Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurement of kLa in multiple-impeller vessel with significant axial dispersion in both phases

The Dynamic Pressure-step Method (DPM) is based on recording time profiles of oxygen concentration in liquid as a response to a concentration change in gas invoked by a small change of overall pressure in the vessel. In contrast to earlier methods (standard dynamic method with inlet gas exchange, or start-up method) the concentration change is performed simultaneously and homogeneously in all bubbles of dispersed gas. The measurements were performed in a vessel of liquid volume 20 l with aspect ratio (H/D) equal to 4 equipped with four Rushton turbines on a common shaft. In experiments, coalescing (distilled water) and noncoalescing (sodium sulphate solution) batches were used, both aerated by air or pure oxygen. Independent experiments with tracers showed the significant axial dispersion in both phases. The experimental k L a values (a) do not depend on oxygen concentration in the gas used, (b) exhibit a simple power dependence on the dissipated power and (c) in this correlation agree within 30% with those obtained in geometrically different vessels. Similar k L a measurements performed by using the standard dynamic and start-up methods produced substantially different results. In the noncoalescing batch experiments, the k L a values even exhibit a decrease at higher mixing intensities
When the genetic architecture matters: evolutionary and ecological implications of self versus nonself recognition in plant self-incompatibility.

It is often assumed that details of the genetic architecture of a trait have little relevance for how evolution proceeds in the long term, as natural selection acts on phenotypes rather than on genotypes directly (e.g. Maynard-Smith, 1978, but see Rubin, 2016). In the recently published article in New Phytologist, Harkness & Brandvain (2021; doi: 10.1111/nph.17249) provide the glaring example of a key trait of plant sexual reproduction for which the effect of population subdivision critically depends on details of how the trait is controlled at the molecular level.
Molecular Dynamic Simulations and Quantum Chemistry Studies of the Sulfone-Based Electrolytes

complexes with anions such as BF4 - and bisfluorosulfonyl imide (FSI - ) using quantum chemistry calculations. The oxidative stability of the sulfone-based electrolytes will be compared with that of linear and cyclic carbonates, and alkyl phosphate-based electrolytes. Development of the many-body polarizable quantum chemistry-based force field for the sulfone-based electrolytes will be reported. This developed polarizable force field has been used in molecular dynamics (MD) simulations of the sulfone-based electrolytes and their mixtures with dimethyl carbonate (DMC). We found the MD simulations accurately described thermophysical properties (density, heat of vaporization) of ethyl methyl sulfone (EMS) and sulfolane solvents as well as conductivity of the EMS and sulfolane doped with lithium (trifluoromethane sulfone)imide (LiTFSI) and LiPF6 salts. The degree of ion aggregation, the structure of the lithium first solvation shell, ion selfdiffusion coefficients and conductivity of the sulfone-based electrolytes will be compared with those previously obtained from MD simulations for the carbonate-based electrolytes doped with LiPF6, LiFSI and LiTFSI. 2
Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer

Lipocalin 2 is a siderophore‐binding protein that regulates iron homeostasis. Lipocalin 2 expression is elevated in multiple tumor types; however, the mechanisms that drive tumor progression upon Lipocalin 2 expression remain unclear. When Lipocalin 2 is over‐expressed, it leads to resistance to 5‐fluorouracil in colon cancer cell lines in vitro and in vivo by inhibiting ferroptosis. Lipocalin 2 inhibits ferroptosis by decreasing intracellular iron levels and stimulating the expression of glutathione peroxidase4 and a component of the cysteine glutamate antiporter, xCT. The increase in xCT levels is dependent on increased levels of ETS1 in Lipocalin 2 over‐expressing cells. Inhibiting Lipocalin 2 function with a monoclonal antibody leads to a decrease in chemo‐resistance and transformation in vitro, and a decrease in tumor progression and chemo‐resistance in xenograft mouse models. Lipocalin 2 and xCT levels exhibit a positive correlation in human tumor samples suggesting that the pathway we have identified in cell lines is operative in human tumor samples. These results indicate that Lipocalin 2 is a potential therapeutic target and that the monoclonal antibody described in our study can serve as the basis for a potential therapeutic in patients who do not respond to chemotherapy.
Contact probing of prestressed adhesive membranes of living cells

Atomic force microscopy (AFM) studies of living biological cells is one of main experimental tools that enable quantitative measurements of deformation of the cells and extraction of information about their structural and mechanical properties. However, proper modelling of AFM probing and related adhesive contact problems are of crucial importance for interpretation of experimental data. The Johnson–Kendall–Roberts (JKR) theory of adhesive contact has often been used as a basis for modelling of various phenomena including cell-cell interactions. However, strictly speaking the original JKR theory is valid only for contact of isotropic linearly elastic spheres, while the cell membranes are often prestressed. For the first time, effects caused by molecular adhesion for living cells are analytically studied taking into account the mechanical properties of cell membranes whose stiffness depends on the level of the tensile prestress. Another important question is how one can extract the work of adhesion between the probe and the cell. An extended version of the Borodich-Galanov method for non-direct extraction of elastic and adhesive properties of contacted materials is proposed to apply to experiments of cell probing. Evidently, the proposed models of adhesive contact for cells with prestressed membranes do not cover all types of biological cells because the structure and properties of the cells may vary considerably. However, the obtained results can be applied to many types of smooth cells and can be used to describe initial stages of contact and various other processes when effects of adhesion are of crucial importance. This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Explicit transformation between non-adhesive and adhesive contact problems by means of the classical Johnson–Kendall–Roberts formalism

The classic Johnson–Kendall–Roberts (JKR) contact theory was developed for frictionless adhesive contact between two isotropic elastic spheres. The advantage of the classical JKR formalism is the use of the principle of superposition of solutions to non-adhesive axisymmetric contact problems. In the recent years, the JKR formalism has been extended to other cases, including problems of contact between an arbitrary-shaped blunt axisymmetric indenter and a linear elastic half-space obeying rotational symmetry of its elastic properties. Here the most general form of the JKR formalism using the minimal number of a priori conditions is studied. The corresponding condition of energy balance is developed. For the axisymmetric case and a convex indenter, the condition is reduced to a set of expressions allowing explicit transformation of force–displacement curves from non-adhesive to corresponding adhesive cases. The implementation of the developed theory is demonstrated by presentation of a two-term asymptotic adhesive solution of the contact between a thin elastic layer and a rigid punch of arbitrary axisymmetric shape. Some aspects of numerical implementation of the theory by means of Finite-Element Method are also discussed. This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Genetic Characterisation of Colistin Resistant Klebsiella pneumoniae Clinical Isolates From North India

Background Increasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (mcr). The present study aimed to identify and characterise mcr and other drug-resistant genes in colistin resistant Klebsiella pneumoniae clinical isolates. Methods Twenty-two colistin resistant K. pneumoniae were analysed for mcr and other drug-resistant genes, efflux pumps, and virulence genes, and for their biofilm forming ability. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed for all mcr-1 positive isolates. S1-PFGE and Southern hybridisation were performed for localisation of mcr-1 and bla NDM. Results Nineteen colistin resistant K. pneumoniae harboured mcr-1 and 3 had mgrB disruption. All isolates harboured bla OXA-48-type and ESBL genes; eight strains (five with mcr-1 and three with mgrB disruption) co-harboured bla NDM. Efflux pumps genes AcrAB and mdtK were detected in all 22 and tol-C in 21 isolates. Virulence-related genes entB and irp-1 were detected in all 22, mrkD in 20, and fimH-1 in 18 isolates; 11 isolates were strong biofilm producers. PFGE clustered mcr-1 positive isolates into eight groups based on ≥90% similarity; MLST revealed diverse sequence types, predominant being ST-15 (n = 4) and ST-16 (n = 4). Both mcr-1 and bla NDM were localised on plasmid and chromosome; mcr-1 was present on IncFII type and bla NDM on IncFIB and IncA/C type plasmids. Conclusions Colistin resistance in K. pneumoniae was predominantly mediated by mcr-1. Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in K. pneumoniae with ability to emerge as super-spreader of drug-resistance.
BRCA1 and BRCA2 Variation in Taiwanese General Population and the Cancer Cohort

BRCA1 and BRCA2 (BRCA) play essential roles in maintaining genome stability. Rapidly evolving human BRCA generates oncogenic variants causing high cancer risk. BRCA variation is ethnic-specific in reflecting adaptation and/or effects of genetic drift. Taiwanese population of 23.8 million is an admixture of multiple ethnic origins; Taiwan’s subtropical and tropical climate and geographically islandic location provide a unique natural environment. Therefore, Taiwanese population provides a unique model to study human BRCA variation. Through collecting, standardizing, annotating, and classifying publicly available BRCA variants derived from Taiwanese general population and the cancer cohort, we identified 335 BRCA variants, of which 164 were from 1,517 non-cancer individuals, 126 from 2,665 cancer individuals, and 45 from both types of individuals. We compared the variant data with those from other ethnic populations such as mainland Chinese, Macau Chinese, Japanese, Korean, Indian, and non-Asians. We observed that the sharing rates with other Asian ethnic populations were correlated with its genetic relationship. Over 60% of the 335 Taiwanese BRCA variants were VUS, unclassified variants, or novel variants, reflecting the ethnic-specific features of Taiwanese BRCA variation. While it remains challenging to classify these variants, our structural and in silico analyses predicted their enrichment of BRCA deleterious variants. We further determined the 3.8% prevalence of BRCA pathogenic variants in the Taiwanese breast cancer cohort, and determined 0.53% prevalence of the BRCA pathogenic variants in Taiwanese general population, with the estimated 126,140 BRCA pathogenic variant carriers. We identified BRCA2 c. 5164_5165delAG at BRCA2 BRC6 motif as a potential founder mutation in Taiwanese population. Our study on BRCA variation in Taiwanese and other East Asian populations demonstrates that ethnic specificity is a common phenomenon for BRCA variation in East Asian population; the data generated from the study provide a reference for clinical applications in BRCA-related cancer in Taiwanese population.
Parametric Estimation of Reference Signal Intensity for Semi-Quantification of Tau Deposition: A Flortaucipir and [18F]-APN-1607 Study

Background Tau positron emission tomography (PET) imaging can reveal the pathophysiology and neurodegeneration that occurs in Alzheimer’s disease (AD) in vivo. The standardized uptake value ratio (SUVR) is widely used for semi-quantification of tau deposition but is susceptible to disturbance from the reference region and the partial volume effect (PVE). To overcome this problem, we applied the parametric estimation of reference signal intensity (PERSI) method—which was previously evaluated for flortaucipir imaging—to two tau tracers, flortaucipir and [18F]-APN-1607. Methods Two cohorts underwent tau PET scanning. Flortaucipir PET imaging data for cohort I (65 healthy controls [HCs], 60 patients with mild cognitive impairment [MCI], and 12 AD patients) were from the AD Neuroimaging Initiative database. [18F]-APN-1607 ([18F]-PM-PBB3) PET imaging data were for Cohort II, which included 21 patients with a clinical diagnosis of amyloid PET-positive AD and 15 HCs recruited at Huashan Hospital. We used white matter (WM) postprocessed by PERSI (PERSI-WM) as the reference region and compared this with the traditional semi-quantification method that uses the whole cerebellum as the reference. SUVRs were calculated for regions of interest including the frontal, parietal, temporal, and occipital lobes; anterior and posterior cingulate; precuneus; and Braak I/II (entorhinal cortex and hippocampus). Receiver operating characteristic (ROC) curve analysis and effect sizes were used to compare the two methods in terms of ability to discriminate between different clinical groups. Results In both cohorts, regional SUVR determined using the PERSI-WM method was superior to using the cerebellum as reference region for measuring tau retention in AD patients (e.g., SUVR of the temporal lobe: flortaucipir, 1.08 ± 0.17 and [18F]-APN-1607, 1.57 ± 0.34); and estimates of the effect size and areas under the ROC curve (AUC) indicated that it also increased between-group differences (e.g., AUC of the temporal lobe for HC vs AD: flortaucipir, 0.893 and [18F]-APN-1607: 0.949). Conclusion The PERSI-WM method significantly improves diagnostic discrimination compared to conventional approach of using the cerebellum as a reference region and can mitigate the PVE; it can thus enhance the efficacy of semi-quantification of multiple tau tracers in PET scanning, making it suitable for large-scale clinical application.
Mild cognitive impairment is not a valid concept and should be replaced by a more restrictive, biologically validated class, named Mild Cognitive Dysfunctions (MCD): a nomothetic network approach.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2 % of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD. Conclusions: Petersen s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.
Neutrophil Lymphocyte Ratio as a Predictor of Glucocorticoid Effectiveness in Covid-19 Treatment

Glucocorticoids have been shown to improve outcomes of patients with severe cases of Covid-19. However, criteria for prescribing glucocorticoids are currently limited. To identify potential for targeting, we perform an observational analysis of mortality of hospitalized patients. Our results agree with current clinical understanding that glucocorticoids benefit patients with severe cases of Covid-19, and that elevated Neutrophil/Lymphocyte Ratio (NLR) is associated with mortality. Furthermore, our results suggest that glucocorticoids could be targeted to patients with elevated NLR (especially in the range 6-25) at time of admission. Finally, we note there are also high-risk patients with low NLR, suggesting varying presentations of severe Covid-19.
Time-Restricted Feeding in Commercial Layer Chickens Improves Egg Quality in Old Age and Points to Lack of Adipostat Activity in Chickens

In mammals, time-restricted feeding (TRF) with no caloric restriction provides health benefits and extends longevity, usually with a minor (∼3%) or no reduction in total food consumption. In the current study, a TRF regimen of 6 h free access to food (08:00–14:00 h) was applied to Leghorn chickens from 25 to 86 weeks of age; control birds ate freely during the light hours (06:00–20:00 h). Unexpectedly, the TRF-treated birds consumed, on average, 11.7% less food than the controls. This was manifested by an average reduction of 9.6% in body weight, 2.6-fold in visceral fat accumulation, and 6.5% in egg weight. Hen-housed egg production was reduced by 3.6% in the TRF group compared with the control, along the first 40 weeks of the follow-up (P < 0.05), and changed into a tendency of 0.7% higher egg production thereafter. Several parameters of egg quality showed significant improvement (P < 0.05) in the TRF group compared with the controls. A comparison of diurnal patterns of feed consumption revealed a higher rate of hourly consumption in the TRF group and increased consumption before dark in the control group. In conclusion, the reduced feed intake in response to the TRF treatment and loss in visceral fat accumulation supports the lack of a strong adipostat activity in chickens and different appetite regulation mechanisms compared with mammals. Therefore, future TRF studies in chickens should be adjusted by extending the ad libitum time window. The lower feed intake by the TRF-treated chickens compared with the ad libitum-fed controls seems to reduce the efficiency of egg production. Nevertheless, the improved egg quality and persistence of egg lay at the older age suggest that similarly to mammals, the TRF treatment delayed at least some of the negative impacts associated with advanced age.
Plasma Lipidomics Profiling Reveals Biomarkers for Papillary Thyroid Cancer Diagnosis

The objective of this study was to identify potential biomarkers and possible metabolic pathways of malignant and benign thyroid nodules through lipidomics study. A total of 47 papillary thyroid carcinomas (PTC) and 33 control check (CK) were enrolled. Plasma samples were collected for UPLC-Q-TOF MS system detection, and then OPLS-DA model was used to identify differential metabolites. Based on classical statistical methods and machine learning, potential biomarkers were characterized and related metabolic pathways were identified. According to the metabolic spectrum, 13 metabolites were identified between PTC group and CK group, and a total of five metabolites were obtained after further screening. Its metabolic pathways were involved in glycerophospholipid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, Phosphatidylinositol signaling system and the metabolism of arachidonic acid metabolism. The metabolomics method based on PROTON nuclear magnetic resonance (NMR) had great potential for distinguishing normal subjects from PTC. GlcCer(d14:1/24:1), PE-NME (18:1/18:1), SM(d16:1/24:1), SM(d18:1/15:0), and SM(d18:1/16:1) can be used as potential serum markers for the diagnosis of PTC.
Distinct Extracellular RNA Profiles in Different Plasma Components

Circulating extracellular RNAs (exRNAs) have great potential to serve as biomarkers for a wide range of diagnostic, therapeutic, and prognostic applications. So far, knowledge of the difference among different sources of exRNAs is limited. To address this issue, we performed a sequential physical and biochemical precipitation to collect four fractions (platelets and cell debris, the thrombin-induced precipitates, extracellular vesicles, and supernatant) from each of 10 plasma samples. From total RNAs of the 40 fractions, we prepared ligation-free libraries to profile full spectrum of all RNA species, without size selection and rRNA reduction. Due to complicated RNA composition in these libraries, we utilized a successive stepwise alignment strategy to map the RNA sequences to different RNA categories, including miRNAs, piwi-interacting RNAs, tRNAs, rRNAs, lincRNAs, snoRNAs, snRNAs, other ncRNAs, protein coding RNAs, and circRNAs. Our data showed that each plasma fraction had its own unique distribution of RNA species. Hierarchical cluster analyses using transcript abundance demonstrated similarities in the same plasma fraction and significant differences between different fractions. In addition, we observed various unique transcripts, and novel predicted miRNAs among these plasma fractions. These results demonstrate that the distribution of RNA species and functional RNA transcripts is plasma fraction-dependent. Appropriate plasma preparation and thorough inspection of different plasma fractions are necessary for an exRNA-based biomarker study.