bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Pichia biosensor for high‐throughput analyses of compounds that can influence mosquito behavior
Authors: Varela Julia Nogueira , Yadav Vikramaditya G. 
Published: December 2020

AbstractMosquitoes utilize their sense of smell to locate prey and feed on their blood. Repellents interfere with the biochemical cascades that detect odors. Consequently, repellants are highly effective and resource‐efficient alternatives for controlling the spread of mosquito‐borne illnesses. Unfortunately, the discovery of repellents is slow, laborious, and error‐prone. To this end, we have taken a giant stride toward improving the speed and accuracy of repellant discovery by constructing a prototypical whole‐cell biosensor for accurate detection of mosquito behavior‐modifying compounds such as repellants. As a proof‐of‐concept, we genetically engineered Pichia pastoris to express the olfactory receptor co‐receptor (Orco) of Anopheles gambiae mosquitoes. This transmembrane protein behaves like a cationic channel upon activation by stimulatory odorants. When the engineered Pichia cells are cultured in calcium‐containing Hank's buffer, induction of the medium with a stimulatory odorant results in an influx of calcium ions into the cells, and the stimulatory effect is quantifiable using the calcium‐sequestering fluorescent dye, fluo‐4‐acetoxymethyl ester. Moreover, the stimulatory effect can be titrated by adjusting either the concentration of calcium ions in the medium or the level of induction of the stimulatory odorant. Subsequent exposure of the activated Pichia cells to a repellant molecule inhibits the stimulatory effect and quenches the fluorescent signal, also in a titratable manner. Significantly, the modular architecture of the biosensor allows easy and efficient expansion of its detection range by co‐expressing Orco with other olfactory receptors. The high‐throughput assay is also compatible with robotic screening infrastructure, and our development represents a paradigm change for the discovery of mosquito repellants.
p21‐activated kinase 4 promotes the progression of esophageal squamous cell carcinoma by targeting LASP1
Authors: Huang Hui , Xue Qianqian , Du Xiaoge , Cui Jie , Wang Jing , Cheng Dan , Li Jiaqiong , Zheng Yaqiu , Huang Guojing , Zhang Keke , Liu Kangdong , Lu Jing , Zhao Jimin , Chen Xinhuan , Dong Ziming , Li Xiang 
Published: December 2020

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage‐independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull‐down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC.
Tocilizumab inhibits IL‐8 and the proangiogenic potential of triple negative breast cancer cells
Authors: Alraouji Noura N. , Aboussekhra Abdelilah 
Published: December 2020

AbstractTriple‐negative breast cancer (TNBC) is the most aggressive subtype of the disease with lack of recognized molecular targets for therapy. TNBC cells are known to secrete high levels of the proinflammatory cytokines interleukin‐6 (IL‐6) and IL‐8, which promote angiogenesis and favor the growth and spread of the disease. In the present study, we have shown that the humanized anti‐IL‐6 receptor tocilizumab (Actemra) is also a potent inhibitor of IL‐8 in TNBC cells. Similar effect was also obtained by specific IL‐6 inhibition either by small interfering RNA or by neutralizing antibody. Likewise, neutralizing IL‐8 with specific antibody downregulated IL‐8 and inhibited the IL‐6/signal transducer and activator of transcription 3 and nuclear factor‐κB pathways. Interestingly, simultaneous co‐inhibition of IL‐6 and IL‐8 did not increase the effects of the single inhibitors. Additionally, we present clear evidence that tocilizumab has potent antiangiogenic effect. Indeed, tocilizumab abolished the ability of TNBC cells to induce the differentiation of endothelial cells into network‐like tubular structures in vitro and impaired neovascularization in humanized breast orthotopic tumor xenografts. This was associated with tocilizumab‐dependent downregulation of the main proangiogenic factor vascular endothelial growth factor A and its coactivator hypoxia‐inducible factor 1 both in vitro and in vivo. Therefore, tocilizumab could be of great therapeutic value for TNBC patients through targeting angiogenesis.
The synthesis of multiblock copolymer brush based on DSPAAC and CuAAC click reaction
Authors: Xiao Lifen , Li Jie , Li Wenyi , Li Wei , Huang Geng 
Published: December 2020

AbstractMultiblock copolymer brushes have broad application in thermoplastic elastomers, drug delivery, porous materials, and nanolithography due to their unique structure and properties. In this research, a novel multiblock copolymer brush (PHEA‐g‐PEG)x‐co‐ (PEG23)y was synthesized by combining the efficient double strain‐promoted azide‐alkyne cycloaddition (DSPAAC) and copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) click reactions. The gel permeation chromatography (GPC), proton nuclear magnetic resonance spectrometer (1H NMR), Fourier transform infrared spectroscopy (FT‐IR), and atomic force microscopy (AFM) were used to characterize the prepared polymers. The results demonstrated that the novel multiblock copolymer brush was successfully prepared. The mole ratio was 1/0.84 between block PHEA‐g‐PEG and block PEG23, and the grafting density was 100%. The AFM image showed the morphologies of cylinder, sphere, and beads on a string owning to the random distribution of PHEA‐g‐PEG and PEG.
On the one‐dimensional Morse potential as limit of a class of multiparameter exponential‐type radial potential
Authors: Peña José Juan , Morales Jesús , García‐Ravelo Jesús , Avendaño Jaime , García‐Martínez Jesús 
Published: December 2020

AbstractDespite their differences, the exponential‐type radial potential and the Morse potential can be compared not only analytically but also through spectroscopic calculations. In this work, the eigensolutions of the Schrödinger equation coming from the hypergeometric differential equation are used to show the relationship that exist between the Morse potential and a class of multiparametric exponential‐type radial (MER) potential. To do that, we rewrite the MER potential and its corresponding energy spectrum such that their main parameters as its depth V0, the equilibrium point re and its width parameter β explicitly appear in the potential. After, through the infinity limit applied to the re parameter we show that the MER potential tends to the Morse potential. Likewise, under the same limit, the energy spectrum and the number of bound states tend to those of the Morse potential which indicates the equivalence of using the Morse potential or MER potentials in the calculation of spectroscopic transitions for diatomic molecules. As a useful application, we select particular values of the involved parameters in the MER potential in such a way that leads to the Poschl–Teller II potential. Thus, after apply the aforementioned limit to this potential, it is shown that energy spectrum and number of states correspond to those of Morse potential. Although the usefulness of the proposal is exemplified in the case of the molecule HCl35 and the radial Posch–Teller potential, the method can be straightforwardly used with other specific exponential‐type radial potentials as well as with other diatomic molecules.
Cisplatin under oriented external electric fields: A deeper insight into electrochemotherapy at the molecular level
Authors: Zhang Li , Ye Ya‐Ling , Zhang Xiao‐Ling , Li Xiang‐Hui , Chen Qiao‐Hong , Chen Jing‐Hua , Sun Wei‐Ming 
Published: December 2020

AbstractElectrochemotherapy is an effective strategy for the treatment of solid tumors by exposing tumor cells to electric fields to enhance the bioactivity of non‐permeable or low permeable anticancer drugs, such as cisplatin. To understand the improved efficiency of cisplatin in the electrochemotherapy, the effects of oriented external electric fields (OEEFs) on the geometric structure and relevant electronic properties of cisplatin have been systemically investigated by density functional theory (DFT) computations in this work. Our results reveal that the presence of selective OEEFs on cisplatin can not only weaken its Pt‐Cl bonds, but also enhance the intramolecular charge transfer in it, which effectively accelerates the critical hydrolysis step involved in the mechanism of biological activity for this drug. Moreover, the chosen OEEFs can facilitate the attack of the singly aquated cis‐[Pt(NH3)2(H2O)Cl]+ on DNA, and enlarge the water solubility of cisplatin and its aquated product. These OEEF‐induced geometric and electronic modifications can indeed help to improve the antitumor activity of cisplatin, which provides a deeper insight into the higher efficacy of electrochemotherapy than traditional chemotherapy from a molecular point of view.
An early experience with the Senhance surgical robotic system in colorectal surgery: a single‐institute study
Authors: Lin Chun‐Chi , Huang Sheng‐Chieh , Lin Hung‐Hsin , Chang Shih‐Ching , Chen Wei‐Shone , Jiang Jeng‐Kai 
Published: December 2020

AbstractBackgroundWe present our initial single‐centre experience with Senhance surgical robot‐assisted colorectal surgery and examine its safety and feasibility.MethodsFrom June 2019 to December 2019, patients who underwent Senhance surgical robot‐assisted colorectal surgery in our hospital were retrospectively analysed. We focused on the short‐term outcomes.ResultsIn total, 46 patients were enrolled in the study. Colorectal cancer was the most common indication for surgery (39 patients). The median total operation time was 283 min, and the median blood loss was 50 cc. Meanwhile, the median number of harvested lymph nodes was 20. Elderly age, advanced American Society of Anaesthesiologists stage, and right‐sided colon surgery were associated with the occurrence of complications greater than grade III.ConclusionOur findings demonstrate the feasibility and safety of the Senhance surgical robotic system in colorectal surgery. Care should be taken regarding the indications and patient selection.
Robustness analysis of uncertain time‐varying systems using integral quadratic constraints with time‐varying multipliers
Authors: Fry J. Micah , Abou Jaoude Dany , Farhood Mazen 
Published: December 2020

SummaryThis article presents a dissipativity approach for robustness analysis using the framework of integral quadratic constraints (IQCs). The derived results apply for linear time‐varying nominal systems with uncertain initial conditions. IQC multipliers are used to describe the sets of allowable uncertainty operators, and signal IQC multipliers are used to describe the sets of allowable disturbance signals. The novel concepts of dichotomic nodes and their corresponding factorizations are introduced, which allow for the aforementioned multipliers to be general time‐varying operators. The results are illustrated via the robustness analysis of a flight controller for an unmanned aircraft system tasked to perform a Split‐S maneuver.
Relationship between environmental variables and egg abundance of the four major Chinese carps, downstream of the Three Gorges Reservoir
Authors: Xu Wei , Yang Zhi , Yi Ran , Yao Jinzhong , Chen Xiaojuan 
Published: December 2020

AbstractReservoir “eco‐operation” is an ecological flow regulation measure, such as mimicking a flood process to stimulate fish spawning. Since 2011, the Three Gorges Reservoir (TGR) eco‐operation trials have been carried out to facilitate the spawning of the four major Chinese carps (FMCC) below the Gezhouba Dam. Until now, the response of FMCC spawning to new hydrologic conditions is seldom documented. Using ecological monitoring data from 2012 to 2017, this study analyses annual variations in environmental factors and FMCC spawning, and the correlations between them. During the date of FMCC egg occurrence, there was no significant difference both in annual mean water temperature (TEM) and water transparency (TRA) among years, while there was significant difference in annual mean river flow. The annual egg abundance of FMCC ranged from 135 to 610 million, with an average of 286 million. The peak spawning of FMCC occurred 3 to 5 times annually, while the scattered spawning occurred about 2 to 3 times. Classification and Regression Trees and Random Forests were used to model the daily egg abundance of FMCC. Daily flow (FLO) and flow increase multiple (FIM) were determined as the most important factors for FMCC spawning. The models predicted daily egg abundance of FMCC in the Shashi section could reach to 3.16 × 107 ind. for FLO exceeding 10,000 m3/s and FIM below 49.12. The results might be helpful to deeply understand the role of flood peak process on fish spawning and the optimization of TGR eco‐operation on FMCC spawning.
Pre‐reinforcing the mortise‐tenon joints with near‐surface‐mounted glued‐in rods
Authors: Wu Guofang , Zhong Yong , Zhao Rongjun , Ren Haiqing 
Published: December 2020

SummaryThis paper reported the effects of the pre‐reinforcement to the mortise‐tenon joints with glued‐in rods that were mounted near the surface of the tenon. Fifteen full‐scale specimens that were manufactured with engineered wood products using computer numerically controlled technology were tested under monotonic loading. The initial stiffnesses and moment carrying capacities of joints with different reinforcement configurations were obtained from the established moment–rotational angle relationships. It was found from the tests that the initial stiffness of the reinforced mortise‐tenon joints increased by 2.9% to 30.8%, and the moment carrying capacity increased by 13.6% to 32.0%. Further conclusions drawn from the numerical simulation included the following: increasing the embedment length and diameter of rods, as well as the steel strength of rods and decreasing the distance to the surface, could help enhance the initial stiffnesses and moment carrying capacities of the joints. The moment and initial stiffness decreased with increasing of tenon's height to width ratio. By choosing appropriate parameters, the proposed pre‐reinforcement methods significantly increased the initial stiffness and moment carrying capacity. This study demonstrated the feasibility of pre‐reinforcing mortise‐tenon joints in new timber constructions via near‐surface‐mounted glued‐in rods and is meaningful for promoting wider application of mortise‐tenon joints in modern timber structures.
Alice im digitalen Wunderland: pädiatrische Lehre in der COVID-19-Pandemie
Authors: Häusler Martin , Bosse Hans Martin , Fischbach Thomas , Graf Norbert , von Kleist-Retzow Jürgen‑Christoph , Kreuder Joachim 
Published: December 2020

ZusammenfassungDie Umstellung der pädiatrischen Lehre im Medizinstudium von Präsenzveranstaltungen auf digitale Formate war und ist für Lehrende und Studierende eine besondere Herausforderung. Basierend auf einer Umfrage unter pädiatrischen Universitätskliniken fasst die AG Lehre der DGKJ im folgenden Beitrag bisherige Erfahrungen zur digitalen Lehre im Sommersemester 2020 zusammen. Die Umfrageteilnehmer von 17 pädiatrischen Universkliniken berichteten über ein umfangreiches Spektrum oft kurzfristig entwickelter digitaler Lehrformate. Dabei waren Vorlesungen und Seminare gut, Unterrichtsformate mit direktem Patientenbezug und Fertigkeiten‑/Kommunikationstrainings deutlich weniger gut durch digitale Formate ersetzbar. Die Implementierung digitaler Unterrichtsformate führte zu einem deutlich erhöhten Zeitaufwand für die Lehrenden. Digitale Lehrangebote benötigen eine gute IT-Infrastruktur, sie sollten in ein Curriculum eingebunden sein und durchweg direkte Austauschmöglichkeiten zwischen Studierenden und Lehrenden vorsehen. Lehrenden sollten Schulungen in Didaktik zur digitalen Lehre und zu IT-Kenntnissen angeboten werden. Diese Ergebnisse decken sich mit der Literatur zu digitalen Lehrformaten allgemein sowie zur Lehre im Rahmen der COVID-19-Pandemie im Besonderen. Die hier vorgestellten Erfahrungen sollen nicht nur die Entwicklung digitaler pädiatrischer Lehrformate während der bestehenden Pandemie erleichtern, sondern auch darüber hinaus die Konzeption neuer digitaler Lehrangebote für die Pädiatrie im Medizinstudium anregen. Insbesondere müssen neue digitale Ersatzformate für den Unterricht am Patienten entwickelt werden.Die Stellungnahme wurde im Konsens von der AG Lehre der DGKJ erarbeitet und vom DGKJ-Vorstand verabschiedet.
Evaluation of a novel deep learning–based classifier for perifissural nodules
Authors: Han Daiwei , Heuvelmans Marjolein , Rook Mieneke , Dorrius Monique , van Houten Luutsen , Price Noah Waterfield , Pickup Lyndsey C. , Novotny Petr , Oudkerk Matthijs , Declerck Jerome , Gleeson Fergus , van Ooijen Peter , Vliegenthart Rozemarijn 
Published: December 2020

Abstract
Objectives
To evaluate the performance of a novel convolutional neural network (CNN) for the classification of typical perifissural nodules (PFN).

Methods
Chest CT data from two centers in the UK and The Netherlands (1668 unique nodules, 1260 individuals) were collected. Pulmonary nodules were classified into subtypes, including “typical PFNs” on-site, and were reviewed by a central clinician. The dataset was divided into a training/cross-validation set of 1557 nodules (1103 individuals) and a test set of 196 nodules (158 individuals). For the test set, three radiologically trained readers classified the nodules into three nodule categories: typical PFN, atypical PFN, and non-PFN. The consensus of the three readers was used as reference to evaluate the performance of the PFN-CNN. Typical PFNs were considered as positive results, and atypical PFNs and non-PFNs were grouped as negative results. PFN-CNN performance was evaluated using the ROC curve, confusion matrix, and Cohen’s kappa.

Results
Internal validation yielded a mean AUC of 91.9% (95% CI 90.6–92.9) with 78.7% sensitivity and 90.4% specificity. For the test set, the reader consensus rated 45/196 (23%) of nodules as typical PFN. The classifier-reader agreement (k = 0.62–0.75) was similar to the inter-reader agreement (k = 0.64–0.79). Area under the ROC curve was 95.8% (95% CI 93.3–98.4), with a sensitivity of 95.6% (95% CI 84.9–99.5), and specificity of 88.1% (95% CI 81.8–92.8).

Conclusion
The PFN-CNN showed excellent performance in classifying typical PFNs. Its agreement with radiologically trained readers is within the range of inter-reader agreement. Thus, the CNN-based system has potential in clinical and screening settings to rule out perifissural nodules and increase reader efficiency.

Key Points
• Agreement between the PFN-CNN and radiologically trained readers is within the range of inter-reader agreement.
• The CNN model for the classification of typical PFNs achieved an AUC of 95.8% (95% CI 93.3–98.4) with 95.6% (95% CI 84.9–99.5) sensitivity and 88.1% (95% CI 81.8–92.8) specificity compared to the consensus of three readers.
The interplay of thermodynamics and ocean dynamics during ENSO growth phase
Authors: Bayr Tobias , Drews Annika , Latif Mojib , Lübbecke Joke 
Published: December 2020

AbstractThe growth of El Niño/Southern Oscillation (ENSO) events is determined by the balance between ocean dynamics and thermodynamics. Here we quantify the contribution of the thermodynamic feedbacks to the sea surface temperature (SST) change during ENSO growth phase by integrating the atmospheric heat fluxes over the temporarily and spatially varying mixed layer to derive an offline “slab ocean” SST. The SST change due to ocean dynamics is estimated as the residual with respect to the total SST change. In observations, 1 K SST change in the Niño3.4 region is composed of an ocean dynamical SST forcing of + 2.6 K and a thermodynamic damping of − 1.6 K, the latter mainly by the shortwave-SST (− 0.9 K) and latent heat flux-SST feedback (− 0.7 K). Most climate models from the Coupled Model Intercomparison Project phase 5 (CMIP5) underestimate the SST change due to both ocean dynamics and net surface heat fluxes, revealing an error compensation between a too weak forcing by ocean dynamics and a too weak damping by atmospheric heat fluxes. In half of the CMIP5 models investigated in this study, the shortwave-SST feedback erroneously acts as an amplifying feedback over the eastern equatorial Pacific, resulting in a hybrid of ocean-driven and shortwave-driven ENSO dynamics. Further, the phase locking and asymmetry of ENSO is investigated in the CMIP5 model ensemble. The climate models with stronger atmospheric feedbacks tend to simulate a more realistic seasonality and asymmetry of the heat flux feedbacks, and they exhibit more realistic phase locking and asymmetry of ENSO. Moreover, the almost linear latent heat flux feedback contributes to ENSO asymmetry in the far eastern equatorial Pacific through an asymmetry in the mixed layer depth. This study suggests that the dynamic and thermodynamic ENSO feedbacks and their seasonality and asymmetries are important metrics to consider for improving ENSO representation in climate models.