bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental observations of Wigner crystals
Authors: Gao Xing , Xue Yu-Cheng , Jiang Yu-Hang , Mao Jin-Hai ,   School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China,   College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China,   Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
Published: November 2024

In 1934, Eugene Wigner at Princeton University predicted the existence of electron crystals. Electrons have both kinetic energy and potential energy of interaction. When the density of electronic states satisfies certain conditions, due to the repulsion between electrons, electrons will tend to arrange themselves in a regular lattice structure, forming electron crystals, which is also known as Wigner crystals. For nearly 90 years, Wigner crystals have fascinated condensed matter physicists. Physicists have designed many ingenious semiconductor heterojunctions to obtain lower electron densities and added magnetic fields to achieve larger effective mass of electron. In 1979, experiments revealed the existence of a phase transition from an electron liquid phase to an electron crystal on the surface of liquid helium, and subsequent experiments observed the characteristics of two-dimensional (2D) Wigner crystals in 2D electron gas under high magnetic fields. However, direct observation of 2D Wigner lattices in real space remains a formidable challenge. Through the graphene sensing layer of WSe2/WS2 moiré superlattice, Hongyuan Li, Feng Wang, et al. observed the real-space morphologies of Wigner crystals in their experiments. And in a recent study, researchers used high-resolution scanning tunneling microscopy to directly image magnetic field-induced Wigner crystals in Bernal stacking bilayer graphene and investigated their structural properties as a function of electron density, magnetic field, and temperature. In this paper, we will introduce some interesting things about Wigner crystals through four representative researches briefly.
Non-destructive in situ monitoring of structural changes of 3D tumor spheroids during the formation, migration, and fusion process
Authors: Ning Ke , Xie Yuanyuan , Sun Wen , Feng LinKe , Fang Can , Pan Rong , Li Yan , Yu Ling
Published: November 2024

For traditional laboratory microscopy observation, the multi-dimensional, real-time,
in situ
observation of three- dimensional (3D) cell spheroids has always been the pain point in cell spheroid observation. In this study, we designed a side-view observation petri dish/device that reflects light, enabling
in situ
observation of the 3D morphology of cell spheroids using conventional inverted laboratory microscopes. We used a 3D-printed handle and frame to support a first surface mirror, positioning the device within a cell culture petri dish to image cell spheroid samples. The imaging conditions, such as the distance between the mirror and the 3D spheroids, the light source, and the impact of the culture medium, were systematically studied to validate the
in-situ
side-view observation. The results proved that placing the surface mirror adjacent to the spheroids enables non-destructive
in situ
real-time tracking of tumor spheroid formation, migration, and fusion dynamics. The correlation between spheroid thickness and dark core appearance under light microscopy and the therapeutic effects of chemotherapy doxorubicin and Natural Killer cells on spheroids’s 3D structure was investigated.
High-throughput expansion microscopy enables scalable super-resolution imaging
Authors: Day John H , Della Santina Catherine M , Maretich Pema , Auld Alexander L , Schnieder Kirsten K , Shin Tay , Boyden Edward S , Boyer Laurie A
Published: November 2024

Expansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate. Our method enables ~4.2 x expansion of cells within individual wells, across multiple wells, and between plates. We also demonstrate that HiExM can be combined with high-throughput confocal imaging platforms to greatly improve the ease and scalability of image acquisition. As an example, we analyzed the effects of doxorubicin, a known cardiotoxic agent, on human cardiomyocytes (CMs) as measured by the Hoechst signal across the nucleus. We show a dose-dependent effect on nuclear DNA that is not observed in unexpanded CMs, suggesting that HiExM improves the detection of cellular phenotypes in response to drug treatment. Our method broadens the application of ExM as a tool for scalable super-resolution imaging in biological research applications.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy
Authors: Reimann Michael W , Bolaños-Puchet Sirio , Courcol Jean-Denis , Egas Santander Daniela , Arnaudon Alexis , Coste Benoît , Delalondre Fabien , Delemontex Thomas , Devresse Adrien , Dictus Hugo , Dietz Alexander , Ecker András , Favreau Cyrille , Ficarelli Gianluca , Gevaert Mike , Herttuainen Joni , Isbister James B , Kanari Lida , Keller Daniel , King James , Kumbhar Pramod , Lapere Samuel , Lazovskis Jᾱnis , Lu Huanxiang , Ninin Nicolas , Pereira Fernando , Planas Judit , Pokorny Christoph , Riquelme Juan Luis , Romani Armando , Shi Ying , Smith Jason P , Sood Vishal , Srivastava Mohit , Van Geit Werner , Vanherpe Liesbeth , Wolf Matthias , Levi Ran , Hess Kathryn , Schürmann Felix , Muller Eilif B , Markram Henry , Ramaswamy Srikanth
Published: November 2024

The function of the neocortex is fundamentally determined by its repeating microcircuit motif, but also by its rich, interregional connectivity. We present a data-driven computational model of the anatomy of non-barrel primary somatosensory cortex of juvenile rat, integrating whole-brain scale data while providing cellular and subcellular specificity. The model consists of 4.2 million morphologically detailed neurons, placed in a digital brain atlas. They are connected by 14.2 billion synapses, comprising local, mid-range and extrinsic connectivity. We delineated the limits of determining connectivity from neuron morphology and placement, finding that it reproduces targeting by Sst+ neurons, but requires additional specificity to reproduce targeting by PV+ and VIP+ interneurons. Globally, connectivity was characterized by local clusters tied together through hub neurons in layer 5, demonstrating how local and interegional connectivity are complicit, inseparable networks. The model is suitable for simulation-based studies, and a 211,712 neuron subvolume is made openly available to the community.
An optimized ensemble model with advanced feature selection for network intrusion detection
Authors: Ahmed Afaq , Asim Muhammad , Ullah Irshad , Zainulabidin  , Ateya Abdelhamied A.
Published: November 2024

In today’s digital era, advancements in technology have led to unparalleled levels of connectivity, but have also brought forth a new wave of cyber threats. Network Intrusion Detection Systems (NIDS) are crucial for ensuring the security and integrity of networked systems by identifying and mitigating unauthorized access and malicious activities. Traditional machine learning techniques have been extensively employed for this purpose due to their high accuracy and low false alarm rates. However, these methods often fall short in detecting sophisticated and evolving threats, particularly those involving subtle variations or mutations of known attack patterns. To address this challenge, our study presents the “Optimized Random Forest (Opt-Forest),” an innovative ensemble model that combines decision forest approaches with genetic algorithms (GAs) for enhanced intrusion detection. The genetic algorithms based decision forest construction offers notable benefits by traversing a wider exploration space and mitigating the risk of becoming stuck in local optima, resulting in the discovery of more accurate and compact decision trees. Leveraging advanced feature selection techniques, including Best-First Search, Particle Swarm Optimization (PSO), Evolutionary Search, and Genetic Search (GS), along with contemporary dataset, this research aims to enhance the adaptability and resilience of NIDS against modern cyber threats. We conducted a comprehensive evaluation of the proposed approach against several well-known machine learning models, including AdaBoostM1 (AbM1), K-nearest neighbor (KNN), J48-Decision Tree (J48), multilayer perceptron (MLP), stochastic gradient descent (SGD), naïve Bayes (NB), and logistic model tree (LMT). The comparative analysis demonstrates the effectiveness and superiority of our method across various performance metrics, highlighting its potential to significantly enhance the capabilities of network intrusion detection systems.
Assessing Teachers’ Readiness to Teach Peace Education in a Philippine State University
Authors: Moscoso Ave Maila D.
Published: November 2024

Anchored to the theory of transformative education, this study determined the teachers' readiness to teach peace education in terms of knowledge, attitude and values, and skills. This paper employed the quantitative research design particularly the descriptive-comparative approach. The respondents were the total enumeration of 55 state university teachers. It was responded to using a validated and reliability-tested questionnaire and was analyzed using descriptive and inferential tools. The results revealed that the teachers possessed a high readiness level to teach peace education. In sex, both male and female possessed a high readiness level to teach peace education. Likewise, in educational attainment, the result was a consistently high readiness level for both bachelor's and postgraduate degrees. In campus affiliation, both campuses had teachers with high readiness to teach peace education. Meanwhile, there was no difference in their readiness when grouped by sex, educational attainment, and campus affiliation. However, a difference was revealed in skills when grouped to campus affiliation, in favor of teachers on the main campus who possessed a higher readiness level compared to teachers from the external campuses. Nevertheless, this did not affect the general result. Hence, the teachers' readiness is essential in materializing peace education. Here, the researcher recommends the inclusion of Peace Education as a stand-alone subject, and that the university administration should give formal training to teachers. In addition, the university, in line with mainstreaming peace education through curriculum innovation, should promote harmonized curricula and pedagogical standards toward an effective peace education program in state colleges and universities. Finally, to be abreast with this innovation, the university must also be established as a center for peace education.
Spiritual Resilience: Navigating College Stress with Religious Support
Authors:   Grand Canyon University, Branham Magen , Valenti Elizabeth ,   Grand Canyon University
Published: November 2024

This study examines the relationship between religious support and stress in college students, focusing on the challenges of the college transition period. The research explores the potential role of religious support in mitigating stress, building on previous findings linking religiosity to coping skills and well-being. Incorporating a convenience sample (N=188) of college students from a private Christian University who identified as religious, the study employed a bivariate Pearson r correlation to examine the relationship between religious support and stress. Results revealed a negative relationship between the variable and highlighted the significance of religious support in alleviating stress during the critical college transition phase. The findings contribute to understanding the potential benefits of incorporating religious and spiritual factors in stress-reduction interventions for college students, emphasizing the importance of addressing stress for overall well-being and academic success.

Keywords: religious support, stress, college students, college transition, coping skills, well-being
Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor‐Based 3D Culture System
Authors: Manfredonia Celeste , Muraro Manuele G. , Hirt Christian , Mele Valentina , Governa Valeria , Papadimitropoulos Adam , Däster Silvio , Soysal Savas D. , Droeser Raoul A. , Mechera Robert , Oertli Daniel , Rosso Raffaele , Bolli Martin , Zettl Andreas , Terracciano Luigi M. , Spagnoli Giulio C. , Martin Ivan , Iezzi Giandomenica
Published: March 2019

Colorectal cancer (CRC) is a leading cause of cancer‐related death. Conventional chemotherapeutic regimens have limited success rates, and a major challenge for the development of novel therapies is the lack of adequate in vitro models. Nonmalignant mesenchymal and immune cells of the tumor microenvironment (TME) are known to critically affect CRC progression and drug responsiveness. However, tumor drug sensitivity is still evaluated on systems, such as cell monolayers, spheroids, or tumor xenografts, which typically neglect the original TME. Here, it is investigated whether a bioreactor‐based 3D culture system can preserve the main TME cellular components in primary CRC samples. Freshly excised CRC fragments are inserted between two collagen scaffolds in a “sandwich‐like” format and cultured under static or perfused conditions up to 3 d. Perfused cultures maintain tumor tissue architecture and densities of proliferating tumor cells to significantly higher extents than static cultures. Stromal and immune cells are also preserved and fully viable, as indicated by their responsiveness to microenvironmental stimuli. Importantly, perfusion‐based cultures prove suitable for testing the sensitivity of primary tumor cells to chemotherapies currently in use for CRC. Perfusion‐based culture of primary CRC specimens recapitulates TME key features and may allow assessment of tumor drug response in a patient‐specific context.
Microscaffolds by Direct Laser Writing for Neurite Guidance Leading to Tailor‐Made Neuronal Networks
Authors: Fendler Cornelius , Denker Christian , Harberts Jann , Bayat Parisa , Zierold Robert , Loers Gabriele , Münzenberg Markus , Blick Robert H.
Published: March 2019

While modern day integrated electronic circuits are essentially designed in a 2D fashion, the brain can be regarded as a 3D circuit. The thus enhanced connectivity enables much more complex signal processing as compared to conventional 2D circuits. Recent technological advances in the development of nano/microscale 3D structuring have led to the development of artificial neuron culturing platforms, which surpass the possibilities of classical 2D cultures. In this work, in vitro culturing of neuronal networks is demonstrated by determining predefined pathways through topological and chemical neurite guiding. Tailor‐made culturing substrates of microtowers and freestanding microtubes are fabricated using direct laser writing by two‐photon polymerization. The first scaffold design that allows for site‐specific cell attachment and directed outgrowth of single neurites along defined paths that can be arranged freely in all dimensions, to build neuronal networks with low cell density, is presented. The neurons cultured in the scaffolds show characteristic electrophysiological properties of vital cells after 10 d in vitro. The introduced scaffold design offers a promising concept for future complex neuronal network studies on defined neuronal circuits with tailor‐made design specific neurite connections beyond 2D.
Off‐Stoichiometric Thiol‐Ene Chemistry to Dendritic Nanogel Therapeutics
Authors: Zhang Yuning , Andrén Oliver C. J. , Nordström Randi , Fan Yanmiao , Malmsten Martin , Mongkhontreerat Surinthra , Malkoch Michael
Published: March 2019

A novel platform of dendritic nanogels is herein presented, capitalizing on the self‐assembly of allyl‐functional polyesters based on dendritic‐linear‐dendritic amphiphiles followed by simple cross‐linking with complementary monomeric thiols via UV initiated off‐stoichiometric thiol‐ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190–295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.
Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature
Authors: Guo Zhaobin , Yang Chih‐Tsung , Maritz Michelle F. , Wu Huanjin , Wilson Puthenparampil , Warkiani Majid Ebrahimi , Chien Chia‐Chi , Kempson Ivan , Aref Amir R. , Thierry Benjamin
Published: March 2019

The therapeutic ratio of radiotherapy is limited by acute or chronic side effects with often severe consequences to patients. The microvasculature is a central player involved in both tumor responses and healthy tissue/organ radiological injuries. However, current preclinical vascular models based on 2D culture offer only limited radiobiological insight due to their failure in recapitulating the 3D nature experienced by endothelial cells within the human microvasculature. To address this issue, the use of a 3D microvasculature‐on‐a‐chip microfluidic technology is demonstrated in radiobiological studies. Within this vasculogenesis model a perfusable network that structurally mimics the human microvasculature is formed and the biological response to ionizing radiation including cellular apoptosis, vessel tight adherens junction breakage, DNA double strand break, and repair is systematically investigated. In comparison to cells grown in a 2D environment, human umbilical vein endothelial cells in the 3D microvasculature‐on‐a‐chip displays significant differences in biological responses, especially at high X‐ray dose. This data confirms the feasibility of using microvascular‐on‐a‐chip models for radiobiological studies. Such vasculogenesis models have strong potential to yield more accurate prediction of healthy tissue responses to ionizing radiation as well as to guide the development of risk‐reducing strategies to prevent radiation‐induced acute and long‐term side‐effects.
Efficient Synthesis of Functionalized Indene Derivatives via Rh(III)‐Catalyzed Cascade Reaction between Oxadiazoles and Allylic Alcohols
Authors: Zhang Jing , Sun Jun‐Shu , Xia Ying‐Qi , Dong Lin
Published: March 2019

A highly efficient rhodium(III)‐catalyzed synthesis of novel functionalized indene derivatives has been achieved via C−H activation/intramolecular aldol condensation. This cascade reaction is an atom economical protocol which could be further applied to build more complex compounds.

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Development of a Non‐Coding‐RNA‐based EMT/CSC Inhibitory Nanomedicine for In Vivo Treatment and Monitoring of HCC
Authors: Guo Ruomi , Wu Zhiqiang , Wang Jing , Li Qingling , Shen Shunli , Wang Weiwei , Zhou Luyao , Wang Wei , Cao Zhong , Guo Yu
Published: March 2019

The objective of this study is to improve the overall prognosis of patients with hepatocellular carcinoma (HCC); therefore, new therapeutic methods that can be used in vivo are urgently needed. In this study, the relationship between the quantities of microRNA (miR)‐125b‐5p in clinical specimens and clinicopathological parameters is analyzed. A folate‐conjugated nanocarrier is used to transfect miR‐125b‐5p in vivo and to observe the therapeutic effect on HCC. The inhibitory effect and mechanism of miR‐125b‐5p on hepatoma cells are also studied. Data from clinical specimens and in vitro experiments confirm that the miR‐125b‐5p quantity is negatively correlated with progression, and the target protein that regulates the epithelial–mesenchymal transition (EMT)/cancer stem cells (CSC) potential in HCC is STAT3. The miR‐125b‐5p/STAT3 axis inhibits the invasion, migration, and growth of HCC via inactivation of the wnt/β‐Catenin pathway. miR‐125b‐5p‐loaded nanomedicine effectively inhibits the EMT/CSC potential of hepatoma cells in vivo together with their magnetic resonance imaging (MRI) visualization characteristics. An HCC‐therapeutic and MRI‐visible nanomedicine platform that achieves noninvasive treatment effect monitoring and timely individualized treatment course adjustment is developed.
1D ZnSSe‐ZnSe Axial Heterostructure and its Application for Photodetectors
Authors: Mu Zeming , Zheng Qi , Liu Ruping , Malik Muhammad Wasim Iqbal , Tang Dongsheng , Zhou Weichang , Wan Qiang
Published: March 2019

Semiconductor heterostructure nanowires (HNWs) are excellent candidates for application in compact optoelectronics devices with high performance due to the heterojunction interface effect. However, the controllable fabrication of high‐quality nano‐heterostructures is elusive. In this paper, the controllable growth and optoelectronics device application of high‐quality ZnS0.49Se0.51/ZnSe axial HNWs are reported. The as‐synthesized HNWs are straight with uniform diameter distribution of 50–100 nm. Microstructural characterization reveals single crystal and abrupt heterojunction interface in these HNWs. The micro‐photoluminescence of single component region and heterojunction zone show one and integrated two near bandgap emission of ZnS0.49Se0.51 and ZnSe, respectively, further demonstrating the abrupt heterojunction interfaces nature in the as‐grown nanowires. Moreover, photodetectors based on single HNW are fabricated and the responsivity, external quantum efficiency, response speed, and detection wavelength range are superior to that of single component nanowire photodetectors at room temperature. These results show that the ZnS0.49Se0.51/ZnSe HNWs and corresponding high‐performance photodetectors are prospective candidates for photonics and optoelectronics applications.
Lithium Dendrites Inhibition via Diffusion Enhancement
Authors: Chen Yongxiu , Dou Xiangyu , Wang Kai , Han Yongsheng
Published: March 2019

The dendritic structure is a disastrous problem of lithium metal batteries as well as other metal rechargeable batteries. The dendritic structures are usually caused by diffusion limitation. Here, a novel strategy is reported to inhibit lithium dendrites based on the understanding of their formation mechanism. An alternating current field perpendicular to the anode is set up, which promotes Li+movement along the anode surface and prevents ions' deposition on the tips from forming dendrites. Furthermore, an external direct current field parallel to the current is employed, which accelerates the transport of Li+in electrolytes to mitigate the concentration gradient nearby the anode and thus inhibits the formation of dendritic structures. A simultaneous employment of these two fields gains five times increase of the lifespan of batteries at the high charging current density of 2 mA cm−2, confirming the effectiveness of this strategy in protecting the metal anode and inhibiting lithium dendrites. This strategy may have a wide feasibility since it does not change the materials and structures of batteries.
Skeletal Rearrangement of Twisted Thia‐Norhexaphyrin: Multiply Annulated Polypyrrolic Aromatic Macrocycles
Authors: Li Qizhao , Ishida Masatoshi , Kai Hiroto , Gu Tingting , Li Chengjie , Li Xin , Baryshnikov Glib , Liang Xu , Zhu Weihua , Ågren Hans , Furuta Hiroyuki , Xie Yongshu
Published: March 2019

A hybrid thia‐norhexaphyrin comprising a directly linked N‐confused pyrrole and thiophene unit (1) revealed unique macrocycle transformations to afford multiply inner‐annulated aromatic macrocycles. Oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone triggered a cleavage of the C−S bond of the thiophene unit, accompanied with skeletal rearrangement to afford unique π‐conjugated products: a thiopyrrolo‐pentaphyrin embedded with a pyrrolo[1,2]isothiazole (2), a sulfur‐free pentaphyrin incorporating an indolizine moiety (3), and a thiopyranyltriphyrinoid containing a 2H‐thiopyran unit (4). Furthermore, 2 underwent desulfurization reactions to afford a fused pentaphyrin containing a pyrrolizine moiety (5) under mild conditions. Using expanded porphyrin scaffolds, oxidative thiophene cleavage and desulfurization of the hitherto unknown N‐confused core‐modified macrocycles would be a practical approach for developing unique polypyrrolic aromatic macrocycles.
Pressure‐Induced Polymerization and Electrical Conductivity of a Polyiodide
Authors: Poręba Tomasz , Ernst Michelle , Zimmer Dominik , Macchi Piero , Casati Nicola
Published: March 2019

We report the high‐pressure structural characterization of an organic polyiodide salt in which a progressive addition of iodine to triiodide groups occurs. Compression leads to the initial formation of discrete heptaiodide units, followed by polymerization to a 3D anionic network. Although the structural changes appear to be continuous, the insulating salt becomes a semiconducting polymer above 10 GPa. The features of the pre‐reactive state and the polymerized state are revealed by analysis of the computed electron and energy densities. The unusually high electrical conductivity can be explained with the formation of new bonds.
Identifizierung von Chemokinliganden durch biochemische Rezeptorfragmentierung und simulierte Peptidevolution
Authors: Fuchs Jens‐Alexander , Brunner Cyrill , Schineis Philipp , Hiss Jan A. , Schneider Gisbert
Published: March 2019

Kurzkettige Peptide können gewisse Nachteile niedermolekularer Inhibitoren von Protein‐Protein‐Interaktionen (PPIs) überwinden. Wir untersuchten die Interaktion zwischen dem humanen Chemokin CCL19 und dem Chemokinrezeptor CCR7, um rezeptorabgeleitete CCL19‐bindende Peptide zu entwerfen. Die Identifizierung einer linearen Bindestelle von CCR7 und der nachfolgende Pharmakophor‐ und Lipophilie‐basierte Entwurf von computergenerierten Peptidbibliotheken führten zu fünf Hexapeptiden mit Affinitäten zu CCL19 im niedrigen mikro‐ bis nanomolaren Bereich. Dieses Ergebnis bestätigt die Anwendbarkeit des Computerverfahrens zur Findung von Peptid‐PPI‐Liganden.
Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity‐Coupled HiTES
Authors: Moon Kyuho , Xu Fei , Seyedsayamdost Mohammad R.
Published: March 2019

The majority of natural product biosynthetic gene clusters in bacteria are silent under standard laboratory growth conditions, making it challenging to uncover any antibiotics that they may encode. Herein, bioactivity assays are combined with high‐throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites. Application of this strategy in Saccharopolyspora cebuensis, with inhibition of Escherichia coli growth as a read‐out, led to the identification of a novel lanthipeptide, cebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram‐negative bacteria, especially against Vibrio species. This approach, referred to as bioactivity‐HiTES, has the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.
Phenology models using herbarium specimens are only slightly improved by using finer‐scale stages of reproduction
Authors: Ellwood Elizabeth R. , Primack Richard B. , Willis Charles G. , HilleRisLambers Janneke
Published: March 2019

Premise of the Study

Herbarium specimens are increasingly used to study reproductive phenology. Here, we ask whether classifying reproduction into progressively finer‐scale stages improves our understanding of the relationship between climate and reproductive phenology.

Methods

We evaluated Acer rubrum herbarium specimens across eastern North America, classifying them into eight reproductive phenophases and four stages of leaf development. We fit models with different reproductive phenology categorization schemes (from detailed to broad) and compared model fits and coefficients describing temperature, elevation, and year effects. We fit similar models to leaf phenology data to compare reproductive to leafing phenology.

Results

Finer‐scale reproductive phenophases improved model fits and provided more precise estimates of reproductive phenology. However, models with fewer reproductive phenophases led to similar qualitative conclusions, demonstrating that A. rubrum reproduces earlier in warmer locations, lower elevations, and in recent years, as well as that leafing phenology is less strongly influenced by temperature than is reproductive phenology.

Discussion

Our study suggests that detailed information on reproductive phenology provides a fuller understanding of potential climate change effects on flowering, fruiting, and leaf‐out. However, classification schemes with fewer reproductive phenophases provided many similar insights and may be preferable in cases where resources are limited.
Self‐assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer
Authors: Li Cai , Li Tianzhong , Huang Linfeng , Yang Mengsu , Zhu Guangyu
Published: March 2019

DNA damage repair through the nucleotide excision repair (NER) pathway is one of the major reasons for the decreased antitumor efficacy of platinum‐based anticancer drugs that have been widely applied in the clinic. Inhibiting the intrinsic NER function may enhance the antitumor activity of cisplatin and conquer cisplatin resistance. Herein, we report the design, optimization, and application of a self‐assembled lipid nanoparticle (LNP) system to simultaneously deliver a cisplatin prodrug together with siRNA targeting endonuclease xeroderma pigmentosum group F (XPF), a crucial component in the NER pathway. The LNP is able to efficiently encapsulate both the platinum prodrug and siRNA molecules with a tuned ratio. Both platinum prodrug and XPF‐targeted siRNA are efficiently carried into cells and released; the former damages DNA and the latter specifically downregulates both mRNA and protein levels of XPF to potentiate the platinum drug, leading to enhanced expression levels of apoptosis markers and improved cytotoxicity in both cisplatin‐sensitive and ‐resistant human lung cancer cells. Our results demonstrate an effective approach to utilize a multi‐targeted nanoparticle system that can specifically silence an NER‐related gene to promote apoptosis induced by cisplatin, especially in cisplatin‐refractory tumors.
Synergy of Single‐ion Conductive and Thermo‐responsive Copolymer Hydrogels Achieving Anti‐Arrhenius Ionic Conductivity
Authors: Guo Shanshan , Lei Rongyuan , Liang Xinmiao , Liu Jiyan , Liu Xueqing , Gao Shuyu , Peng Xianghong , Bian Shilong , Chen Yangwei , Jin Yi , Cai Shaojun , Liu Zhihong , Feng Jiwen
Published: March 2019

Artificial intelligence sensations have aroused scientific interest from electronic conductors to bio‐inspired ionic conductors. The conductivity of electrons decreases with increasing temperature, while the ionic conductivity agrees with an Arrhenius equation or a modified Vogel–Tammann–Fulcher (VTF) equation. Herein, thermo‐responsive poly(N‐isopropyl amide) (PNIPAm) and single‐ion‐conducting poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic lithium salt) (PAMPSLi) were copolymerized via a facile radical polymerization to demonstrate a very intriguing anti‐Arrhenius ionic conductivity behaviour during thermally induced volume‐phase transition. These smart hydrogels presented very promising scaffolds for architecting flexible, wearable or advanced functional ionic devices.
Multiple response optimization of alkaline pretreatment of sisal fiber (Agave sisalana) assisted by ultrasound
Authors: Brito Jeane Q. A. , Dias Fábio De S. , Cunha Silvio , Ramos Luiz P. , Teixeira Leonardo S. G.
Published: March 2019

A procedure for the alkaline pretreatment of sisal fiber assisted by ultrasound was optimized to obtain a higher solubilization of hemicellulose and the removal of lignin with cellulose fraction maintenance. A full factorial design 23 was used for the evaluation of the effects of the variables (sonication time, NaOH concentration, and sonication amplitude) on the pretreatment. The optimal values for the variables using the Doehlert matrix for the sonication time, NaOH concentration, and sonication amplitude were 27 min, 4.1% (m/v), and 50%, respectively. The X‐ray diffractometry and scanning electron microscopy analyses, after pretreatment, showed changes in chemical structure and morphology due to the removal of 82% of hemicellulose and 86% of lignin from sisal fiber. The soft reaction conditions and relatively short times demonstrated the effectiveness of the combined action of ultrasound with alkaline pretreatment to improve the accessibility to cellulose in this important step of the ethanol production process from biomass.
Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK‐rearranged non‐small‐cell lung cancer
Authors: Song Peng , Zhang Fanshuang , Li Yan , Yang Guangjian , Li Wenbin , Ying Jianming , Gao Shugeng
Published: March 2019

Background

TP53 mutations are the most prevalent mutations detected in non‐small‐cell lung cancer (NSCLC) and have been revealed as a negative prognostic biomarker of outcome. The impact of concomitant TP53 mutations in ALK‐rearranged NSCLC remains uncertain.

Methods

Tumor samples from 64 ALK‐rearranged NSCLC patients receiving crizotinib treatment were subjected to next‐generation sequencing (NGS) to identify TP53 mutational status. The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed.

Results

Among the 64 ALK‐rearranged patients, 15 (23.4%) patients showed a TP53 mutation. Of these, six cases had disruptive mutations and nine with nondisruptive mutations. The objective response rate (ORR) and disease control rate (DCR) for TP53 mutated patients were both significantly lower compared with those for TP53 wild‐type patients (p = 0.003 and 0.023, respectively). A significantly shorter progression‐free survival (PFS) was found in TP53 mutated patients compared with TP53 wild‐type patients (p = 0.045). Nondisruptive TP53 mutations were associated with a shorter PFS in comparison with disruptive TP53 mutations in ALK‐rearranged patients (p = 0.069). When nondisruptive TP53 mutated patients were in comparison with TP53 wild‐type patients, nondisruptive TP53 mutations were associated with a significant reduced PFS (p = 0.003).

Conclusions

TP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK‐rearranged NSCLC patients.
Overexpression of long non‐coding RNA NORAD promotes invasion and migration in malignant melanoma via regulating the MIR‐205‐EGLN2 pathway
Authors: Chen Yong , Cao Ke , Li Jingjing , Wang Aijun , Sun Lichun , Tang Jintian , Xiong Wei , Zhou Xiao , Chen Xiang , Zhou Jianda , Liu Yan
Published: March 2019

Growing evidence suggests that long non‐coding RNAs NORAD and miR‐205 play a significant role in regulating cancer progression and metastasis. In this study, high expression of NORAD was firstly observed in melanoma tissues and human malignant melanoma cell lines, our aim was to study the interaction of them in the process of invasion and migration of malignant melanoma cells. NORAD, miR‐205, and EGLN2 mRNA level in MM cells was detected by qRT‐PCR. In situ hybridization (ISH) was performed to detect NORAD expression in MM tissues specimens. Effects of NORAD and miR‐205 on Prolyl hydroxylase 2 (EGLN2) expression was explored by western blot in MM cells line. Dual‐luciferase reporter assay was performed to verify the interaction relationship between NORAD and miR‐205, as well as, miR‐205 and EGLN2. Transwell assay was conducted to explore the effects of NORAD and miR‐205 in vitro. Xenografts in nude mice experiment were used to confirm the role of NORAD and miR‐205 in vivo. In vitro, NORAD knockdown significantly inhibited migration and invasion of malignant melanoma cells and elevated the expression of miR‐205, there was an interaction between miR‐205 and NORAD in the RNA‐induced silencing complex. Upregulation of miR‐205 induced significant inhibition of migratory and invasive ability compared with the scrambled control. However, downregulating NORAD largely reversed this effect. Furthermore, the regulatory effects of miR‐205 on EGLN2 levels and the induction of endoplasmic reticulum stress were reversed by NORAD. In vivo, deletion of miR‐205 induced tumor growth in nude mice. NORAD may play critical roles in tumorigenesis and progression of malignant melanoma by regulating of the miR‐205‐EGLN2 pathway, and may serve as a new therapeutic target.
Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C‐Lock linker
Authors: Shi Baoying , Wu Min , Li Zhaohui , Xie Zhangming , Wei Xiaoyue , Fan Jiansheng , Xu Yingchun , Ding Ding , Akash Sajid Hamid , Chen Shuqing , Cao Sheldon
Published: March 2019

Antibody‐drug conjugates (ADCs) belong to a promising class of biopharmaceuticals in which target‐killing of tumor cells was achieved by marrying the potency of the cytotoxic payload with the tumor specificity of the antibody. Here we developed a novel ADC (ZV0508) that targets 5T4 oncofetal antigen, which is overexpressed in many carcinomas on both bulk tumor cells and cancer stem cells. A novel cytotoxic payload called Duostatin‐5 (Duo‐5) which was derived from monomethyl auristatin F (MMAF) was attached to a 5T4 targeting antibody (ZV05) by interchain cysteine cross‐linking conjugation via a disubstituted C‐Lock linker. We have investigated the antitumor efficacy of ZV0508 by in vitro and in vivo studies, and compared its antitumor activity with ZV05‐mcMMAF (ZV0501), in which MMAF was linked via a conventional noncleavable maleimidocaproyl linker. As results, ZV0508 exhibited ideal antiproliferative effects through blocking cell cycle and inducing cell apoptosis. The in vivo studies revealed that both ZV0501 and ZV0508 exhibited excellent antitumor activities even at a single dose. Although ZV0508 was inferior to ZV0501 in vitro, it elicited more durable antitumor responses than ZV0501 in vivo. The superior in vivo activity of ZV0508 may be due to the combined use of the disubstituted C‐Lock linker and the novel payload Duo‐5, resulting in a more stable and potent ADC. Taken together, these data suggest ZV0508 is a worthy candidate for the treatment of 5T4 positive cancers.
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth
Authors: Yan Ruhong , Liu Meng , Hu Yae , Wang Lina , Wang Can , Jiang Yizhi , Zhou Quansheng , Qi Xiaofei , Dong Ningzheng , Wu Qingyu
Published: March 2019

Transmembrane serine proteases have been implicated in the development and progression of solid and hematological cancers. Human airway trypsin‐like protease 4 (HAT‐L4) is a transmembrane serine protease expressed in epithelial cells and exocrine glands. In the skin, HAT‐L4 is important for normal epidermal barrier function. Here, we report an unexpected finding of ectopic HAT‐L4 expression in neutrophils and monocytes from acute myeloid leukemia (AML) patients. Such expression was not detected in bone marrow cells from normal individuals or patients with chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia. In AML patients who underwent chemotherapy, persistent HAT‐L4 expression in bone marrow cells was associated with minimal residual disease and poor prognostic outcomes. In culture, silencing HAT‐L4 expression in AML–derived THP‐1 cells by short hairpin RNAs inhibited matrix metalloproteinase‐2 activation and Matrigel invasion. In mouse xenograft models, inhibition of HAT‐L4 expression reduced the proliferation and growth of THP‐1 cell–derived tumors. Our results indicate that ectopic HAT‐L4 expression is a pathological mechanism in AML and that HAT‐L4 may be used as a cell surface marker for AML blast detection and targeting.
Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein‐Barr Virus: An analysis of a prospective study in southern China
Authors: Hu Ting , Lin Chu‐Yang , Xie Shang‐Hang , Chen Geng‐Hang , Lu Yu‐Qiang , Ling Wei , Huang Qi‐Hong , Liu Qing , Cao Su‐Mei
Published: March 2019

Background

The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design.

Methods

A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE).

Results

With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE.

Conclusion

Smoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV.
Work for greater diversity, inclusion in college sports
Authors: Elfman Lois
Published: March 2019

When the 2019 National Collegiate Athletic Association Inclusion Forum takes place this April in Atlanta, Katrice A. Albert, Ph.D., the NCAA's executive vice president of inclusion and human resources, will play a vital role. For Albert, a national leader on issues of cultural competence, educational and workforce diversity, educational access, gender, and dynamics of power, this is the first position in her distinguished higher education career situated directly within the world of intercollegiate athletics.
Modeling and Validating Fixed‐Bed Reactors: A State‐of‐the‐Art Review
Authors: Stegehake Carolin , Riese Julia , Grünewald Marcus
Published: March 2019

Modeling of heat and mass transfer in fixed‐bed reactors for heterogeneously catalyzed gas phase reactions is possible using different methods. Homogeneous and heterogeneous continuum models as well as particle resolved modeling of fixed‐bed reactors show high potential for application. Considering those approaches, advantages and disadvantages as well as underlying assumptions and boundary conditions are discussed. Additionally, methods for experimental validation are presented and discussed focusing on the two‐dimensional homogeneous models.
The sucked surgical sponge: Rare case of Gossypiboma after vaginal hysterectomy
Authors: Oehme Florian , Rühle Annika , Stickel Michael , Metzger Jürg , Gass Jörn‐Markus
Published: March 2019

Key Clinical Message

Retained surgical material needs to be a possible differential diagnosis for patients presenting with unspecific abdominal pain after especially cavitary emergency surgery. Even though international standard checklists concerning sponge handling and counting exist, RSM could never be ruled out completely.
Nanoparticle Ripening : A Versatile Approach for the Size and Shape Control of Metallic Iron Nanoparticles
Authors: Lacroix Lise‐Marie , Meffre Anca , Gatel Christophe , Fazzini Pier‐Francesco , Lachaize Sébastien , Respaud Marc , Chaudret Bruno
Published: March 2019

A novel approach for the synthesis of Fe(0) nanoparticles (NPs) with tunable sizes and shapes is reported. Ultrasmall Fe(0) NPs were reacted under mild conditions in the presence of a mixture of palmitic acid and amine ligands. These NPs acted not only as preformed seeds but also as an internal iron(II) source that was produced by the partial dissolution of the NPs by the acid. This fairly simple approach allows the strict separation of the nucleation and the growth steps. By changing the acid concentration, a fine tuning of the relative ratio between the remaining Fe(0) seeds and the iron(II) reservoir was achieved, giving access to both size (from 7 to 20 nm) and shape (spheres, cubes or stars) control. The partial dissolution of the ultrasmall Fe(0) NPs into iron(II) source and the successive growth was further studied by using combined TEM and Mössbauer spectroscopy. The successive corrosion, coalescence, and ripening observed could be understood in the framework of an environment‐dependent growth model.
Preparation and Measuring of Brain GABAAR‐coupled Cl‐/HCO3‐‐ Activity for Integral Assessment of Aquatic Toxicity
Authors: Menzikov Sergey A.
Published: March 2019

The wide use of aromatic hydrocarbons in various industries is having a negative effect on the environment and human health. Therefore, a key focus of current toxicology is the development and use of protein reporters with high sensitivity to various aromatic hydrocarbons (including phenolics and drugs). One molecular target for a wide range of pharmacology drugs and aromatic hydrocarbons (including phenol) is the neuronal GABAAR‐coupled Cl‐/HCO3‐‐ATPase. In this study, we present a protocol for isolation of the membrane‐bound Cl‐/HCO3‐‐ATPase from neuronal cells of animal brain. We then describe an uncomplicated in vitro method for measuring this ATPase activity for assessment of toxicity after interaction of this protein with an aquatic sample. This assay offers new avenues for using the Cl‐/HCO3‐‐ATPase as a biomarker of water toxicity. This biotest is efficient, requires very little of the enzyme, and retains its sensitivity at low levels of various compounds. © 2019 by John Wiley & Sons, Inc.
Selective Transformations of Triglycerides into Fatty Amines, Amides, and Nitriles by using Heterogeneous Catalysis
Authors: Jamil Md. A. R. , Siddiki S. M. A. Hakim , Touchy Abeda Sultana , Rashed Md. Nurnobi , Poly Sharmin Sultana , Jing Yuan , Ting Kah Wei , Toyao Takashi , Maeno Zen , Shimizu Ken‐ichi
Published: March 2019

The use of triglycerides as an important class of biomass is an effective strategy to realize a more sustainable society. Herein, three heterogeneous catalytic methods are reported for the selective one‐pot transformation of triglycerides into value‐added chemicals: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 under H2 promoted by ZrO2‐supported Pt clusters; ii) the amidation of triglycerides under gaseous NH3 catalyzed by high‐silica H‐beta (Hβ) zeolite at 180 °C; iii) the Hβ‐promoted synthesis of nitriles from triglycerides and gaseous NH3 at 220 °C. These methods are widely applicable to the transformation of various triglycerides (C4–C18 skeletons) into the corresponding amines, amides, and nitriles.