bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractStrain 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

AbstractDNA 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

AbstractFluorescent 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

AbstractPhosphoketolase (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

AbstractThe 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

AbstractHOXA 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

AbstractPentosidine (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

AbstractWhen 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

AbstractThe 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

AbstractMalaria 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

AbstractThe 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

AbstractBrain 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

AbstractCardiovascular 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

AbstractPandemic 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.