Miracle-dz/UniFAR-FTUs huggingface dataset:
Pomegranate Seed Oil as a Source of Conjugated Linolenic Acid (CLnA) Has No Effect on Atherosclerosis Development but Improves Lipid Profile and Affects the Expression of Lipid Metabolism Genes in apoE/LDLR−/− Mice

The aim of this study was to evaluate the anti-atherosclerotic effect of pomegranate seed oil as a source of conjugated linolenic acid (CLnA) (cis-9,trans-11,cis-13; punicic acid) compared to linolenic acid (LnA) and conjugated linoleic acid (CLA) (cis-9,trans-11) in apoE/LDLR−/− mice. In the LONG experiment, 10-week old mice were fed for the 18 weeks. In the SHORT experiment, 18-week old mice were fed for the 10 weeks. Diets were supplied with seed oils equivalent to an amount of 0.5% of studied fatty acids. In the SHORT experiment, plasma TCh and LDL+VLDL cholesterol levels were significantly decreased in animals fed CLnA and CLA compared to the Control. The expression of PPARα in liver was four-fold increased in CLnA group in the SHORT experiment, and as a consequence the expression of its target gene ACO was three-fold increased, whereas the liver’s expression of SREBP-1 and FAS were decreased in CLnA mice only in the LONG experiment. Punicic acid and CLA isomers were determined in the adipose tissue and liver in animals receiving pomegranate seed oil. In both experiments, there were no effects on the area of atherosclerotic plaque in aortic roots. However, in the SHORT experiment, the area of atherosclerosis in the entire aorta in the CLA group compared to CLnA and LnA was significantly decreased. In conclusion, CLnA improved the lipid profile and affected the lipid metabolism gene expression, but did not have the impact on the development of atherosclerotic plaque in apoE/LDLR−/− mice.
Novel Benzimidazole Derived Imine Ligand and Its Co(III) and Cu(II) Complexes as Anticancer Agents: Chemical Synthesis, DFT Studies, In Vitro and In Vivo Biological Investigations

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1–C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand’s reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich–Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C27H23Cl2CoFN5O3 exhibited profound anti-proliferative activity against the EAC cell line with a significant IC50 value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF165, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated.
Weakly Supervised Collaborative Learning for Airborne Pollen Segmentation and Classification from SEM Images

Existing pollen identification methods heavily rely on the scale and quality of pollen images. However, there are many impurities in real-world SEM images that should be considered. This paper proposes a collaborative learning method to jointly improve the performance of pollen segmentation and classification in a weakly supervised manner. It first locates pollen regions from the raw images based on the detection model. To improve the classification performance, we segmented the pollen grains through a pre-trained U-Net using unsupervised pollen contour features. The segmented pollen regions were fed into a deep convolutional neural network to obtain the activation maps, which were used to further refine the segmentation masks. In this way, both segmentation and classification models can be collaboratively trained, supervised by just pollen contour features and class-specific information. Extensive experiments on real-world datasets were conducted, and the results prove that our method effectively avoids impurity interference and improves pollen identification accuracy (86.6%) under the limited supervision (around 1000 images with image-level labels).
High Efficiency Regeneration System from Blueberry Leaves and Stems

The main propagation approach is tissue culture in blueberries, and tissue culture is an effective and low-cost method with higher economic efficiency in blueberries. However, there is a lack of stable and efficient production systems of industrialization of tissue culture in blueberries. In this study, the high-efficiency tissue culture and rapid propagation technology system were established based on blueberry leaves and stems. The optimal medium for callus induction was WPM (woody plant medium) containing 2.0 mg/L Forchlorfenuron (CPPU), 0.2 mg/L 2-isopentenyladenine (2-ip) with a 97% callus induction rate and a callus differentiation rate of 71% by using blueberry leaves as explants. The optimal secondary culture of the leaf callus medium was WPM containing 3.0 mg/L CPPU with an increment coefficient of 24%. The optimal bud growth medium was WPM containing 1.0 mg/L CPPU, 0.4 mg/L 2-ip, with which the growth of the bud was better, stronger and faster. The optimal rooting medium was 1/2 Murashige and Skoog (1/2MS) medium containing 2.0 mg/L naphthylacetic acid (NAA), with which the rooting rate was 90% with shorter rooting time and more adventitious root. In addition, we established a regeneration system based on blueberry stems. The optimal preculture medium in blueberry stem explants was MS medium containing 2-(N-morpholino) ethanesulfonic acid (MES) containing 0.2 mg/L indole-3-acetic acid (IAA), 0.1 mg/L CPPU, 100 mg/L NaCl, with which the germination rate of the bud was 93%. The optimal medium for fast plant growth was MS medium containing MES containing 0.4 mg/L zeatin (ZT), 1 mg/L putrescine, 1 mg/L spermidine, 1 mg/L spermidine, which had a good growth state and growth rate. The optimal cultivation for plantlet growth was MS medium containing MES containing 0.5 mg/L isopentene adenine, with which the plantlet was strong. The optimal rooting medium for the stem was 1/2MS medium containing 2.0 mg/L NAA, with which the rooting rate was 93% with a short time and more adventitious root. In conclusion, we found that stem explants had higher regeneration efficiency for a stable and efficient production system of industrialization of tissue culture. This study provides theoretical guidance and technical support in precision breeding and standardization and industrialization in the blueberry industry.
A Highly Versatile X-ray and Electron Beam Diamond Dosimeter for Radiation Therapy and Protection

Radiotherapy is now recognized as a pillar in the fight against cancer. Two different types are currently used in clinical practice: (1) external beam radiotherapy, using high-energy X-rays or electron beams, both in the MeV-range, and (2) intraoperative radiotherapy, using low-energy X-rays (up to 50 keV) and MeV-range electron beams. Versatile detectors able to measure the radiation dose independently from the radiation nature and energy are therefore extremely appealing to medical physicists. In this work, a dosimeter based on a high-quality single-crystal synthetic diamond sample was designed, fabricated and characterized under low-energy X-rays, as well as under high-energy pulsed X-rays and electron beams, demonstrating excellent linearity with radiation dose and dose-rate. Detector sensitivity was measured to be 0.299 ± 0.002 µC/Gy under 6 MeV X-ray photons, and 0.298 ± 0.004 µC/Gy under 6 MeV electrons, highlighting that the response of the diamond dosimeter is independent of the radiation nature. Moreover, in the case of low-energy X-rays, an extremely low limit of detection (23 nGy/s) was evaluated, pointing out the suitability of the device to radiation protection dosimetry.
CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds

In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds. Here, we present a new version of this web application: CLC-Pred 2.0. It also employs the PASS (Prediction of Activity Spectra for Substance) approach based on substructural atom centric MNA descriptors and a Bayesian algorithm. CLC-Pred 2.0 provides three types of qualitative prediction: (1) cytotoxicity against 391 tumor and 47 normal human cell lines based on ChEMBL and PubChem data (128,545 structures) with a mean accuracy of prediction (AUC), calculated by the leave-one-out (LOO CV) and the 20-fold cross-validation (20F CV) procedures, of 0.925 and 0.923, respectively; (2) cytotoxicity against an NCI60 tumor cell-line panel based on the Developmental Therapeutics Program’s NCI60 data (22,726 structures) with different thresholds of IG50 data (100, 10 and 1 nM) and a mean accuracy of prediction from 0.870 to 0.945 (LOO CV) and from 0.869 to 0.942 (20F CV), respectively; (3) 2170 molecular mechanisms of actions based on ChEMBL and PubChem data (656,011 structures) with a mean accuracy of prediction 0.979 (LOO CV) and 0.978 (20F CV). Therefore, CLC-Pred 2.0 is a significant extension of the capabilities of the initial web application.
New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents—Synthesis, Characterization and Cytotoxicity Studies—And Comparative DNA-Binding Study of Related Phen Complexes

Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in the gas phase using DFT at the B3LYP/LANL2DZ level of theory and the calculated vibrational frequencies were analyzed. Solid-state characterization is in agreement with pentacoordinate complexes of the general formula [Cu(L-dipeptide)(batho)]·x solvent, similar to other [Cu(L-dipeptide)(diimine)] complexes. In solution, the major species are heteroleptic, as in the solid state. The mode of binding to the DNA was evaluated by different techniques, to understand the role of the diimine and the dipeptide. To this end, studies were also performed with complexes [CuCl2(diimine)], [Cu(L-dipeptide)(diimine)] and free diimines, with phenanthroline, neocuproine and 3,4,7,8-tetramethyl-phenanthroline. The cytotoxicity of the complexes was determined on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), and A549 (lung epithelial) and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). [Cu(L-dipeptide)(batho)] complexes are highly cytotoxic as compared to cisplatin and [Cu(L-dipeptide)(phenanthroline)] complexes, being potential candidates to study their in vivo activity in the treatments of aggressive tumors for which there is no curative pharmacological treatment.
Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis

Background: The COVID-19 pandemic represents one of the world’s most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. Methods: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. Results: We identified 78 bibliographic citations. After the reviewers’ screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34–0.72) and 0.28 (0.20–0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.
Alloys by precision electrodeposition

We show that a Cu–Ni alloy film of arbitrary composition may be grown by electrodepositing well-defined submonolayer quantities of Cu and Ni in alternation. Active computer control of the deposition process is used to compensate for undesired electrochemical processes, such as partial redissolution of the Ni. Magnetic measurements were used to characterize alloy homogeneity. With this electrodeposition method it is possible to tailor the composition profile of a film with subnanometer precision. As an example, Cu0.19Ni0. 81/Cu0.79Ni0. 21 alloy/alloy multilayers were fabricated which gave prominent satellite peaks in high angle x-ray diffraction patterns.
An improved method of calculating the lattice friction stress using an atomistic model

The authors present an efficient and accurate method of calculating the lattice friction barrier to dislocation motion. This method makes use of an atomistic model of the dislocation core structure. Results of calculations for the lattice friction barrier and the Peierls stress of 1/2a(110) edge dislocations in the ionic crystals MgO and KCl are presented and compared with experiment.
Notes on hyperloops in N = 4 Chern-Simons-matter theories

: We present new circular Wilson loops in three-dimensional N = 4 quiver Chern-Simons-matter theory on S 3 . At any given node of the quiver, a two-parameter family of operators can be obtained by opportunely deforming the 1/4 BPS Gaiotto-Yin loop. Including then adjacent nodes, the coupling to the bifundamental matter ﬁelds allows to enlarge this family and to construct loop operators based on superconnections. We discuss their classiﬁcation, which depends on both discrete data and continuous parameters subject to an identiﬁcation. The resulting moduli spaces are conical manifolds, similar to the conifold of the 1/6 BPS loops of the ABJ(M) theory.
Detecting parameter shift in garch models

This paper applies recent theories of testing for parameter constancy to the conditional variance in a GARCH model. The supremum Lagrange multiplier test for conditional Gaussian GARCH models and its robustified variants are discussed. The asymptotic null distribution of the test statistics are derived from the weak convergence of the scores, and the critical values from the hitting probability of squared Bessel process. Monte Carlo studies on the finite sample size and power performance of the supremum LM tests are conducted. Applications of these tests to S&P 500 indicate that the hypothesis of stable conditional variance parameters can be rejected.
Comparison of time-series registration methods in breast dynamic infrared imaging

Abstract Automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time−temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. The aim of this work is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user−independent. We implemented and evaluated 3 different 3D time−series registration methods: 1. Linear affine, 2. Non−linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70 ±0.03, 0.74 ±0.03 and 0.81 ±0.09 (out of 1) for Affine, Bspline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons’ registration method outperforms also with the best breast alignment and non−negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons’ registration as an effective technique for time−series dynamic infrared registration, to stabilize the local temperature oscillation.
Deformation of a capsule in simple shear flow: Effect of membrane prestress

We investigate the effect of an initial isotropic prestress on the mechanics of a spherical capsule freely suspended in a simple shear flow. The capsule consists of a drop of liquid enclosed by a very thin hyperelastic membrane. A sufficient prestress may prevent the buckling instability that arises at low shear rates when the membrane bending resistance is neglected. A small perturbation analysis of the capsule deformation is first obtained for small prestress and weak viscous stresses. When the viscous shear stress and the preinflation are large, a numerical model of the capsule deformation shows how prestress decreases the capsule deformation for a given shear rate and how it significantly increases the elastic tension in the membrane at a given deformation level. These results may help the experimentalists to detect the presence of an osmotic pressure difference in a semipermeable capsule.
The Latent Markov Chain with Multivariate Random Effects

An analytically tractable latent Markov chain with correlated random effects from Gamma distributions is developed by combining techniques developed in latent class modeling and random effects modeling of survival and recurrent binary events data. Continuous unobserved heterogeneity in both classification error and latent class membership is allowed for. The model is used to compare a number of instruments that measure male labor market status in the British Household Panel Survey. Instrument specific, correlated random effects for classification errors are specified. Although the presented methodology is limited to binary events and specific distributional forms for the random effects, the analysis illustrates the importance of trying to understand and allow for potential complexities in classification error processes, if measurement error adjustments are to be relied on. The standard result of such analyses, that nontreatment of dependent classification errors leads to underestimation of the number of “changers,” is emphasized here.
Analytical bounds on the minimizers of (nonconvex) regularized least-squares

This is a theoretical study on the minimizers of cost-functions composed of an l 2 data-fidelity term and a possibly nonsmooth or nonconvex regularization term acting on the differences or the discrete gradients of the image or the signal to restore. More precisely, we derive general nonasymptotic analytical bounds characterizing the local and the global minimizers of these cost-functions. We first derive bounds that compare the restored data with the noisy data. For edge-preserving regularization, we exhibit a tight data-independent bound on the l ∞ norm of the residual (the estimate of the noise), even if its l 2 norm is being minimized. Then we focus on the smoothing incurred by the (local) minimizers in terms of the differences or the discrete gradient of the restored image (or signal).
p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs

Malignant peripheral nerve sheath tumors (MPNSTs) are chemotherapy resistant sarcomas that are a leading cause of death in neurofibromatosis type 1 (NF1). Although NF1-related MPNSTs derive from neural crest cell origin, they also exhibit intratumoral heterogeneity. TP53 mutations are associated with significantly decreased survival in MPNSTs, however the mechanisms underlying TP53-mediated therapy responses are unclear in the context of NF1-deficiency. We evaluated the role of two commonly altered genes, MET and TP53, in kinome reprograming and cellular differentiation in preclinical MPNST mouse models. We previously showed that MET amplification occurs early in human MPNST progression and that Trp53 loss abrogated MET-addiction resulting in MET inhibitor resistance. Here we demonstrate a novel mechanism of therapy resistance whereby p53 alters MET stability, localization, and downstream signaling leading to kinome reprogramming and lineage plasticity. Trp53 loss also resulted in a shift from RAS/ERK to AKT signaling and enhanced sensitivity to MEK and mTOR inhibition. In response to MET, MEK and mTOR inhibition, we observed broad and heterogeneous activation of key differentiation genes in Trp53-deficient lines suggesting Trp53 loss also impacts lineage plasticity in MPNSTs. These results demonstrate the mechanisms by which p53 loss alters MET dependency and therapy resistance in MPNSTS through kinome reprogramming and phenotypic flexibility.