bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Pseudo State-Feedback Controller Design for Affine Fuzzy Large-Scale Systems with $${{\varvec{H}}}_{\boldsymbol{\infty }}$$ Performance
Authors: Zamani Iman , Shafieirad Mohsen , Manthouri Mohammad , Sarbaz Mohammad , Ibeas Asier
Published: September 2022

This paper treats robust controller design for Affine Fuzzy Large-Scale Systems (AFLSS) composed of Takagi–Sugeno-Kang type fuzzy subsystems with offset terms, disturbances, uncertainties, and interconnections. Instead of fuzzy parallel distributed compensation, a decentralized nonlinear pseudo state-feedback is developed for each subsystem to stabilize the overall AFLSS. Using Lyapunov stability, sufficient conditions with low codemputational effort and free gains are derived in terms of matrix inequalities. The proposed controller guarantees asymptotic stability, robust stabilization, and $${H}_{\infty }$$

H
∞

control performance of the AFLSS. A numerical example is given to illustrate the feasibility and effectiveness of the proposed approach.
An Integrative Decision-Making Mechanism for Consumers’ Brand Selection using 2-Tuple Fuzzy Linguistic Perceptions and Decision Heuristics
Authors: Giráldez-Cru Jesús , Chica Manuel , Cordón Oscar
Published: September 2022

Consumers perform decision-making (DM) processes to select their preferred brands during their entire consumer journeys. These DM processes are based on the multiple perceptions they have about the products available in the market they are aware of. These consumers usually perform different DM strategies and employ diverse heuristics depending on the nature of the purchase, ranging from more pure optimal choices to faster decisions. Therefore, the design of realistic DM approaches for modeling these consumer behaviors requires a good representation of consumer perceptions and a reliable process for integrating their corresponding heuristics. In this work, we use fuzzy linguistic information to represent consumer perceptions and propose four consumer DM heuristics to model the qualitative linguistic information for the consumer buying decision. In particular, we use 2-tuple fuzzy linguistic variables, which is a substantially more natural and realistic representation without falling in a loss of information. The set of selected heuristics differ in the degree of involvement the consumers give to their decisions. Additionally, we propose a heuristic selection mechanism to integrate the four heuristics in a single DM procedure by using a regulation parameter. Our experimental analysis shows that the combination of these heuristics in a portfolio manner improves the performance of our model with a realistic representation of consumer perceptions. The model’s outcome matches the expected behavior of the consumers in several real market scenarios.
Innovations in Pediatric Therapeutics Development: Principles for the Use of Bridging Biomarkers in Pediatric Extrapolation
Authors: Fleming Thomas R. , Garnett Christine E. , Conklin Laurie S. , Corriol-Rohou Solange , Hariharan Sudharshan , Hsu Daphne , Mueller-Velten Guenther , Mulugeta Yeruk , Portman Ronald , Rothmann Mark D. , Stockbridge Norman L. , Wandel Simon , Zhang Jialu , Yao Lynne
Published: September 2022

Even with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention’s effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a ‘bridging biomarker’ should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences ‘feels, functions, survives’ measures; secondly, the experimental intervention should not have important unintended effects on ‘feels, functions, survives’ measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention’s net effect on ‘feels, functions, survives’ measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention’s efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could increase availability of reliably evaluated therapies approved for use in pediatric settings, enabling children and their caregivers to make informed choices about health care.
Direct Multi‐Modal Inversion of Geophysical Logs Using Deep Learning
Authors: Alyaev Sergey , Elsheikh Ahmed H.
Published: September 2022

Geosteering of wells requires fast interpretation of geophysical logs which is a non‐unique inverse problem. Current work presents a proof‐of‐concept approach to multi‐modal probabilistic inversion of logs using a single evaluation of an artificial deep neural network (DNN). A mixture density DNN (MDN) is trained using the ”multiple‐trajectory‐prediction” loss functions, which avoids mode collapse typical for traditional MDNs, and allows multi‐modal prediction ahead of data. The proposed approach is verified on the real‐time stratigraphic inversion of gamma‐ray logs. The multi‐modal predictor outputs several likely inverse solutions/predictions, providing more accurate and realistic solutions compared to a deterministic regression using a DNN. For these likely stratigraphic curves, the model simultaneously predicts their probabilities, which are implicitly learned from the training geological data. The stratigraphy predictions and their probabilities obtained in milliseconds from the MDN can enable better real‐time decisions under geological uncertainties.
Estimation of On‐Road PM2.5 Distributions by Combining Satellite Top‐of‐Atmosphere With Microscale Geographic Predictors for Healthy Route Planning
Authors: Tong Chengzhuo , Shi Zhicheng , Shi Wenzhong , Zhang Anshu
Published: September 2022

How to reduce the health risks for commuters, caused by air pollution such as PM2.5 has always been an urgent issue needing to be solved. Proposed in this study, is a novel framework which enables greater avoidance of pollution and hence assists the provision of healthy travel. This framework is based on the estimation of on‐road PM2.5 throughout the whole city. First, the micro‐scale PM2.5 is predicted by land use regression (LUR) modeling enhanced by the use of the Landsat‐8 top‐of‐atmosphere (TOA) data and microscale geographic predictors. In particular, the green view index (GVI) factor derived, the sky view factor, and the index‐based built‐up index, are incorporated within the TOA‐LUR modeling. On‐road PM2.5 distributions are then mapped in high‐spatial‐resolution. The maps obtained can be used to find healthy travel routes with less PM2.5. The proposed framework was applied in high‐density Hong Kong by Landsat 8 images. External testing was based on mobile measurements. The results showed that the estimation performance of the proposed seasonal TOA‐LUR Geographical and Temporal Weighted Regression models is at a high‐level with an R2 of 0.70–0.90. The newly introduced GVI index played an important role in these estimations. The PM2.5 distribution maps at high‐spatial‐resolution were then used to develop an application providing Hong Kong residents with healthy route planning services. The proposed framework can, likewise, be applied in other cities to better ensure people's health when traveling, especially those in high‐density cities.
High‐Resolution Imaging of Fault Zone Structure Along the Creeping Section of the Haiyuan Fault, NE Tibet, From Data Recorded by Dense Seismic Arrays
Authors: Zhang Zhou , Deng Yangfan , Qiu Hongrui , Peng Zhigang , Liu‐Zeng Jing
Published: September 2022

High‐resolution imaging of fault zone structures is essential for understanding earthquake physics and fault mechanics. As a major left‐lateral strike‐slip fault in northeastern Tibet, fine structures of the damage zone in the creeping (Laohushan) section of the Haiyuan fault remain unclear. To resolve geometry and velocity reduction of the damage zone, we deployed a dense temporary network of 110 seismic stations around the creeping section of the Haiyuan fault. Travel time delays from teleseismic P arrivals suggest an approximately 1‐km‐wide low‐velocity zone, likely illuminating a broader damage zone around the Haiyuan fault. A catalog is constructed for local earthquakes based on phase picks identified from a machine learning technique. The amplification of waveforms from these local events and waveform modeling of fault zone trapped waves indicate a narrower inner damage zone with depth‐dependent width (ranging from 150 to 50 m) that extends to a depth of approximately 4 km. These values are generally consistent with those found on other noncreeping faults in California, suggesting that these damage zone properties are not affected by fault slip behaviors at shallow depth. In addition, a clear bi‐material velocity contrast across the fault is revealed by the analysis of teleseismic P arrivals. Assuming the contrast extends to a depth of 15 km, we find that P‐wave velocity is approximately 5% slower in the crustal block north of the fault. Our study shows that a temporary dense seismic network is effective in illuminating cross‐fault velocity contrast and fault geometry.
Shallow Crustal Response to Arabia‐Eurasia Convergence in Northwestern Iran: Constraints From Multifrequency P‐Wave Receiver Functions
Authors: Wang Xu , Chen Ling , Talebian Morteza , Ai Yinshuang , Jiang Mingming , Yao Huajian , He Yumei , Ghods Abdolreza , Sobouti Farhad , Wan Bo , Chu Yang , Hou Guangbing , Chen Qi‐Fu , Chung Sun‐Lin , Xiao Wenjiao , Wu Fu‐Yuan , Zhu Rixiang
Published: September 2022

The Neo‐Tethys subduction and subsequent Arabia‐Eurasia continental collision invoked widespread Cenozoic tectono‐magmatism throughout the Iranian Plateau. We herein develop a new method to image the shallow crustal S‐wave velocity (Vs) structure by joint inversion of multifrequency waveforms and horizontal‐to‐vertical ratios around the direct P phase in P‐wave receiver functions. Synthetic tests demonstrate the validity of our method in constraining the absolute Vs values beneath single stations down to ∼12‐km depth. By applying this method to a seismic array of 63 stations with an average spacing of ∼10 km along the main profile, we construct a detailed shallow crustal Vs model across the northwestern Iranian Plateau. The model is characterized by distinct high‐ and low‐velocity anomalies beneath the Iranian hinterland and the Zagros foreland fold‐and‐thrust belt, respectively. In combination with geological observations and laboratory data, the imaged high‐velocity anomalies (with Vs of 3.2–3.9 km/s) may denote arc to intraplate magmatism beneath Central Iran and Alborz to the north, whereas the low‐velocity anomalies (with Vs of ∼1.65 km/s) probably represent the marl/shale layers in Late Cretaceous and Paleocene beneath Zagros. The magmatic rocks at the Iranian hinterland exhibit strong variations in absolute Vs, reflecting different bulk compositions with more mafic inland. The shale/marl layers could have acted as décollements to accommodate crustal deformation. Our observations underline both the key role of lithology‐controlled layering in sedimentary deformation at the Zagros fold‐and‐thrust belt and the change in compositions and forming‐environments of magmatic rocks at the Iranian hinterland.
Changes in Early Summer Precipitation Characteristics Over South China and Taiwan: CESM2‐LE and CMIP6 Multi‐Model Simulations and Projections
Authors: Huang Wan‐Ru , Liu Pin‐Yi , Lee Shih‐Yu , Wu Chi‐Hua
Published: September 2022

The May and June precipitation (known as early summer precipitation; ESP) is an important water resource for South China and Taiwan (SCTW). This study explores the similarities and differences between the Community Earth System Model Version 2‐Large Ensemble (CESM2‐LE) and the Coupled Model Intercomparison Project Phase 6 (CMIP6) multi‐model ensemble in simulating the characteristics of ESP over SCTW in the present day, and in projecting the related changes at the end of 21st century. For the present‐day simulation, our results showed that CESM2‐LE and CMIP6 outperformed each other for different examined features. CESM2‐LE was slightly better than CMIP6 in capturing the magnitude of ESP over SCTW, while CMIP6 was more capable of representing the interdecadal shifts in the occurrence timing of the ESP maximum. Both the CESM2‐LE and CMIP6 projections indicated that ESP will be enhanced and the phase of maximum ESP will be delayed, from peaking around mid‐June in the present to late June in the future. These changes can be attributed to an enhanced short‐wave trough over southwest China and a late intensification of the southwesterly wind ahead of the short‐wave trough, which help transport more moisture from the north of the South China Sea to SCTW, particularly in mid‐to‐late June. In addition, relative to CMIP6, CESM2‐LE showed less uncertainty in the projected increase in ESP and phase delay. This finding highlights that model diversity may play a more important role than internal variability in attributing the uncertainty of projected changes in ESP over SCTW.
Martian Atmospheric Spectral End‐Members Retrieval From ExoMars Thermal Infrared (TIRVIM) Data
Authors: Alemanno G. , D’Amore M. , Maturilli A. , Helbert J. , Arnold G. , Korablev O. , Ignatiev N. , Grigoriev A. , Shakun A. , Trokhimovskiy A.
Published: September 2022

Key knowledge about planetary composition can be recovered from the study of thermal infrared spectral range datasets. This range has a huge diagnostic potential because it contains diagnostic absorptions from a planetary surface and atmosphere. The main goal of this study is to process and interpret the dataset from the Thermal Infrared channel (TIRVIM) which is part of the Atmospheric Chemistry Suite of the ExoMars2016 Trace Gas Orbiter mission to find and characterize dust and water ice clouds in the atmosphere. The method employed here is based on the application of principal component analysis and target transformation techniques to extract the independent variable components present in the analyzed dataset. Spectral shapes of both atmospheric dust and water ice aerosols have been recovered from the analysis of TIRVIM data. The comparison between our results with those previously obtained on Thermal Emission Spectrometer (TES) data and with previous analysis on TIRVIM data, validates the methodology here applied, showing that it allows to correctly recover the atmospheric spectral endmembers present in the TIRVIM data. Moreover, comparison with atmospheric retrievals on PFS, TES and IRIS data, allowed us to assess the temporal stability and homogeneity of dust and water ice components in the Martian atmosphere over a time period of almost 50 years.
Glass Ionomer Cement as a preventative fissure sealant for first permanent molars in high caries risk patients waiting general anaesthetic—a case series
Authors: Mummery Toby Andrew , Popat Riddhi
Published: September 2022

Objective/aim

The aim of this case series was to assess the ongoing suitability of Glass Ionomer Cement Fissure Sealants for use in paediatric patients. These had been used through the COVID pandemic due to their status as a non-aerosol-generating procedure.

Materials and methods

A retrospective clinical review was undertaken to identify cases where GIC Fissure Sealants were used in paediatric patients awaiting exodontia general anaesthetic within Harrogate and District NHS Foundation Trust Community Dental Service. Identified cases were then collated to form this case series. These were reviewed regarding the number of GIC fissure sealants placed, and retention at the GA appointment and any subsequent follow-up appointments.

Results

The results showed favourable results of GIC fissure sealants, with an average retention of 77% – in line with the wider literature results for GIC fissure sealants.

Discussion

The results showed a favourable retention rate, particularly given patient challenges leading to them requiring exodontia GA. Review of alternative fissure sealant materials may be beneficial on a local level to compare results with the available literature and confirm ongoing suitability.

Conclusions

The results appear to support the ongoing use of GIC-FS where close patient monitoring is available.
Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells
Authors: Zhang Shuai , Li Yumei , Liu Shuqing , Ma Pei , Guo Mengfei , Zhou E. , Duan Limin , Fan Jinshuo , Liao Tingting , Tan Qi , Wang Xuan , Wu Feng , Jin Yang
Published: September 2022

A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.
ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness
Authors: Werner Marcel , Dyas Anna , Parfentev Iwan , Schmidt Geske E. , Mieczkowska Iga K. , Müller-Kirschbaum Lukas C. , Müller Claudia , Kalkhof Stefan , Reinhardt Oliver , Urlaub Henning , Alves Frauke , Gallwas Julia , Prokakis Evangelos , Wegwitz Florian
Published: September 2022

Basal-like breast cancer (BLBC) is a highly aggressive breast cancer subtype frequently associated with poor prognosis. Due to the scarcity of targeted treatment options, conventional cytotoxic chemotherapies frequently remain the standard of care. Unfortunately, their efficacy is limited as BLBC malignancies rapidly develop resistant phenotypes. Using transcriptomic and proteomic approaches in human and murine BLBC cells, we aimed to elucidate the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in these mammary tumors. Specifically, we identified and characterized a novel short isoform of Roundabout Guidance Receptor 3 (ROBO3s), upregulated in BLBC in response to chemotherapy and encoding for a protein variant lacking the transmembrane domain. We established an important role for the ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving resistance of BLBC cells to cytotoxic drugs. By uncovering the conservation of ROBO3s expression across multiple cancer types, as well as its association with reduced BLBC-patient survival, we emphasize its potential as a prognostic marker and identify a novel attractive target for anti-cancer drug development.
FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis
Authors: Cai Kun , Chen Shiyu , Zhu Changhao , Li Lin , Yu Chao , He Zhiwei , Sun Chengyi
Published: September 2022

Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.
A multi-centre prospective evaluation of THEIA™ to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) in the New Zealand screening program
Authors: Vaghefi Ehsan , Yang Song , Xie Li , Han David , Yap Aaron , Schmeidel Ole , Marshall John , Squirrell David
Published: September 2022

Purpose

To validate the potential application of THEIA™ as clinical decision making assistant in a national screening program.

Methods

A total of 900 patients were recruited from either an urban large eye hospital, or a semi-rural optometrist led screening provider, as they were attending their appointment as part of New Zealand Diabetic Eye Screening Programme. The de-identified images were independently graded by three senior specialists, and final results were aggregated using New Zealand grading scheme, which was then converted to referable/non-referable and Healthy/mild/more than mild/sight threatening categories.

Results

THEIA™ managed to grade all images obtained during the study. Comparing the adjudicated images from the specialist grading team, “ground truth”, with the grading by the AI platform in detecting “sight threatening” disease, at the patient level THEIA™ achieved 100% imageability, 100% [98.49–100.00%] sensitivity and [97.02–99.16%] specificity, and negative predictive value of 100%. In other words, THEIA™ did not miss any patients with “more than mild” or “sight threatening” disease. The level of agreement between the clinicians and the aggregated results was (k value: 0.9881, 0.9557, and 0.9175), and the level of agreement between THEIA™ and the aggregated labels was (k value: 0.9515).

Conclusion

This multi-centre prospective trial showed that THEIA™ did not miss referable disease when screening for diabetic retinopathy and maculopathy. It also had a very high level of granularity in reporting the disease level. As THEIA™ has been tested on a variety of cameras, operating in a range of clinics (rural/urban, ophthalmologist-led\optometrist-led), we believe that it will be a suitable addition to a public diabetic screening program.
Observation of formation and local structures of metal-organic layers via complementary electron microscopy techniques
Authors: Peng Xinxing , Pelz Philipp M. , Zhang Qiubo , Chen Peican , Cao Lingyun , Zhang Yaqian , Liao Hong-Gang , Zheng Haimei , Wang Cheng , Sun Shi-Gang , Scott Mary C.
Published: September 2022

Metal-organic layers (MOLs) are highly attractive for application in catalysis, separation, sensing and biomedicine, owing to their tunable framework structure. However, it is challenging to obtain comprehensive information about the formation and local structures of MOLs using standard electron microscopy methods due to serious damage under electron beam irradiation. Here, we investigate the growth processes and local structures of MOLs utilizing a combination of liquid-phase transmission electron microscopy, cryogenic electron microscopy and electron ptychography. Our results show a multistep formation process, where precursor clusters first form in solution, then they are complexed with ligands to form non-crystalline solids, followed by the arrangement of the cluster-ligand complex into crystalline sheets, with additional possible growth by the addition of clusters to surface edges. Moreover, high-resolution imaging allows us to identify missing clusters, dislocations, loop and flat surface terminations and ligand connectors in the MOLs. Our observations provide insights into controllable MOL crystal morphology, defect engineering, and surface modification, thus assisting novel MOL design and synthesis.
Cell type-specific calcium imaging of central sensitization in mouse dorsal horn
Authors: Warwick Charles , Salsovic Joseph , Hachisuka Junichi , Smith Kelly M. , Sheahan Tayler D. , Chen Haichao , Ibinson James , Koerber H. Richard , Ross Sarah E.
Published: September 2022

Allodynia is a state in which pain is elicited by innocuous stimuli. Capsaicin applied to the skin results in an allodynia that extends to a broad region beyond the application site. This sensitization is thought to be mediated by spinal networks; however, we do not have a clear picture of which spinal neurons mediate this phenomenon. To address this gap, we used two-photon calcium imaging of excitatory interneurons and spinal projection neurons in the mouse spinal dorsal horn. To distinguish among neuronal subtypes, we developed CICADA, a cell profiling approach to identify cell types during calcium imaging. We then identified capsaicin-responsive and capsaicin-sensitized neuronal populations. Capsaicin-sensitized neurons showed emergent responses to innocuous input and increased receptive field sizes consistent with psychophysical reports. Finally, we identified spinal output neurons that showed enhanced responses from innocuous input. These experiments provide a population-level view of central sensitization and a framework with which to model somatosensory integration in the dorsal horn.
Attosecond dynamics of multi-channel single photon ionization
Authors: Peschel Jasper , Busto David , Plach Marius , Bertolino Mattias , Hoflund Maria , Maclot Sylvain , Vinbladh Jimmy , Wikmark Hampus , Zapata Felipe , Lindroth Eva , Gisselbrecht Mathieu , Dahlström Jan Marcus , L’Huillier Anne , Eng-Johnsson Per
Published: September 2022

Photoionization of atoms and molecules is one of the fastest processes in nature. The understanding of the ultrafast temporal dynamics of this process often requires the characterization of the different angular momentum channels over a broad energy range. Using a two-photon interferometry technique based on extreme ultraviolet and infrared ultrashort pulses, we measure the phase and amplitude of the individual angular momentum channels as a function of kinetic energy in the outer-shell photoionization of neon. This allows us to unravel the influence of channel interference as well as the effect of the short-range, Coulomb and centrifugal potentials, on the dynamics of the photoionization process.
Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression
Authors: Zhou Jin , Pang Jeremy , Tripathi Madhulika , Ho Jia Pei , Widjaja Anissa Anindya , Shekeran Shamini Guna , Cook Stuart Alexander , Suzuki Ayako , Diehl Anna Mae , Petretto Enrico , Singh Brijesh Kumar , Yen Paul Michael
Published: September 2022

Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepaticDOHHmRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aHand mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid β-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AHpathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression.
Interrupted-time-series analysis of the immediate impact of COVID-19 mitigation measures on preterm birth in China
Authors: Xie Yanxia , Mu Yi , Chen Peiran , Liu Zheng , Wang Yanping , Li Qi , Li Mingrong , Liang Juan , Zhu Jun
Published: September 2022

Preliminary evidence from China and other countries has suggested that coronavirus disease 2019 (COVID-19) mitigation measures have caused a decline in preterm births, but evidence is conflicting. Utilising a national representative data of 11,714,947 pregnant women in China, we explored the immediate changes in preterm birth rates during the COVID-19 mitigation period using an interrupted-time-series analysis. We defined the period prior to February 1, 2020 as the baseline, followed by the COVID-19 mitigation stage. In the first month of the COVID-19 mitigation, a significant absolute decrease in preterm birth rates of 0.68% (95%CI:−1.10% to −0.26%) in singleton, and of 2.80% (95%CI:−4.51% to −1.09%) in multiple births was noted. This immediate decline in Wuhan was greater than that at the national level among singleton births [−2.21% (95%CI:−4.09% to −0.34% vs. −0.68%)]. Here we report an immediate impact of COVID-19 mitigation measures on preterm birth in China.
Electron-donating amine-interlayer induced n-type doping of polymer:nonfullerene blends for efficient narrowband near-infrared photo-detection
Authors: Liu Quan , Zeiske Stefan , Jiang Xueshi , Desta Derese , Mertens Sigurd , Gielen Sam , Shanivarasanthe Rachith , Boyen Hans-Gerd , Armin Ardalan , Vandewal Koen
Published: September 2022

Inherently narrowband near-infrared organic photodetectors are highly desired for many applications, including biological imaging and surveillance. However, they suffer from a low photon-to-charge conversion efficiencies and utilize spectral narrowing techniques which strongly rely on the used material or on a nano-photonic device architecture. Here, we demonstrate a general and facile approach towards wavelength-selective near-infrared phtotodetection through intentionally n-doping 500–600 nm-thick nonfullerene blends. We show that an electron-donating amine-interlayer can induce n-doping, resulting in a localized electric field near the anode and selective collection of photo-generated carriers in this region. As only weakly absorbed photons reach this region, the devices have a narrowband response at wavelengths close to the absorption onset of the blends with a high spectral rejection ratio. These spectrally selective photodetectors exhibit zero-bias external quantum efficiencies of ~20–30% at wavelengths of 900–1100 nm, with a full-width-at-half-maximum of ≤50 nm, as well as detectivities of >1012 Jones.
Stereoretentive cross-coupling of chiral amino acid chlorides and hydrocarbons through mechanistically controlled Ni/Ir photoredox catalysis
Authors: Lee Geun Seok , Park Beomsoon , Hong Soon Hyeok
Published: September 2022

The direct modification of naturally occurring chiral amino acids to their amino ketone analogs is a significant synthetic challenge. Here, an efficient and robust cross-coupling reaction between chiral amino acid chlorides and unactivated C(sp3)–H hydrocarbons is achieved by a mechanistically designed Ni/Ir photoredox catalysis. This reaction, which proceeds under mild conditions, enables modular access to a wide variety of chiral amino ketones that retain the stereochemistry of the starting amino acids. In-depth mechanistic analysis reveals that the strategic generation of an N-acyllutidinium intermediate is critical for the success of this reaction. The barrierless reduction of the N-acyllutidinium intermediate facilitates the delivery of chiral amino ketones with retention of stereochemistry. This pathway avoids the formation of a detrimental nickel intermediate, which could be responsible for undesirable decarbonylation and transmetalation reactions that limit the utility of previously reported methods.
Self-sorting in macroscopic supramolecular self-assembly via additive effects of capillary and magnetic forces
Authors: Tan Minghui , Tian Pan , Zhang Qian , Zhu Guiqiang , Liu Yuchen , Cheng Mengjiao , Shi Feng
Published: September 2022

Supramolecular self-assembly of μm-to-mm sized components is essential to construct complex supramolecular systems. However, the selective assembly to form designated structures at this length scale is challenging because the short-ranged molecular recognition could hardly direct the assembly of macroscopic components. Here we demonstrate a self-sorting mechanism to automatically identify the surface chemistry of μm-to-mm components (A: polycations; B: polyanions) based on the A-B attraction and the A-A repulsion, which is realized by the additivity and the competence between long-ranged magnetic/capillary forces, respectively. Mechanistic studies of the correlation between the magnetic/capillary forces and the interactive distance have revealed the energy landscape of each assembly pattern to support the self-sorting results. By applying this mechanism, the assembly yield of ABA trimers has been increased from 30%~40% under conventional conditions to 100% with self-sorting. Moreover, we have demonstrated rapid and spontaneous self-assembly of advanced chain-like structures with alternate surface chemistry.
Identification of risk loci for primary aldosteronism in genome-wide association studies
Authors: Le Floch Edith , Cosentino Teresa , Larsen Casper K. , Beuschlein Felix , Reincke Martin , Amar Laurence , Rossi Gian-Paolo , De Sousa Kelly , Baron Stéphanie , Chantalat Sophie , Saintpierre Benjamin , Lenzini Livia , Frouin Arthur , Giscos-Douriez Isabelle , Ferey Matthis , Abdellatif Alaa B. , Meatchi Tchao , Empana Jean-Philippe , Jouven Xavier , Gieger Christian , Waldenberger Melanie , Peters Annette , Cusi Daniele , Salvi Erika , Meneton Pierre , Touvier Mathilde , Deschasaux Mélanie , Druesne-Pecollo Nathalie , Boulkroun Sheerazed , Fernandes-Rosa Fabio L. , Deleuze Jean-François , Jeunemaitre Xavier , Zennaro Maria-Christina
Published: September 2022

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.
Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks
Authors: Ignea Codruta , Raadam Morten H. , Koutsaviti Aikaterini , Zhao Yong , Duan Yao-Tao , Harizani Maria , Miettinen Karel , Georgantea Panagiota , Rosenfeldt Mads , Viejo-Ledesma Sara E. , Petersen Mikael A. , Bredie Wender L. P. , Staerk Dan , Roussis Vassilios , Ioannou Efstathia , Kampranis Sotirios C.
Published: September 2022

Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C16 scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.
The genus Serratia revisited by genomics
Authors: Williams David J. , Grimont Patrick A. D. , Cazares Adrián , Grimont Francine , Ageron Elisabeth , Pettigrew Kerry A. , Cazares Daniel , Njamkepo Elisabeth , Weill François-Xavier , Heinz Eva , Holden Matthew T. G. , Thomson Nicholas R. , Coulthurst Sarah J.
Published: September 2022

The genusSerratiahas been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity ofSerratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages ofSerratia.
Electronic modulation of metal-support interactions improves polypropylene hydrogenolysis over ruthenium catalysts
Authors: Kots Pavel A. , Xie Tianjun , Vance Brandon C. , Quinn Caitlin M. , de Mello Matheus Dorneles , Boscoboinik J. Anibal , Wang Cong , Kumar Pawan , Stach Eric A. , Marinkovic Nebojsa S. , Ma Lu , Ehrlich Steven N. , Vlachos Dionisios G.
Published: September 2022

Ruthenium (Ru) is the one of the most promising catalysts for polyolefin hydrogenolysis. Its performance varies widely with the support, but the reasons remain unknown. Here, we introduce a simple synthetic strategy (using ammonia as a modulator) to tune metal-support interactions and apply it to Ru deposited on titania (TiO2). We demonstrate that combining deuterium nuclear magnetic resonance spectroscopy with temperature variation and density functional theory can reveal the complex nature, binding strength, and H amount. H2 activation occurs heterolytically, leading to a hydride on Ru, an H+ on the nearest oxygen, and a partially positively charged Ru. This leads to partial reduction of TiO2 and high coverages of H for spillover, showcasing a threefold increase in hydrogenolysis rates. This result points to the key role of the surface hydrogen coverage in improving hydrogenolysis catalyst performance.
Determination of topological edge quantum numbers of fractional quantum Hall phases by thermal conductance measurements
Authors: Srivastav Saurabh Kumar , Kumar Ravi , Spånslätt Christian , Watanabe K. , Taniguchi T. , Mirlin Alexander D. , Gefen Yuval , Das Anindya
Published: September 2022

To determine the topological quantum numbers of fractional quantum Hall (FQH) states hosting counter-propagating (CP) downstream (Nd) and upstream (Nu) edge modes, it is pivotal to study quantized transport both in the presence and absence of edge mode equilibration. While reaching the non-equilibrated regime is challenging for charge transport, we target here the thermal Hall conductance GQ, which is purely governed by edge quantum numbers Nd and Nu. Our experimental setup is realized with a hexagonal boron nitride (hBN) encapsulated graphite gated single layer graphene device. For temperatures up to 35 mK, our measured GQ at ν = 2/3 and 3/5 (with CP modes) match the quantized values of non-equilibrated regime (Nd + Nu)κ0T, where κ0T is a quanta of GQ. With increasing temperature, GQ decreases and eventually takes the value of the equilibrated regime ∣Nd − Nu∣κ0T. By contrast, at ν = 1/3 and 2/5 (without CP modes), GQ remains robustly quantized at Ndκ0T independent of the temperature. Thus, measuring the quantized values of GQ in two regimes, we determine the edge quantum numbers, which opens a new route for finding the topological order of exotic non-Abelian FQH states.
Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy
Authors: Jin Shouheng , He Xing , Ma Ling , Zhuang Zhen , Wang Yiliang , Lin Meng , Cai Sihui , Wei Lu , Wang Zheyu , Zhao Zhiyao , Wu Yaoxing , Sun Lin , Li Chunwei , Xie Weihong , Zhao Yong , Songyang Zhou , Peng Ke , Zhao Jincun , Cui Jun
Published: September 2022

In addition to investigating the virology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovering the host–virus dependencies are essential to identify and design effective antiviral therapy strategy. Here, we report that the SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and provide evidence indicating that prevention of ACE2 SUMOylation can block SARS-CoV-2 infection. E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. TOLLIP deficiency results in the stabilization of ACE2 and elevated SARS-CoV-2 infection. In conclusion, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination as a potential way to combat SARS-CoV-2 infection.
Taz protects hematopoietic stem cells from an aging-dependent decrease in PU.1 activity
Authors: Kim Kyung Mok , Mura-Meszaros Anna , Tollot Marie , Krishnan Murali Shyam , Gründl Marco , Neubert Laura , Groth Marco , Rodriguez-Fraticelli Alejo , Svendsen Arthur Flohr , Campaner Stefano , Andreas Nico , Kamradt Thomas , Hoffmann Steve , Camargo Fernando D. , Heidel Florian H. , Bystrykh Leonid V. , de Haan Gerald , von Eyss Björn
Published: September 2022

Specific functions of the immune system are essential to protect us from infections caused by pathogens such as viruses and bacteria. However, as we age, the immune system shows a functional decline that can be attributed in large part to age-associated defects in hematopoietic stem cells (HSCs)—the cells at the apex of the immune cell hierarchy. Here, we find that the Hippo pathway coactivator TAZ is potently induced in old HSCs and protects these cells from functional decline. We identify Clca3a1 as a TAZ-induced gene that allows us to trace TAZ activity in vivo. Using CLCA3A1 as a marker, we can isolate “young-like” HSCs from old mice. Mechanistically, Taz acts as coactivator of PU.1 and to some extent counteracts the gradual loss of PU.1 expression during HSC aging. Our work thus uncovers an essential role for Taz in a previously undescribed fail-safe mechanism in aging HSCs.
Cooperative-effect-induced one-way steering in open cavity magnonics
Authors: Guan Si-Yu , Wang Hong-Fu , Yi Xuexi
Published: September 2022

We propose to generate and control stationary one-way steering with strong entanglement between photon and magnon modes by the cooperative effect of coherent coupling and dissipative coupling. Due to the combination of two couplings, the system becomes a parity-time-like symmetric non-Hermitian system, and two exceptional points (EPs)-like appear in the real and imaginary parts of the eigenvalues. We demonstrate that the especially obvious quantum entanglement and perfect one-way steering can be obtained around two EPs-like. The continuous variable entanglement and steering produced by this cooperative effect show stronger robustness to environment temperature and system dissipation than that induced by nonlinearity. The one-way steering directivity can be controlled by the relative phase of cooperative dissipation and the frequency detuning of the magnon mode. Our work shows the controllability advantage of the open cavity magnonic system and may open up a platform for the generation of stationary one-way steering.
Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues
Authors: Callaghan Neal I. , Durland Lauren J. , Ireland Ronald G. , Santerre J. Paul , Simmons Craig A. , Davenport Huyer Locke
Published: September 2022

The development of induced-pluripotent stem cell (iPSC)-derived cell types offers promise for basic science, drug testing, disease modeling, personalized medicine, and translatable cell therapies across many tissue types. However, in practice many iPSC-derived cells have presented as immature in physiological function, and despite efforts to recapitulate adult maturity, most have yet to meet the necessary benchmarks for the intended tissues. Here, we summarize the available state of knowledge surrounding the physiological mechanisms underlying cell maturation in several key tissues. Common signaling consolidators, as well as potential synergies between critical signaling pathways are explored. Finally, current practices in physiologically relevant tissue engineering and experimental design are critically examined, with the goal of integrating greater decision paradigms and frameworks towards achieving efficient maturation strategies, which in turn may produce higher-valued iPSC-derived tissues.
Production of scaffold-free cell-based meat using cell sheet technology
Authors: Tanaka Ryu-ichiro , Sakaguchi Katsuhisa , Yoshida Azumi , Takahashi Hironobu , Haraguchi Yuji , Shimizu Tatsuya
Published: September 2022

In the production of cell-based meat, it is desirable to reduce animal-derived materials as much as possible to meet the challenges of sustainability. Here, we demonstrate the “cell sheet-based meat”: scaffold-free cell-based meat using cell sheet technology and characterize its texture and nutrients. Bovine myoblast cell sheets were prepared using temperature-responsive culture dishes (TRCDs) and 10 stacked cell sheets to fabricate three-dimensional tissue of 1.3–2.7 mm thickness. Hardness was increased by incubation on the TRCD and was further increased by boiling as is characteristic of natural meat. The wet weight percentage of total protein in the cell sheet was about half that of beef. In this method, large-sized items of cell sheet-based meat were also created by simply scaling up the TRCD. This method promises an environment-friendly food product.