bluuebunny/crossref_metadata_2025 huggingface dataset:
Conducting double-blind placebo-controlled clinical trials of transcranial alternating current stimulation (tACS)
Authors: Frohlich Flavio , Riddle Justin
Published: May 2021

Many psychiatric and neurological illnesses can be conceptualized as oscillopathies defined as pathological changes in brain network oscillations. We previously proposed the application of rational design for the development of non-invasive brain stimulation for the modulation and restoration of cortical oscillations as a network therapeutic. Here, we show how transcranial alternating current stimulation (tACS), which applies a weak sine-wave electric current to the scalp, may serve as a therapeutic platform for the treatment of CNS illnesses. Recently, an initial series of double-blind, placebo-controlled treatment trials of tACS have been published. Here, we first map out the conceptual underpinnings of such trials with focus on target identification, engagement, and validation. Then, we discuss practical aspects that need to be considered for successful trial execution, with particular regards to ensuring successful study blind. Finally, we briefly review the few published double-blind tACS trials and conclude with a proposed roadmap to move the field forward with the goal of moving from pilot trials to convincing efficacy studies of tACS.
Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons
Authors: Anzell Anthony R. , Fogo Garrett M. , Gurm Zoya , Raghunayakula Sarita , Wider Joseph M. , Maheras Kathleen J. , Emaus Katlynn J. , Bryson Timothy D. , Wang Madison , Neumar Robert W. , Przyklenk Karin , Sanderson Thomas H.
Published: May 2021

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.
Heterodyne sensing of microwaves with a quantum sensor
Authors: Meinel Jonas , Vorobyov Vadim , Yavkin Boris , Dasari Durga , Sumiya Hitoshi , Onoda Shinobu , Isoya Junichi , Wrachtrup Jörg
Published: May 2021

Diamond quantum sensors are sensitive to weak microwave magnetic fields resonant to the spin transitions. However, the spectral resolution in such protocols is ultimately limited by the sensor lifetime. Here, we demonstrate a heterodyne detection method for microwaves (MW) leading to a lifetime independent spectral resolution in the GHz range. We reference the MW signal to a local oscillator by generating the initial superposition state from a coherent source. Experimentally, we achieve a spectral resolution below 1 Hz for a 4 GHz signal far below the sensor lifetime limit of kilohertz. Furthermore, we show control over the interaction of the MW-field with the two-level system by applying dressing fields, pulsed Mollow absorption and Floquet dynamics under strong longitudinal radio frequency drive. While pulsed Mollow absorption leads to improved sensitivity, the Floquet dynamics allow robust control, independent from the system’s resonance frequency. Our work is important for future studies in sensing weak microwave signals in a wide frequency range with high spectral resolution.
Hotspot exons are common targets of splicing perturbations
Authors: Glidden David T. , Buerer Jeramiah L. , Saueressig Camillo F. , Fairbrother William G.
Published: May 2021

High-throughput splicing assays have demonstrated that many exonic variants can disrupt splicing; however, splice-disrupting variants distribute non-uniformly across genes. We propose the existence of exons that are particularly susceptible to splice-disrupting variants, which we refer to as hotspot exons. Hotspot exons are also more susceptible to splicing perturbation through drug treatment and knock-down of RNA-binding proteins. We develop a classifier for exonic splice-disrupting variants and use it to infer hotspot exons. We estimate that 1400 exons in the human genome are hotspots. Using panels of splicing reporters, we demonstrate how the ability of an exon to tolerate a mutation is inversely proportional to the strength of its neighboring splice sites.
Interconversion of multiferroic domains and domain walls
Authors: Hassanpour E. , Weber M. C. , Zemp Y. , Kuerten L. , Bortis A. , Tokunaga Y. , Taguchi Y. , Tokura Y. , Cano A. , Lottermoser Th. , Fiebig M.
Published: May 2021

Systems with long-range order like ferromagnetism or ferroelectricity exhibit uniform, yet differently oriented three-dimensional regions called domains that are separated by two-dimensional topological defects termed domain walls. A change of the ordered state across a domain wall can lead to local non-bulk physical properties such as enhanced conductance or the promotion of unusual phases. Although highly desirable, controlled transfer of these properties between the bulk and the spatially confined walls is usually not possible. Here, we demonstrate this crossover by confining multiferroic Dy0.7Tb0.3FeO3 domains into multiferroic domain walls at an identified location within a non-multiferroic environment. This process is fully reversible; an applied magnetic or electric field controls the transformation. Aside from expanding the concept of multiferroic order, such interconversion can be key to addressing antiferromagnetic domain structures and topological singularities.
Equilibrium and non-equilibrium furanose selection in the ribose isomerisation network
Authors: Dass Avinash Vicholous , Georgelin Thomas , Westall Frances , Foucher Frédéric , De Los Rios Paolo , Busiello Daniel Maria , Liang Shiling , Piazza Francesco
Published: May 2021

The exclusive presence of β-D-ribofuranose in nucleic acids is still a conundrum in prebiotic chemistry, given that pyranose species are substantially more stable at equilibrium. However, a precise characterisation of the relative furanose/pyranose fraction at temperatures higher than about 50 °C is still lacking. Here, we employ a combination of NMR measurements and statistical mechanics modelling to predict a population inversion between furanose and pyranose at equilibrium at high temperatures. More importantly, we show that a steady temperature gradient may steer an open isomerisation network into a non-equilibrium steady state where furanose is boosted beyond the limits set by equilibrium thermodynamics. Moreover, we demonstrate that nonequilibrium selection of furanose is maximum at optimal dissipation, as gauged by the temperature gradient and energy barriers for isomerisation. The predicted optimum is compatible with temperature drops found in hydrothermal vents associated with extremely fresh lava flows on the seafloor.
Optoelectronic mixing with high-frequency graphene transistors
Authors: Montanaro A. , Wei W. , De Fazio D. , Sassi U. , Soavi G. , Aversa P. , Ferrari A. C. , Happy H. , Legagneux P. , Pallecchi E.
Published: May 2021

Graphene is ideally suited for optoelectronics. It offers absorption at telecom wavelengths, high-frequency operation and CMOS-compatibility. We show how high speed optoelectronic mixing can be achieved with high frequency (~20 GHz bandwidth) graphene field effect transistors (GFETs). These devices mix an electrical signal injected into the GFET gate and a modulated optical signal onto a single layer graphene (SLG) channel. The photodetection mechanism and the resulting photocurrent sign depend on the SLG Fermi level (EF). At low EF (<130 meV), a positive photocurrent is generated, while at large EF (>130 meV), a negative photobolometric current appears. This allows our devices to operate up to at least 67 GHz. Our results pave the way for GFETs optoelectronic mixers for mm-wave applications, such as telecommunications and radio/light detection and ranging (RADAR/LIDARs.)
Author Correction: Moderate Nrf2 Activation by Genetic Disruption of Keap1 Has Sex-Specific Effects on Bone Mass in Mice
Authors: Yin Yukun , Corry Kylie A. , Loughran John P. , Li Jiliang
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Simulating the computational mechanisms of cognitive and behavioral psychotherapeutic interventions: insights from active inference
Authors: Smith Ryan , Moutoussis Michael , Bilek Edda
Published: May 2021

Cognitive-behavioral therapy (CBT) leverages interactions between thoughts, feelings, and behaviors. To deepen understanding of these interactions, we present a computational (active inference) model of CBT that allows formal simulations of interactions between cognitive interventions (i.e., cognitive restructuring) and behavioral interventions (i.e., exposure) in producing adaptive behavior change (i.e., reducing maladaptive avoidance behavior). Using spider phobia as a concrete example of maladaptive avoidance more generally, we show simulations indicating that when conscious beliefs about safety/danger have strong interactions with affective/behavioral outcomes, behavioral change during exposure therapy is mediated by changes in these beliefs, preventing generalization. In contrast, when these interactions are weakened, and cognitive restructuring only induces belief uncertainty (as opposed to strong safety beliefs), behavior change leads to generalized learning (i.e., “over-writing” the implicit beliefs about action-outcome mappings that directly produce avoidance). The individual is therefore equipped to face any new context, safe or dangerous, remaining in a content state without the need for avoidance behavior—increasing resilience from a CBT perspective. These results show how the same changes in behavior during CBT can be due to distinct underlying mechanisms; they predict lower rates of relapse when cognitive interventions focus on inducing uncertainty and on reducing the effects of automatic negative thoughts on behavior.
Intracellular localization of the mycobacterial stressosome complex
Authors: Ramesh Malavika , Nitharwal Ram Gopal , Behra Phani Rama Krishna , Fredrik Pettersson B. M. , Dasgupta Santanu , Kirsebom Leif A.
Published: May 2021

Microorganisms survive stresses by alternating the expression of genes suitable for surviving the immediate and present danger and eventually adapt to new conditions. Many bacteria have evolved a multiprotein "molecular machinery" designated the "Stressosome" that integrates different stress signals and activates alternative sigma factors for appropriate downstream responses. We and others have identified orthologs of some of the Bacillus subtilis stressosome components, RsbR, RsbS, RsbT and RsbUVW in several mycobacteria and we have previously reported mutual interactions among the stressosome components RsbR, RsbS, RsbT and RsbUVW from Mycobacterium marinum. Here we provide evidence that "STAS" domains of both RsbR and RsbS are important for establishing the interaction and thus critical for stressosome assembly. Fluorescence microscopy further suggested co-localization of RsbR and RsbS in multiprotein complexes visible as co-localized fluorescent foci distributed at scattered locations in the M. marinum cytoplasm; the number, intensity and distribution of such foci changed in cells under stressed conditions. Finally, we provide bioinformatics data that 17 (of 244) mycobacteria, which lack the RsbRST genes, carry homologs of Bacillus cereus genes rsbK and rsbM indicating the existence of alternative σF activation pathways among mycobacteria.
A study of deregulated MMR pathways and anticancer potential of curcuma derivatives using computational approach
Authors: Bhattacharya Priyanjali , Patel Trupti N.
Published: May 2021

Plant derived products have steadily gained momentum in treatment of cancer over the past decades. Curcuma and its derivatives, in particular, have diverse medicinal properties including anticancer potential with proven safety as supported by numerous in vivo and in vitro studies. A defective Mis-Match Repair (MMR) is implicated in solid tumors but its role in haematologic malignancies is not keenly studied and the current literature suggests that it is limited. Nonetheless, there are multiple pathways interjecting the mismatch repair proteins in haematologic cancers that may have a direct or indirect implication in progression of the disease. Here, through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L.andCurcuma caesia Roxb.) which in turn, profoundly controls MMR protein function. These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and thus revive the MMR function preventing genomic instability. These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways.
Enhancement of anisotropy energy of SmCo5 by ceasing the coupling at 2c sites in the crystal lattice with Cu substitution
Authors: Haider Syed Kamran , Ngo Hieu Minh , Kim Dongsoo , Kang Young Soo
Published: May 2021

SmCo5 and SmCo5−xCux magnetic particles were produced by co-precipitation followed by reduction diffusion. HRTEM confirmed the Cu substitution in the SmCo5 lattice. Non-magnetic Cu was substituted at “2c” site in the SmCo5 crystal lattice and effectively stopped the coupling in its surroundings. This decoupling effect decreased magnetic moment from SmCo5 (12.86 μB) to SmCo4Cu (10.58 μB) and SmCo3Cu2 (7.79 μB) and enhanced anisotropy energy from SmCo5 (10.87 Mega erg/cm3) to SmCo4Cu (14.05 Mega erg/cm3) and SmCo3Cu2 (14.78 Mega erg/cm3). Enhancement of the anisotropy energy increased the coercivity as its values for SmCo5, SmCo4Cu and SmCo3Cu2 were recorded as 4.5, 5.97 and 6.99 kOe respectively. Being six times cheaper as compared to Co, substituted Cu reduced the price of SmCo3Cu2 up to 2%. Extra 15% Co was added which not only enhanced the Mr value but also reduced the 5% of the total cost because of additional weight added to the SmCo3Cu2. Method reported in this work is most energy efficient method on the synthesis of Sm–Co–Cu ternary alloys until now.
Adaptation to recent outcomes attenuates the lasting effect of initial experience on risky decisions
Authors: Kóbor Andrea , Kardos Zsófia , Takács Ádám , Éltető Noémi , Janacsek Karolina , Tóth-Fáber Eszter , Csépe Valéria , Nemeth Dezso
Published: May 2021

Both primarily and recently encountered information have been shown to influence experience-based risky decision making. The primacy effect predicts that initial experience will influence later choices even if outcome probabilities change and reward is ultimately more or less sparse than primarily experienced. However, it has not been investigated whether extended initial experience would induce a more profound primacy effect upon risky choices than brief experience. Therefore, the present study tested in two experiments whether young adults adjusted their risk-taking behavior in the Balloon Analogue Risk Task after an unsignaled and unexpected change point. The change point separated early “good luck” or “bad luck” trials from subsequent ones. While mostly positive (more reward) or mostly negative (no reward) events characterized the early trials, subsequent trials were unbiased. In Experiment 1, the change point occurred after one-sixth or one-third of the trials (brief vs. extended experience) without intermittence, whereas in Experiment 2, it occurred between separate task phases. In Experiment 1, if negative events characterized the early trials, after the change point, risk-taking behavior increased as compared with the early trials. Conversely, if positive events characterized the early trials, risk-taking behavior decreased after the change point. Although the adjustment of risk-taking behavior occurred due to integrating recent experiences, the impact of initial experience was simultaneously observed. The length of initial experience did not reliably influence the adjustment of behavior. In Experiment 2, participants became more prone to take risks as the task progressed, indicating that the impact of initial experience could be overcome. Altogether, we suggest that initial beliefs about outcome probabilities can be updated by recent experiences to adapt to the continuously changing decision environment.
Diagnostic biomarkers in tear fluid: from sampling to preanalytical processing
Authors: Bachhuber Franziska , Huss André , Senel Makbule , Tumani Hayrettin
Published: May 2021

Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two collection methods with regard to implementation, acceptance, and impact on sample composition. Tear fluid was collected from fifteen healthy volunteers with capillary tubes and Schirmer strips and analyzed for total protein and IgG concentrations. Sampling parameters and perception by test persons were compared. The use of capillary tubes was more convenient for the participants while causing more effort for the collector. Tear flow rates as well as the relative and absolute amount of IgG were higher when Schirmer strips were used. Consecutive collections with Schirmer strips significantly influenced tear flow rates, IgG, and protein concentrations. A moderate correlation was observed between tear flow rates and IgG concentrations for both methods. Samples collected with both methods can be analyzed by isoelectric focusing, a potential diagnostic application in the field of neurology. The specific advantages and limitations of tear fluid sampling with either capillary tubes or Schirmer strips demonstrate the need for a thorough investigation of collection methods with regard to the application of interest.
Simultaneous determination of low molecule benzotriazoles and benzotriazole UV stabilizers in wastewater by ultrasound-assisted emulsification microextraction followed by GC–MS detection
Authors: Kotowska Urszula , Struk-Sokołowska Joanna , Piekutin Janina
Published: May 2021

A rapid, sensitive, economically and ecologically friendly method based on one-step ultrasound-assisted emulsification microextraction and in situ derivatization followed by gas chromatography–mass spectrometry for simultaneous determination of low molecular benzotriazoles and benzotriazole-based ultraviolet filters was developed. The optimized method allows quantification of benzotriazole, 4-methylbenzotriazole, 5-methylbenzotriazole; 5-chlorobenzotriazole, 2-(2′-hydroxy-3′-tert-butyl-5′-methylphenyl)-5-chlorobenzortriazole and 2-(2′-hydroxy-5′-(1,1,3,3-tetramethylbutyl)phenyl)benzotriazole in municipal and industrial (dairy) wastewater. The method was validated using real influent and effluent wastewater and samples at various stages of the purification process. Relative recoveries obtained using wastewater as sample matrix were between 77 and 137%, method limits of detection from 0.001 to 0.035 µg/L, method limits of quantification from 0.003 to 0.116 µg/L, the repeatability expressed by the coefficient of variation did not exceed 12%. The use of the method for the determination of tested compounds in municipal and industrial wastewater showed their presence in most of the tested samples, in concentrations from LoD to 6.110 µg/L. The conducted studies of samples from municipal wastewater treatment plant located in north-east Poland showed that the effectiveness of benzotriazole removal by this plant wasfrom 29 to 84%. The load of tested compounds released into the environment by this facility ranges from 2 to 269 mg/day/1000 inhabitants.
Paracoccus denitrificans: a genetically tractable model system for studying respiratory complex I
Authors: Jarman Owen D. , Biner Olivier , Wright John J. , Hirst Judy
Published: May 2021

Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a crucial metabolic enzyme that couples the free energy released from NADH oxidation and ubiquinone reduction to the translocation of four protons across the inner mitochondrial membrane, creating the proton motive force for ATP synthesis. The mechanism by which the energy is captured, and the mechanism and pathways of proton pumping, remain elusive despite recent advances in structural knowledge. Progress has been limited by a lack of model systems able to combine functional and structural analyses with targeted mutagenic interrogation throughout the entire complex. Here, we develop and present the α-proteobacterium Paracoccus denitrificans as a suitable bacterial model system for mitochondrial complex I. First, we develop a robust purification protocol to isolate highly active complex I by introducing a His6-tag on the Nqo5 subunit. Then, we optimize the reconstitution of the enzyme into liposomes, demonstrating its proton pumping activity. Finally, we develop a strain of P. denitrificans that is amenable to complex I mutagenesis and create a catalytically inactive variant of the enzyme. Our model provides new opportunities to disentangle the mechanism of complex I by combining mutagenesis in every subunit with established interrogative biophysical measurements on both the soluble and membrane bound enzymes.
Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells
Authors: Hara Hideyuki , Chida Junji , Uchiyama Keiji , Pasiana Agriani Dini , Takahashi Etsuhisa , Kido Hiroshi , Sakaguchi Suehiro
Published: May 2021

Misfolding of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, which forms infectious protein aggregates, the so-called prions, is a key pathogenic event in prion diseases. No pathogens other than prions have been identified to induce misfolding of PrPC into PrPSc and propagate infectious prions in infected cells. Here, we found that infection with a neurotropic influenza A virus strain (IAV/WSN) caused misfolding of PrPC into PrPSc and generated infectious prions in mouse neuroblastoma cells through a hit-and-run mechanism. The structural and biochemical characteristics of IAV/WSN-induced PrPSc were different from those of RML and 22L laboratory prions-evoked PrPSc, and the pathogenicity of IAV/WSN-induced prions were also different from that of RML and 22L prions, suggesting IAV/WSN-specific formation of PrPSc and infectious prions. Our current results may open a new avenue for the role of viral infection in misfolding of PrPC into PrPSc and formation of infectious prions.
Paracetamol (acetaminophen) rescues cognitive decline, neuroinflammation and cytoskeletal alterations in a model of post-operative cognitive decline (POCD) in middle-aged rats
Authors: Garrone B. , Durando L. , Prenderville J. , Sokolowska E. , Milanese C. , Di Giorgio F. P. , Callaghan C. , Bianchi M.
Published: May 2021

Post-operative cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of pain in elderly is complicated because analgesic opiates elicit major side effects. In contrast, paracetamol (acetaminophen) has shown analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of paracetamol, compared to the opioid analgesic buprenorphine, in a model of POCD by investigating cognitive decline, allodynia, peripheral and hippocampal cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received isoflurane anaesthesia. We demonstrated that cognitive decline and increased allodynia following surgery was prevented in paracetamol-treated animals, but not in animals which were exposed to anesthesia alone or underwent the surgery and received buprenorphine. Behavioral alterations were associated with different peripheral cytokine changes between buprenorphine and paracetamol treated animals. Buprenorphine showed no central effects, while paracetamol showed modulatory effects on hippocampal cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of paracetamol as first-choice analgesic in POCD.
Atmospheric feedback explains disparate climate response to regional Arctic sea-ice loss
Authors: Levine Xavier J. , Cvijanovic Ivana , Ortega Pablo , Donat Markus G. , Tourigny Etienne
Published: May 2021

Arctic sea-ice loss is a consequence of anthropogenic global warming and can itself be a driver of climate change in the Arctic and at lower latitudes, with sea-ice minima likely favoring extreme events over Europe and North America. Yet the role that the sea-ice plays in ongoing climate change remains uncertain, partly due to a limited understanding of whether and how the exact geographical distribution of sea-ice loss impacts climate. Here we demonstrate that the climate response to sea-ice loss can vary widely depending on the pattern of sea-ice change, and show that this is due to the presence of an atmospheric feedback mechanism that amplifies the local and remote signals when broader scale sea-ice loss occurs. Our study thus highlights the need to better constrain the spatial pattern of future sea-ice when assessing its impacts on the climate in the Arctic and beyond.
A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells
Authors: O’Connor Margaret H. , Muir Roshell , Chakhtoura Marita , Fang Michael , Moysi Eirini , Moir Susan , Carey Alison J. , Terk Alyssa , Nichols Carmen N. , Metcalf Talibah , Petrovas Constantinos , Cameron Mark J. , Tardif Virginie , Haddad Elias K.
Published: May 2021

Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILCFR) that to our knowledge has not been previously identified. ILCFRhave a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILCFRinhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILCFRto the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILCFRin regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.
Environmental DNA monitoring of oncogenic viral shedding and genomic profiling of sea turtle fibropapillomatosis reveals unusual viral dynamics
Authors: Farrell Jessica A. , Yetsko Kelsey , Whitmore Liam , Whilde Jenny , Eastman Catherine B. , Ramia Devon Rollinson , Thomas Rachel , Linser Paul , Creer Simon , Burkhalter Brooke , Schnitzler Christine , Duffy David J.
Published: May 2021

Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally co-induced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. We applied environmental (e)DNA-based viral monitoring to assess viral shedding as a direct means of transmission, and the relationship between tumor burden, surgical resection and ChHV5 shedding. To elucidate the abundance and transcriptional status of ChHV5 across early, established, regrowth and internal tumors we conducted genomics and transcriptomics. We determined that ChHV5 is shed into the water column, representing a likely transmission route, and revealed novel temporal shedding dynamics and tumor burden correlations. ChHV5 was more abundant in the water column than in marine leeches. We also revealed that ChHV5 is latent in fibropapillomatosis, including early stage, regrowth and internal tumors; higher viral transcription is not indicative of poor patient outcome, and high ChHV5 loads predominantly arise from latent virus. These results expand our knowledge of the cellular and shedding dynamics of ChHV5 and can provide insights into temporal transmission dynamics and viral oncogenesis not readily investigable in tumors of terrestrial species.
Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses
Authors: Sun Hung-Yu , Chen Tzu-Ying , Tan Yu-Ching , Wang Chun-Hsiang , Young Kung-Chia
Published: May 2021

The risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.
The conjugation strategy affects antibody orientation and targeting properties of nanocarriers
Authors: Brückner Maximilian , Simon Johanna , Landfester Katharina , Mailänder Volker
Published: May 2021

The immobilization of antibodies on the nanocarrier surface is influenced by the choice of an appropriate conjugation strategy. We show that a choosing the carbohydrate side chain on the Fc part of antibodies results in a better targeting ability.
Correlating MOF-808 parameters with mixed-matrix membrane (MMM) CO2 permeation for a more rational MMM development
Authors: Thür Raymond , Van Havere Daan , Van Velthoven Niels , Smolders Simon , Lamaire Aran , Wieme Jelle , Van Speybroeck Veronique , De Vos Dirk , Vankelecom Ivo F. J.
Published: May 2021

Correlation of mixed-matrix membrane CO2/N2 separation performance with the corresponding metal-organic framework (MOF) structural parameters shows that the MOF CO2 adsorption enthalpy is the best predictor of the membrane performance.
Metal–organic framework/graphene oxide composites for CO2 capture by microwave swing adsorption
Authors: Muschi Mégane , Devautour-Vinot Sabine , Aureau Damien , Heymans Nicolas , Sene Saad , Emmerich Rudolf , Ploumistos Alexandros , Geneste Amine , Steunou Nathalie , Patriarche Gilles , De Weireld Guy , Serre Christian
Published: May 2021

Metal–organic frameworks/graphene oxide in situ composites are promising candidates for the CO2 capture microwave swing adsorption process.
Facile one-pot synthesis of PdM (M = Ag, Ni, Cu, Y) nanowires for use in mixed matrix membranes for efficient hydrogen separation
Authors: Kumar Abhishek , Huang Liang , Hu Leiqing , Yin Deqiang , Lin Haiqing , Swihart Mark T.
Published: May 2021

A general synthesis method is demonstrated for producing PdM (M= Ag, Cu, Ni, and Y) nanowire networks. As a prototypical application, these nanowires are incorporated into polybenzimidazole to create mixed matrix membranes for H2/CO2 separation.
Advances in differentiation and identification of foodborne bacteria using near infrared spectroscopy
Authors: Tian Yanlong , Gao Xuejun , Qi Wen-Liang , Wang Yi , Wang Xiao , Zhou Jiacai , Lu Daoli , Chen Bin
Published: May 2021

Rapid and sensitive detection of foodborne bacteria is a growing concern for ensuring safe food supply and preventing human foodborne infections.
A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma
Authors: Zhang Jing , Qian Xing-Kai , Song Pei-Fang , Li Xiao-Dong , Wang An-Qi , Huo Hong , Yao Jing-Chun , Zhang Gui-Min , Zou Li-Wei
Published: May 2021

A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors.
A polysaccharide from natural Cordyceps sinensis regulates the intestinal immunity and gut microbiota in mice with cyclophosphamide-induced intestinal injury
Authors: Chen Shuping , Wang Junqiao , Fang Qiuyue , Dong Nan , Fang Qingying , Cui Steve W. , Nie Shaoping
Published: May 2021

A polysaccharide from C. sinensis regulated the balance between Treg and Th17 cells, and modulated microbiota composition in the gut of mice with Cy-induced intestinal injury.
Gut microbiota mediated the protective effects of tuna oil on collagen-induced arthritis in mice
Authors: Lu Chenyang , Chen Ju , Yi Congmin , Han Jiaojiao , Shi Qiuyue , Li Jingjing , Liu Bing , Zhou Jun , Su Xiurong
Published: May 2021

Tuna oil (TO) treatments ameliorated inflammation, rebalanced bone remodeling and changed gut microbiota in collagen-induced arthritis (CIA) mice. We clarified that gut microbiota mediated the protective effects of TO on CIA in mice.
Recent advances in the synthesis of smart hydrogels
Authors: Sikdar Partha , Uddin Md. Mazbah , Dip Tanvir Mahady , Islam Shafiqul , Hoque Md. Saiful , Dhar Avik K. , Wu Shuangyan
Published: May 2021

Understanding the surrounding atmosphere and reacting accordingly with a precise action are always fascinating features of a material.
Plastic strain relaxation and alloy instability in epitaxial corundum-phase (Al,Ga)2O3 thin films on r-plane Al2O3
Authors: Grundmann Marius , Stralka Tillmann , Lorenz Michael , Selle Susanne , Patzig Christian , Höche Thomas
Published: May 2021

The growth of (AlxGa1−x)2O3 alloy thin films in the corundum phase on r-plane (01.2) Al2O3 substrates is investigated.
A nanoporous CeO2 nanowire array by acid etching preparation: an efficient electrocatalyst for ambient N2 reduction
Authors: Ji Yuyao , Liu Xingquan
Published: May 2021

In 0.1 M HCl, this catalyst achieves a high faradaic efficiency of 4.7% with a NH3 yield of 38.6 μg h−1 mg−1cat. at −0.3 V vs. reversible hydrogen electrode, outperforming most reported Ce-based NRR electrocatalysts under ambient conditions.
The formation mechanism and chirality evolution of chiral carbon dots prepared via radical assisted synthesis at room temperature
Authors: Branzi Lorenzo , Lucchini Giacomo , Cattaruzza Elti , Pinna Nicola , Benedetti Alvise , Speghini Adolfo
Published: May 2021

Cysteine-based chiral carbon dots (CDs) were prepared via room temperature radical assisted synthesis. These investigations pave the way for novel synthetic strategies for production of CDs with high control of the chirality.
Homo- and co-polymerisation of di(propylene glycol) methyl ether methacrylate – a new monomer
Authors: Constantinou Anna P. , Patias Georgios , Somuncuoğlu Birsen , Brock Toby , Lester Daniel W. , Haddleton David M. , Georgiou Theoni K.
Published: May 2021

A new methacrylate monomer with two propylene glycol groups on the side chain, di(propylene glycol) methyl ether methacrylate (diPGMA), was synthesised and homo- and co-polymerised for the first time.
In situ-formed flexible three-dimensional honeycomb-like film for a LiF/Li3N-enriched hybrid organic–inorganic interphase on the Li metal anode
Authors: Ma Chengwei , Mu Ge , Lv Haijian , Liu Chengcai , Bi Jiaying , Fu Jiale , Mu Daobin , Wu Borong , Wu Feng
Published: May 2021

An in situ formed flexible three dimensional honeycomb-like PTFEMA film is designed to construct LiF/Li3N-riched hybrid organic–inorganic interphase.
Agar/carbon dot crosslinked polyacrylamide double-network hydrogels with robustness, self-healing, and stimulus-response fluorescence for smart anti-counterfeiting
Authors: Xie Shaowen , Chen Yin , Guo Ziyu , Luo Yuecong , Tan Haihu , Xu Lijian , Xu Jianxiong , Zheng Jie
Published: May 2021

A low cost and biocompatible agar/carbon dots crosslinked polyacrylamide double-network hydrogels with robustness, self-healing, and stimulus-response fluorescence was designed for smart anti-counterfeiting.
Metal oxide adsorption on fullerene C60 and its potential for adsorption of pollutant gases; density functional theory studies
Authors: Haghgoo Sanaz , Nekoei A.-Reza
Published: May 2021

Combinations of C60 and metal oxides (MOx) are interesting, not only because they display the individual properties of C60 and of MOx nanoparticles, but they may also exhibit synergetic properties that are advantageous for gas sensing applications.
Novel quinoline-based fluorescent bioimaging probe, KSNP117, for sentinel lymph node mapping
Authors: Elbatrawy Ahmed A. , Lee Da Sol , Lee Sang Bong , Jeon Hui-Jeon , Lee Sijoon , Kang Kyung-ku , Sung Soo-Eun , Han Ye Ri , Cho Sung Jin , Kim Dong-Su , Kim Kil Soo , Nam Ghilsoo , Jeon Yong Hyun
Published: May 2021

A novel near-infrared fluorescent imaging probe, KSNP117, was developed. Its excellent stability and biocompatibility were confirmed in vitro and in vivo, and its biomedical application for sentinel lymph node mapping was successfully demonstrated.
Friction-directed self-assembly of Janus lithographic microgels into anisotropic 2D structures
Authors: Kodakkadan Yadu Nath Vakkipurath , Maslen Charlie , Cigler Petr , Štěpánek František , Rehor Ivan
Published: May 2021

Janus-type hydrogel platelets are subjected to sliding on a tilted plane. Due to anisotropic friction, they self-orientate which allows for their and subsequent self-assembly into periodic structures with translational and rotational order.
Joint timing‐offset and channel estimation for physical layer network coding in frequency selective environments
Authors: Abdallah Saeed , Saad Mohamed , Alnajjar Khawla , El‐Moursy Ali A.
Published: May 2021

This paper considers the problem of joint timing‐offset and channel estimation for physical‐layer network coding systems operating in frequency‐selective environments. Three different algorithms are investigated for the joint estimation of the channel coefficients and the fractional timing offset. The first algorithm is based on the maximum‐likelihood (ML) criterion assuming baud‐rate (BR) sampling. The second algorithm also assumes BR sampling and is based on the special properties of Zadoff‐Chu training sequences. In the third algorithm, oversampling at double the baud‐rate (DBR) is used and the least‐squares (LS) estimation criterion applied. While the above algorithms assume that the integer timing offset is known, three generalized‐likelihood‐ratio tests (GLRTs) are also considered for integer offset error correction that integrate very well with the proposed estimation algorithms. Our simulation studies show that the DBR‐LS estimator provides the highest estimation accuracy, significantly outperforming both BR estimators and performing very close to the corresponding Cramer–Rao bound. A gain of 4 dB is observed in symbol‐error‐rate performance using the DBR‐LS algorithm. The DBR‐GLRT also provides substantially higher probability of error correction.
State prediction based control schemes for nonlinear systems with input delay and external disturbance
Authors: Zhu Bing , Chen Mou , Li Tao
Published: May 2021

In this paper, a control scheme based on state prediction is proposed for a class of nonlinear systems subject to input delay and external disturbance. Firstly, as for constant input delay, an improved control scheme that combining state prediction with dynamic surface control (DSC) technique is proposed, which can compensate for the input delay completely. Secondly, by considering the constant input delay and external disturbance, an effective controller based on state prediction, DSC technique and disturbance observer is presented to tackle the disturbed input‐delayed nonlinear systems. Thirdly, as for time‐varying input delay and external disturbance, a control scheme that includes state prediction, DSC technique, input saturation and sliding mode disturbance observer is further proposed to tackle the tracking control for the addressed nonlinear systems. Besides, some theorems are given to ensure that all signals in the closed‐loop systems can be semi‐globally ultimately uniformly bounded (UUB) under the proposed control schemes. Finally, by utilising the dynamic model of quadrotor unmanned aerial vehicle (UAV), some simulations are presented to illustrate the effectiveness of our proposed results.
Adaptive colour restoration and detail retention for image enhancement
Authors: He Kangjian , Tao Dapeng , Xu Dan
Published: May 2021

Computer vision‐based crowd understanding and analysis technology has been widely used in public safety due to the rapid growth of population and the frequent occurrence of various accidents. Improving imaging quality is the key to improve the performance of crowd analysis, density estimation, target recognition, segmentation, and detection in computer vision tasks. Due to the complex imaging environment such as fog and low illumination, some images taken in outdoor environment often have the problems of colour distortion, lack of details, and the poor imaging quality, which affect the subsequent visual tasks. To improve the imaging quality and visual effect, an adaptive colour restoration and detail retention‐based method is proposed for image enhancement. First, to overcome the problem of colour distortion caused by low illumination and fog, a multi‐channel fusion based adaptive image colour restoration method is proposed. To make the enhancement result more consistent with human observation, the detail retention‐based method is applied to enhance the details. Experimental results demonstrate that the authors' results are effective and outperform the compared methods both in visual and objective evaluations.
C‐ITS road‐side unit deployment on highways with ITS road‐side systems: A techno‐economic approach
Authors: Degrande Thibault , Van den Eynde Simon , Vannieuwenborg Frederic , Colle Didier , Verbrugge Sofie
Published: May 2021

Connectivity and cooperation are considered important prerequisites to automated driving, as they are crucial elements in increasing the safety of future automated vehicles and their full integration in the overall transport system. Although many European Member States, as part of the C‐Roads Platform, have implemented and are still implementing Road‐side Units (RSUs) for Cooperative Intelligent Transportation Systems (C‐ITS) within pilot deployment projects, the platform aspires a wide extension of deployments in the coming years. Therefore, this paper investigates techno‐economic aspects of C‐ITS RSU deployments from a road authority viewpoint. A two‐phased approach is used, in which firstly the optimal RSU locations are determined, taking into account existing road‐side infrastructure. Secondly, a cost model translates the amount of RSUs into financial results. It was found that traffic density has a significant impact on required RSU density, hence impacting costs. Furthermore, major cost saving can be obtained by leveraging existing road‐side infrastructure. The proposed methodology is valuable for other member states, and in general, to any other country aspiring to roll out C‐ITS road infrastructure. Results can be used to estimate required investment costs based on legacy infrastructure, as well as to benchmark with the envisioned benefits from the deployed C‐ITS services.
A multi‐step airport delay prediction model based on spatial‐temporal correlation and auxiliary features
Authors: Zhang Hao , Song Chunyue , Zhang Jie , Wang Hui , Guo Jinlong
Published: May 2021

Airport delay prediction system is fundamental to intelligent air traffic management. However, the prediction of airport delay is affected strongly by spatial‐temporal dependencies and other exogenous dependencies, which would bring serious challenges in prediction. In this paper, the APR‐LSTM model is proposed to address these challenges. The model is driven by the real‐world flight operation data. In the proposed prediction model, the dynamic air traffic delay networks are fed into PageRank algorithm to capture the dynamic spatial dependencies. The input sequences of airport delay vector is weighted by spatial dependencies before sending into the long short‐term memory network (LSTM) and sequence to sequence model, which can realise the multi‐step prediction and the joint mining of spatial‐temporal dependencies. Subsequently, the temporal attention mechanism and auxiliary features are introduced to obtain the long‐term temporal dependencies by exploring the relevance of different time steps and improve the accuracy of prediction model. Furthermore, the results of comparative experiments indicated that the proposed model achieve the best performance compared with other benchmark models. Finally, the spatial‐temporal correlation of different airports, the delay characterisations of networks and the application of prediction results are demonstrated in detail, enabling the interpretability of APR‐LSTM model.