, a lake that only has transient subsurface hydrologic connections to the stream and no surface connections. The interaction of groundwater and lake water, and the subsurface connectivity between the lake and the headwater spring determine the resulting stream temperature. Radiation dominated the non‐advective fluxes in the stream energy balance. Sensible and latent heat fluxes play a secondary role, but their effects generally cancel out. During snowfall events, the latent heat associated with melting of direct snowfall onto the water surface was responsible for rapid stream cooling. An increase in advective inputs from groundwater and hillslope pathways did not result in observed cooling of stream water during rainfall events. The results from this study will assist water resource and fisheries managers in adapting to stream temperature changes under a warming climate.