bluuebunny/crossref_metadata_2025_split huggingface dataset:
An in situ hydrogel-mediated chemo-immunometabolic cancer therapy
Authors: Wang Bo , Chen Jing , Caserto Julia S. , Wang Xi , Ma Minglin 
Published: July 2022

AbstractMetabolic reprogramming of the tumor microenvironment (TME) and poor immunogenicity are two of the challenges that cancer immunotherapies have to overcome for improved clinical benefits. Among various immunosuppressive metabolites that keep anti-tumor immunity in check, the tryptophan catabolite kynurenine (Kyn) is an attractive target for blockade given its role in mediating immunosuppression through multiple pathways. Here, we present a local chemo-immunometabolic therapy through injection of a supramolecular hydrogel concurrently releasing doxorubicin that induces immunogenic tumor cell death and kynureninase that disrupts Kyn-mediated immunosuppressive pathways in TME. The combination synergically enhances tumor immunogenicity and unleashes anti-tumor immunity. In mouse models of triple negative breast cancer and melanoma, a single low dose peritumoral injection of the therapeutic hydrogel promotes TME transformation toward more immunostimulatory, which leads to enhanced tumor suppression and extended mouse survival. In addition, the systemic anti-tumor surveillance induced by the local treatment exhibits an abscopal effect and prevents tumor relapse post-resection. This versatile approach for local chemo-immunometabolic therapy may serve as a general strategy for enhancing anti-tumor immunity and boosting the efficacy of cancer immunotherapies.
Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains
Authors: Case James Brett , Mackin Samantha , Errico John M. , Chong Zhenlu , Madden Emily A. , Whitener Bradley , Guarino Barbara , Schmid Michael A. , Rosenthal Kim , Ren Kuishu , Dang Ha V. , Snell Gyorgy , Jung Ana , Droit Lindsay , Handley Scott A. , Halfmann Peter J. , Kawaoka Yoshihiro , Crowe James E. , Fremont Daved H. , Virgin Herbert W. , Loo Yueh-Ming , Esser Mark T. , Purcell Lisa A. , Corti Davide , Diamond Michael S. 
Published: July 2022

AbstractOmicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo.
Rapid northern hemisphere ice sheet melting during the penultimate deglaciation
Authors: Stoll Heather M. , Cacho Isabel , Gasson Edward , Sliwinski Jakub , Kost Oliver , Moreno Ana , Iglesias Miguel , Torner Judit , Perez-Mejias Carlos , Haghipour Negar , Cheng Hai , Edwards R. Lawrence 
Published: July 2022

AbstractThe rate and consequences of future high latitude ice sheet retreat remain a major concern given ongoing anthropogenic warming. Here, new precisely dated stalagmite data from NW Iberia provide the first direct, high-resolution records of periods of rapid melting of Northern Hemisphere ice sheets during the penultimate deglaciation. These records reveal the penultimate deglaciation initiated with rapid century-scale meltwater pulses which subsequently trigger abrupt coolings of air temperature in NW Iberia consistent with freshwater-induced AMOC slowdowns. The first of these AMOC slowdowns, 600-year duration, was shorter than Heinrich 1 of the last deglaciation. Although similar insolation forcing initiated the last two deglaciations, the more rapid and sustained rate of freshening in the eastern North Atlantic penultimate deglaciation likely reflects a larger volume of ice stored in the marine-based Eurasian Ice sheet during the penultimate glacial in contrast to the land-based ice sheet on North America as during the last glacial.
The different prognostic significance of polysialic acid and CD56 expression in tumor cells and lymphocytes identified in breast cancer
Authors: Soukhtehzari Sepideh , Berish Richard B. , Fazli Ladan , Watson Peter H. , Williams Karla C. 
Published: July 2022

AbstractProtein glycosylation, the attachment of carbohydrates onto proteins, is a fundamental process that alters the biological activity of proteins. Changes to glycosylation states are associated with many forms of cancer including breast cancer. Through immunohistological analysis of breast cancer patient tumors, we have discovered the expression of an atypical glycan—polysialic acid (polySia)—in breast cancer. Notably, we have identified polySia expression in not only tumor cells but also on tumor-infiltrating lymphocytes (TILs) and our study reveals ST8Sia4 as the predominant polysialyltransferase expressed. Evaluation of ST8Sia4 expression in tumor cells identified an association between high expression levels and poor patient outcomes whereas ST8Sia4 expression in infiltrating stromal cells was associated with good patient outcomes. Investigation into CD56, a protein known to be polysialylated, found CD56 and polySia expression on breast tumor cells and TILs. CD56 expression did not positively correlate with polySia expression except in patient tumors which expressed HER2. In these HER2 expressing tumors, CD56 expression was significantly associated with HER2 expression score. Evaluation of CD56 tumor cell expression identified a significant association between CD56 expression and poor patient outcomes. By contrast, CD56 expression on TILs was significantly associated with good clinical outcomes. Tumors with CD56+ TILs were also consistently polySia TIL positive. Interestingly, in tumors where TILs were CD56 low-to-negative, a polySia+ lymphocyte population was still identified and the presence of these lymphocytes was a poor prognostic indicator. Overall, this study provides the first detailed report of polySia and CD56 in breast cancer and demonstrates that the prognostic significance is dependent on the cell type expression within the tumor.
Effects of different inspiratory muscle warm-up loads on mechanical, physiological and muscle oxygenation responses during high-intensity running and recovery
Authors: Marostegan Anita B. , Gobatto Claudio A. , Rasteiro Felipe M. , Hartz Charlini S. , Moreno Marlene A. , Manchado-Gobatto Fúlvia B. 
Published: July 2022

AbstractInspiratory muscle warm-up (IMW) has been used as a resource to enhance exercises and sports performance. However, there is a lack of studies in the literature addressing the effects of different IMW loads (especially in combination with a shorter and applicable protocol) on high-intensity running and recovery phase. Thus, this study aimed to investigate the effects of three different IMW loads using a shorter protocol on mechanical, physiological and muscle oxygenation responses during and after high-intensity running exercise. Sixteen physically active men, randomly performed four trials 30 s all-out run, preceded by the shorter IMW protocol (2 × 15 breaths with a 1-min rest interval between sets, accomplished 2 min before the 30 s all-out run). Here, three IMW load conditions were used: 15%, 40%, and 60% of maximal inspiratory pressure (MIP), plus a control session (CON) without the IMW. The force, velocity and running power were measured (1000 Hz). Two near-infrared spectroscopy (NIRS) devices measured (10 Hz) the muscle’s oxygenation responses in biceps brachii (BB) and vastus lateralis (VL). Additionally, heart rate (HR) and blood lactate ([Lac]) were also monitored. IMW loads applied with a shorter protocol promoted a significant increase in mean and minimum running power as well as in peak and minimum force compared to CON. In addition, specific IMW loads led to higher values of peak power, mean velocity (60% of MIP) and mean force (40 and 60% of MIP) in relation to CON. Physiological responses (HR and muscles oxygenation) were not modified by any IMW during exercise, as well as HR and [Lac] in the recovery phase. On the other hand, 40% of MIP presented a higher tissue saturation index (TSI) for BB during recovery phase. In conclusion, the use of different loads of IMW may improve the performance of a physically active individual in a 30 s all-out run, as verified by the increased peak, mean and minimum mechanical values, but not in performance assessed second by second. In addition, 40% of the MIP improves TSI of the BB during the recovery phase, which can indicate greater availability of O2 for lactate clearance.
Predicting high recombinant protein producer strains of Pichia pastoris MutS using the oxygen transfer rate as an indicator of metabolic burden
Authors: Wollborn David , Munkler Lara Pauline , Horstmann Rebekka , Germer Andrea , Blank Lars Mathias , Büchs Jochen 
Published: July 2022

AbstractThe methylotrophic yeast Pichia pastoris (Komagataella phaffii) is a widely used host for recombinant protein production. In this study, a clonal library of P. pastoris MutS strains (S indicates slow methanol utilization) was screened for high green fluorescent protein (GFP) production. The expression cassette was under the control of the methanol inducible AOX promoter. The growth behavior was online-monitored in 48-well and 96-well microtiter plates by measuring the oxygen transfer rate (OTR). By comparing the different GFP producing strains, a correlation was established between the slope of the cumulative oxygen transfer during the methanol metabolization phase and the strain’s production performance. The correlation corresponds to metabolic burden during methanol induction. The findings were validated using a pre-selected strain library (7 strains) of high, medium, and low GFP producers. For those strains, the gene copy number was determined via Whole Genome Sequencing. The results were consistent with the described OTR correlation. Additionally, a larger clone library (45 strains) was tested to validate the applicability of the proposed method. The results from this study suggest that the cumulative oxygen transfer can be used as a screening criterion for protein production performance that allows for a simple primary screening process, facilitating the pre-selection of high producing strains.
Automated methodology for optimal selection of minimum electrode subsets for accurate EEG source estimation based on Genetic Algorithm optimization
Authors: Soler Andres , Moctezuma Luis Alfredo , Giraldo Eduardo , Molinas Marta 
Published: July 2022

AbstractHigh-density Electroencephalography (HD-EEG) has proven to be the EEG montage that estimates the neural activity inside the brain with highest accuracy. Multiple studies have reported the effect of electrode number on source localization for specific sources and specific electrode configurations. The electrodes for these configurations are often manually selected to uniformly cover the entire head, going from 32 to 128 electrodes, but electrode configurations are not often selected according to their contribution to estimation accuracy. In this work, an optimization-based study is proposed to determine the minimum number of electrodes that can be used and to identify the optimal combinations of electrodes that can retain the localization accuracy of HD-EEG reconstructions. This optimization approach incorporates scalp landmark positions of widely used EEG montages. In this way, a systematic search for the minimum electrode subset is performed for single- and multiple-source localization problems. The Non-dominated Sorting Genetic Algorithm II (NSGA-II) combined with source reconstruction methods is used to formulate a multi-objective optimization problem that concurrently minimizes (1) the localization error for each source and (2) the number of required EEG electrodes. The method can be used for evaluating the source localization quality of low-density EEG systems (e.g. consumer-grade wearable EEG). We performed an evaluation over synthetic and real EEG datasets with known ground-truth. The experimental results show that optimal subsets with 6 electrodes can attain an equal or better accuracy than HD-EEG (with more than 200 channels) for a single source case. This happened when reconstructing a particular brain activity in more than 88% of the cases in synthetic signals and 63% in real signals, and in more than 88% and 73% of cases when considering optimal combinations with 8 channels. For a multiple-source case of three sources (only with synthetic signals), it was found that optimized combinations of 8, 12 and 16 electrodes attained an equal or better accuracy than HD-EEG with 231 electrodes in at least 58%, 76%, and 82% of cases respectively. Additionally, for such electrode numbers, lower mean errors and standard deviations than with 231 electrodes were obtained.
Genome doubling enabled the expansion of yeast vesicle traffic pathways
Authors: Purkanti Ramya , Thattai Mukund 
Published: July 2022

AbstractVesicle budding and fusion in eukaryotes depend on a suite of protein types, such as Arfs, Rabs, coats and SNAREs. Distinct paralogs of these proteins act at distinct intracellular locations, suggesting a link between gene duplication and the expansion of vesicle traffic pathways. Genome doubling, a common source of paralogous genes in fungi, provides an ideal setting in which to explore this link. Here we trace the fates of paralog doublets derived from the 100-Ma-old hybridization event that gave rise to the whole genome duplication clade of budding yeast. We find that paralog doublets involved in specific vesicle traffic functions and pathways are convergently retained across the entire clade. Vesicle coats and adaptors involved in secretory and early-endocytic pathways are retained as doublets, at rates several-fold higher than expected by chance. Proteins involved in later endocytic steps and intra-Golgi traffic, including the entire set of multi-subunit and coiled-coil tethers, have reverted to singletons. These patterns demonstrate that selection has acted to expand and diversify the yeast vesicle traffic apparatus, across species and time.
CRISPR/Cas9-based genome-wide screening of Dictyostelium
Authors: Ogasawara Takanori , Watanabe Jun , Adachi Remi , Ono Yusuke , Kamimura Yoichiro , Muramoto Tetsuya 
Published: July 2022

AbstractGenome-wide screening is powerful method used to identify genes and pathways associated with a phenotype of interest. The simple eukaryote Dictyostelium discoideum has a unique life cycle and is often used as a crucial research model for a wide range of biological processes and rare metabolites. To address the inadequacies of conventional genetic screening approaches, we developed a highly efficient CRISPR/Cas9-based genome-wide screening system for Dictyostelium. A genome-wide library of 27,405 gRNAs and a kinase library of 4,582 gRNAs were compiled and mutant pools were generated. The resulting mutants were screened for defects in cell growth and more than 10 candidate genes were identified. Six of these were validated and five recreated mutants presented with growth abnormalities. Finally, the genes implicated in developmental defects were screened to identify the unknown genes associated with a phenotype of interest. These findings demonstrate the potential of the CRISPR/Cas9 system as an efficient genome-wide screening method.
Protein–protein interaction and non-interaction predictions using gene sequence natural vector
Authors: Zhao Nan , Zhuo Maji , Tian Kun , Gong Xinqi 
Published: July 2022

AbstractPredicting protein–protein interaction and non-interaction are two important different aspects of multi-body structure predictions, which provide vital information about protein function. Some computational methods have recently been developed to complement experimental methods, but still cannot effectively detect real non-interacting protein pairs. We proposed a gene sequence-based method, named NVDT (Natural Vector combine with Dinucleotide and Triplet nucleotide), for the prediction of interaction and non-interaction. For protein–protein non-interactions (PPNIs), the proposed method obtained accuracies of 86.23% for Homo sapiens and 85.34% for Mus musculus, and it performed well on three types of non-interaction networks. For protein-protein interactions (PPIs), we obtained accuracies of 99.20, 94.94, 98.56, 95.41, and 94.83% for Saccharomyces cerevisiae, Drosophila melanogaster, Helicobacter pylori, Homo sapiens, and Mus musculus, respectively. Furthermore, NVDT outperformed established sequence-based methods and demonstrated high prediction results for cross-species interactions. NVDT is expected to be an effective approach for predicting PPIs and PPNIs.
A previous hemorrhagic stroke protects against a subsequent stroke via microglia alternative polarization
Authors: Lee Shin-Shin , Pang Li , Cheng Yin , Liu Jia Xin , Ng Anson Cho Kiu , Leung Gilberto Ka Kit 
Published: July 2022

AbstractMicroglia in hemorrhagic stroke contribute to both acute-phase exacerbation and late-phase attenuation of injury. Here, by using the mouse model, we reported that the shift in polarization of microglia from M1 to M2 phenotype could be altered by a past ‘mini’ stroke, resulting in better neurological function recovery, faster attenuation of lesion volume, and better survival. In mice with a previous stroke, M2 predominance appeared markedly in advance compared to mice without a previous stroke. Mechanistically, the RBC-mediated M2 polarization of microglia was synergistically enhanced by T cells: microglia cocultured with RBCs alone resulted in mild alterations to M2 markers, whereas in the presence of T cells, they expressed an early and sustained M2 response. These results suggest that by harnessing the microglia-mediated M2 polarization response, we could help mitigate devastating sequelae before a prospective hemorrhagic stroke even happens.
Improved linear cryptanalysis on 25‐round SMS4
Authors: Fu Lishi , Jin Chenhui 
Published: July 2022

AbstractSMS4 is the Chinese national standard for WLAN, which is also an ISO/IEC international standard. This paper presents a linear cryptanalysis on 25‐round SMS4 for the first time. Firstly, this paper adopts a new statistic in linear cryptanalysis, which is aimed to compute the distance between one cipher system and one random permutation, which can be used to distinguish the right key from the wrong keys by the different probability distributions they follow. Secondly, the attack principal and data complexity are given when this new statistic is used in multiple linear cryptanalysis. Thirdly, this paper presents 21‐round linear approximations with absolute correlation by fixing the least significant input bit of the Sbox with nonzero mask in the first round to be 1. Furthermore, this paper gives 48 21‐round linear approximations with absolute correlation . Based on the restrictions between those 48 linear approximations and fast Fourier transformation technique, the whole attack needs known plaintexts, 25‐round SMS4 encryptions along with memory accesses, and bytes of memory, which is the best cryptanalysis result on SMS4 so far. Finally, this paper generalizes the linear cryptanalysis method with conditioned linear approximation, which can also be adopted in attacking other ciphers.
Robust linear unmixing with enhanced constraint of classification for hyperspectral remote sensing imagery
Authors: Yu Haoyang , Chi Jinxue , Shang Xiaodi , Shen Xueji , Chanussot Jocelyn , Shi Yimin 
Published: July 2022

AbstractAlthough hyperspectral data, especially spaceborne images, are rich in spectral information, their spatial resolution is usually low due to the limitation of sensor design and other factors. Therefore, for the application of hyperspectral images, unmixing technology is a key processing technology, such as linear mixing model and its derived algorithms have made a certain progress. However, a real scene often contains both pure and mixed pixels. The existing methods usually ignore the consideration and analysis of this situation in the process of model design and simulation experiment. In this context, this paper proposes a robust linear unmixing model with the enhanced constraint of classification for hyperspectral image. In general, it designs a framework combining unmixing and classification. In the task for real scene data, endmembers are extracted first, and then the hard classification term constructed after the expansion of endmembers (training samples) based on similarity is introduced to provide the sparsity constraint of the overall model, so as to realize relatively complete adjustment and effective image unmixing under complex conditions. Considering the scene with different distributions, the simulation experiment designs several groups of data tests, including different proportions of pure and mixing pixels. The unmixing results of three simulated datasets and two real datasets show that the unmixing results of this method are better than those of the other six comparison methods. This model improves the accuracy of unmixing and realizes effective unmixing.
Automatic emergency braking/anti‐lock braking system coordinated control with road adhesion coefficient estimation for heavy vehicle
Authors: Shaohua Li , Guiyang Wang , Hesen Wang , Lipeng Zhang 
Published: July 2022

AbstractThe road adhesion coefficient is a key factor influencing automatic emergency braking (AEB) and anti‐lock braking system (ABS) safety control of trucks. With the fading factor introduced, and the covariance gain adjusted in real time, the strong tracking unscented Kalman filter (STUKF) algorithm is modified to estimate the road adhesion coefficient more accurately. Composed of an ABS fuzzy sliding mode controller (SMC) and an AEB controller, an AEB/ABS coordinated control strategy with an adhesion coefficient estimation is designed for a three‐axle heavy vehicle. The control effects are verified through experiments on various road conditions based on a hardware‐in‐loop test platform. The test results show that the proposed control strategy has a better braking efficiency than the traditional AEB/ABS and AEB control strategy without adhesion coefficient estimation and can decrease braking distance by 8.4% and braking time by 5.9%, which is beneficial to the vehicle longitudinal safety.