bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutralizing the pathological effects of extracellular histones with small polyanions
Authors: Meara Connor H. O’ , Coupland Lucy A. , Kordbacheh Farzaneh , Quah Benjamin J. C. , Chang Chih-Wei , Simon Davis David A. , Bezos Anna , Browne Anna M. , Freeman Craig , Hammill Dillon J. , Chopra Pradeep , Pipa Gergely , Madge Paul D. , Gallant Esther , Segovis Courtney , Dulhunty Angela F. , Arnolda Leonard F. , Mitchell Imogen , Khachigian Levon M. , Stephens Ross W. , von Itzstein Mark , Parish Christopher R.
Published: December 2020

Extracellular histones in neutrophil extracellular traps (NETs) or in chromatin from injured tissues are highly pathological, particularly when liberated by DNases. We report the development of small polyanions (SPAs) (~0.9–1.4 kDa) that interact electrostatically with histones, neutralizing their pathological effects. In vitro, SPAs inhibited the cytotoxic, platelet-activating and erythrocyte-damaging effects of histones, mechanistic studies revealing that SPAs block disruption of lipid-bilayers by histones. In vivo, SPAs significantly inhibited sepsis, deep-vein thrombosis, and cardiac and tissue-flap models of ischemia-reperfusion injury (IRI), but appeared to differ in their capacity to neutralize NET-bound versus free histones. Analysis of sera from sepsis and cardiac IRI patients supported these differential findings. Further investigations revealed this effect was likely due to the ability of certain SPAs to displace histones from NETs, thus destabilising the structure. Finally, based on our work, a non-toxic SPA that inhibits both NET-bound and free histone mediated pathologies was identified for clinical development.
Ultrafast strain engineering and coherent structural dynamics from resonantly driven optical phonons in LaAlO3
Authors: Hortensius J. R. , Afanasiev D. , Sasani A. , Bousquet E. , Caviglia A. D.
Published: December 2020

Strain engineering has been extended recently to the picosecond timescales, driving ultrafast metal–insulator phase transitions and the propagation of ultrasonic demagnetization fronts. However, the nonlinear lattice dynamics underpinning interfacial optoelectronic phase switching have not yet been addressed. Here we perform time-resolved all-optical pump-probe experiments to study ultrafast lattice dynamics initiated by impulsive light excitation tuned in resonance with a polar lattice vibration in LaAlO3 single crystals, one of the most widely utilized substrates for oxide electronics. We show that ionic Raman scattering drives coherent rotations of the oxygen octahedra around a high-symmetry crystal axis. By means of DFT calculations we identify the underlying nonlinear phonon–phonon coupling channel. Resonant lattice excitation is also shown to generate longitudinal and transverse acoustic wave packets, enabled by anisotropic optically induced strain. Importantly, shear strain wave packets are found to be generated with high efficiency at the phonon resonance, opening exciting perspectives for ultrafast material control.
Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer
Authors: Abdel-Wahab Reham , Yap Timothy A. , Madison Russell , Pant Shubham , Cooke Matthew , Wang Kai , Zhao Haitao , Bekaii-Saab Tanios , Karatas Elif , Kwong Lawrence N. , Meric-Bernstam Funda , Borad Mitesh , Javle Milind
Published: December 2020

DNA repair gene aberrations (GAs) occur in several cancers, may be prognostic and are actionable. We investigated the frequency of DNA repair GAs in gallbladder cancer (GBC), association with tumor mutational burden (TMB), microsatellite instability (MSI), programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression. Comprehensive genomic profiling (CGP) of 760 GBC was performed. We investigated GAs in 19 DNA repair genes including direct DNA repair genes (ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MLH1, MSH2, MSH6, PALB2, POLD1, POLE, PRKDC, and RAD50) and caretaker genes (BAP1, CDK12, MLL3, TP53, and BLM) and classified patients into 3 groups based on TMB level: low (< 5.5 mutations/Mb), intermediate (5.5–19.5 mutations/Mb), and high (≥ 19.5 mutations/Mb). We assessed MSI status and PD-1 & PD-L1 expression. 658 (86.6%) had at least 1 actionable GA. Direct DNA repair gene GAs were identified in 109 patients (14.2%), while 476 (62.6%) had GAs in caretaker genes. Both direct and caretaker DNA repair GAs were significantly associated with high TMB (P = 0.0005 and 0.0001, respectively). Tumor PD-L1 expression was positive in 119 (15.6%), with 17 (2.2%) being moderate or high. DNA repair GAs are relatively frequent in GBC and associated with coexisting actionable mutations and a high TMB.
Influence of fluorophore and linker length on the localization and trafficking of fluorescent sterol probes
Authors: Králová Jarmila , Jurášek Michal , Mikšátková Lucie , Marešová Anna , Fähnrich Jan , Cihlářová Petra , Drašar Pavel , Bartůněk Petr , Král Vladimír
Published: December 2020

Fluorescent sterol probes, comprising a fluorophore connected to a sterol backbone by means of a linker, are promising tools for enabling high-resolution imaging of intracellular cholesterol. In this study, we evaluated how the size of the linker, site of its attachment and nature of the fluorophore, affect the localization and trafficking properties of fluorescent sterol probes. Varying lengths of linker using the same fluorophore affected cell penetration and retention in specific cell compartments. A C-4 linker was confirmed as optimal. Derivatives of heterocyclic sterol precursors attached with identical C-4 linker to different fluorophores at diverse positions also showed significant differences in their binding properties to various intracellular compartments and kinetics of trafficking. Two novel red-emitting probes with good cell permeability, fast intracellular labelling and slightly different distribution displayed very promising characteristics for sterol probes. These probes also strongly labelled endo/lysosomal compartment in cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, that overlapped with filipin staining of cholesterol. Overall, the present study demonstrates that the physicochemical properties of the fluorophore/linker pairing determine the kinetics of uptake and distribution and subsequently influence the applicability of final probes.
A new insight into role of phosphoketolase pathway in Synechocystis sp. PCC 6803
Authors: Bachhar Anushree , Jablonsky Jiri
Published: December 2020

Phosphoketolase (PKET) pathway is predominant in cyanobacteria (around 98%) but current opinion is that it is virtually inactive under autotrophic ambient CO2condition (AC-auto). This creates an evolutionary paradox due to the existence of PKET pathway in obligatory photoautotrophs. We aim to answer the paradox with the aid of bioinformatic analysis along with metabolic, transcriptomic, fluxomic and mutant data integrated into a multi-level kinetic model. We discussed the problems linked to neglected isozyme,pket2 (sll0529) and inconsistencies towards the explanation of residual flux via PKET pathway in the case of silencedpket1(slr0453) inSynechocystissp. PCC 6803. Our in silico analysis showed: (1) 17% flux reduction via RuBisCO for Δpket1under AC-auto, (2) 11.2–14.3% growth decrease for Δpket2in turbulent AC-auto, and (3) flux via PKET pathway reaching up to 252% of the flux via phosphoglycerate mutase under AC-auto. All results imply that PKET pathway plays a crucial role under AC-auto by mitigating the decarboxylation occurring in OPP pathway and conversion of pyruvate to acetyl CoA linked to EMP glycolysis under the carbon scarce environment. Finally, our model predicted that PKETs have low affinity to S7P as a substrate.
Deep learning networks reflect cytoarchitectonic features used in brain mapping
Authors: Kiwitz Kai , Schiffer Christian , Spitzer Hannah , Dickscheid Timo , Amunts Katrin
Published: December 2020

The distribution of neurons in the cortex (cytoarchitecture) differs between cortical areas and constitutes the basis for structural maps of the human brain. Deep learning approaches provide a promising alternative to overcome throughput limitations of currently used cytoarchitectonic mapping methods, but typically lack insight as to what extent they follow cytoarchitectonic principles. We therefore investigated in how far the internal structure of deep convolutional neural networks trained for cytoarchitectonic brain mapping reflect traditional cytoarchitectonic features, and compared them to features of the current grey level index (GLI) profile approach. The networks consisted of a 10-block deep convolutional architecture trained to segment the primary and secondary visual cortex. Filter activations of the networks served to analyse resemblances to traditional cytoarchitectonic features and comparisons to the GLI profile approach. Our analysis revealed resemblances to cellular, laminar- as well as cortical area related cytoarchitectonic features. The networks learned filter activations that reflect the distinct cytoarchitecture of the segmented cortical areas with special regard to their laminar organization and compared well to statistical criteria of the GLI profile approach. These results confirm an incorporation of relevant cytoarchitectonic features in the deep convolutional neural networks and mark them as a valid support for high-throughput cytoarchitectonic mapping workflows.
LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
Authors: Thakuri Bal Krishna Chand , Zhang Jinyu , Zhao Juan , Nguyen Lam N. , Nguyen Lam N. T. , Khanal Sushant , Cao Dechao , Dang Xindi , Schank Madison , Wu Xiao Y. , Morrison Zheng D. , Gazzar Mohamed El , Li Zhengke , Jiang Yong , Ning Shunbin , Wang Ling , Moorman Jonathan P. , Yao Zhi Q.
Published: December 2020

HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that plays a pivotal role in regulating myeloid cell development via targeting HOXA1 gene expression. We and others have previously shown that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells, expand during chronic viral (HCV, HIV) infections. However, the role of HOTAIRM1 in the development and suppression of MDSCs during viral infection remains unknown. In this study, we demonstrate that the expressions of HOTAIRM1 and its target HOXA1 are substantially upregulated to promote the expressions of immunosuppressive molecules, including arginase 1, inducible nitric oxide synthase, signal transducer and activator of transcription 3, and reactive oxygen species, in CD33+ myeloid cells derived from hepatitis C virus (HCV)-infected patients. We show that HCV-associated exosomes (HCV-Exo) can modulate HOTAIRM1, HOXA1, and miR124 expressions to regulate MDSC development. Importantly, overexpression of HOTAIRM1 or HOXA1 in healthy CD33+ myeloid cells promoted the MDSC differentiation and suppressive functions; conversely, silencing of HOTAIRM1 or HOXA1 expression in MDSCs from HCV patients significantly reduced the MDSC frequency and their suppressive functions. In essence, these results indicate that the HOTAIRM1-HOXA1-miR124 axis enhances the differentiation and suppressive functions of MDSCs and may be a potential target for immunomodulation in conjunction with antiviral therapy during chronic viral infection.
Pentosidine and carboxymethyl-lysine associate differently with prevalent osteoporotic vertebral fracture and various bone markers
Authors: Nakano Masaki , Nakamura Yukio , Suzuki Takako , Miyazaki Akiko , Takahashi Jun , Saito Mitsuru , Shiraki Masataka
Published: December 2020

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22–2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r =  − 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76–0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms.
Attosecond streaking using a rescattered electron in an intense laser field
Authors: Kim Yang Hwan , Ivanov Igor A. , Hwang Sung In , Kim Kyungseung , Nam Chang Hee , Kim Kyung Taec
Published: December 2020

When an atom or molecule is exposed to a strong laser field, an electron can tunnel out from the parent ion and moves along a specific trajectory. This ultrafast electron motion is sensitive to a variation of the laser field. Thus, it can be used as a fast temporal gate for the temporal characterization of the laser field. Here, we demonstrate a new type of attosecond streaking wherein a rescattered electron trajectory is manipulated by an ultrashort laser pulse. The vector potential of the laser pulse is directly recorded in the photoelectron spectra of the rescattered electron. In contrast to high harmonic generation methods, our approach has no directional ambiguity in space, leading to complete in situ temporal characterization. In addition, it provides timing information on ionization and re-scattering events. Therefore, our approach can be a useful tool for the investigation of strong-field processes triggered by rescattering, such as non-sequential double ionization and laser-induced electron diffraction.
Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol
Authors: Linciano Pasquale , Citti Cinzia , Russo Fabiana , Tolomeo Francesco , Laganà Aldo , Capriotti Anna Laura , Luongo Livio , Iannotta Monica , Belardo Carmela , Maione Sabatino , Forni Flavio , Vandelli Maria Angela , Gigli Giuseppe , Cannazza Giuseppe
Published: December 2020

The two most important and studied phytocannabinoids present in Cannabis sativa L. are undoubtedly cannabidiol (CBD), a non-psychotropic compound, but with other pharmacological properties, and Δ9-tetrahydrocannabinol (Δ9-THC), which instead possesses psychotropic activity and is responsible for the recreative use of hemp. Recently, the homolog series of both CBDs and THCs has been expanded by the isolation in a medicinal cannabis variety of four new phytocannabinoids possessing on the resorcinyl moiety a butyl-(in CBDB and Δ9-THCB) and a heptyl-(in CBDP and Δ9-THCP) aliphatic chain. In this work we report a new series of phytocannabinoids that fills the gap between the pentyl and heptyl homologs of CBD and Δ9-THC, bearing a n-hexyl side chain on the resorcinyl moiety that we named cannabidihexol (CBDH) and Δ9-tetrahydrocannabihexol (Δ9-THCH), respectively. However, some cannabinoids with the same molecular formula and molecular weight of CBDH and Δ9-THCH have been already identified and reported as monomethyl ether derivatives of the canonical phytocannabinoids, namely cannabigerol monomethyl ether (CBGM), cannabidiol monomethyl ether (CBDM) and Δ9-tetrahydrocannabinol monomethyl ether (Δ9-THCM). The unambiguously identification in cannabis extract of the n-hexyl homologues of CBD and Δ9-THC different from the corresponding methylated isomers (CBDM, CBGM and Δ9-THCM) was achieved by comparison of the retention time, molecular ion, and fragmentation spectra with those of the authentic standards obtained via stereoselective synthesis, and a semi-quantification of these cannabinoids in the FM2 medical cannabis variety was provided. Conversely, no trace of Δ9-THCM was detected. Moreover, CBDH was isolated by semipreparative HPLC and its identity was confirmed by comparison with the spectroscopic data of the corresponding synthetic standard. Thus, the proper recognition of CBDH, CBDM and Δ9-THCH closes the loop and might serve in the future for researchers to distinguish between these phytocannabinoids isomers that show a very similar analytical behaviour. Lastly, CBDH was assessed for biological tests in vivo showing interesting analgesic activity at low doses in mice.
Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion
Authors: Paone Silvio , D’Alessandro Sarah , Parapini Silvia , Celani Francesco , Tirelli Valentina , Pourshaban Manoochehr , Olivieri Anna
Published: December 2020

Malaria is still a devastating disease with 228 million cases globally and 405,000 lethal outcomes in 2018, mainly in children under five years of age. The threat of emerging malaria strains resistant to currently available drugs has made the search for novel drug targets compelling. The process by which Plasmodium falciparum parasites invade the host cell has been widely studied, but only a few erythrocyte proteins involved in this process have been identified so far. The erythrocyte protein Rac1 is a GTPase that plays an important role in host cell invasion by many intracellular pathogens. Here we show that Rac1 is recruited in proximity to the site of parasite entry during P. falciparum invasion process and that subsequently localizes to the parasitophorous vacuole membrane. We also suggest that this GTPase may be involved in erythrocyte invasion by P. falciparum, by testing the effect of specific Rac1 inhibitory compounds. Finally, we suggest a secondary role of the erythrocyte GTPase also in parasite intracellular development. We here characterize a new erythrocyte protein potentially involved in P. falciparum invasion of the host cell and propose the human GTPase Rac1 as a novel and promising antimalarial drug target.
Spatial calibration and PM2.5 mapping of low-cost air quality sensors
Authors: Chu Hone-Jay , Ali Muhammad Zeeshan , He Yu-Chen
Published: December 2020

The data quality of low-cost sensors has received considerable attention and has also led to PM2.5 warnings. However, the calibration of low-cost sensor measurements in an environment with high relative humidity is critical. This study proposes an efficient calibration and mapping approach based on real-time spatial model. The study carried out spatial calibration, which automatically collected measurements of low-cost sensors and the regulatory stations, and investigated the spatial varying pattern of the calibrated low-cost sensor data. The low-cost PM2.5 sensors are spatially calibrated based on reference-grade measurements at regulatory stations. Results showed that the proposed spatial regression approach can explain the variability of the biases from the low-cost sensors with an R-square value of 0.94. The spatial calibration and mapping algorithm can improve the bias and decrease to 39% of the RMSE when compared to the nonspatial calibration model. This spatial calibration and real-time mapping approach provide a useful way for local communities and governmental agencies to adjust the consistency of the sensor network for improved air quality monitoring and assessment.
Chronically infused angiotensin II induces depressive-like behavior via microglia activation
Authors: Park Hyun-Sun , You Min-Jung , Yang Bohyun , Jang Kyu Beom , Yoo Jongman , Choi Hyun Jin , Lee Sang-Hyuk , Bang Minji , Kwon Min-Soo
Published: December 2020

Brain inflammation is one of hypotheses explaining complex pathomechanisms of depression. Angiotensin II (ANGII), which is associated with hypertension, also induces brain inflammation. However, there is no animal study showing the direct relationship between ANGII and depression. To address this issue, ANGII-containing osmotic pumps were implanted into adult male C57BL/6 mice subcutaneously for subacute (7 days) and chronic (at least 21 days) periods and behavioral and molecular analyses were conducted. Chronic infusion of ANGII into mice induced depressive-like behaviors, including the tail suspension test and forced swimming test, which were reversed by imipramine. Chronic infusion of ANGII also induced microglial activation in the hippocampus with increase of Il-1β mRNA and decrease of Arg1 mRNA. In addition, chronic ANGII infusion activated the hypothalamic–pituitary–adrenal axis (HPA axis) and resulted in decreased hippocampal glucocorticoid receptor level. However, subacute ANGII infusion did not induce significant molecular and behavioral changes in mice compared to that of control. The molecular and behavioral changes by chronic ANGII infusion were reversed by co-treatment of minocycline or telmisartan. In addition, ANGII treatment also induced the pro-inflammatory changes in BV-2 microglial cells. Our results indicate that ANGII can induce depressive-like behaviors via microglial activation in the hippocampus and HPA axis hyperactivation in mice. These might suggest possible mechanism on depressive symptom in chronic hypertensive state.
The effect of diabetes and the common diabetogenic TBC1D4 p.Arg684Ter variant on cardiovascular risk in Inuit in Greenland
Authors: Overvad Maria , Diaz Lars Jorge , Bjerregaard Peter , Pedersen Michael Lynge , Larsen Christina Viskum Lytken , Senftleber Ninna , Grarup Niels , Hansen Torben , Jørgensen Marit Eika
Published: December 2020

Cardiovascular disease (CVD) is a well-known complication of diabetes, but the association has not been studied among Inuit in Greenland. The aim was to examine the association between diabetes and incident CVD among Inuit in Greenland and determine if the common diabetogenic TBC1D4 variant confers increased risk of CVD. We followed an initial study population of 4127 adults in Greenland who had participated in at least one population-based health survey, in national registers. We used Poisson regression to calculate incidence rate ratios (IRR) of cardiovascular endpoints, comparing participants with and without diabetes and comparing homozygous TBC1D4 carriers with heterozygous carriers and non-carriers combined. Close to 10% had diabetes and age range was 18–96 years (45% male). Of the 3924 participants without prior CVD, 362 (~ 9%) had CVD events during a median follow-up of 10 years. Multivariate IRR for the effect of diabetes on CVD was 1.12 (95% CI: 0.80, 1.57) p = 0.50. Using a recessive genetic model, we compared homozygous TBC1D4 carriers with wildtype and heterozygous carriers combined, with a multivariate IRR of 1.20 (95% CI: 0.69, 2.11) p = 0.52. Neither diabetes nor the TBC1D4 variant significantly increased CVD risk among Inuit in Greenland in adjusted models.
Exploring optimal control of epidemic spread using reinforcement learning
Authors: Ohi Abu Quwsar , Mridha M. F. , Monowar Muhammad Mostafa , Hamid Md. Abdul
Published: December 2020

Pandemic defines the global outbreak of a disease having a high transmission rate. The impact of a pandemic situation can be lessened by restricting the movement of the mass. However, one of its concomitant circumstances is an economic crisis. In this article, we demonstrate what actions an agent (trained using reinforcement learning) may take in different possible scenarios of a pandemic depending on the spread of disease and economic factors. To train the agent, we design a virtual pandemic scenario closely related to the present COVID-19 crisis. Then, we apply reinforcement learning, a branch of artificial intelligence, that deals with how an individual (human/machine) should interact on an environment (real/virtual) to achieve the cherished goal. Finally, we demonstrate what optimal actions the agent perform to reduce the spread of disease while considering the economic factors. In our experiment, we let the agent find an optimal solution without providing any prior knowledge. After training, we observed that the agent places a long length lockdown to reduce the first surge of a disease. Furthermore, the agent places a combination of cyclic lockdowns and short length lockdowns to halt the resurgence of the disease. Analyzing the agent’s performed actions, we discover that the agent decides movement restrictions not only based on the number of the infectious population but also considering the reproduction rate of the disease. The estimation and policy of the agent may improve the human-strategy of placing lockdown so that an economic crisis may be avoided while mitigating an infectious disease.
Ultrastrong catalyst-free polycrystalline diamond
Authors: Li Qiang , Zhan Guodong , Li Dong , He Duanwei , Moellendick Timothy Eric , Gooneratne Chinthaka P. , Alalsayednassir Alawi G.
Published: December 2020

Diamond is the hardest naturally occurring material found on earth but single crystal diamond is brittle due to the nature of catastrophic cleavage fracture. Polycrystalline diamond compact (PDC) materials are made by high pressure and high temperature (HPHT) technology. PDC materials have been widely used in several industries. Wear resistance is a key material property that has long been pursued for its valuable industrial applications. However, the inevitable use of catalysts introduced by the conventional manufacturing process significantly reduces their end-use performance and limits many of their potential applications. In this work, an ultra-strong catalyst-free polycrystalline diamond compact material has been successfully synthesized through innovative ultra-high pressure and ultra-high temperature (UHPHT) technology. These results set up new industry records for wear resistance and thermal stability for PDC cutters utilized for drilling in the oil and gas industry. The new material also broke all single-crystal diamond indenters, suggesting that the new material is too hard to be measured by the current standard single-crystal diamond indentation method. This represents a major breakthrough in hard materials that can expand many potential scientific research and industrial applications.
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques
Authors: Li Z. , Khanna M. , Grimley S. L. , Ellenberg P. , Gonelli C. A. , Lee Wen Shi , Amarasena T. H. , Kelleher A. D. , Purcell D. F. J. , Kent S. J. , Ranasinghe C.
Published: December 2020

Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) recombinant Modified Vaccinia Ankara Virus (MVA)-gag pol-IL-4R antagonist boost followed by an i.m SOSIP-gp140 boost. The viral vector—expressed IL-4R antagonist transiently inhibited IL-4/IL-13 signalling at the vaccination site. The SOSIP booster not only induced gp140-specific IgG, ADCC (antibody-dependent cellular cytotoxicity) and some neutralisation activity, but also bolstered the HIV-specific cellular and humoral responses. Specifically, superior sustained systemic and mucosal HIV Gag-specific poly-functional/cytotoxic CD4+ and CD8+ T cells were detected with the IL-4R antagonist adjuvanted strategy compared to the unadjuvanted control. In the systemic compartment elevated Granzyme K expression was linked to CD4+ T cells, whilst Granzyme B/TIA-1 to CD8+ T cells. In contrast, the cytotoxic marker expression by mucosal CD4+ and CD8+ T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4+ T cells at the first line of defence, and cytotoxic CD4+ and CD8+ T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation.
Anomalous blueshift of aperture resonance enabled by the loss of a thin film
Authors: Kyoung Jisoo
Published: December 2020

The substrate effects on aperture resonance have been widely studied because the resonance peak position is key for sensing, communications, and field enhancement applications. So far, the theoretical works have focused on the lossless infinite substrate case, which only explains the resonance peak redshift by the substrate index. The loss effect has not been investigated yet because lossy infinite substrate significantly reduces the aperture transmission. Therefore, this work studied the loss effect on aperture resonance via an analytic model of the transmission though slot antennas on a finite substrate. When the substrate thickness was very thin compared to the wavelength, the transmittance remained high even for a large imaginary part of the refractive index; furthermore, the developed model predicted a strong blueshift when this imaginary part exceeds the real part. Besides, the zero of the imaginary part of the coupling strength was crucial in determining the resonance frequency for both infinite and finite substrates. Thus, this study can contribute to the material characterization, label-free detection, and efficient design of active metamaterials.
Single-cell analysis supports a luminal-neuroendocrine transdifferentiation in human prostate cancer
Authors: Dong Baijun , Miao Juju , Wang Yanqing , Luo Wenqin , Ji Zhongzhong , Lai Huadong , Zhang Man , Cheng Xiaomu , Wang Jinming , Fang Yuxiang , Zhu Helen He , Chua Chee Wai , Fan Liancheng , Zhu Yinjie , Pan Jiahua , Wang Jia , Xue Wei , Gao Wei-Qiang
Published: December 2020

Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.
NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors
Authors: Somwar Romel , Hofmann Nicolle E. , Smith Bryan , Odintsov Igor , Vojnic Morana , Linkov Irina , Tam Ashley , Khodos Inna , Mattar Marissa S. , de Stanchina Elisa , Flynn Daniel , Ladanyi Marc , Drilon Alexander , Shinde Ujwal , Davare Monika A.
Published: December 2020

Tyrosine kinase domains dynamically fluctuate between two main structural forms that are referred to as type I (DFG-in) or type II (DFG-out) conformations. Comprehensive data comparing type I and type II inhibitors are currently lacking for NTRK fusion-driven cancers. Here we used a type II NTRK inhibitor, altiratinib, as a model compound to investigate its inhibitory potential for larotrectinib (type I inhibitor)-resistant mutations in NTRK. Our study shows that a subset of larotrectinib-resistant NTRK1 mutations (V573M, F589L and G667C) retains sensitivity to altiratinib, while the NTRK1V573Mand xDFG motif NTRK1G667Cmutations are highly sensitive to type II inhibitors, including altiratinib, cabozantinib and foretinib. Moreover, molecular modeling suggests that the introduction of a sulfur moiety in the binding pocket, via methionine or cysteine substitutions, specifically renders the mutant kinase hypersensitive to type II inhibitors. Future precision treatment strategies may benefit from selective targeting of these kinase mutants based on our findings.
A spot test for direct quantification of acid green 16 adsorbed on a molecularly imprinted polymer through diffuse reflectance measurements
Authors: Mortari Bianca , Khan Sabir , Wong Ademar , Sotomayor Maria D. P. T.
Published: December 2020

This work describes a novel technique for the direct quantification of Acid Green 16 (AG16) adsorbed on a molecularly imprinted polymer (MIP) through the application of diffuse reflectance spectrophotometry (DRS) directly in a slid material.
Near-infrared laser-triggered drug release in a tellurium nanosystem for simultaneous chemo-photothermal cancer therapy
Authors: Duan Linqi , Liu Ting , Chen Tianfeng
Published: December 2020

Herein, we synthesize a shape-controllable Te nanosystem, which can control the release of DOX under weakly acidic conditions to kill tumor cells, and is more effective in combination with photothermal/chemo-therapy.
Deep learning-based morphology classification of activated sludge flocs in wastewater treatment plants
Authors: Satoh Hisashi , Kashimoto Yukari , Takahashi Naoki , Tsujimura Takashi
Published: December 2020

A deep learning-based two-label classifier 1 recognized a 20% morphological change in the activated flocs. Classifier-2 quantitatively recognized an abundance of filamentous bacteria in activated flocs.
Effect of the protein hydrolysate of rice syrup meal on the endurance exercise performance of BALB/c mice
Authors: Chang Yeok Boo , Hong Ki-Bae , Kim Min Guk , Suh Hyung Joo , Jo Kyungae
Published: December 2020

Rice is a staple food in Korea.
Metabolically engineered bacteria as light-controlled living therapeutics for anti-angiogenesis tumor therapy
Authors: Liu Xingang , Wu Min , Wang Meng , Duan Yukun , Phan ChiUyen , Qi Guobin , Tang Guping , Liu Bin
Published: December 2020

A living therapeutic system based on attenuated Salmonella was developed via metabolic engineering using an aggregation-induced emission (AIE) photosensitizer MA.
N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny
Authors: Kavanagh Emma L. , Halasz Melinda , Dowling Paul , Withers Jo , Lindsay Sinéad , Higgins Michaela J. , Irwin Jane A. , Rudd Pauline M. , Saldova Radka , McCann Amanda
Published: December 2020

Therapeutic-induced-senescent (TIS) Cal51 TNBC cells display differential N-glycan moieties compared to non-senescent cells, depending on cellular location and EV progeny.
Near-infrared small molecule coupled with rigidness and flexibility for high-performance multimodal imaging-guided photodynamic and photothermal synergistic therapy
Authors: Li Xiaozhen , Fang Fang , Sun Bo , Yin Chao , Tan Jihua , Wan Yingpeng , Zhang Jinfeng , Sun Pengfei , Fan Quli , Wang Pengfei , Li Shengliang , Lee Chun-Sing
Published: December 2020

A simple π-conjugated oligomer nanotheranostic with intrinsic multifunctionality was developed for 808 nm laser-triggered effective NIR-II fluorescence/photoacoustic imaging and photodynamic/photothermal synergistic therapy.
An aromatic-rich cage-based MOF with inorganic chloride ions decorating the pore surface displaying the preferential adsorption of C2H2and C2H6over C2H4
Authors: Jiang Zhenzhen , Fan Lihui , Zhou Ping , Xu Tingting , Hu Simin , Chen Jingxian , Chen De-Li , He Yabing
Published: December 2020

An aromatic-rich chloride-embedded nanocage-based MOF displayed an unusual adsorption relationship towards C2hydrocarbons, with the potential for C2H4separation and purification application.
Covalent and non-covalent binding in vanadium–protein adducts
Authors: Ugone Valeria , Sanna Daniele , Ruggiu Simone , Sciortino Giuseppe , Garribba Eugenio
Published: December 2020

An integrated method, generalizable to any metals and proteins, based on ESI-MS, EPR and molecular modelling was applied to study the covalent and non-covalent binding of the potential drug [VIVO(nalidixato)2(H2O)] to lysozyme and cytochrome c.
Photocatalytic intramolecular radical cyclization involved synergistic SET and HAT: synthesis of 3,3-difluoro-γ-lactams
Authors: Zhuang Xiaohui , Shi Xiayue , Zhu Rui , Sun Bin , Su WeiKe , Jin Can
Published: December 2020

A mild and metal-free protocol for visible-light induced intramolecular radical cyclization of N-allyl(propargyl)-2-bromo-2,2-difluoro-N-arylacetamide has been developed.
Synthesis and pH-stimuli responsive research of gemini amine-oxide surfactants containing amides
Authors: Chen Hanyu , Fu Duojiao , Zhou Xiqin , Liu Hongqin , Xu Baocai
Published: December 2020

The series of gemini amine-oxide surfactants with the formula CnH2n+1CONH(CH2)2N+O–(CH3)–(CH2)3–(CH3)N+O– (CH2)2NHCOCnH2n+1 (n = 11, 13, 15, and 17) have been synthesized, and their pH-stimuli responsive behavior in aqueous solution has been studied.
Multilayered composite-coated ionically crosslinked food-grade hydrogel beads generated from algal alginate for controlled and sustained release of bioactive compounds
Authors: Lai Wing-Fu , Wong Eric , Wong Wing-Tak
Published: December 2020

Multilayered composite-coated hydrogel beads are generated from algal alginate as carriers of bioactive compounds. They show high potential for applications in functional food development, nutraceutical delivery, and pharmaceutical formulation.
From circular synthesis to material manufacturing: advances, challenges, and future steps for using flow chemistry in novel application area
Authors: Sivo Alessandra , Galaverna Renan de Souza , Gomes Gustavo Rodrigues , Pastre Julio Cezar , Vilé Gianvito
Published: December 2020

We review the emerging use of flow technologies for circular chemistry and material manufacturing, highlighting advances, challenges, and future directions.
A polyoxometalate@covalent triazine framework as a robust electrocatalyst for selective benzyl alcohol oxidation coupled with hydrogen production
Authors: Li Zhen , Zhang Junhao , Jing Xiaoting , Dong Jing , Liu Huifang , Lv Hongjin , Chi Yingnan , Hu Changwen
Published: December 2020

Electrocatalytic oxidation has been proven as a sustainable and promising alternative to traditional chemical transformation, but its further development is limited by the use of noble-metal electrocatalysts.
Cross-linked (R)-(+)-lipoic acid nanoparticles with prodrug loading for synergistic cancer therapy
Authors: Yang Fan , Chen Yun , Zhang Jing , Liao Chunyan , Zhang Shiyong
Published: December 2020

Pro-CPT@cLAMs are featured by their low toxicity and synergistic antitumor effect of carriers.
Flexible polymer/fabric fractal monopole antenna for wideband applications
Authors: Al‐Sehemi Abdullah , Al‐Ghamdi Ahmed , Dishovsky Nikolay , Atanasova Gabriela , Atanasov Nikolay
Published: December 2020

A novel flexible polymer/fabric fractal monopole antenna with a wideband performance is presented. A thin sheet of highly conductive fabric and a natural rubber‐based composite have been used for conductive and non‐conductive parts of the antenna, which allow keeping the antenna as flexible and thin as possible. The proposed antenna has been simulated, prototyped and tested. Results show that the antenna has a simulated impedance bandwidth of 3.8 GHz (2.2–6.0 GHz) and a measured impedance bandwidth of 3.7 GHz (2.3–6.0 GHz) to cover the most commonly used standards in wireless communication systems. The radiation efficiency of the antenna reaches over 93% throughout the operating frequency band with satisfactory radiation patterns and gain.
Numerical demonstration of triangular shaped photonic crystal fibre‐based biosensor in the Terahertz range
Authors: Ahmed Kawsar , Paul Bikash Kumar , Ahmed Fahad , Jabin Md. Asaduzzaman , Uddin Muhammad Shahin
Published: December 2020

In this study, a novel design of microstructure ring‐based triangular mold photonic crystal fibre has been numerically investigated and introduced as an alcohol sensor in Terahertz (THz) band region to get a very high relative‐sensitivity and negligible confinement‐loss profile. Perfectly Matched Layer contains circular air holes with a semi‐poly crystalline symmetric core structure in the triangular cladding region. The entire evaluation process is done by analyzing 2,888,310 mesh elements with the finite element method. Also, the proposed model is justified for an operating frequency of the THz band gap between 1.4 THz and 3.5 THz along with a base material of TOPAS. Last of all, the relative sensitivity profiles of the proposed model are 79.39%, 79.99%, and 80.27% respectively to the water, ethanol, benzene at an optimum frequency of 1.5 THz. In fact, the most optimum performance indicators are 1.18 × 10−12 dB/m, 1.8 × 10−5 µm2, 80%, 0.1 ps/THz/cm and 0.1‐1.5 respectively to the confinement‐loss (Lc), effective area (Aeff), power fraction (η′), dispersion (β2) and V‐Parameter (Veff) at the following optimum frequency for the proposed structure. By evaluating these performance profiles, the proposed model can prove itself a better choice than any other prior model in the field of sensing.
Multi-aspect impact of eco-innovations (“sustainable goods”) as a form of development of innovative potential of the region
Authors: Khasanova Asiya , Dotsenko Elena , Ezdina Natalya , Khasanov Magdi
Published: December 2020

The article considers spatial distribution of innovations as one of the forms of implementation of the mechanism of their evolution, which leads to the formation of “centers” and “peripheries” of the innovation potential of the national economy. The paper takes into account the features of the spatial organization of the economy, formed as a result of the allocation and reallocation of assets under the influence of competition processes, which are reflected in neoclassical theories of economic growth.
Probability-Statistical Models to Forecast Hydraulic Fracturing Efficiency
Authors: Gabdrakhmanova Klara Fatkullinovna , Izmaylova Gulnara Rishadovna , Samigullin Eldar Faritovich , Gilmanov Rishat Sabirovich
Published: December 2020

The article discusses the criteria for choosing fracture parameters by length, height and amount of proppant to be injected. The criteria, chosen on the basis of for probabilistic and statistical analysis are to ensure adequate application of multiand single-stage hydraulic fracturing technique. The statistical indicators analysis of the multistage hydraulic fracturing application on the AS12-3 horizon made it possible to clarify the ranges of main hydraulic fractures parameters in terms of their length, volume, number of fractures and the weight of the injected proppant.
Formalization of target and assessment of quality of the cyber-physical control systems for emissions reduction technologies
Authors: Solnitsev Remir , Korshunov Gennady
Published: December 2020

Monitoring and inventory is a necessary but not sufficient condition to reduce emissions in the energy and industry. The ultimate task of controlling air purification technologies in combination with monitoring is effectively achieved while minimizing the human factor. The creation and application of cyber-physical technology management systems provide a solution to a set of related environmental problems. In addition, the development of models based on cyber-physical systems forms new requirements for the development of technologies for their creation. A special feature of such technologies is close interaction between computing methods with design and production facilities. These issues have not been sufficiently reflected in publications. The article presents the target setting for the creation of cyber-physical technology control systems based on local laws of preservation and the decomposition of the target into macroscopic quality assessments. A mathematical model and methods of quality assessment at the life cycle stages of such systems based on recalculation of probability densities of a priori data are presented. Examples of cyber-physical emission reduction systems in the energy and industry developed under the nature-technology concept are given.
MicroCHP Based on the Brayton Microturbine with the Changed Order of Processes for the energy supply in low-rise housing
Authors: Zhinov Andrey A. , Shevelev Denis V. , Lipihin Evgeni G.
Published: December 2020

For autonomous power supply it’s suggested to use microCHP (micro combined heat and power plant) based on the Brayton microturbine with the changed order of processes (reversed Brighton cycle). The paper presents the characteristic ranges of thermal and electric power of autonomous consumers in various climate zones and thermodynamic calculations for the two types of microturbine. In the first case, the parameters of the turbine unit are set according to the characteristics of modern vehicles turbochargers, in the second based on the parameters of modern gas microturbines. The work of microCHP based on the microturbine with the changed order of processes was considered for both traditional and low-temperature heating systems. The electric power of microCHP ranges from 2 to 15 kW, thermal power - from 45 to 160 kW. The peculiarity of MicroCHP is combustion of fuel at atmospheric pressure, which allows the use of natural gas from low-pressure networks, solid fuel, and garbage. It is concluded that this turbine unit is able to solve the problem of electricity and heat supply to most isolated consumers in various climate zones.
Features and results of assessment the thermal conductivity of building materials and products by the active method of thermal non-destructive testing
Authors: Karpov Denis , Pavlov Mikhail , Mukhametova Liliya , Mikhin Anton A.
Published: December 2020

Thermal control (passive and active) is a non-destructive testing method. During passive thermal control, the test object is characterized by a temperature field formed during its operation. In active thermal control, the test object is additionally thermally stimulated. This technique is widely used in various areas of construction, energy, mechanical engineering, transport. This paper proposes a variant of active thermal non-destructive assessment of the thermal conductivity coefficient of building materials and products on the example of a fragment of a building structure made of silicate bricks. The test object is subjected to thermal stimulation by an external source of thermal energy before reaching a steady-state thermal regime. Thermography of the test object surfaces is carried out. The average integral temperatures of surfaces or individual sections of the test object are calculated. The coefficient of thermal conductivity of the test object is determined, which is used to calculate its thermal resistance (resistance to heat transfer). After that, the coefficient of heat transfer is calculated. The method was implemented in laboratory conditions. It can be used in natural and operational conditions for accurate and quick determination of the key thermophysical properties of building materials and products.