bluuebunny/crossref_metadata_2025 huggingface dataset:
DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma
Authors: Alam Sk. Kayum , Zhang Yongchang , Wang Li , Zhu Zhu , Hernandez Christina E. , Zhou Yuling , Yang Nong , Lei Jian , Chen Xiaoyan , Zeng Liang , Klein Mark A. , Hoeppner Luke H.
Published: October 2021

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-refractory lung adenocarcinoma (LUAD) progression is a major clinical problem. New approaches to predict and prevent acquired resistance to EGFR TKIs are urgently needed. Here, we show that dopamine and cyclic AMP-regulated phosphoprotein, Mr 32000 (DARPP-32) physically recruits ERBB3 (HER3) to EGFR to mediate switching from EGFR homodimers to EGFR:ERBB3 heterodimers to bypass EGFR TKI-mediated inhibition by potentiating ERBB3-dependent activation of oncogenic signaling. In paired LUAD patient-derived specimens before and after EGFR TKI-refractory disease progression, we reveal that DARPP-32 and kinase-activated EGFR and ERBB3 proteins are overexpressed upon acquired resistance. In mice, DARPP-32 ablation sensitizes gefitinib-resistant xenografts to EGFR TKIs, while DARPP-32 overexpression increases gefitinib-refractory LUAD progression in gefitinib-sensitive lung tumors. We introduce a DARPP-32-mediated, ERBB3-dependent mechanism the LUAD cells use to evade EGFR TKI-induced cell death, potentially paving the way for the development of therapies to better combat therapy-refractory LUAD progression.
Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology
Authors: Szebényi Kornélia , Wenger Léa M. D. , Sun Yu , Dunn Alexander W. E. , Limegrover Colleen A. , Gibbons George M. , Conci Elena , Paulsen Ole , Mierau Susanna B. , Balmus Gabriel , Lakatos András
Published: October 2021

Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible. Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and displays early molecular pathology of C9ORF72 ALS/FTD. Using a combination of single-cell RNA sequencing and biological assays, we reveal distinct transcriptional, proteostasis and DNA repair disturbances in astroglia and neurons. We show that astroglia display increased levels of the autophagy signaling protein P62 and that deep layer neurons accumulate dipeptide repeat protein poly(GA), DNA damage and undergo nuclear pyknosis that could be pharmacologically rescued by GSK2606414. Thus, patient-specific iPSC-derived cortical organoid slice cultures are a reproducible translational platform to investigate preclinical ALS/FTD mechanisms as well as novel therapeutic approaches.
The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells
Authors: Wenzel Jan , Lampe Josephine , Müller-Fielitz Helge , Schuster Raphael , Zille Marietta , Müller Kristin , Krohn Markus , Körbelin Jakob , Zhang Linlin , Özorhan Ümit , Neve Vanessa , Wagner Julian U. G. , Bojkova Denisa , Shumliakivska Mariana , Jiang Yun , Fähnrich Anke , Ott Fabian , Sencio Valentin , Robil Cyril , Pfefferle Susanne , Sauve Florent , Coêlho Caio Fernando Ferreira , Franz Jonas , Spiecker Frauke , Lembrich Beate , Binder Sonja , Feller Nina , König Peter , Busch Hauke , Collin Ludovic , Villaseñor Roberto , Jöhren Olaf , Altmeppen Hermann C. , Pasparakis Manolis , Dimmeler Stefanie , Cinatl Jindrich , Püschel Klaus , Zelic Matija , Ofengeim Dimitry , Stadelmann Christine , Trottein François , Nogueiras Ruben , Hilgenfeld Rolf , Glatzel Markus , Prevot Vincent , Schwaninger Markus
Published: October 2021

Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (Mpro) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, Mpro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the Mpro-induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.
Enhanced photocatalytic and photodynamic activity of chitosan and garlic loaded CdO–TiO2 hybrid bionanomaterials
Authors: Dhanalekshmi K. I. , Magesan P. , Umapathy M. J. , Zhang Xiang , Srinivasan N. , Jayamoorthy K.
Published: October 2021

Herein, the work addresses the synthesis of biomaterials (chitosan and garlic) loaded CdO–TiO2 hybrid nanocomposites for photocatalytic water treatment and photodynamic cancer therapeutic applications that were reported the first time. CdO–TiO2 (CT) nanocomposites were synthesized and loaded with the biomaterials such as chitosan and garlic by simple sol–gel method. The nanomaterials were characterized and the photodegradation of three model pollutants, Methylene blue (MB), Methyl orange (MO) and Rhodamine B (Rh-B) was opted to investigate the efficiency of the synthesized photocatalyst under the solar light. From the results, the garlic-loaded CdO–TiO2 (AS-CT) hybrid nanocomposites exhibit a superior photocatalytic activity than the chitosan-loaded CdO–TiO2 (CS-CT) and CdO–TiO2 (CT) nanocomposites under the irradiation of solar light. Additionally, the cell viability of the synthesized nanocomposites was carried out in HeLa cell lines under different concentrations, light doses and incubation periods using an LED light source. Compared to the CS-CT and CT nanocomposites, an efficient photodynamic activity was achieved in the case of AS-CT hybrid nanocomposites. Actually, the end-use properties required for both processes in AS-CT nanocomposites appear similar due to the presence of organo sulphurus compounds.
Earthworm activity optimized the rhizosphere bacterial community structure and further alleviated the yield loss in continuous cropping lily (Lilium lancifolium Thunb.)
Authors: Lu Yaoxiong , Gao Peng , Wang Yunsheng , Li Wei , Cui Xinwei , Zhou Jiamin , Peng Fuyuan , Dai Liangying
Published: October 2021

The soil microbial community plays a vital role in the biogeochemical cycles of bioelements and maintaining healthy soil conditions in agricultural ecosystems. However, how the soil microbial community responds to mitigation measures for continuous cropping obstacles remains largely unknown. Here we examined the impact of quicklime (QL), chemical fungicide (CF), inoculation with earthworm (IE), and a biocontrol agent (BA) on the soil microbial community structure, and the effects toward alleviating crop yield decline in lily. High-throughput sequencing of the 16S rRNA gene from the lily rhizosphere after 3 years of continuous cropping was performed using the Illumina MiSeq platform. The results showed that Proteobacteria, Acidobacteria, Bacteroidetes, Actinobacteria, Chloroflexi and Gemmatimonadetes were the dominant bacterial phyla, with a total relative abundance of 86.15–91.59%. On the other hand, Betaproteobacteriales, Rhizobiales, Myxococcales, Gemmatimonadales, Xanthomonadales, and Micropepsales were the dominant orders with a relative abundance of 28.23–37.89%. The hydrogen ion concentration (pH) and available phosphorus (AP) were the key factors affecting the structure and diversity of the bacterial community. The yield of continuous cropping lily with using similar treatments decreased yearly for the leaf blight, but that of IE was significantly (p < 0.05) higher than with the other treatments in the same year, which were 17.9%, 18.54%, and 15.69% higher than that of blank control (CK) over 3 years. In addition, IE significantly (p < 0.05) increased organic matter (OM), available nitrogen (AN), AP, and available potassium (AK) content in the lily rhizosphere soil, optimized the structure and diversity of the rhizosphere bacterial community, and increased the abundance of several beneficial bacterial taxa, including Rhizobiales, Myxococcales, Streptomycetales and Pseudomonadales. Therefore, enriching the number of earthworms in fields could effectively optimize the bacterial community structure of the lily rhizosphere soil, promote the circulation and release in soil nutrients and consequently alleviate the loss of continuous cropping lily yield.
Investigation of age-related facial variation among Angelman syndrome patients
Authors: Agbolade Olalekan , Nazri Azree , Yaakob Razali , Ghani Abdul Azim , Cheah Yoke Kqueen
Published: October 2021

Angelman syndrome (AS) is one of the common genetic disorders that could emerge either from a 15q11–q13 deletion or paternal uniparental disomy (UPD) or imprinting or UBE3A mutations. AS comes with various behavioral and phenotypic variability, but the acquisition of subjects for experiment and automating the landmarking process to characterize facial morphology for Angelman syndrome variation investigation are common challenges. By automatically detecting and annotating subject faces, we collected 83 landmarks and 10 anthropometric linear distances were measured from 17 selected anatomical landmarks to account for shape variability. Statistical analyses were performed on the extracted data to investigate facial variation in each age group. There is a correspondence in the results achieved by relative warp (RW) of the principal component (PC) and the thin-plate spline (TPS) interpolation. The group is highly discriminated and the pattern of shape variability is higher in children than other groups when judged by the anthropometric measurement and principal component.
Characterization of ovarian cancer-derived extracellular vesicles by surface-enhanced Raman spectroscopy
Authors: Ćulum Nina M. , Cooper Tyler T. , Lajoie Gilles A. , Dayarathna Thamara , Pasternak Stephen H. , Liu Jiahui , Fu Yangxin , Postovit Lynne-Marie , Lagugné-Labarthet François
Published: October 2021

EVs derived from normal ovarian (hIOSE) and ovarian cancer (OVCAR3, OV-90, EOC6, EOC18) cells were analysed by SERS. The SERS spectra of normal and cancer EVs were differentiated by PCA and machine learning, through which we achieved >99% accuracy.
Role of fluorine on the structure and second-harmonic-generation property of inorganic selenites and tellurites
Authors: Kong Fang , Jiang Ting-Kun , Mao Jiang-Gao
Published: October 2021

Inclusion of the most electronegative fluorine can regulate the distortion direction and magnitude of the structure, bandgap, and second-harmonic-generation (SHG) efficiency of materials effectively.
Hypoiodite-catalysed oxidative homocoupling of arenols and tandem oxidation/cross-coupling of hydroquinones with arenes
Authors: Uyanik Muhammet , Nagata Dai , Ishihara Kazuaki
Published: October 2021

A transition-metal-free method for the oxidative C–C homocoupling and tandem oxidation/cross-coupling is reported.
Methane activation on dual-atom catalysts supported on graphene
Authors: Wu Chongchong , Yang Weijie , Wang Jacky Jingyi , Li Hao , Gates Ian D.
Published: October 2021

Dual-atom Fe catalysts supported by three nitrogen doped graphene (Fe–TM/GP, where TM = Ti, V, Cr, Mn, Fe, Co, Ni, and Cu) are explored for methane adsorption and activation.
Formation of double-cone-shaped ZnO mesocrystals by addition of ethylene glycol to ZnO dissolved choline chloride–urea deep eutectic solvents and observation of their manners of growth
Authors: Wagata Hajime , Harada Ginji , Nakashima Eriko , Asaga Motoki , Watanabe Tomoaki , Tanaka Yuya , Tada Masaru , Yubuta Kunio
Published: October 2021

ZnO mesocrystals were grown in ZnO dissolved CU-DESs with addition of ethylene glycol. Their manner of growth was observed and discussed.
Investigation of the blue color center in β-Ga2O3 crystals by the EFG method
Authors: Fu Bo , Mu Wenxiang , Li Yang , Shi Yujun , Li Yanbin , Jia Zhitai , Tao Xutang
Published: October 2021

This work investigated the blue color center in β-Ga2O3 crystals grown by the EFG and obtained an effective method to eliminate it.
Reactions in non-aqueous alkali and alkaline-earth metal–oxygen batteries: a thermodynamic study
Authors: Pierini Adriano , Brutti Sergio , Bodo Enrico
Published: October 2021

The disproportionation of alkali and alkaline-earth metal superoxide is investigated using multiconfigurational methods.
Ultrafast relaxation investigated by photoelectron circular dichroism: an isomeric comparison of camphor and fenchone
Authors: Blanchet Valérie , Descamps Dominique , Petit Stéphane , Mairesse Yann , Pons Bernard , Fabre Baptiste
Published: October 2021

We study the isomeric effects using time resolved photoelectron circular dichroism (TR-PECD).
Sustainable production of levulinic acid and its derivatives for fuel additives and chemicals: progress, challenges, and prospects
Authors: Sajid Muhammad , Farooq Usman , Bary Ghulam , Azim Muhammad Mohsin , Zhao Xuebing
Published: October 2021

The research progress on the production of levulinic acid and its derivatives for fuel additives and chemicals from various sugars and biomass feedstocks have been comprehensively reviewed, focusing on the chemical processes and mechanisms.
Acoustofluidic medium exchange for preparation of electrocompetent bacteria using channel wall trapping
Authors: Gerlt M. S. , Ruppen P. , Leuthner M. , Panke S. , Dual J.
Published: October 2021

Comprehensive integration of process steps into a miniaturised version of synthetic biology workflows remains a crucial task in automating the design of biosystems. We present an acoustofluidic chip, capable of automated medium exchange of bacteria.
Biomedical applications of metal–organic framework (MOF)-based nano-enzymes
Authors: Qiu Yuzhi , Tan Guijian , Fang Yuqian , Liu Si , Zhou Yubin , Kumar Abhinav , Trivedi Manoj , Liu Dong , Liu Jianqiang
Published: October 2021

In the present review, the types and activities of nanometer-sized enzymes are summarized, with recent progress of nanometer-sized enzymes in the field of biomedical detection.
A polarity-sensitive fluorescent probe based on a difluoroboron derivative for monitoring the variation of lipid droplets
Authors: Wang Hui , Hu Lei , Shen Shuting , Yu Kun , Wang Yaxuan
Published: October 2021

We design LD-L, a polarity-sensitive fluorescent probe, which can specifically detect lipid droplets and monitor variations in their number.
Self-assembled (NH4)2V7O16 hierarchical structures with improved electrochemical performance for aqueous Li-ion batteries
Authors: Ma Yining , Shu Rui , Xu Tongxiang , Li Jing , Zhu Dandan , Jin Xiaodong , Wu Mingchen , Cao Xun
Published: October 2021

(NH4)2V7O16 hierarchical structures were successfully prepared via a rotating hydrothermal method and exhibited superior long-term cyclic stability.
The synthesis of degradable sulfur-containing polymers: precise control of structure and stereochemistry
Authors: Yue Tian-Jun , Wang Li-Yang , Ren Wei-Min
Published: October 2021

This review comprehensively summarized the recent progresses made in the precise synthesis of sulfur-containing polymers from the structure control, stereochemistry control and the topological structure modification aspects.
SREBP-1c and lipogenesis in the liver: an update
Authors: Ferré Pascal , Phan Franck , Foufelle Fabienne
Published: October 2021

Sterol Regulatory Element Binding Protein-1c is a transcription factor that controls the synthesis of lipids from glucose in the liver, a process which is of utmost importance for the storage of energy. Discovered in the early nineties by B. Spiegelman and by M. Brown and J. Goldstein, it has generated more than 5000 studies in order to elucidate its mechanism of activation and its role in physiology and pathology. Synthetized as a precursor found in the membranes of the endoplasmic reticulum, it has to be exported to the Golgi and cleaved by a mechanism called regulated intramembrane proteolysis. We reviewed in 2002 its main characteristics, its activation process and its role in the regulation of hepatic glycolytic and lipogenic genes. We particularly emphasized that Sterol Regulatory Element Binding Protein-1c is the mediator of insulin effects on these genes. In the present review, we would like to update these informations and focus on the response to insulin and to another actor in Sterol Regulatory Element Binding Protein-1c activation, the endoplasmic reticulum stress.
Thermally reconfigurable helical shape memory alloy–based metamaterial
Authors: Phon Ratanak , Lee Minjae , Kim Yelim , Iqbal* Shahid , Lim Sungjoon
Published: October 2021

This paper presents our investigation and experimental validation of a thermally reconfigurable shape memory alloy (SMA)‐based metamaterial with the offered degree of freedom of SMA mechanical features. The metamaterial unit cell consists of a two‐way helical SMA acting as the resonator element and a cartridge heater for controlling the excitation temperature of the helical SMA. Experimental results of electrical control of the cartridge heater's excitation temperature show that as the temperature increases from room temperature (25°C) to approximately 92°C—corresponding to input DC voltages of 0 and 4 V, respectively—the metamaterial structure acts as a switchable absorber with an absorptivity of 97.2% and a reflector with a reflectivity of 89.4% at 7.13 GHz. Additionally, it deforms to its initial state as the temperature decreases to room temperature.
Modified incremental conductance MPPT algorithm for SPV‐based grid‐tied and stand‐alone systems
Authors: Pathak Pawan Kumar , Padmanaban Sanjeevikumar , Yadav Anil Kumar , Alvi P. A. , Khan Baseem
Published: October 2021

This paper deals with power generation through solar photovoltaic (SPV) system and its implementation as grid‐tied and stand‐alone systems. The major setbacks of SPV system of low conversion efficacy, that can be enhanced through the maximum power point tracking (MPPT) algorithm. A modified incremental conductance (MIC), termed as error based incremental conductance MPPT, has been proposed, and its behaviour is comprehensively compared with classical perturb and observe (P&O) and incremental conductance (IC) techniques. Dealing with the on‐grid application of SPV system, maximum power obtained through MIC is fed to a three‐phase grid operating at unity power factor (UPF), and the quality of grid current is monitored. Further, the power obtained through MIC finds its application in designing an SPV‐diesel generator (DG) based hybrid renewable energy system (HRES) for areas either not connected to the grid or have insufficient fossils. The stochastic nature of source or uncertain load demand leads to deviation in system frequency. This paper proposes an intelligent, comprehensive supervisory optimal‐fuzzy‐proportional‐integral‐derivative (O‐F‐PID) controller for load frequency control (LFC). The performance of proposed O‐F‐PID controller has been vividly compared with the designed optimal‐PID (O‐PID) and conventional PID (C‐PID) controllers under varying source and load demand conditions.
A cooperative lane change approach for heterogeneous platoons under different communication topologies
Authors: Nie Guangming , Xie Bo , Lu Huiqiu , Tian Yantao
Published: October 2021

To improve the platoon's passability and traffic efficiency, a cooperative lane change approach is proposed when the platoon encounters a slow obstacle vehicle ahead in this paper. The algorithm is designed for the heterogeneous platoon, that is, the vehicles are dynamically decoupled and have different parameters. The vehicles in the platoon can have different communication topologies. To complete the lane change process quickly, all vehicles in the platoon perform simultaneously. The approach is mainly divided into two parts: trajectory planning and cooperative control. In the trajectory planning part, combined with the polynomial method and the optimization method, the leading vehicle plans an optimal lane change trajectory according to its own states and the obstacle vehicle's states. A distributed model predictive control algorithm is designed in the cooperative control part to meet the requirement that all vehicles should change lanes simultaneously. Besides, the sufficient conditions to achieve the asymptotic stability are also given, and the simulation results can show the effectiveness of the algorithm.
Developing a situation and threat assessment framework for a next generation roadside animal detection system
Authors: Mohammadi Ahmad , Park Peter Y. , Mukherjee Abir , Liu Xia
Published: October 2021

Collisions involving large animals are a serious safety, economic and ecological concern. Some North American jurisdictions have installed a roadside animal detection system (RADS) that can warn the possible presence of large animals on rural highway sections. This study provides a conceptual framework for developing a next generation (NG) RADS. This study focuses on developing a process that can estimate the varying levels of threat posed by animals on the roadway using real‐time data on animal and vehicle positions. To estimate the level of threat, the study used a fuzzy rule‐based algorithm that integrates four input indicators (e.g., physical distance between animal and vehicle). The methodology was tested using real‐world traffic and animal data collected from a conventional RADS in British Columbia, Canada. The NG RADS has significant advantages over the conventional RADS. In particular, the NG RADS can disseminate varying levels of warning according to the estimated level of the threat rather than the constant level of warning generated by a conventional RADS. The NG RADS can also use a Vehicle‐to‐Infrastructure communication technology to establish direct wireless communication with vehicles at risk, for instance, to automatically control a vehicle's speed to avoid a collision with a large animal.
A multi‐aperture coupling liquid attenuator
Authors: Yan Dandan , Xing Lei , Xu Qian , Zhang Guoxuan , Zhu Jiajia
Published: October 2021

A liquid attenuator with multi‐aperture coupling is proposed. It consists of two coupled rectangular waveguide cavities, two transparent containers and pure water. By utilising the multi‐aperture coupling structure, the proposed design achieves large attenuation with good flatness across a wide frequency range. The pure water is employed as the liquid loading to dissipate the energy. Both simulations and measurements have been conducted. It is demonstrated that the proposed attenuator exhibits an attenuation of 59.2 dB with an attenuation flatness of ±0.9 dB from 2.19 to 3.64 GHz (the reflection coefficient is less than −10 dB across the band). Compared with conventional waveguide attenuators, this design provides a wider frequency working range, a more compact size, larger and flatter attenuation and better heat dissipation. It can be a promising candidate for high power applications.
An interleaved high step‐up DC–DC converter with ZVS capability for renewable energy systems applications
Authors: Bagherian Alireza , Nouri Tohid , Shaneh Mahdi , Radmehr Mehdi
Published: October 2021

In this paper, an interleaved zero voltage switching high step‐up converter based on active clamp, coupled inductor (CI), built‐in transformer (BIT), and switched capacitor (SC) is proposed. The main novelty of the proposed converter is that the secondary winding of the CI is inserted between the primary winding of the CI and the primary winding of the BIT. Therefore, the voltage gain can be achieved in proportionate to the multiplication of the turn ratios of the CIs and BIT. The configuration of the proposed converter not only increases the voltage gain, but also reduces the current and voltage stress of the power switches and restricts the input current ripple, which decreases the conduction losses and increases the lifetime of the input source. Also, zero voltage switching turn‐ON and turn‐OFF conditions for all switches are achieved by employing an active clamp configuration. The voltage across the diodes clamped to the output voltage and the reverse recovery problem is reduced due to the leakage inductors. Finally, a 600 W prototype with 24–400 V voltage conversion is built to verify the performance and theoretical analysis.
Brachiopodes (Rhynchonellida) du sommet du Toarcien inférieur et du Toarcien moyen de l’Unité centrale des Rides sud-rifaines (nord Maroc)
Authors: Benzaggagh Mohamed
Published: October 2021

Les niveaux du sommet du Toarcien inférieur et du Toarcien moyen de l’Unité centrale des Rides sud-rifaines (Maroc), en particulier dans les coupes d’El Heitouf et de Sned, sont riches en macrofaune benthique (gastéropodes, lamellibranches et brachiopodes). Neuf espèces de brachiopodes de l’ordre des Rhynchonellida appartenant à six genres ont été répertoriées. Il s’agit de :Gibbirhynchia reyi,Homoeorhynchia batalleri,Quadratirhynchia vasconcellosi,Pseudogibbirhynchiajurensis,Rhynchonelloidella marini,Soaresirhynchia babtisrensis,Soaresirhynchia bouchardi,Soaresirhynchiasp. etSoaresirhynchia tamazirta.H. batalleri, largement dominante, est représentée par cinq groupes d’individus, qui se distinguent par le nombre de côtes (deux à six) sur le pli médian dorsal. Chaque groupe est représenté par des spécimens juvéniles à adultes, représentant des stades successifs de l’évolution ontogénique. Les espèces répertoriées, décrites et illustrées, complètent les données antérieures sur ce groupe fossile dans le domaine paléogéographique des Rides sud-rifaines. La plupart des espèces répertoriées sont communes aux bassins péritéthysiens des marges nord et sud de la Téthys occidentale, en particulier l’Afrique du Nord et l’Europe du Sud-Ouest.
Bedarfe für körperliche Aktivität bei Pflegebedürftigen in stationären Pflegeeinrichtungen: Leistungsfähigkeit und Sensitivität
Authors: Köppel Maximilian
Published: October 2021

Durch den demografischen Wandel wird die Anzahl von Pflegeheimbewohnern in der Zukunft weiter ansteigen. Die Heimbewohner weisen eine extrem niedrige körperliche Leistungsfähigkeit auf, welche durch gezielte bewegungstherapeutische Maßnahmen adressiert werden kann. Insbesondere die konditionellen Fähigkeiten sind auch bei Hochbetagten gut trainierbar. Für die Zukunft müssen die Pflegeheime dringend auf körperliches Training und Bewegungsförderungsmaßnahmen zurückgreifen.
Machine Learning-Based Ultrasound Texture Analysis in Differentiation of Benign Phyllodes Tumors from Borderline-Malignant Phyllodes Tumors
Authors: Basara Akin Isil , Ozgul Hakan Abdullah , Altay Canan , Guray Durak Merih , Aksoy Suleyman Ozkan , Sevinc Ali Ibrahim , Secil Mustafa , Gulmez Hakan , Balci Pinar
Published: October 2021

Purpose Phyllodes tumors (PTs) are uncommon fibroepithelial breast lesions that are classified as three different forms as benign phyllodes tumor (BPT), borderline phyllodes tumor (BoPT), and malignant phyllodes tumor (MPT). Conventional radiologic methods make only a limited contribution to exact diagnosis, and texture analysis data increase the diagnostic performance. In this study, we aimed to evaluate the contribution of texture analysis of US images (TAUI) of PTs in order to discriminate between BPTs and BoPTs-MPTs.

Methods The number of patients was 63 (41 BPTs, 12 BoPTs, and 10 MPTs). Patients were divided into two groups (Group 1-BPT, Group 2-BoPT/MPT). TAUI with LIFEx software was performed retrospectively. An independent machine learning approach, MATLAB R2020a (Math- Works, Natick, Massachusetts) was used with the dataset with p < 0.004. Two machine learning approaches were used to build prediction models for differentiating between Group 1 and Group 2. Receiver operating characteristics (ROC) curve analyses were performed to evaluate the diagnostic performance of statistically significant texture data between phyllodes subgroups.

Results In TAUI, 10 statistically significant second order texture values were identified as significant factors capable of differentiating among the two groups (p < 0.05). Both of the models of our dataset make a diagnostic contribution to the discrimination between BopTs-MPTs and BPTs.

Conclusion In PTs, US is the main diagnostic method. Adding machine learning-based TAUI to conventional US findings can provide optimal diagnosis, thereby helping to choose the correct surgical method. Consequently, decreased local recurrence rates can be achieved.
Prevalence and risk factors of upper gastrointestinal cancers missed during endoscopy: a nationwide registry-based study
Authors: Januszewicz Wladyslaw , Witczak Klaudiusz , Wieszczy Paulina , Socha Magda , Turkot Maryla H. , Wojciechowska Urszula , Didkowska Joanna , Kaminski Michal F. , Regula Jaroslaw
Published: October 2021

Background A significant proportion of upper gastrointestinal cancers (UGICs) remain undetected during esophagogastroduodenoscopy (EGD). We investigated the characteristics and risk factors of UGICs missed during endoscopy.

Methods In this nationwide registry-based study, we analyzed two large Polish datasets (National Health Fund and National Cancer Registry) to identify individuals who underwent EGD and were subsequently diagnosed with UGIC. Cancers diagnosed < 6 months after EGD were defined as “prevalent” and those within ≥ 6– < 36 months as “missed.” We compared the characteristics of missed and prevalent cancers, and analyzed the risk factors for missed UGICs in a multivariable regression model.

Results We included 4 105 399 patients (mean age 56.0 years [SD 17.4]; 57.5 % female) who underwent 5 877 674 EGDs in 2012–2018. Within this cohort, 33 241 UGICs were diagnosed, of which 1993 (6.0 %) were missed. Within esophageal neoplasms, adenocarcinomas were more frequently missed than squamous cell cancers (6.1 % vs. 4.2 %), with a relative risk of 1.4 (95 % confidence interval [CI] 1.1–1.8, P = 0.01). Most gastric cancers were adenocarcinomas, of which 5.7 % were classified as missed. Overall, a higher proportion of missed UGICs than prevalent cancers presented at an advanced stage (42.2 % vs. 36.2 %, P < 0.001). Risk factors for missed UGICs included initial EGD performed within primary (vs. secondary) care (odds ratio [OR] 1.3, 95 %CI 1.2–1.5), female sex (OR 1.3, 95 %CI 1.2–1.4), and higher comorbidity (Charlson comorbidity index ≥ 5 vs. 0; OR 6.0, 95 %CI 4.7–7.5).

Conclusions Among UGICs, esophageal adenocarcinomas were missed most frequently. Missed cancers occur more frequently within the primary care sector and are found more often in women and individuals with multiple comorbidities.
Determination of a treatment response threshold for the Eosinophilic Esophagitis Endoscopic Reference Score
Authors: Cotton Cary C. , Woosley John T. , Moist Susan E. , McGee Sarah J. , Iuga Alina , Shaheen Nicholas J. , Dellon Evan S.
Published: October 2021

Background Endoscopic features of eosinophilic esophagitis (EoE) are measured using the validated EoE Endoscopic Reference Score (EREFS); however, a threshold for treatment response has not been defined. We aimed to determine a cut-point for endoscopic response as measured by EREFS.

Methods We performed a secondary analysis of a randomized clinical trial comparing budesonide slurry with swallowed fluticasone multidose inhaler for initial treatment of EoE. In the parent trial, EREFS was determined before and after treatment (score range 0–9), as were histologic findings and dysphagia symptoms. We performed tabular, flexible trend, and dependent mixture analyses of measures of treatment response to select the best clinical EREFS threshold.

Results In the 111 included patients (mean age 39 years; 67 % male; 96 % white), an EREFS threshold of ≤ 2 was 80 % sensitive (95 % confidence interval [CI] 69 % to 88 %) and 83 % specific (95 %CI 67 % to 94 %) for histologic response (peak of < 15 eosinophils per high-power field). Flexible trend analysis and dependent mixture modeling similarly suggested that a threshold of ≤ 2 best captured the correlation of EREFS with histologic and symptomatic measures. Dependent mixture modeling found near-total membership in the response class at EREFS of 0 or 1 and > 75 % at EREFS of 2 or 3.

Conclusions An EREFS of ≤ 2 was the best clinical threshold for endoscopic response to topical steroid treatment, and was consistent with clinical and histologic response. Therefore, future studies can report a binary outcome of endoscopic response when EREFS is 2 or less.
Mechanistic Investigations on Microbial Type I Terpene Synthases through Site-Directed Mutagenesis
Authors: Dickschat Jeroen S. , Xu Houchao
Published: October 2021

During the past three decades many terpene synthases have been characterised from all kingdoms of life. Enzymes of type I, from bacteria, fungi and protists, commonly exhibit several highly conserved motifs and single residues, and the available crystal structures show a shared α-helical fold, while the overall sequence identity is generally low. Several enzymes have been studied by site-directed mutagenesis, giving valuable insights into terpene synthase catalysis and the intriguing mechanisms of terpene synthases. Some mutants are also preparatively useful and give higher yields than the wild type or a different product that is otherwise difficult to access. The accumulated knowledge obtained from these studies is presented and discussed in this review.

1 Introduction

2 Residues for Substrate Binding and Catalysis

3 Residues with Structural Function

4 Residues Contouring the Active Site Cavity

5 Other Residues

6 Conclusions
Hypervalent Bromine(III) Compounds: Synthesis, Applications, Prospects
Authors: Winterson Bethan , Patra Tuhin , Wirth Thomas
Published: October 2021

Hypervalent compounds play a prominent role in homogeneous oxidation catalysis. Despite the higher reactivity of hypervalent bromine compounds when compared to their isoelectronic iodine analogues, the corresponding λ3-bromanes are much less explored. This can be attributed to the discernible lack of convenient strategies for their synthesis. This short review highlights the available methods for the synthesis of various organo-λ3-bromanes, with a major focus on the recent developments and reactivities in the last few years. Additionally, limitations and future prospects of hypervalent bromine chemistry are discussed.

1 Introduction

2 Diaryl-λ3-bromanes

3 Dialkyl-λ3-bromanes

4 Dihetero-λ3-bromanes

5 Alkenyl-λ3-bromanes

6 Alkynyl-λ3-bromanes

7 Conclusion and Prospects
Facile Synthesis of Quaternary α-Fluoronitriles by Cobalt-Catalyzed Hydrocyanation of Monofluoroalkenes
Authors: Wang Xi-Sheng , Li Yanlin , Cui Ru , Wu Tian-Rui
Published: October 2021

An exclusively regioselective hydrocyanation of monofluoroalkenes has been developed, with which a series of aliphatic quaternary α-fluoronitriles were synthesized in a facile and efficient manner. This novel method is featured with mild conditions, good functional groups compatibilities, and high reactivity.
Effect of Accelerated Aging on the Sorption and Solubility Percentages of Silicone Facial Prostheses
Authors: Nóbrega Adhara Smith , Neto Clóvis Lamartinede Moraes Melo , dos Santos Daniela Micheline , Bertoz André Pinheirode Magalhães , MeloMoreno André Luiz de , Goiato Marcelo Coelho
Published: October 2021

Objective This study aimed to evaluate the effect of accelerated aging on the sorption and solubility percentages of the MDX4-4210 and A-2186 silicones.

Materials and Methods Two silicones (A-2186 and MDX4-4210) and three intrinsic pigments (bronze, black, and pink) were used in this study. Thus, six groups were created (n = 10): Group 1 = bronze MDX4-4210; Group 2 = black MDX4-4210; Group 3 = pink MDX4-4210; Group 4 = bronze A-2186; Group 5 = black A-2186; and Group 6 = pink A-2186. The dimensions of all samples were the same (45-mm diameter (ø) × 1-mm thickness). The samples were aged for a total of 1,008 hours. In this period of 1,008 hours of accelerated aging, the sorption and solubility percentages of each sample were calculated at three time points (252, 504, and 1,008 hours).

Statistical Analysis Three-way analysis of variance (ANOVA) and the Tukey test were performed (α = 0.05).

Result Accelerated aging can significantly increase the sorption and solubility percentages of the MDX4-4210 and A-2186 silicones.
Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome
Authors: Meoded Avner , Kukreja Marcia , Orman Gunes , Boltshauser Eugen , Huisman Thierry A.G.M.
Published: October 2021

We report on the conventional and diffusion tensor imaging (DTI) findings of a 2-year-old child with clinical presentation of Joubert's Syndrome (JS) and brainstem structural abnormalities as depicted by neuroimaging.

Conventional magnetic resonance imaging (MRI) showed a “molar tooth” configuration of the brainstem. A band-like formation coursing in an apparent axial plane anterior to the interpeduncular fossa was noted and appeared to partially cover the interpeduncular fossa.

DTI maps and three-dimensional (3D) tractography demonstrated a prominent red-encoded white matter bundle anterior to the midbrain. Probable aberrant course of the bilateral corticospinal tracts (CST) was also depicted. Absence of the decussation of the superior cerebellar peduncles and elongated thickened, horizontal superior cerebellar peduncle (SCP) reflecting the molar tooth sign were also shown.

Our report and the review of the published cases suggest that DTI and tractography may be very helpful to differentiate between interpeduncular heterotopias and similarly located white matter bundles corroborating the underlying etiology of axonal guidance disorders in the complex group of ciliopathies including JS. Our case represents an important additional puzzle piece to explore the variability of these ciliopathies.
Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome
Authors: Anurat Kingthong , Khongkhatithum Chaiyos , Tim-Aroon Thipwimol , Limwongse Chanin , Thampratankul Lunliya
Published: October 2021

Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.
Heat transfer in microwave transistors at cryogenic temperatures
Authors: McConnon Aili
Published: October 2021

Heat transfer in transistors at cryogenic temperatures occurs by radiation of atomic vibrations and limits the noise performance of modern microwave amplifiers.
A new torsion tester based on an electronic autocollimator for characterizing the torsional behaviors of microfibers
Authors: Hu Jianhui , Zeng Liang , Hu Peng , He Yuming , Liu Dabiao
Published: October 2021

Torsional properties of single fibers have considerable effects on the performance of fabrics. A new torsion tester with high resolution is developed based on the torsion-balance method and the autocollimation principle for measuring the torsional properties of single fibers. The tester can measure the torque accurately using the torsion wire of known torsional rigidity. The angular displacement of the torsion wire is measured by a non-contact electronic autocollimator. The calibration results show that the maximum torque capability is around 6 × 10−6 N m with a theoretical resolution of about 8 × 10−11 N m. The instrument’s validity is verified by comparing the measurement result with that obtained by a torsion pendulum. Torsion tests on four industrially microfibers, including glass fiber, polyimide fiber, carbon fiber, and gold wire, are performed with the tester, which gives shear moduli 71.0 ± 0.4, 5.6 ± 0.1, 22.6 ± 3.1, and 34.3 ± 0.5 GPa, respectively. Young’s moduli of these fibers are also provided. It is demonstrated that these fibers have a high anisotropy in mechanical properties.
A micro-vibration apparatus for dynamic mechanical analysis of ultrathin polymer films
Authors: Bai Pei , Xiao Yuhan , Yang Weiqing , Duan Mobin , Guo Yunlong
Published: October 2021

We present the design and validation of an apparatus, which is developed based on micro-vibration in cyclic bulge and contraction, to determine dynamic mechanical properties of ultrathin polymer films. By controlling air pressure acting on a polymer membrane, the apparatus exerts simple harmonic or other type periodic stresses on the film, and the resultant real-time deformation of the freely standing film is recorded by using a high-speed CCD camera. From the image frame sequences and the gas pressure data, the real-time stress and strain of the polymer film are attained. Consequently, the dynamic mechanical properties, including biaxial storage and loss moduli, and loss factor can be determined for polymer films with thickness down to 20 nm. This apparatus could also be used to determine other mechanical properties such as fatigue and yield for nanoconfined films of soft matter.
How high is the entropy in high entropy ceramics?
Authors: Schneider Jochen M.
Published: October 2021

In this Perspective, I raise the question whether the terms high entropy ceramics, high entropy nitrides, high entropy oxides, high entropy borides, etc., are meaningful considering the magnitude of the calculated configurational entropy. Here, the origin of Boltzmann's equation is reviewed and the implications for application are discussed. This back to the roots’ excursion may be helpful for approaching an answer to the question raised in the title and for re-evaluating literature reports connecting superior performance with configurational entropy of so-called high entropy ceramics.
Local stress tensor calculation by the method-of-plane in microscopic systems with macroscopic flow: A formulation based on the velocity distribution function
Authors: Kusudo Hiroki , Omori Takeshi , Yamaguchi Yasutaka
Published: October 2021

In this work, we developed a calculation method of local stress tensor applicable to non-equilibrium molecular dynamics (NEMD) systems, which evaluates the macroscopic momentum advection and the kinetic term of the stress in the framework of the Method-of-Plane (MoP), in a consistent way to guarantee the mass and momentum conservation. From the relation between the macroscopic velocity distribution function and the microscopic molecular passage across a fixed control plane, we derived a method to calculate the basic properties of the macroscopic momentum conservation law including the density, the velocity, the momentum flux, and the two terms of the stress tensor, i.e., the interaction and the kinetic terms, defined on a surface with a finite area. Any component of the streaming velocity can be obtained on a control surface, which enables the separation of the kinetic momentum flux into the advection and stress terms in the framework of MoP, and this enables strict satisfaction of the mass and momentum conservation for an arbitrary closed control volume (CV) set in NEMD systems. We validated the present method through the extraction of the density, velocity, and stress distributions in a quasi-one-dimensional steady-state Couette flow system and in a quasi-2D steady-state NEMD system with a moving contact line. We showed that with the present MoP, in contrast to the volume average method, the conservation law was satisfied even for a CV set around the moving contact line, which was located in a strongly inhomogeneous region.
Multi-beam energy moments of measured compound ion velocity distributions
Authors: Goldman M. V. , Newman D. L. , Eastwood J. P. , Lapenta G. , Burch J. L. , Giles B.
Published: October 2021

Compound ion distributions, fi(v), have been measured with high-time resolution by NASA's Magnetospheric Multi-Scale Mission (MMS) and have been found in reconnection simulations. A compound distribution, fi(v), consisting, for example, of essentially disjoint pieces will be called a multi-beam distribution and modeled as a sum of “beams,” fi(v) = f1(v) + ⋯ + fN(v). Velocity moments of fi(v) are taken beam by beam and summed. Such multi-beam moments of fi(v) have advantages over the customary standard velocity moments of fi(v), for which there is only one mean flow velocity. For example, the standard thermal energy moment of a pair of equal and opposite cold particle beams is non-zero even though each beam has zero thermal energy. We therefore call this thermal energy pseudothermal. By contrast, a multi-beam moment of two or more beams has no pseudothermal energy. We develop three different ways of approximating a compound ion velocity distribution, fi(v), as a sum of beams and finding multi-beam moments for both a compound fi(v) measured by MMS in the dayside magnetosphere during reconnection and a compound fi(v) found in a particle-in-cell simulation of magnetotail reconnection. The three methods are (i) a visual method in which the velocity centroid of each beam is estimated and the beam densities are determined self-consistently, (ii) a k-means method in which particles in a particle representation of fi(v) are sorted into a minimum energy configuration of N (= k) clusters, and (iii) a nonlinear least squares method based on a fit to a sum of N kappa functions. Multi-beam energy moments are calculated and compared with standard moments for the thermal energy density, pressure tensor, thermal energy flux (heat plus enthalpy fluxes), bulk kinetic energy density, ram pressure, and bulk kinetic energy flux. Applying this new formalism to real data demonstrates in detail how multi-beam techniques provide new insights into the energetics of observed space plasmas.