bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turbulence and
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flow correlations across the L-H transition in DIII-D deuterium and hydrogen plasmas
Authors: Schmitz Lothar 
Published: January 2023

The isotope dependence of the low- to high confinement-mode (L- to H-mode) transition power threshold
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LH
presents significant challenges for the initial (non-nuclear) hydrogen operations phase of the international thermonuclear experimental reactor (ITER). Here, we examine the isotope dependence of turbulence and

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flow correlation properties in the L-mode edge plasma, leading up to the L-H transition. At marginal auxiliary power (near
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), turbulence is initially suppressed periodically during limit cycle oscillations (LCO) that precede the transition to sustained H-mode confinement. We present evidence that the long-range (toroidal) correlation of the

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edge plasma flow across the LCO phase is much weaker in hydrogen than in deuterium in the DIII-D tokamak, congruent with the higher threshold power
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LH
required to access LCO and H-mode in hydrogen. Concomitantly, the time required to initially quench edge turbulence via localized edge

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flow shear is significantly longer in hydrogen (1–1.5 ms) than in deuterium (approx. 100 µs). No toroidal long-range correlation of the turbulence amplitude is observed, in agreement with expectations based on the relatively short poloidal turbulence correlation length. Radial edge turbulence and flow correlation lengths are longer in deuterium than in hydrogen plasmas as one would expect from ‘naïve’ gyro-Bohm isotope transport scaling, despite the substantially higher thermal flux across the last closed flux surface in hydrogen before the L-H transition.

This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.
Genetic Divergence Analysis among Sesame (Sesamum IndicumL.) Accessions in Middle Awash, Ethiopia
Authors: Gimbichu Mesay Tadesse , Gurmu Gudeta Nepir , Ayana Negash Geleta 
Published: January 2023

ABSTRACTThis research was conducted to assess genetic distance, extent, and pattern of diversity among sesame accessions. A total of 64 sesame Accessions were evaluated in an 8 x 8 lattice design with two replications in 2021 at Werer Agricultural Research Center. Analysis of variance revealed that there was a statistically significant difference among the accessions for all traits except for 50% days to emergence and the number of seeds per pod. Principal components analysis showed the first five PCAs viz. PC1 (21.9%), PC2 (11.00%), PC3 (15.6%), PC4 (18.3%), and PC5 (9.5) with a total contribution of 76.3% variation. The dendrogram was constructed using the Unweighted Pair-group Method with Arithmetic Means to separate Accessions into five distinct clusters. Sesame accessions with high seed yield and high mean values for other desirable traits were grouped into Cluster I Cluster V. Cluster IV and Cluster V had the highest inter-cluster distance. Accession in Cluster V (Acc.241297) could be crossed with other clusters to come up with promising segregation for further improvement programs.
Design and fabrication of a low-cost microfluidic cartridge with integrated pressure-driven check valve for molecular diagnostics platforms
Authors: Downen R. Scott , Dong Quan , Chen Julius Lee , Li Zhenyu 
Published: January 2023

AbstractThis paper describes the design, fabrication, and preliminary testing of a low-cost, easy to manufacture microfluidics cartridge capable of fluid storage and manipulation through a custom pressure-driven check valve. Cartridge components are fabricated using a desktop CNC and laser cutter, the check valve is fabricated using PDMS in a custom acrylic mold, and the components are assembled using a thermal diffusion welder. Following assembly, preliminary testing of the cartridge, including fluid manipulation and use for molecular diagnostics, was performed. To pull a sample into the lysing chamber, a vacuum over 1.4PSI was required. No opening of the valve to the reaction chamber was observed. Moving fluid across the custom valve from the lysing chamber to the reaction chamber then required a vacuum over 4.5PSI. Finally, a proof-of-concept demonstration of one potential application was performed using a custom benchtop LAMP system for molecular diagnostic testing. The low-cost nature of the design, ease of manufacturing, fluid storage and manipulation demonstrated make this design ideal for research and high-volume testing in low resource environments.Abstract FigureGraphical abstractCustom cartridge is fabricated using a combination of a) benchtop laser cutter and b) benchtop micromilling machine. c) Components are then assembled with a 0.22µm micron filter and custom plug-style check valve. d) The cartridge assembly is then bonded using a thermal diffusion bonder. e) By pulling a vacuum through the first air trap, a sample can be pulled into the pre-filled lysing chamber. f) Pulling a vacuum through the second air trap, the lysed sample can then be pulled into the pre-filled reaction chamber. g) For a proof of concept, the filled cartridge was then tested in a custom benchtop Loop Mediated Isothermal System. Following a heating cycle, reaction fluoresce can be monitored. h) An S-Curve observed through the custom LAMP system, thus demonstrating feasibility of the cartridge for use with molecular diagnostic platforms.
Analysis of the genome-scale metabolic model ofBacillus subtilisto design novel in-silico strategies for native and recombinant L-asparaginase overproduction
Authors: Barge Nisha Sanjay , Sahoo Ansuman , Dasu Veeranki Venkata 
Published: January 2023

ABSTRACTL-asparaginase is an enzyme with widescale use in the food and medicine industry. It is used as a chemotherapeutic drug in the treatment of acute lymphoblastic leukemia. Limitations of side effects associated with commercially available L-asparaginase necessitate the search for alternative sources.Bacillus subtilisis an emerging host for the production of chemicals and therapeutic products. This study deals with L-asparaginase production inBacillus subtilisusing systems metabolic engineering approach. System biology offers a detailed understanding of organism metabolism at the network level unlike the conventional molecular approach of metabolic engineering allowing one to study the effects of metabolite production on growth. Metabolism ofBacillus subtilisis studied using genome-scale metabolic model iYO844 which consists of relationships between the genes and proteins present inBacillus subtilis. Also, the model contains information about all the metabolic reactions and pathways allowing convenient metabolic engineering methods. Computational methods like flux balance analysis, flux variability analysis, robustness analysis, etc. are carried out to study the metabolic capabilities ofBacillus subtilis. The model predicted a specific growth rate of 0.6242 h-1, which was comparable to the experimental value. Further, the model is used to simulate recombinant L-asparaginase production generating a maximum production rate of 0.4028 mmol gDW-1h-1. Flux scanning based on enforced objective flux and OptKnock design strategies are used for strain development ofBacillus subtilisfor higher production of both native and recombinant L-asparaginase.
An engineered ACE2 decoy broadly neutralizes Omicron subvariants and shows therapeutic effect in SARS-CoV-2-infected cynomolgus macaques
Authors: Urano Emiko , Itoh Yumi , Suzuki Tatsuya , Sasaki Takanori , Kishikawa Jun-ichi , Akamatsu Kanako , Higuchi Yusuke , Sakai Yusuke , Okamura Tomotaka , Mitoma Shuya , Sugihara Fuminori , Takada Akira , Kimura Mari , Hirose Mika , Sasaki Tadahiro , Koketsu Ritsuko , Tsuji Shunya , Yanagida Shota , Shioda Tatsuo , Hara Eiji , Matoba Satoaki , Matsuura Yoshiharu , Kanda Yasunari , Arase Hisashi , Okada Masato , Takagi Junichi , Kato Takayuki , Hoshino Atsushi , Yasutomi Yasuhiro , Saito Akatsuki , Okamoto Toru 
Published: January 2023

AbstractThe Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previously reported its broad spectrum and therapeutic potential in rodent models. Here, we show that engineered ACE2 decoy retains the neutralization activity against Omicron subvariants including the currently emerging XBB and BQ.1 which completely evade antibodies in clinical use. The culture of SARS-CoV-2 under suboptimal concentration of neutralizing drugs generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against engineered ACE2 decoy. As the efficient drug delivery to respiratory tract infection of SARS-CoV-2, inhalation of aerosolized decoy treated mice infected with SARS-CoV-2 at a 20-fold lower dose than the intravenous administration. Finally, engineered ACE2 decoy exhibited the therapeutic efficacy for COVID-19 in cynomolgus macaques. Collectively, these results indicate that engineered ACE2 decoy is the promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation can be considered as a non-invasive approach to enhance efficacy in the treatment of COVID-19.
Femtomolar-level PCR-free quantification of microRNA cancer biomarkers in serum
Authors: Kanavarioti Anastassia 
Published: January 2023

AbstractWe developed a technology to measure microRNA (miRNA) copies in serum and tested it on a commercially available combined human serum (H6914 from Sigma-Aldrich). Copies of miR-15b and miR-16, believed to be constant among healthy and diseased individuals, were measured and agreed with the ones reported by Mitchell PS et al. (2008). Cancer biomarkers let7-b, miR-21, miR-141 and miR-375 varied 3,000 to 6,000 copies per 1 microLiter H6914 (5-10 femtomolar (fM)). Detection and quantification of oligos and miRNAs at such low concentration was shown earlier. It is accomplished by repurposing the commercial MinION nanopore platform to conduct single-molecule voltage-driven ion-channel measurements, employing osmium-tagged oligo probes, and using a publicly available algorithm. These miRNAs were quantified in the serum of healthy individuals or cancer patients using novel optimized probes and a detailed protocol that delivers miRNA copies with better than 85% confidence across all concentrations. A linear correlation, the same with healthy and cancer serum samples, is observed between miR-15b copies and RNA concentration in serum. The assay’s simplicity, readiness, sensitivity, and precision advocate for its use as a Laboratory Developed Test (LDT) for disease-screening based on miRNA dysregulation.
Lung inflammation is associated with lipid deposition
Authors: Potashnikova Daria M , Tvorogova Anna V , Saidova Aleena A , Sotnikova Tatiana N , Arifulin Eugene A , Lipina Tatiana V , Shirokova Olesya M , Melnikov Eugene S , Rodina Tatiana A , Valyaeva Anna A , Zharikova Anastasia A , Zayratyants George O , Zayratyants Oleg V , Sheval Eugene V , Vasilieva Elena J 
Published: January 2023

AbstractLung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.
Predicting alcohol-related memory problems in older adults: A machine learning study with multi-domain features
Authors: Kamarajan Chella , Pandey Ashwini K. , Chorlian David B. , Meyers Jacquelyn L. , Kinreich Sivan , Pandey Gayathri , Subbie-Saenz de Viteri Stacey , Zhang Jian , Kuang Weipeng , Barr Peter B. , Aliev Fazil , Anokhin Andrey P. , Plawecki Martin H. , Kuperman Samuel , Almasy Laura , Merikangas Alison , Brislin Sarah J. , Bauer Lance , Hesselbrock Victor , Chan Grace , Kramer John , Lai Dongbing , Hartz Sarah , Bierut Laura J. , McCutcheon Vivia V. , Bucholz Kathleen K. , Dick Danielle M. , Schuckit Marc A. , Edenberg Howard J. , Porjesz Bernice 
Published: January 2023

AbstractMemory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (Memorygroup) were compared with a matchedControlgroup who did not have memory problems. The Random Forests model identified specific features from each domain that contributed to the classification of Memory vs. Control group (AUC=88.29%). Specifically, individuals from the Memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except some connections involving anterior cingulate cortex which were predominantly hypoconnected. Other significant contributing features were (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past 5 years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past 12 months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive “uplift” life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity collected ∼18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict alcohol-related memory problems that arise in later life.
Indoleamine Dioxygenase and Tryptophan Dioxygenase Activities are Regulated through Control of Cell Heme Allocation by Nitric Oxide
Authors: Biswas Pranjal , Stuehr Dennis J. 
Published: January 2023

AbstractIndoleamine-2, 3-dioxygenase (IDO1) and Tryptophan-2, 3-dioxygenase (TDO) catalyze the conversion of L-tryptophan to N-formyl- kynurenine and thus play primary roles in metabolism, inflammation, and tumor immune surveillance. Because their activities depend on their heme contents which range from 30- 60% heme-saturated in biological settings and go up or down in a dynamic manner, we studied how their heme levels may be impacted by nitric oxide (NO) in mammalian cells. We utilized cells expressing TDO or IDO1 either naturally or via transfection and determined their activities, heme contents, and expression levels as a function of NO exposure. We found NO has a bimodal effect: A narrow range of very low NO exposure promoted cells to allocate heme into TDO and IDO1 and boosted their activities several fold, while beyond this range the NO exposure transitioned to have a negative impact on their heme contents and activities. NO did not alter dioxygenase protein expression levels and its bimodal impact was observed when NO was released by a chemical donor or was generated naturally by immune-stimulated macrophage cells. NO-driven heme allocations to IDO1 and TDO required participation of a GAPDH- heme complex and for IDO1 required chaperone Hsp90 activity. Thus, cells can up- or down-regulate their IDO1 and TDO activities through a bimodal control of heme allocation by NO. This mechanism has important biomedical implications and helps explain why the IDO1 and TDO activities in animals go up and down in response to immune stimulation.
Massive solubility changes of neuronal proteins upon simulated traumatic brain injury reveal the role of shockwave in irreversible damage
Authors: Saei Amir Ata , Gharibi Hassan , Lyu Hezheng , Nilsson Brady , Jafari Maryam , von Holst Hans , Zubarev Roman A. 
Published: January 2023

AbstractThe immediate molecular consequences of traumatic brain injuries or TBI are poorly understood. Here, we simulated TBI using an innovative laboratory apparatus that employs a 5.1 kg dummy head holding neuronal cells and generating a ≤4,000 g-force acceleration upon impact. Dynamic impact led to both reduction in neuron viability and massive solubility changes in the proteome profiled using Proteome Integral Solubility Alteration (PISA) assay. The affected proteins mapped not only to the expected pathways like cell adhesion, collagen and laminin structures, as well as response to stress, but also to other dense protein networks, such as immune response, complement and coagulation cascades. The cellular effects are found to be mainly due to the shockwave rather than the g-force acceleration. Soft materials could reduce the impact severity only until being fully compressed. This study shows way to develop a proteome-based meter for measuring irreversible shockwave-induced cell damage and provides a resource for identifying TBI protein biomarkers and potential drug targets for developing products aiming at primary prevention and intervention.
The (Limited?) Utility of Brain Age as a Biomarker for Capturing Fluid Cognition in Older Individuals
Authors: Tetereva Alina , Pat Narun 
Published: January 2023

AbstractFluid cognition usually declines as people grow older. For decades, neuroscientists have been on a quest to search for a biomarker that can help capture fluid cognition. One well-known candidate is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI data. Here we aim to formally evaluate the utility of Brain Age as a biomarker for capturing fluid cognition among older individuals. Using 504 aging participants (36-100 years old) from the Human Connectome Project in Aging, we created 26 age-prediction models for Brain Age based on different combinations of MRI modalities. We first tested how much Brain Age from these age-prediction models added to what we had already known from a person’s chronological age in capturing fluid cognition. Based on the commonality analyses, we found a large degree of overlap between Brain Age and chronological age, so much so that, at best, Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition. Next, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition, thus not improving the models’ utility to capture cognitive abilities. Lastly, we tested how much Brain Age missed the variation in the brain MRI that could explain fluid cognition. To capture this variation in the brain MRI that explained fluid cognition, we computed Brain Cognition, or a predicted value based on prediction models built to directly predict fluid cognition (as opposed to chronological age) from brain MRI data. We found that Brain Cognition captured up to an additional 11% of the total variation in fluid cognition that was missing from the model with only Brain Age and chronological age, leading to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.
Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP-2-mediated endocytosis
Authors: Matsubayashi Hideaki T. , Mountain Jack , Yao Tony , Peterson Amy F. , Roy Abhijit Deb , Inoue Takanari 
Published: January 2023

AbstractClass IA phosphoinositide 3-kinase (PI3K) galvanizes fundamental cellular processes such as migration, proliferation, and differentiation. To enable multifaceted roles, the catalytic subunit p110 utilizes a multi- domain, regulatory subunit p85 through its inter SH2 domain (iSH2). In cell migration, their product PI(3,4,5)P3generates locomotive activity. While non-catalytic roles are also implicated, underlying mechanisms and its relationship to PI(3,4,5)P3signaling remain elusive. Here, we report that a disordered region of iSH2 contains previously uncharacterized AP-2 binding motifs which can trigger clathrin and dynamin-mediated endocytosis independent of PI3K catalytic activity. The AP-2 binding motif mutants of p85 aberrantly accumulate at focal adhesions and upregulate both velocity and persistency in fibroblast migration. We thus propose the dual functionality of PI3K in the control of cell motility, catalytic and non- catalytic, arising distinctly from juxtaposed regions within iSH2.
Population-level neural correlates of flexible avoidance learning in medial prefrontal cortex
Authors: Ehret Benjamin , Boehringer Roman , Amadei Elizabeth A. , Cervera Maria R. , Henning Christian , Galgali Aniruddh , Mante Valerio , Grewe Benjamin F. 
Published: January 2023

AbstractThe medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a novel tone-signaled active avoidance paradigm in mice. We developed a novel analysis approach based on dimensionality reduction and decoding that allowed us to identify and isolate population activity patterns related the tone stimulus, learned avoidance actions and general motion. While tone-related activity was not informative about behavior, avoidance-related activity was predictive of upcoming avoidance actions. Moreover, avoidance-related activity distinguished between two different learned avoidance actions, consistent with a model in which mPFC contributes to the selection between different goal-directed actions. Overall, our results suggest that mPFC circuit dynamics transform sensory inputs into specific behavioral outputs through distributed population-level computations.