bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment
Authors: Wallace-Povirk Adrianne , Rubinsak Lisa , Malysa Agnes , Dzinic Sijana H. , Ravindra Manasa , Schneider Mathew , Glassbrook James , O’Connor Carrie , Hou Zhanjun , Kim Seongho , Back Jessica , Polin Lisa , Morris Robert T. , Gangjee Aleem , Gibson Heather , Matherly Larry H.
Published: July 2022

Novel therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. In addition, therapies that target unique vulnerabilities in the tumor microenvironment (TME) of EOC have largely been unrealized. One strategy to achieve selective drug delivery for EOC therapy involves use of targeted antifolates via their uptake by folate receptor (FR) proteins, resulting in inhibition of essential one-carbon (C1) metabolic pathways. FRα is highly expressed in EOCs, along with the proton-coupled folate transporter (PCFT); FRβ is expressed on activated macrophages, a major infiltrating immune population in EOC. Thus, there is great potential for targeting both the tumor and the TME with agents delivered via selective transport by FRs and PCFT. In this report, we investigated the therapeutic potential of a novel cytosolic C1 6-substituted pyrrolo[2,3-d]pyrimidine inhibitor AGF94, with selectivity for uptake by FRs and PCFT and inhibition of de novo purine nucleotide biosynthesis, against a syngeneic model of ovarian cancer (BR-Luc) which recapitulates high-grade serous ovarian cancer in patients. In vitro activity of AGF94 was extended in vivo against orthotopic BR-Luc tumors. With late-stage subcutaneous BR-Luc xenografts, AGF94 treatment resulted in substantial anti-tumor efficacy, accompanied by significantly decreased M2-like FRβ-expressing macrophages and increased CD3+ T cells, whereas CD4+ and CD8+ T cells were unaffected. Our studies demonstrate potent anti-tumor efficacy of AGF94 in the therapy of EOC in the context of an intact immune system, and provide a framework for targeting the immunosuppressive TME as an essential component of therapy.
NMDAR mediated dynamic changes in m6A inversely correlates with neuronal translation
Authors: Gowda Naveen Kumar Chandappa , Nawalpuri Bharti , Ramakrishna Sarayu , Jhaveri Vishwaja , Muddashetty Ravi S.
Published: July 2022

Epitranscriptome modifications are crucial in translation regulation and essential for maintaining cellular homeostasis. N6 methyladenosine (m6A) is one of the most abundant and well-conserved epitranscriptome modifications, which is known to play a pivotal role in diverse aspects of neuronal functions. However, the role of m6A modifications with respect to activity-mediated translation regulation and synaptic plasticity has not been studied. Here, we investigated the role of m6A modification in response to NMDAR stimulation. We have consistently observed that 5 min NMDAR stimulation causes an increase in eEF2 phosphorylation. Correspondingly, NMDAR stimulation caused a significant increase in the m6A signal at 5 min time point, correlating with the global translation inhibition. The NMDAR induced increase in the m6A signal is accompanied by the redistribution of the m6A marked RNAs from translating to the non-translating pool of ribosomes. The increased m6A levels are well correlated with the reduced FTO levels observed on NMDAR stimulation. Additionally, we show that inhibition of FTO prevents NMDAR mediated changes in m6A levels. Overall, our results establish RNA-based molecular readout which corelates with the NMDAR-dependent translation regulation which helps in understanding changes in protein synthesis.
Preoperative prediction of the pathological stage of advanced gastric cancer by 18F-fluoro-2-deoxyglucose positron emission tomography
Authors: Yamada Kota , Urakawa Naoki , Kanaji Shingo , Hasegawa Hiroshi , Yamamoto Masashi , Yamashita Kimihiro , Matsuda Takeru , Oshikiri Taro , Suzuki Satoshi , Kakeji Yoshihiro
Published: July 2022

In recent years, the usefulness of neoadjuvant chemotherapy for resectable advanced gastric cancer, particularly stage III, has been reported. Preoperative staging is mainly determined by computed tomography (CT), and the usefulness of 18F-fluoro-2-deoxyglucose positron emission tomography/CT (FDG-PET/CT) for gastric cancer has been limited in usefulness. The study aimed to evaluate the usefulness of FDG-PET/CT in preoperative diagnosis of advanced gastric cancer. We retrospectively enrolled 113 patients with gastric cancer who underwent preoperative FDG-PET/CT. All patients underwent gastrectomy with lymph-node dissection. The maximum standardized uptake value (SUVmax) of the primary tumor (T-SUVmax) and lymph nodes (N-SUVmax) were measured for all patients. The cutoff values of T-SUVmax for pathological T3/4 from receiver operating characteristic analysis were 8.28 for differentiated and 4.32 for undifferentiated types. The T-SUVmax and N-SUVmax cutoff values for pathological lymph-node metastasis were 4.32 and 1.82, respectively. Multivariate analysis showed that T-SUVmax for differentiated types was a significant predictor of pathological T3/4, and N-SUVmax was a significant predictor of lymph-node metastasis. In conclusion, the SUVmax of FDG-PET/CT was a useful predictor of pathological T3/4 and lymph-node metastasis in gastric cancer. The diagnosis by preoperative FDG-PET/CT is promising to contribute a more accurate staging of gastric cancer than by CT scan alone.
Whole-genome analysis and mutation pattern of SARS-CoV-2 during first and second wave outbreak in Gwangju, Republic of Korea
Authors: Chatterjee Shilpa , Kim Choon-Mee , Lee You Mi , Seo Jun-Won , Kim Da Young , Yun Na Ra , Kim Dong-Min
Published: July 2022

To investigate the specific genomic features and mutation pattern, whole and near-complete SARS-CoV-2 genome sequences were analyzed. Clinical samples were collected from 18 COVID-19–positive patients and subjected to nucleic acid purification. Cell culture was performed to extract various SARS-CoV-2 isolates. Whole-genome analysis was performed using next-generation sequencing, and phylogenetic analyses were conducted to determine genetic diversity of the various SARS-CoV-2 isolates. The next-generation sequencing data identified 8 protein-coding regions with 17 mutated proteins. We identified 51 missense point mutations and deletions in 5′ and 3′ untranslated regions. The phylogenetic analysis revealed that V and GH are the dominant clades of SARS-CoV-2 circulating in the Gwangju region of South Korea. Moreover, statistical analysis confirmed a significant difference between viral load (P < 0.001) and number of mutations (P < 0.0001) in 2 mutually exclusive SARS-CoV-2 clades which indicates frequent genomic alterations in SARS-CoV-2 in patients with high viral load. Our results provide an in-depth analysis of SARS-COV-2 whole genome which we believe, can shed light in the understanding of SARS-COV-2 pathogenesis and mutation pattern which can aid in the development of prevention methods as well as future research into the pathogenesis of SARS-CoV-2 and therapeutic development.
No evidence of increased mutations in the germline of a group of British nuclear test veterans
Authors: Moorhouse Alexander J. , Scholze Martin , Sylvius Nicolas , Gillham Clare , Rake Christine , Peto Julian , Anderson Rhona , Dubrova Yuri E.
Published: July 2022

The potential germline effects of radiation exposure to military veterans present at British nuclear tests in Australia and the South Pacific is of considerable interest. We analyzed germline mutations in 60 families of UK military personnel comprising 30 control and 30 nuclear test veterans (NTV). Using whole-genome sequencing we studied the frequency and spectra of de novo mutations to investigate the transgenerational effect of veterans’ (potential) exposure to radiation at nuclear bomb test sites. We find no elevation in total de novo single nucleotide variants, small insertion-deletions, structural variants or clustered mutations among the offspring of nuclear test veterans compared to those of control personnel. We did observe an elevated occurrence of single base substitution mutations within mutation signature SBS16, due to a subset of NTV offspring. The relevance of this elevation to potential exposure of veteran fathers and, future health risks, require further investigation. Overall, we find no evidence of increased mutations in the germline of a group of British nuclear test veterans.ISRCTN Registry 17461668.
Caging and photo-triggered uncaging of singlet oxygen by excited state engineering of electron donor–acceptor-linked molecular sensors
Authors: Sasikumar Devika , Takano Yuta , Zhao Hanjun , Kohara Reiko , Hamada Morihiko , Kobori Yasuhiro , Biju Vasudevanpillai
Published: July 2022

Singlet oxygen (1O2), one of the most sought-after species in oxidative chemical reactions and photodynamic cancer therapy, is activated and neutralized in the atmosphere and living cells. It is essential to see "when" and "where" 1O2 is produced and delivered to understand and utilize it. There is an increasing demand for molecular sensor tools to capture, store, and supply 1O2, controlled by light and engineered singlet and triplet states, indicating the 1O2-capturing-releasing state. Here, we demonstrate the outstanding potential of an aminocoumarin-methylanthracene-based electron donor–acceptor molecule (1). Spectroscopic measurements confirm the formation of an endoperoxide (1-O2) which is not strongly fluorescent and remarkably different from previously reported 1O2 sensor molecules. Moreover, the photoexcitation on the dye in 1-O2 triggers fluorescence enhancement by the oxidative rearrangement and a competing 1O2 release. The unique ability of 1 will pave the way for the spatially and temporally controlled utilization of 1O2 in various areas such as chemical reactions and phototherapies.
Advantages of deep learning with convolutional neural network in detecting disc displacement of the temporomandibular joint in magnetic resonance imaging
Authors: Lee Yeon-Hee , Won Jong Hyun , Kim Seunghyeon , Auh Q.-Schick , Noh Yung-Kyun
Published: July 2022

This study investigated the usefulness of deep learning-based automatic detection of anterior disc displacement (ADD) from magnetic resonance imaging (MRI) of patients with temporomandibular joint disorder (TMD). Sagittal MRI images of 2520 TMJs were collected from 861 men and 399 women (average age 37.33 ± 18.83 years). A deep learning algorithm with a convolutional neural network was developed. Data augmentation and the Adam optimizer were applied to reduce the risk of overfitting the deep-learning model. The prediction performances were compared between the models and human experts based on areas under the curve (AUCs). The fine-tuning model showed excellent prediction performance (AUC = 0.8775) and acceptable accuracy (approximately 77%). Comparing the AUC values of the from-scratch (0.8269) and freeze models (0.5858) showed lower performances of the other models compared to the fine-tuning model. In Grad-CAM visualizations, the fine-tuning scheme focused more on the TMJ disc when judging ADD, and the sparsity was higher than that of the from-scratch scheme (84.69% vs. 55.61%, p < 0.05). The three fine-tuned ensemble models using different data augmentation techniques showed a prediction accuracy of 83%. Moreover, the AUC values of ADD were higher when patients with TMD were divided by age (0.8549–0.9275) and sex (male: 0.8483, female: 0.9276). While the accuracy of the ensemble model was higher than that of human experts, the difference was not significant (p = 0.1987–0.0671). Learning from pre-trained weights allowed the fine-tuning model to outperform the from-scratch model. Another benefit of the fine-tuning model for diagnosing ADD of TMJ in Grad-CAM analysis was the deactivation of unwanted gradient values to provide clearer visualizations compared to the from-scratch model. The Grad-CAM visualizations also agreed with the model learned through important features in the joint disc area. The accuracy was further improved by an ensemble of three fine-tuning models using diversified data. The main benefits of this model were the higher specificity compared to human experts, which may be useful for preventing true negative cases, and the maintenance of its prediction accuracy across sexes and ages, suggesting a generalized prediction.
Protection of hamsters challenged with SARS-CoV-2 after two doses of MVC-COV1901 vaccine followed by a single intranasal booster with nanoemulsion adjuvanted S-2P vaccine
Authors: Lin Yi-Jiun , Lin Meei-Yun , Chuang Ya-Shan , Liu Luke Tzu-Chi , Kuo Tsun-Yung , Chen Charles , Ganesan Shyamala , Fattom Ali , Bitko Vira , Lien Chia-En
Published: July 2022

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.
Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines
Authors: Jantalika Tanachapa , Manochantr Sirikul , Kheolamai Pakpoom , Tantikanlayaporn Duangrat , Saijuntha Weerachai , Pinlaor Somchai , Chairoungdua Arthit , Paraoan Luminita , Tantrawatpan Chairat
Published: July 2022

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the damaged epithelial cells of the biliary tract. Previous studies have reported that the multi-potent mesenchymal stem cells (MSCs) activate a series of tumor signaling pathways by releasing several cytokines to influence tumor cell development. However, the roles and mechanisms of human chorion-derived MSCs (CH-MSCs) in cholangiocarcinoma progression have not been fully addressed. This present study aims to examine the effects of conditioned media derived from CH-MSCs (CH-CM) on CCA cell lines and investigate the respective underlying mechanism of action. For this purpose, MSCs were isolated from chorion tissue, and three cholangiocarcinoma cell lines, namely KKU100, KKU213A, and KKU213B, were used. MTT assay, annexin V/PI analysis, and JC-1 staining were used to assess the effects of CH-CM on proliferation and apoptosis of CCA cells, respectively. Moreover, the effect of CH-CM on caspase-dependent apoptotic pathways was also evaluated. The western blotting assay was also used for measuring the expression of JAK2/STAT3 signaling pathway-associated proteins. The results showed that CH-CM suppressed proliferation and promoted apoptosis of CCA cell lines. CH-CM treatment-induced loss of mitochondrial membrane potential (∆Ψm) in CCA cell lines. The factors presented in the CH-CM also inhibited JAK2/STAT3 signaling, reduced the expression of BCL-2, and increased BAX expression in CCA cells. In conclusion, our study suggests that the CH-CM has a potent anti-cancer effect on cholangiocarcinoma cells and thus provides opportunities for use in alternative cell therapy or in combination with a conventional chemotherapeutic drug to increase the efficiency of CCA treatment.
Evaluating delay of gamma oscillations in patients with schizophrenia using evoked response audiometry system
Authors: Yanagi Masaya , Tsuchiya Aki , Hosomi Fumiharu , Terada Toru , Ozaki Satoshi , Shirakawa Osamu , Hashimoto Mamoru
Published: July 2022

Impaired gamma oscillations found in a 40-Hz auditory steady-state response (ASSR) in patients with schizophrenia are the robust findings that can be used for future biomarker-based therapeutics. To apply these significant observations into the clinical practice, a clinical system for evoked response audiometry (ERA) may be available. In this study, the delayed 40-Hz ASSR, which was reported as a potent biomarker for schizophrenia, was examined using the ERA system in patients with schizophrenia and its clinical relevance was investigated. The phase of ASSR was significantly delayed in patients with schizophrenia compared with the healthy subjects. The delayed phase was associated with severity of the disease symptoms in the patients. A phase delay with aging was found in healthy subjects, but not in patients with schizophrenia. These findings show availability of the ERA system to identify the delayed 40-Hz ASSR and its clinical implication in patients with schizophrenia. Further applications of the ERA system in clinical psychiatry are warranted in developing biological assessments of schizophrenia with 40-Hz ASSR.
Resolving missing protein problems using functional class scoring
Authors: Wong Bertrand Jern Han , Kong Weijia , Wong Limsoon , Goh Wilson Wen Bin
Published: July 2022

Despite technological advances in proteomics, incomplete coverage and inconsistency issues persist, resulting in “data holes”. These data holes cause the missing protein problem (MPP), where relevant proteins are persistently unobserved, or sporadically observed across samples, hindering biomarker discovery and proper functional characterization. Network-based approaches can provide powerful solutions for resolving these issues. Functional Class Scoring (FCS) is one such method that uses protein complex information to recover missing proteins with weak support. However, FCS has not been evaluated on more recent proteomic technologies with higher coverage, and there is no clear way to evaluate its performance. To address these issues, we devised a more rigorous evaluation schema based on cross-verification between technical replicates and evaluated its performance on data acquired under recent Data-Independent Acquisition (DIA) technologies (viz. SWATH). Although cross-replicate examination reveals some inconsistencies amongst same-class samples, tissue-differentiating signal is nonetheless strongly conserved, confirming that FCS selects for biologically meaningful networks. We also report that predicted missing proteins are statistically significant based on FCS p values. Despite limited cross-replicate verification rates, the predicted missing proteins as a whole have higher peptide support than non-predicted proteins. FCS also predicts missing proteins that are often lost due to weak specific peptide support.
Inverse-cavity structure for low-threshold miniature lasers
Authors: Kim Gunpyo , Song Seok Ho , Yoon Jae Woong
Published: July 2022

Creating micro and nano lasers, high threshold gain is an inherent problem that have critically restricted their great technological potentials. Here, we propose an inverse-cavity laser structure where its threshold gain in the shortest-cavity regime is order-of-magnitude lower than the conventional cavity configurations. In the proposed structure, a resonant feedback mechanism efficiently transfers external optical gain to the cavity mode at a higher rate for a shorter cavity, hence resulting in the threshold gain reducing with decreasing cavity length in stark contrast to the conventional cavity structures. We provide a fundamental theory and rigorous numerical analyses confirming the feasibility of the proposed structure. Remarkably, the threshold gain reduces down by a factor ~ 10−3 for a vertical-cavity surface-emitting laser structure and ~ 0.17 for a lattice-plasmonic nanocavity structure. Therefore, the proposed approach may produce extremely efficient miniature lasers desirable for variety of applications potentially beyond the present limitations.
Sepsis modulates cortical excitability and alters the local and systemic hemodynamic response to seizures
Authors: Ferlini Lorenzo , Nonclercq Antoine , Su Fuhong , Creteur Jacques , Taccone Fabio Silvio , Gaspard Nicolas
Published: July 2022

Non-convulsive seizures and status epilepticus are frequent and associated with increased mortality in septic patients. However, the mechanism through which seizures impact outcome in these patients is unclear. As previous studies yielded an alteration of neurovascular coupling (NVC) during sepsis, we hypothesized that non-convulsive seizures, might further impair NVC, leading to brain tissue hypoxia. We used a previously developed ovine model of sepsis. Animals were allocated to sham procedure or sepsis; septic animals were studied either during the hyperdynamic phase (sepsis group) or after septic shock occurrence (septic shock group). After allocation, seizures were induced by cortical application of penicillin. We recorded a greater seizure-induced increase in the EEG gamma power in the sepsis group than in sham. Using a neural mass model, we also found that the theoretical activity of the modeled inhibitory interneurons, thought to be important to reproduce gamma oscillations, were relatively greater in the sepsis group. However, the NVC was impaired in sepsis animals, despite a normal brain tissue oxygenation. In septic shock animals, it was not possible to induce seizures. Cortical activity declined in case of septic shock, but it did not differ between sham or sepsis animals. As the alteration in NVC preceded cortical activity reduction, we suggest that, during sepsis progression, the NVC inefficiency could be partially responsible for the alteration of brain function, which might prevent seizure occurrence during septic shock. Moreover, we showed that cardiac output decreased during seizures in sepsis animals instead of increasing as in shams. The alteration of the seizure-induced systemic hemodynamic variations in sepsis might further affect cerebrovascular response to neuronal activation. Our findings support the hypothesis that anomalies in the cerebral blood flow regulation may contribute to the sepsis-associated encephalopathy and that seizures might be dangerous in such a vulnerable setting.
Older adults process the probability of winning sooner but weigh it less during lottery decisions
Authors: Chen Hsiang-Yu , Lombardi Gaia , Li Shu-Chen , Hare Todd A.
Published: July 2022

Empirical evidence has shown that visually enhancing the saliency of reward probabilities can ease the cognitive demands of value comparisons and improve value-based decisions in old age. In the present study, we used a time-varying drift diffusion model that includes starting time parameters to better understand (1) how increasing the saliency of reward probabilities may affect the dynamics of value-based decision-making and (2) how these effects may interact with age. We examined choices made by younger and older adults in a mixed lottery choice task. On a subset of trials, we used a color-coding scheme to highlight the saliency of reward probabilities, which served as a decision-aid. The results showed that, in control trials, older adults started to consider probability relative to magnitude information sooner than younger adults, but that their evidence accumulation processes were less sensitive to reward probabilities than that of younger adults. This may indicate a noisier and more stochastic information accumulation process during value-based decisions in old age. The decision-aid increased the influence of probability information on evidence accumulation rates in both age groups, but did not alter the relative timing of accumulation for probability versus magnitude in either group.
Chronic social defeat stress increases the amounts of 12-lipoxygenase lipid metabolites in the nucleus accumbens of stress-resilient mice
Authors: Akiyama Satoshi , Nagai Hirotaka , Oike Shota , Horikawa Io , Shinohara Masakazu , Lu Yabin , Futamura Takashi , Shinohara Ryota , Kitaoka Shiho , Furuyashiki Tomoyuki
Published: July 2022

Severe and prolonged social stress induces mood and cognitive dysfunctions and precipitates major depression. Neuroinflammation has been associated with chronic stress and depression. Rodent studies showed crucial roles of a few inflammation-related lipid mediators for chronic stress-induced depressive-like behaviors. Despite an increasing number of lipid mediators identified, systematic analyses of synthetic pathways of lipid mediators in chronic stress models have not been performed. Using LC–MS/MS, here we examined the effects of chronic social defeat stress on multiple synthetic pathways of lipid mediators in brain regions associated with stress susceptibility in mice. Chronic social defeat stress increased the amounts of 12-lipoxygenase (LOX) metabolites, 12-HETE and 12-HEPE, specifically in the nucleus accumbens 1 week, but not immediately, after the last stress exposure. The increase was larger in stress-resilient mice than stress-susceptible mice. The S isomer of 12-HETE was selectively increased in amount, indicating the role of 12S-LOX activity. Among the enzymes known to have 12S-LOX activity, only Alox12 mRNA was reliably detected in the brain and enriched in brain endothelial cells. These findings suggest that chronic social stress induces a late increase in the amounts of 12S-LOX metabolites derived from the brain vasculature in the nucleus accumbens in a manner associated with stress resilience.
Comprehensive climatic suitability evaluation of peanut in Huang-Huai-Hai region under the background of climate change
Authors: Wei Sicheng , Li Kaiwei , Yang Yueting , Wang Chunyi , Liu Cong , Zhang Jiquan
Published: July 2022

The climate changes influence the growing suitability of peanut, an important oil crop. Climatic suitability evaluation in the Huang-Huai-Hai region, the main peanut producing region of China, which can optimize peanut planting structure and provide basis for increasing output. In this study, the temperature, precipitation, sunshine and comprehensive suitability models were established by using the climatic suitability function in different growth periods of peanut. In this study, the climate suitability function of peanut in different growth periods was used to establish the temperature, precipitation, sunshine and comprehensive suitability model. Combined with the meteorological data after Anusplin interpolation, the spatial distribution and chronological change of peanut climate suitability were analyzed. The results show that with climate change, the overall climate becomes warmer and drier and the temperature and precipitation suitability increase, but the sunshine suitability decreases. Based on the comprehensive suitability model, the suitability evaluation results are divided into four levels: the most suitable, suitable, sub-suitable and unsuitable. Among them, the most suitable peanut planting areas in the Huang-Huai-Hai region are concentrated in the west of the Haihe River Basin and the Huaihe River Basin. The data from the next 30 years show that both the most suitable and suitable areas have been expanded. Through the verification of yield correlation analysis and spatial distribution of disaster frequency, it can be seen that the evaluation results have high accuracy, which can be used to guide and optimize peanut production practices.
Examination of sub-harmonic responses along with various initial conditions induced by multi-staged clutch damper system
Authors: Yoon Jong-Yun , Kim Byeongil
Published: July 2022

Using the harmonic balance method to investigate the nonlinear dynamic behaviors pertaining to sub-harmonic responses is difficult compared with that of super-harmonic cases because of the limitations of the HBM. Since sub-harmonic motions differ under various initial conditions, difficulties can arise when this method is used to calculate all possible solutions within sub-harmonic resonances. To explore complex dynamic behaviors in sub-harmonic resonant areas, this study suggests mathematical and numerical techniques to estimate sub-harmonic responses depending on various initial conditions. First, sub-harmonic responses are calculated under various excitation conditions relevant to the sub-harmonic input locations of the HBM formula. Second, the HBM results are verified by comparing them with the results of the numerical simulation (NS) under various initial conditions with respect to different frequency up-sweeping paths. Finally, the positive real part of the eigenvalues is examined to anticipate bifurcation characteristics, which reflect the relevance of the complex dynamic behaviors in the eigenvalues’ unstable solutions. Overall, this study successfully proves that the techniques and methods described are suitable for examining complex sub-harmonic responses, and suggests basic ideas for analyzing nonlinear dynamic behaviors in sub-harmonic resonances using the HBM.
Real-time prediction of formation pressure gradient while drilling
Authors: Abdelaal Ahmed , Elkatatny Salaheldin , Abdulraheem Abdulazeez
Published: July 2022

Accurate real-time pore pressure prediction is crucial especially in drilling operations technically and economically. Its prediction will save costs, time and even the right decisions can be taken before problems occur. The available correlations for pore pressure prediction depend on logging data, formation characteristics, and combination of logging and drilling parameters. The objective of this work is to apply artificial neural networks (ANN) and adaptive neuro-fuzzy inference system (ANFIS) to introduce two models to estimate the formation pressure gradient in real-time through the available drilling data. The used parameters include rate of penetration (ROP), mud flow rate (Q), standpipe pressure (SPP), and rotary speed (RS). A data set obtained from some vertical wells was utilized to develop the predictive model. A different set of data was utilized for validating the proposed artificial intelligence (AI) models. Both models forecasted the output with a good correlation coefficient (R) for training and testing. Moreover, the average absolute percentage error (AAPE) did not exceed 2.1%. For validation stage, the developed models estimated the pressure gradient with a good accuracy. This study proves the reliability of the proposed models to estimate the pressure gradient while drilling using drilling data. Moreover, an ANN-based correlation is provided and can be directly used by introducing the optimized weights and biases, whenever the drilling parameters are available, instead of running the ANN model.
Multi-centennial mass balance of perennial ice deposits in Alpine caves mirrors the evolution of glaciers during the Late Holocene
Authors: Racine Tanguy M. F. , Reimer Paula J. , Spötl Christoph
Published: July 2022

Mid-latitude alpine caves preserve a record of past solid precipitation during winter, locally spanning several centuries to millennia. Dating organic macro-remains trapped in ice layers allows the determination of timing and duration of past periods of positive and negative ice mass balance. We present here the largest comparative study of ice cave sites yet published, using Bayesian age-modelling on a database comprising 107 radiocarbon dates, spread over eight caves in the Austrian Alps. We show that periods of positive mass balance coincide with past glacier advances. We find organic and macro-remain rich layers dated to the Medieval Climate Anomaly (between 850 and 1200 CE) marking widespread ice retreat. We demonstrate positive ice mass balance at all studied sites for the Little Ice Age, coinciding with the largest glacier advances in the Holocene between 1400 and 1850 CE. At the sites with records spanning over 2000 years, positive mass balance is also observed during the periods from 300 BCE to 100 CE and 600–800 CE. These subterranean ice deposits show widespread evidence of accelerated negative mass balances in recent years and their record is under imminent threat of disappearing.
Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis
Authors: Tomic Barbara , Smoljo Tomislav , Lalic Hrvoje , Dembitz Vilma , Batinic Josip , Batinic Drago , Bedalov Antonio , Visnjic Dora
Published: July 2022

Acute myeloid leukemia (AML) is characterized by arrested differentiation making differentiation therapy a promising treatment strategy. Recent success of inhibitors of mutated isocitrate dehydrogenase (IDH) invigorated interest in differentiation therapy of AML so that several new drugs have been proposed, including inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis. Cytarabine, a backbone of standard AML therapy, is known to induce differentiation at low doses, but the mechanism is not completely elucidated. We have previously reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) and brequinar, a DHODH inhibitor, induced differentiation of myeloid leukemia by activating the ataxia telangiectasia and Rad3-related (ATR)/checkpoint kinase 1 (Chk1) via pyrimidine depletion. In this study, using immunoblotting, flow cytometry analyses, pharmacologic inhibitors and genetic inactivation of Chk1 in myeloid leukemia cell lines, we show that low dose cytarabine induces differentiation by activating Chk1. In addition, cytarabine induces differentiation ex vivo in a subset of primary AML samples that are sensitive to AICAr and DHODH inhibitor. The results of our study suggest that leukemic cell differentiation stimulated by low doses of cytarabine depends on the activation of Chk1 and thus shares the same pathway as pyrimidine synthesis inhibitors.
New damage model for simulating radiation-induced direct damage to biomolecular systems and experimental validation using pBR322 plasmid
Authors: Park Jinhyung , Jung Kwang-Woo , Kim Min Kyu , Gwon Hui-Jeong , Jung Jong-Hyun
Published: July 2022

In this work, we proposed a new damage model for estimating radiation-induced direct damage to biomolecular systems and validated its the effectiveness for pBR322 plasmids. The proposed model estimates radiation-induced damage to biomolecular systems by: (1) simulation geometry modeling using the coarse-grained (CG) technique to replace the minimum repeating units of a molecule with a single bead, (2) approximation of the threshold energy for radiation damage through CG potential calculation, (3) calculation of cumulative absorption energy for each radiation event in microscopic regions of CG models using the Monte Carlo track structure (MCTS) code, and (4) estimation of direct radiation damage to biomolecular systems by comparing CG potentials and absorption energy. The proposed model replicated measured data with an average error of approximately 14.2% in the estimation of radiation damage to pBR322 plasmids using the common MCTS code Geant4-DNA. This is similar to the results of previous simulation studies. However, in existing damage models, parameters are adjusted based on experimental data to increase the reliability of simulation results, whereas in the proposed model, they can be determined without using empirical data. Because the proposed model proposed is applicable to DNA and various biomolecular systems with minimal experimental data, it provides a new method that is convenient and effective for predicting damage in living organisms caused by radiation exposure.
The evaluation of Bcftools mpileup and GATK HaplotypeCaller for variant calling in non-human species
Authors: Lefouili Messaoud , Nam Kiwoong
Published: July 2022

Identification of genetic variations is a central part of population and quantitative genomics studies based on high-throughput sequencing data. Even though popular variant callers such as Bcftools mpileup and GATK HaplotypeCaller were developed nearly 10 years ago, their performance is still largely unknown for non-human species. Here, we showed by benchmark analyses with a simulated insect population that Bcftools mpileup performs better than GATK HaplotypeCaller in terms of recovery rate and accuracy regardless of mapping software. The vast majority of false positives were observed from repeats, especially for GATK HaplotypeCaller. Variant scores calculated by GATK did not clearly distinguish true positives from false positives in the vast majority of cases, implying that hard-filtering with GATK could be challenging. These results suggest that Bcftools mpileup may be the first choice for non-human studies and that variants within repeats might have to be excluded for downstream analyses.
Existence of weakly quasisymmetric magnetic fields without rotational transform in asymmetric toroidal domains
Authors: Sato Naoki
Published: July 2022

A quasisymmetry is a special symmetry that enhances the ability of a magnetic field to trap charged particles. Quasisymmetric magnetic fields may allow the realization of next generation fusion reactors (stellarators) with superior performance when compared with tokamak designs. Nevertheless, the existence of such magnetic configurations lacks mathematical proof due to the complexity of the governing equations. Here, we prove the existence of weakly quasisymmetric magnetic fields by constructing explicit examples. This result is achieved by a tailored parametrization of both magnetic field and hosting toroidal domain, which are optimized to fulfill quasisymmetry. The obtained solutions hold in a toroidal volume, are smooth, possess nested flux surfaces, are not invariant under continuous Euclidean isometries, have a non-vanishing current, exhibit a vanishing rotational transform, and fit within the framework of anisotropic magnetohydrodynamics. Due to the vanishing rotational transform, these solutions are however not suitable for particle confinement.
A simulation of diffractive liquid crystal smart window for privacy application
Authors: Han Chan-Hee , Eo Hyeonseok , Choi Tae-Hoon , Kim Wook-Sung , Oh Seung-Won
Published: July 2022

Using a single substrate, we demonstrate a simple two-dimensional (2-D) phase grating cell with an octothorp electrode. Owing to the large spatial phase difference in any direction, the proposed grating cell has a high haze value in the opaque state (76.7%); Moreover, it has the advantages of a one-dimensional (1-D) phase grating cell, such as high fabricability, fast response time, and low operating voltage. Furthermore, the proposed grating cell has a faster response time than the 2-D grating cell (comparable to a 1-D grating cell). All the electro-optic parameters have been calculated using a commercial modeling tool. Consequently, we expect our proposed grating cell to find applications in virtual reality (VR)/augmented reality (AR) systems or window displays with fast response times.
Post-mortem evidence of a diverse distribution pattern of atherosclerosis in the South African population
Authors: van Rensburg Walter J. Janse
Published: July 2022

Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. The disease profile of CVD varies considerably between different demographic groups and socioeconomic status. Atherosclerosis remains a major risk factor for CVD, and thus, believed to be a good indicator of the CVD profile in a population, yet little is known on its prevalence in sub-Saharan African populations. We aimed to determine the prevalence of atherosclerosis in a diverse South African population as found with post-mortem investigations. A retrospective file-audit was done on 10,240 forensic post-mortem reports done at a forensic pathology mortuary in South Africa, over 10-years. European descent males had the highest prevalence, with roughly one-quarter having coronary artery (CA) or large vessel (LV) atherosclerosis. European descent females followed closely, with one-fifth of the population having CA atherosclerosis and approximately a quarter having LV atherosclerosis. African descent males and females had a substantially lower prevalence in atherosclerosis for both CAs and LVs than European descendants. The mixed-ancestry population had a slightly higher prevalence of atherosclerosis in CAs and LVs than in the African population; however, it was still far lower than the European group. Some deviations in prevalence were noted within certain groups over the course of 10-years. The substantial difference in prevalence of atherosclerosis shows that in our region a diverse distribution pattern between ethnic groups and genders is present. However, follow-up studies are required to elucidate aetiological factors in cardiovascular health in our region.
Spatio-temporal coupling controlled laser for electron acceleration
Authors: Wang Lu , Niedermayer Uwe , Ma Jingui , Liu Weihao , Zhang Dongfang , Qian Liejia
Published: July 2022

Limited by the difficulty in acceleration synchronization, it has been a long-term challenge for on-chip dielectric laser-based accelerators to bridge the gap between non-relativistic and relativistic regimes. Here, we propose a laser-based accelerators based on a spatio-temporal coupling controlled laser pulse, which enables the acceleration of a non-relativistic electron to a sub-MeV level in a single acceleration structure (chirped spatial grating). It provides high precision temporal and spatial tuning of the driving laser via dispersion manipulation, leading to a synchronous acceleration of the velocity increasing electrons over a large energy range. Additionally, the spatio-temporal coupling scheme is a general method and can be extended to driving fields of other wavelengths such as terahertz pulses. Our results bring possibilities to MeV-scale portable electron sources and table-top acceleration experiments.
Effects of oral non-protein calorie supplements on nutritional status among maintenance hemodialysis patients with protein-energy wasting: a multi-center randomized controlled trial
Authors: Wen Luona , Tang Chunrong , Liu Yun , Jiang Jie , Zou Dee , Chen Wenxuan , Xu Shilin , Wang Yuqi , Qiu Jingxian , Zhong Xiaoshi , Liu Yan , Tan Rongshao
Published: July 2022

Non-protein calorie supplements could improve the nutritional status of MHD patients with PEW.
Structural characteristics of sulfated polysaccharides from Sargassum horneri and immune-enhancing activity of polysaccharides combined with lactic acid bacteria
Authors: Kim Young-Sang , Hwang Jin , Lee Sang Gil , Jo Hee Young , Oh Myung Jin , Liyanage N. M. , Je Jun-Geon , An Hyun Joo , Jeon You-Jin
Published: July 2022

Sargassum horneri (SH), a marine brown alga, is known to contain a variety of bioactive ingredients and previous studies reported sulfated polysaccharides in SH as a potential candidate for a functional ingredient.
The oxidative potential of particulate matter (PM) in different regions around the world and its relation to air pollution sources
Authors: Farahani Vahid Jalali , Altuwayjiri Abdulmalik , Pirhadi Milad , Verma Vishal , Ruprecht Ario Alberto , Diapouli Evangelia , Eleftheriadis Konstantinos , Sioutas Constantinos
Published: July 2022

Biomass burning and secondary organic aerosols formed by photochemical reactions lead to the highest oxidative potential among urban emission sources and therefore are one of the most hazardous sources in terms of ambient PM toxicity.
Polyethylene-glycol-modified zwitterionic polymer assisted protein aggregation arrest and refolding
Authors: Debas Alisha , Matsumura Kazuaki , Rajan Robin
Published: July 2022

The heat-induced aggregation of lysozyme was prevented when heated in the presence of poly-sulfobetaine and PEG copolymers, which were also effective in easing the refolding of the denatured protein.
Understanding and design of non-conservative optical matter systems using Markov state models
Authors: Chen Shiqi , Parker John A. , Peterson Curtis W. , Rice Stuart A. , Scherer Norbert F. , Ferguson Andrew L.
Published: July 2022

Non-conservative and permutationally-invariant Markov state models inform understanding and control of self-assembling optical matter systems.
Ultrastable dihydrophenazine-based polymer from industrial waste as a sustainable lithium-ion battery cathode material
Authors: Wang Yujie , Huang Yuanzhu , Hua Ying , Du Ya , Yang Haishen
Published: July 2022

An industrial-waste-derived polymer, PBMEP, was effectively synthesized as a superior sustainable LIB cathode material with robust cycling stability, high working potentials, and excellent rate capability.
Self-healable triboelectric nanogenerators based on ionic poly(hindered urea) network materials cross-linked with fluorinated block copolymers
Authors: Nellepalli Pothanagandhi , Patel Twinkal , Kim Minsoo P. , Park Junyoung , Ye Zhibin , Jung Hyun Wook , Ko Hyunhyub , Oh Jung Kwon
Published: July 2022

The versatility of a reactive block copolymer approach to fabricate ionic poly(hindered urea)-based covalent adaptive networks having pendant fluorinated species formulated with ionic liquid for effective self-healable triboelectric nanogenerators.
One-step synthesized amphiphilic carbon dots for the super-resolution imaging of endoplasmic reticulum in live cells
Authors: Li Jiajia , Zhang Longdi , Chen Juan , Zhang Ruilong , Liu Zhengjie , Zhao Jun , Liu Bianhua , Han Ming-yong , Han Guangmei , Zhang Zhongping
Published: July 2022

Amphiphilic carbon dots (Phe-CDs) were synthesized directly via one-step hydrothermal reaction for specific ER targeting without further modification. The Phe-CDs were photostable enough to allow STED super-resolution imaging of ER in live cells.
Reduced graphene oxide–zinc sulfide (RGO–ZnS) nanocomposite: a new photocatalyst for oxidative cyclization of benzylamines to benzazoles under visible-light irradiation
Authors: Hosseini-Sarvari Mona , Sheikh Hossein
Published: July 2022

A simple route for the preparation of a reduced graphene oxide–zinc sulfide (RGO–ZnS) nanocomposite via one-pot hydrothermal synthesis has been reported.
Caged bulky organic dyes in a polyaromatic framework and their spectroscopic peculiarities
Authors: Ueda Mayuko , Kishida Natsuki , Catti Lorenzo , Yoshizawa Michito
Published: July 2022

Here we report that the open large cavity of an M2L4 polyaromatic cage can efficiently bind sterically demanding organic dyes with coumarin, perylene bisimide, and porphyrin cores in aqueous solution. The spectroscopic properties of the caged dyes are largely modulated in the cavity.
Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery
Authors: Guan Xiaowen , Meng Fanqi , Tan Hongwei , Wang Xiaoni , Li Jingjing , Wei Juanjuan , Ouyang Jin , Na Na
Published: July 2022

Supramolecular nanomaterials of WP5⊃G–siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest and host molecules, initiating weak acidic-responsive, precise and visualized intracellular delivery for efficient therapies.
Flexible organic crystals. Understanding the tractable co-existence of elastic and plastic bending
Authors: Divya Indira S. , Kandasamy Saravanan , Hasebe Shodai , Sasaki Toshiyuki , Koshima Hideko , Woźniak Krzysztof , Varughese Sunil
Published: July 2022

Structural and mechanical studies of benzil and oxalate crystals highlight the microscopic and macroscopic basis for the co-existence of orthogonal mechanical traits and the elastic to plastic transformation under different stress settings.