Miracle-dz/UniFAR-FTUs huggingface dataset:
A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures

Calcium (Ca2+) imaging reveals a variety of correlated firing in cultures of dissociated hippocampal neurons, pinpointing the non‐synaptic paracrine release of glutamate as a possible mediator for such firing patterns, although the biophysical underpinnings remain unknown. An intriguing possibility is that extracellular glutamate could bind metabotropic receptors linked with inositol trisphosphate (IP3) mediated release of Ca2+ from the endoplasmic reticulum of individual neurons, thereby modulating neural activity in combination with sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA) and voltage‐gated Ca2+ channels (VGCC). However, the possibility that such release may occur in different neuronal compartments and can be inherently stochastic poses challenges in the characterization of such interplay between various Ca2+ channels. Here we deploy biophysical modeling in association with Monte Carlo parameter sampling to characterize such interplay and successfully predict experimentally observed Ca2+ patterns. The results show that the neurotransmitter level at the plasma membrane is the extrinsic source of heterogeneity in somatic Ca2+ transients. Our analysis, in particular, identifies the origin of such heterogeneity to an intrinsic differentiation of hippocampal neurons in terms of multiple cellular properties pertaining to intracellular Ca2+ signaling, such as VGCC, IP3 receptor, and SERCA expression. In the future, the biophysical model and parameter estimation approach used in this study can be upgraded to predict the response of a system of interconnected neurons.
Permanent and Transitory Components of Business Cycles: Their Relative Importance and Dynamic Relationship

This paper investigates the relationship between permanent and transitory components of U.S. recessions in an empirical model allowing for business cycle asymmetry. Using a common stochastic trend representation for real GNP and consumption, we divide real GNP into permanent and transitory components, the dynamics of which are different in booms vs. recessions. We find evidence of substantial asymmetries in postwar recessions, and that both the permanent and transitory component have contributed to these recessions. We also allow for the timing of switches from boom to recession for the permanent component to be correlated with switches from boom to recession in the transitory component. The parameter estimates suggest a specific pattern of recessions: switches in the permanent component lead switches in the transitory component both when entering and leaving recessions.
Structure of a fungal 1,3-β-glucan synthase

1,3-β-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-β-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo–electron microscopy structure of Saccharomyces cerevisiae 1,3-β-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A–type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-β-glucan synthase.
Human vascularised synovium-on-a-chip: a mechanically stimulated, microfluidic model to investigate synovial inflammation and monocyte recruitment

Healthy synovium is critical for joint homeostasis. Synovial inflammation (synovitis) is implicated in the onset, progression and symptomatic presentation of arthritic joint diseases such as rheumatoid arthritis and osteoarthritis. Thus, the synovium is a promising target for the development of novel, disease-modifying therapeutics. However, target exploration is hampered by a lack of good pre-clinical models that accurately replicate human physiology and that are developed in a way that allows for widespread uptake. The current study presents a multi-channel, microfluidic, organ-on-a-chip (OOAC) model, comprising a 3D configuration of the human synovium and its associated vasculature, with biomechanical and inflammatory stimulation, built upon a commercially available OOAC platform. Healthy human fibroblast-like synoviocytes (hFLS) were co-cultured with human umbilical vein endothelial cells (HUVECs) with appropriate matrix proteins, separated by a flexible, porous membrane. The model was developed within the Emulate organ-chip platform enabling the application of physiological biomechanical stimulation in the form of fluid shear and cyclic tensile strain. The hFLS exhibited characteristic morphology, cytoskeletal architecture and matrix protein deposition. Synovial inflammation was initiated through the addition of interleukin−1β (IL−1β) into the synovium channel resulting in the increased secretion of inflammatory and catabolic mediators, interleukin-6 (IL−6), prostaglandin E2 (PGE2), matrix metalloproteinase 1 (MMP−1), as well as the synovial fluid constituent protein, hyaluronan. Enhanced expression of the inflammatory marker, intercellular adhesion molecule-1 (ICAM-1), was observed in HUVECs in the vascular channel, accompanied by increased attachment of circulating monocytes. This vascularised human synovium-on-a-chip model recapitulates a number of the functional characteristics of both healthy and inflamed human synovium. Thus, this model offers the first human synovium organ-chip suitable for widespread adoption to understand synovial joint disease mechanisms, permit the identification of novel therapeutic targets and support pre-clinical testing of therapies.
Sun and Sky Radiometric Measurements at the CART ARM SGP Site

Abstract Cimel sunphotometers/radiometers (CSPHOT) are facility instruments at the three AtmosphericRadiation Measurement (ARM) sites at the Southern Great Plains (SGP) in Oklahoma, Tropical WesternPacific (TWP) in Nauru, and North Slope in Alaska (NSA). Here inferred aerosol optical thickness(AOT) and precipitable water (PW) measurements at the SGP site are compared with measurementsusing other instruments. Aerosol size distribution derived from direct solar measurements and from theaureole sky brightness measurements are also compared. Results show that the quality of themeasurements is high, suitable for modeling of other radiation quantities. Introduction A sun/sky scanning radiometer CSPHOT has been operating as a facility instrument at the ARM SGPsite since April 1998 (and before that, during intensive operational periods [IOPs]). Sincespring/summer of 1999 the instruments have been providing data from the other two ARM sites at theTWP and NSA as well. CSPHOT is also part of AERONET (Holben et al. 1998), a worldwide networkof sunphotometers maintained by the National Aeronautics and Space Administration (NASA) GoddardSpace Flight Center (GSFC). Thus, ARM measurements of atmospheric optical properties can berelated to those measured elsewhere, thereby providing a global data set for extending applicability ofalgorithms that are evaluated using measurements at the SGP site.From direct solar measurements, CSPHOT provides measurement of the atmospheric transmittance toyield apparent AOT and PW. From the sky brightness measurements along the solar almucantar and thesolar principal plane, column averaged size distribution is obtained by inverting the solar aureolemeasurements. Here we illustrate the quality of CSPHOT measurements. Specifically, measured
Immunogenicity and safety of COVID-19 vaccines among people living with HIV: A systematic review and meta-analysis

Abstract Available data suggest that the immunogenicity of COVID-19 vaccines might decrease in the immunocompromised population, but data on vaccine immunogenicity and safety among people living with HIV (PLWH) are still lacking. The purpose of this meta-analysis is to compare the immunogenicity and safety of COVID-19 vaccines in PLWH with healthy controls. We comprehensively searched the following databases: PubMed, Cochrane Library, and EMBASE. The risk ratio (RR) of seroconversion after the first and second doses of a COVID-19 vaccine was separately pooled using random-effects meta-analysis. Seroconversion rate was lower among PLWH compared with healthy individuals after the first (RR = 0.77, 95% conﬁdent interval (CI) 0.64–0.92) and second doses (RR = 0.97, 95%CI 0.95–0.99). The risk of total adverse reactions among PLWH is similar to the risk in the healthy group, after the first (RR = 0.87, 95%CI 0.70–1.10) and second (RR = 0.83, 95%CI 0.65–1.07) doses. This study demonstrates that the immunogenicity and safety of SARS-CoV-2 vaccine in fully vaccinated HIV-infected patients were generally satisfactory. A second dose was related to seroconversion enhancement. Therefore, we considered that a booster dose may provide better seroprotection for PLWH. On the basis of a conventional two-dose regimen for COVID-19 vaccines, the booster dose is very necessary.
Co-feeding enhances the yield of methyl ketones

Abstract The biotechnological production of methyl ketones is a sustainable alternative to fossil-derived chemical production. To date, the best host for microbial production of methyl ketones is a genetically engineered Pseudomonas taiwanensis VLB120 ∆6 pProd strain, achieving yields of 101 mgg−1 on glucose in batch cultivations. For competitiveness with the petrochemical production pathway, however, higher yields are necessary. Co-feeding can improve the yield by fitting the carbon-to-energy ratio to the organism and the target product. In this work, we developed co-feeding strategies for P. taiwanensis VLB120 ∆6 pProd by combined metabolic modeling and experimental work. In a first step, we conducted flux balance analysis with an expanded genome-scale metabolic model of iJN1463 and found ethanol as the most promising among five cosubstrates. Next, we performed cultivations with ethanol and found the highest reported yield in batch production of methyl ketones with P. taiwanensis VLB120 to date, namely, 154 mg g−1 methyl ketones. However, ethanol is toxic to the cell, which reflects in a lower substrate consumption and lower product concentrations when compared to production on glucose. Hence, we propose cofeeding ethanol with glucose and find that, indeed, higher concentrations than in ethanol-fed cultivation (0.84 g Laq−1 with glucose and ethanol as opposed to 0.48 g Laq−1 with only ethanol) were achieved, with a yield of 85 mg g−1. In a last step, comparing experimental with computational results suggested the potential for improving the methyl ketone yield by fed-batch cultivation, in which cell growth and methyl ketone production are separated into two phases employing optimal ethanol to glucose ratios. One-Sentence Summary By combining computational and experimental work, we demonstrate that feeding ethanol in addition to glucose improves the yield of biotechnologically produced methyl ketones.
Approximate Queries over Concurrent Updates

Approximate Query Processing (AQP) systems produce estimation of query answers using small random samples. It is attractive for the users who are willing to trade accuracy for low query latency. On the other hand, real-world data are often subject to concurrent updates. If the user wants to perform real-time approximate data analysis, the AQP system must support concurrent updates and sampling. Towards that, we recently developed a new concurrent index, AB-tree, to support efficient sampling under updates. In this work, we will demonstrate the feasibility of supporting realtime approximate data analysis in online transaction settings using index-assisted sampling.
The Application of tree-based ML algorithm in steel plates Ffaults identi􀅮ication

This research aims to apply a series of classical machine learning algorithms based on decision trees (Decision Tree, Adaboosting, Bagging, RandomForest)toverifythe ten-foldcross-validationof the steelplatefaultdata. The source of the data set was the Research Center of Sciences of Communication in Italy and has been used two times by M Buscema when it is provided [15, 16]. The data set includes 7 different types of steel plate faults: Pastry, Z_Scratch, K_Scatch, Stains, Dirtiness, Bumps, and Other Faults. It is found that the Bagging algorithm outperforms the other methods and achieves 96.30% and 90% accuracy on the training and testing set, respectively. This will allowusto􀅫indabnormalitiesonthesurfaceofthesteelplatetimelyandreducelosses. Basedonthesealgorithms, wecan cooperatewith ironand steelpractitionerstodesignmoreappropriatealgorithmstoachievehigherrecog-nition accuracy in the future.
a randomised controlled trial with nested qualitative interviews on space, place and treatment delivery

Background/aim : Single elements within the physical environment promote better health-outcomes in hospitals. Creating optimal facilities for exercise therapy may increase treatment effects. We investigated the influence of the treatment room on effects of exercise therapy. Methods: In a mixed-method randomised controlled double-blind trial, middle-aged individuals reporting knee or hip pain performed eight weeks of exercise therapy in A) a newly built physically enhanced environment, B) a standard environment or C) were waitlisted, receiving no intervention. Participants and therapists were blind to study aim. Primary outcome was participants’ Global Perceived Effect (GPE, 7-point Likert scale). Six nested focus group interviews with participants (n=25) and individual interviews with therapists (n=2), explored experiences of the environment. Registration identifier: NCT02043613. Results : 42 exercised in the physically enhanced environment, 40 in the standard environment, 21 were waitlisted. Participants from the standard environment reported greater improvement for GPE (0.98, 95%CI 0.5 to 1.4) than participants from the physically enhanced environment (0.37, 95%CI -0.2 to 0.9), between-group difference 0.61 95%CI -0.1 to 1.3, p=0.07, this was contrary to our hypothesis. In interviews, participants from the standard environment expressed greater social-cohesion and feeling at-home. Qualitative themes identified; reflection, sense of fellowship and transition. Waitlist group reported no improvement (-0.05 95%CI -0.5 to 0.4). Secondary patient-reported outcomes and qualitative findings supported the primary finding, while improvements in muscle strength and aerobic capacity did not differ between exercise groups. Conclusion : Results suggest that the physical environment contributes to treatment response. Matching patients’ preferences to treatment rooms may improve patient-reported outcomes.
The Effects of Dialysis Modality and Emotional Distress on Fatigue in Patients Undergoing Dialysis

Introduction: Fatigue is a common but often overlooked symptom in dialysis patients. Factors affecting fatigue in dialysis patients are currently unclear. There are few studies on the effects of mental factors and dialysis modality on fatigue. This study aims to explore the potential relationship between fatigue and insomnia, as well as psychiatric disorders such as anxiety and depression among patients who undergo peritoneal dialysis (PD) or hemodialysis (HD). Methods: There were 96 HD patients and 160 PD patients at our hospital who voluntarily participated in the survey. A questionnaire survey was conducted to gather general characteristics of the patients and to evaluate fatigue, sleep quality, anxiety, and depression levels among PD and HD patients. Results: The overall fatigue score was 53.83 ± 14.22 for the PD group and 57.92 ± 16.35 for the HD group. Notably, the fatigue level was lower in the PD group compared to the HD group (p < 0.05). Univariate analysis indicated that fatigue was associated with occupational status and income in the PD group, as well as educational level and income in the HD group (p < 0.05). Correlation analysis revealed that patients in both groups who were older and had higher scores for insomnia, anxiety, and depression experienced more severe fatigue. Moreover, body mass index was positively correlated with fatigue status in the PD group, while duration of dialysis showed a positive association with fatigue in the HD group. Multivariate regression analysis identified income and depression as major factors influencing fatigue in the PD group, and duration of dialysis, income, and depression in the HD group. Conclusion: Patients who undergo dialysis exhibit high levels of fatigue, with the severity of fatigue being less pronounced in the PD group compared to the HD group. Fatigue in these patients is associated with the duration of dialysis, income level, and presence of depression.
An improved multi-scale branching convolutional neural network for rolling bearing fault diagnosis

The vibration signals measured in practical engineering are usually complex and noisy, which brings challenges to fault diagnosis. In addition, industrial scenarios also put forward higher requirements for the accuracy and computational efficiency of diagnostic models. Aiming at these problems, an improved multiscale branching convolutional neural network is proposed for rolling bearing fault diagnosis. The proposed method first applies the multiscale feature learning strategy to extract rich and compelling fault information from diverse and complex vibration signals. Further, the lightweight dynamic separable convolution is elaborated and coupled into the feature extractor to "slim down" the model, reduce the computational loss on the one hand, and further improve the model’s adaptive learning ability for different inputs hand. Extensive experiments indicate that the proposed method is significantly improved compared with existing multi-scale neural networks.
Intra- vs. Interhost Evolution of SARS-CoV-2 Driven by Uncorrelated Selection—The Evolution Thwarted

Abstract In viral evolution, a new mutation has to proliferate within the host (Stage I) in order to be transmitted and then compete in the host population (Stage II). We now analyze the intrahost single nucleotide variants (iSNVs) in a set of 79 SARS-CoV-2 infected patients with most transmissions tracked. Here, every mutation has two measures: 1) iSNV frequency within each individual host in Stage I; 2) occurrence among individuals ranging from 1 (private), 2–78 (public), to 79 (global) occurrences in Stage II. In Stage I, a small fraction of nonsynonymous iSNVs are sufficiently advantageous to rise to a high frequency, often 100%. However, such iSNVs usually fail to become public mutations. Thus, the selective forces in the two stages of evolution are uncorrelated and, possibly, antagonistic. For that reason, successful mutants, including many variants of concern, have to avoid being eliminated in Stage I when they first emerge. As a result, they may not have the transmission advantage to outcompete the dominant strains and, hence, are rare in the host population. Few of them could manage to slowly accumulate advantageous mutations to compete in Stage II. When they do, they would appear suddenly as in each of the six successive waves of SARS-CoV-2 strains. In conclusion, Stage I evolution, the gate-keeper, may contravene the long-term viral evolution and should be heeded in viral studies.
Hydrogen Peroxide Affects the Electroretinogram of Isolated Perfused Rat Retina

Abstract Purpose To evaluate the effects of H2O2 as an oxidant on the electroretinogram (ERG) in isolated rat retina. Methods Retinas were isolated from rat eyes and perfused with a nutrient solution. ERGs were recorded every 3 min. Once the signal was at a steady state, H2O2 was added to the perfusion solution. Results H2O2 caused instantaneous and transient changes in amplitudes and implicit times of the ERG, followed by changes in retinal survival curves. H2O2 0.2 mM produced a rapid increase in b-wave amplitude, followed by a return to the initial value and a survival curve above the control (without H2O2). A slight increase in a-wave was observed, followed by a decrease and a recovery above the control. The slow PIII decreased and then recovered to the initial value. H2O2 0.6 mM induced a small increase in b-wave amplitude, followed by a rapid decrease without recovery. The a-wave and slow PIII decreased rapidly without recovery. The implicit times of the a-wave and b-wave increased moderately with a low dose of H2O2, whereas they significantly increased with a high dose. Whatever the dose, the slow PIII implicit time increased significantly, followed by a return to the initial value. Barium increased the a-wave and b-wave, and then H2O2 reduced the two waves with a stronger effect on the a-wave. Aspartate and barium isolated the fast PIII, which decreased after H2O2 application. Conclusions H2O2 affects retinal function as shown by ERGs in isolated rat retina. The response differs with the dose of H2O2, suggesting that mechanisms underlying the action at low doses might be different from those at high doses. Our results also suggest an effect of H2O2 on ionic currents and/or neurotransmitter releases involved in the generation of the ERG and indicate a more pronounced effect on photoreceptors than on postsynaptic cells.
Taurine Supplementation for 48-Months Improved Glucose Tolerance and Changed ATP-Related Enzymes in Avians

Avians differ from mammals, especially in brain architecture and metabolism. Taurine, an amino acid basic to metabolism and bioenergetics, has been shown to have remarkable effects on metabolic syndrome and ameliorating oxidative stress reactions across species. However, less is known regarding these metabolic relationships in the avian model. The present study serves as a preliminary report that examined how taurine might affect avian metabolism in an aged model system. Two groups of pigeons (Columba livia) of mixed sex, a control group and a group that received 48 months of taurine supplementation (0.05% w/v) in their drinking water, were compared by using blood panels drawn from their basilic vein by a licensed veterinarian. From the blood panel data, taurine treatment generated higher levels of three ATP-related enzymes: glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), and creatine kinase (CK). In this preliminary study, the role that taurine treatment might play in the adult aged pigeon’s metabolism on conserved traits such as augmenting insulin production as well as non-conserved traits maintaining high levels of ATP-related enzymes was examined. It was found that taurine treatment influenced the avian glucose metabolism similar to mammals but differentially effected avian ATP-related enzymes in a unique way (i.e., ∼×2 increase in CK and LDH with a nearly ×4 increase in GLDH). Notably, long-term supplementation with taurine had no negative effect on parameters of lipid and protein metabolism nor liver enzymes. The preliminary study suggests that avians may serve as a unique model system for investigating taurine metabolism across aging with long-term health implications (e.g., hyperinsulinemia). However, the suitability of using the model would require researchers to tightly control for age, sex, dietary intake, and exercise conditions as laboratory-housed avian present with very different metabolic panels than free-flight avians, and their metabolic profile may not correlate one-to-one with mammalian data.