bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bright single photon emitters with enhanced quantum efficiency in a two-dimensional semiconductor coupled with dielectric nano-antennas
Authors: Sortino Luca , Zotev Panaiot G. , Phillips Catherine L. , Brash Alistair J. , Cambiasso Javier , Marensi Elena , Fox A. Mark , Maier Stefan A. , Sapienza Riccardo , Tartakovskii Alexander I. 
Published: October 2021

AbstractSingle photon emitters in atomically-thin semiconductors can be deterministically positioned using strain induced by underlying nano-structures. Here, we couple monolayer WSe2 to high-refractive-index gallium phosphide dielectric nano-antennas providing both optical enhancement and monolayer deformation. For single photon emitters formed on such nano-antennas, we find very low (femto-Joule) saturation pulse energies and up to 104 times brighter photoluminescence than in WSe2 placed on low-refractive-index SiO2 pillars. We show that the key to these observations is the increase on average by a factor of 5 of the quantum efficiency of the emitters coupled to the nano-antennas. This further allows us to gain new insights into their photoluminescence dynamics, revealing the roles of the dark exciton reservoir and Auger processes. We also find that the coherence time of such emitters is limited by intrinsic dephasing processes. Our work establishes dielectric nano-antennas as a platform for high-efficiency quantum light generation in monolayer semiconductors.
Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy
Authors: Abbas Hussein A. , Hao Dapeng , Tomczak Katarzyna , Barrodia Praveen , Im Jin Seon , Reville Patrick K. , Alaniz Zoe , Wang Wei , Wang Ruiping , Wang Feng , Al-Atrash Gheath , Takahashi Koichi , Ning Jing , Ding Maomao , Beird Hannah C. , Mathews Jairo T. , Little Latasha , Zhang Jianhua , Basu Sreyashi , Konopleva Marina , Marques-Piubelli Mario L. , Solis Luisa M. , Parra Edwin Roger , Lu Wei , Tamegnon Auriole , Garcia-Manero Guillermo , Green Michael R. , Sharma Padmanee , Allison James P. , Kornblau Steven M. , Rai Kunal , Wang Linghua , Daver Naval , Futreal Andrew 
Published: October 2021

AbstractIn contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8+ cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy-resistant patients. Trajectory analysis reveals a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8+ T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.
Conformer-specific polar cycloaddition of dibromobutadiene with trapped propene ions
Authors: Kilaj Ardita , Wang Jia , Straňák Patrik , Schwilk Max , Rivero Uxía , Xu Lei , von Lilienfeld O. Anatole , Küpper Jochen , Willitsch Stefan 
Published: October 2021

AbstractDiels–Alder cycloadditions are efficient routes for the synthesis of cyclic organic compounds. There has been a long-standing discussion whether these reactions proceed via stepwise or concerted mechanisms. Here, we adopt an experimental approach to explore the mechanism of the model polar cycloaddition of 2,3-dibromo-1,3-butadiene with propene ions by probing its conformational specificities in the entrance channel under single-collision conditions in the gas phase. Combining a conformationally controlled molecular beam with trapped ions, we find that both conformers of the diene, gauche and s-trans, are reactive with capture-limited reaction rates. Aided by quantum-chemical and quantum-capture calculations, this finding is rationalised by a simultaneous competition of concerted and stepwise reaction pathways, revealing an interesting mechanistic borderline case.
Palmitoylation targets the calcineurin phosphatase to the phosphatidylinositol 4-kinase complex at the plasma membrane
Authors: Ulengin-Talkish Idil , Parson Matthew A. H. , Jenkins Meredith L. , Roy Jagoree , Shih Alexis Z. L. , St-Denis Nicole , Gulyas Gergo , Balla Tamas , Gingras Anne-Claude , Várnai Péter , Conibear Elizabeth , Burke John E. , Cyert Martha S. 
Published: October 2021

AbstractCalcineurin, the conserved protein phosphatase and target of immunosuppressants, is a critical mediator of Ca2+signaling. Here, to discover calcineurin-regulated processes we examined an understudied isoform, CNAβ1. We show that unlike canonical cytosolic calcineurin, CNAβ1 localizes to the plasma membrane and Golgi due to palmitoylation of its divergent C-terminal tail, which is reversed by the ABHD17A depalmitoylase. Palmitoylation targets CNAβ1 to a distinct set of membrane-associated interactors including the phosphatidylinositol 4-kinase (PI4KA) complex containing EFR3B, PI4KA, TTC7B and FAM126A. Hydrogen-deuterium exchange reveals multiple calcineurin-PI4KA complex contacts, including a calcineurin-binding peptide motif in the disordered tail of FAM126A, which we establish as a calcineurin substrate. Calcineurin inhibitors decrease PI4P production during Gq-coupled GPCR signaling, suggesting that calcineurin dephosphorylates and promotes PI4KA complex activity. In sum, this work discovers a calcineurin-regulated signaling pathway which highlights the PI4KA complex as a regulatory target and reveals that dynamic palmitoylation confers unique localization, substrate specificity and regulation to CNAβ1.
Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma
Authors: Pu Weilin , Shi Xiao , Yu Pengcheng , Zhang Meiying , Liu Zhiyan , Tan Licheng , Han Peizhen , Wang Yu , Ji Dongmei , Gan Hualei , Wei Wenjun , Lu Zhongwu , Qu Ning , Hu Jiaqian , Hu Xiaohua , Luo Zaili , Li Huajun , Ji Qinghai , Wang Jiucun , Zhang Xiaoming , Wang Yu-Long 
Published: October 2021

AbstractThe tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.
Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies
Authors: Thomson Benjamin R. , Liu Pan , Onay Tuncer , Du Jing , Tompson Stuart W. , Misener Sol , Purohit Raj R. , Young Terri L. , Jin Jing , Quaggin Susan E. 
Published: October 2021

AbstractPrimary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm’s canal (SC), comprising the conventional aqueous humor outflow pathway of the eye. Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC. Single-cell transcriptomic analysis of normal and glaucomatous Angpt1 deficient eyes allowed us to identify distinct TM and SC cell populations and discover additional TM-SC signaling pathways. Furthermore, confirming the importance of angiopoietin signaling in SC, delivery of a recombinant ANGPT1-mimetic promotes developmental SC expansion in healthy and Angpt1 deficient eyes, blunts intraocular pressure (IOP) elevation and RGC loss in a mouse model of PCG and lowers IOP in healthy adult mice. Our data highlight the central role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis and provide new candidates for SC-targeted glaucoma therapy.
Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer
Authors: Cho Jae-Won , Park Seyeon , Kim Gamin , Han Heonjong , Shim Hyo Sup , Shin Sunhye , Bae Yong-Soo , Park Seong Yong , Ha Sang-Jun , Lee Insuk , Kim Hye Ryun 
Published: October 2021

AbstractPatients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations exhibit an unfavorable response to PD-1 inhibitor through unclear mechanisms. Hypothesizing thatEGFRmutations alter tumor-immune interactions, we compare tumor-infiltrating lymphocytes between EGFR mutant (EGFR-MT) and wild type (EGFR-WT) tumors through single-cell transcriptomic analysis. We find that B cells, CXCL13-producing follicular helper CD4+T (TFH)-like cells, and tissue-resident memory CD8+T (TRM)-like cells decreased in EGFR-MT tumors. The NOTCH-RBPJ regulatory network, which is vital for persistence of TRMstate, is perturbed, and the interactions between TFHand B cells through the CXCL13-CXCR5 axis disappear in EGFR-MT tumors. Notably, the proportion of TRM-like cells is predictive for anti-PD-1 response in NSCLC. Our findings suggest that the impairment of TFH-B-TRMcooperation in tertiary lymphoid structure formation, accompanied by the dysregulation of TRMhomeostasis and the loss of TFH-B crosstalk, underlies unfavorable anti-PD-1 response in EGFR-MT lung tumors.
A gravity-driven sintering method to fabricate geometrically complex compact piezoceramics
Authors: Shan Yao , Liu Shiyuan , Wang Biao , Hong Ying , Zhang Chao , Lim C. W. , Zhang Guangzu , Yang Zhengbao 
Published: October 2021

AbstractHighly compact and geometrically complex piezoceramics are required by a variety of electromechanical devices owing to their outstanding piezoelectricity, mechanical stability and extended application scenarios. 3D printing is currently the mainstream technology for fabricating geometrically complex piezoceramic components. However, it is hard to print piezoceramics in a curve shape while also keeping its compactness due to restrictions on the ceramic loading and the viscosity of feedstocks. Here, we report a gravity-driven sintering (GDS) process to directly fabricate curved and compact piezoceramics by exploiting gravitational force and high-temperature viscous behavior of sintering ceramic specimens. The sintered lead zirconate titanate (PZT) ceramics possess curve geometries that can be facilely tuned via the initial mechanical boundary design, and exhibit high piezoelectric properties comparable to those of conventional-sintered compact PZT (d33 = 595 pC/N). In contrast to 3D printing technology, our GDS process is suitable for scale-up production and low-cost production of piezoceramics with diverse curved surfaces. Our GDS strategy is an universal and facile route to fabricate curved piezoceramics and other functional ceramics with no compromise of their functionalities.
Rapid digital light 3D printing enabled by a soft and deformable hydrogel separation interface
Authors: Wu Jingjun , Guo Jing , Linghu Changhong , Lu Yahui , Song Jizhou , Xie Tao , Zhao Qian 
Published: October 2021

AbstractThe low productivity of typical 3D printing is a major hurdle for its utilization in large-scale manufacturing. Innovative techniques have been developed to break the limitation of printing speed, however, sophisticated facilities or costly consumables are required, which still substantially restricts the economic efficiency. Here we report that a common stereolithographic 3D printing facility can achieve a very high printing speed (400 mm/h) using a green and inexpensive hydrogel as a separation interface against the cured part. In sharp contrast to other techniques, the unique separation mechanism relies on the large recoverable deformation along the thickness direction of the hydrogel interface during the layer-wise printing. The hydrogel needs to be extraordinarily soft and unusually thick to remarkably reduce the adhesion force which is a key factor for achieving rapid 3D printing. This technique shows excellent printing stability even for fabricating large continuous solid structures, which is extremely challenging for other rapid 3D printing techniques. The printing process is highly robust for fabricating diversified materials with various functions. With the advantages mentioned above, the presented technique is believed to make a large impact on large-scale manufacturing.
Technology agnostic frequency characterization methodology for memristors
Authors: Manouras Vasileios , Stathopoulos Spyros , Serb Alex , Prodromakis Themis 
Published: October 2021

AbstractOver the past decade, memristors have been extensively studied for a number of applications, almost exclusively with DC characterization techniques. Studies of memristors in AC circuits are sparse, with only a few examples found in the literature, and characterization methods with an AC input are also sparingly used. However, publications concerning the usage of memristors in this working regime are currently on the rise. Here we propose a "technology agnostic" methodology for memristor testing in certain frequency bands. A measurement process is initially proposed, with specific instructions on sample preparation, followed by an equipment calibration and measurement protocol. This article is structured in a way which aims to facilitate the usage of any available measurement equipment and it can be applied on any type of memristive technology. The second half of this work is centered around the representation of data received from following this process. Bode plot and Nyquist plot representations are considered and the information received from them is evaluated. Finally, examples of expected behaviors are given, characterizing simulated scenarios which represent different internal device models and different switching behaviors, such as capacitive or inductive switching. This study aims at providing a cohesive way for memristor characterization, to be used as a good starting point for frequency applications, and for understanding physical processes inside the devices, by streamlining the measuring process and providing a frame in which data representation and comparison will be facilitated.
Risk factors associated with the severity of COVID-19 in a region of the Brazilian Amazon
Authors: Sardinha Daniele Melo , do Socorro Pompeu de Loiola Rosane , Ferreira Ana Lúcia da Silva , de Sá Carmem Aliandra Freire , Rodrigues Yan Corrêa , Lima Karla Valéria Batista , e Guimarães Ricardo José de Paula Souza , Lima Luana Nepomuceno Gondim Costa 
Published: October 2021

AbstractThe Brazilian Northern region registered a high incidence of COVID-19 cases, particularly in the state of Pará. The present study investigated the risk factors associated with the severity of COVID-19 in a Brazilian Amazon region of 100,819 cases. An epidemiological, cross-sectional, analytical and demographic study, analyzing data on confirmed cases for COVID-19 available at the Brazilian Ministry of Health's surveillance platform, was conducted. Variables such as, municipalities of residence, age, gender, signs and symptoms, comorbidities were included and associated with COVID-19 cases and outcomes. The spatial distribution was performed using the ArcGIS program. A total of 100,819 cases were evaluated. Overall, patients had the mean age of 42.3 years, were female (51.2%) and with lethality reaching 4.79% of cases. Main symptoms included fever (66.5%), cough (61.9%) and sore throat (39.8%). Regarding comorbidities, most of the patients presented cardiovascular disease (5.1%) and diabetes (4.2%). Neurological disease increased risk of death by nearly 15 times, followed by obesity (5.16 times) and immunodeficiency (5.09 time). The municipalities with the highest incidence rate were Parauapebas, Canaã dos Carajás and Jacareacanga. Similarity between the Lower Amazon, Marajó and Southwest mesoregions of Pará state were observed concerning the highest morbidity rates. The obtained data demonstrated that the majority of cases occurred among young adults, females, with the classic influenza symptoms and chronic diseases. Finally, data suggest that the highest incidences were no longer in the metropolitan region of the state. The higher lethality rate than in Brazil may be associated with the greater impacts of the disease in this Amazonian population, or factors associated with fragile epidemiological surveillance in the notification of cases of cure.
Modelling infectious diseases with herd immunity in a randomly mixed population
Authors: Law Kian Boon , M. Peariasamy Kalaiarasu , Mohd Ibrahim Hishamshah , Abdullah Noor Hisham 
Published: October 2021

AbstractThe conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.
The effects of an object’s height and weight on force calibration and kinematics when post-stroke and healthy individuals reach and grasp
Authors: Feingold-Polak Ronit , Yelkin Anna , Edelman Shmil , Shapiro Amir , Levy-Tzedek Shelly 
Published: October 2021

AbstractImpairment in force regulation and motor control impedes the independence of individuals with stroke by limiting their ability to perform daily activities. There is, at present, incomplete information about how individuals with stroke regulate the application of force and control their movement when reaching, grasping, and lifting objects of different weights, located at different heights. In this study, we assess force regulation and kinematics when reaching, grasping, and lifting a cup of two different weights (empty and full), located at three different heights, in a total of 46 participants: 30 sub-acute stroke participants, and 16 healthy individuals. We found that the height of the reached target affects both force calibration and kinematics, while its weight affects only the force calibration when post-stroke and healthy individuals perform a reach-to-grasp task. There was no difference between the two groups in the mean and peak force values. The individuals with stroke had slower, jerkier, less efficient, and more variable movements compared to the control group. This difference was more pronounced with increasing stroke severity. With increasing stroke severity, post-stroke individuals demonstrated altered anticipation and preparation for lifting, which was evident for either cortical lesion side.
Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota
Authors: Zhao Yingchun , Liu Xinglong , Zheng Yinan , Liu Wencong , Ding Chuanbo 
Published: October 2021

AbstractAronia melanocarpais a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine.Aronia melanocarpapolysaccharide (AMP) is the main component of theAronia melanocarpafruit. This research evaluated the delay and protection of AMP obtained fromAronia melanocarpafruit on aging mice byd-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.