Anisotropic flow and the valence quark skeleton of hadrons

We study transverse momentum anisotropies, in particular, the elliptic flow $v_2$ due to the interference effect sourced by valence quarks in high-energy hadron-hadron collisions. Our main formula is derived as the high-energy (eikonal) limit of the impact-parameter dependent cross section in quantum field theory, which agrees with that in terms of the impact parameter in the classical picture. As a quantitative assessment of the interference effect, we calculate $v_2$ in the azimuthal distribution of gluons at a comprehensive coverage of the impact parameter and the transverse momentum in high-energy pion-pion collisions. In a broad range of the impact parameter, a sizable amount of $v_2$, comparable with that produced due to saturated dense gluons or final-state interactions, is found to develop. In our calculations, the valence sector of the pion wave function is obtained numerically from the Basis Light-Front Quantization, a non-perturbative light-front Hamiltonian approach. And our formalism is generic and can be applied to other small collision systems like proton-proton collisions

Design and Synthesis of AMPK Activators and GDF15 Inducers

Targeting growth differentiation factor 15 (GDF15) is a recent strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Here, we designed, synthesized, and pharmacologically evaluated in vitro a novel series of AMPK activators to upregulate GDF15 levels. These compounds were structurally based on the (1-dibenzylamino-3-phenoxy)propan-2-ol structure of the orphan ubiquitin E3 ligase subunit protein Fbxo48 inhibitor, BC1618. This molecule showed a better potency than metformin, increasing GDF15 mRNA levels in human Huh-7 hepatic cells. Based on BC1618, structural modifications have been performed to create a collection of diversely substituted new molecules. Of the thirty-five new compounds evaluated, compound 21 showed a higher increase in GDF15 mRNA levels compared with BC1618. Metformin, BC1618, and compound 21 increased phosphorylated AMPK, but only 21 increased GDF15 protein levels. Overall, these findings indicate that 21 has a unique capacity to increase GDF15 protein levels in human hepatic cells compared with metformin and BC1618

The TLR9 ligand, CpG-ODN, Induces Protection Against Cerebral Ischemia/Reperfusion Injury via Activation of pi3k/Akt Signaling.

Toll-like receptors (TLRs) have been shown to be involved in cerebral ischemia/reperfusion (I/R) injury. TLR9 is located in intracellular compartments and recognizes CpG-DNA. This study examined the effect of CpG-ODN on cerebral I/R injury. C57BL/6 mice were treated with CpG-ODN by i.p. injection 1 hour before the mice were subjected to cerebral ischemia (60 minutes) followed by reperfusion (24 hours). Scrambled-ODN served as control-ODN. Untreated mice, subjected to cerebral I/R, served as I/R control. The effect of inhibitory CpG-ODN (iCpG-ODN) on cerebral I/R injury was also examined. In addition, we examined the therapeutic effect of CpG-ODN on cerebral I/R injury by administration of CpG-ODN 15 minutes after cerebral ischemia. CpG-ODN administration significantly decreased cerebral I/R-induced infarct volume by 69.7% (6.4±1.80% vs 21.0±2.85%, P\u3c0.05), improved neurological scores, and increased survival rate, when compared with the untreated I/R group. Therapeutic administration of CpG-ODN also significantly reduced infarct volume by 44.7% (12.6±2.03% vs 22.8±2.54%, P\u3c0.05) compared with untreated I/R mice. Neither control-ODN, nor iCpG-ODN altered I/R-induced cerebral injury or neurological deficits. Nissl staining showed that CpG-ODN treatment preserved neuronal morphology in the ischemic hippocampus. Immunoblot showed that CpG-ODN administration increased Bcl-2 levels by 41% and attenuated I/R-increased levels of Bax and caspase-3 activity in ischemic brain tissues. Importantly, CpG-ODN treatment induced Akt and GSK-3β phosphorylation in brain tissue and cultured microglial cells. PI3K inhibition with LY294002 abolished CpG-ODN-induced protection. CpG-ODN significantly reduces cerebral I/R injury via a PI3K/Akt-dependent mechanism. Our data also indicate that CpG-ODN may be useful in the therapy of cerebral I/R injury

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials

BackgroundIn recent years, we have observed the pivotal role of immunotherapy in improving survival for patients with non-small cell lung cancer (NSCLC). However, the effectiveness of immunotherapy in the perioperative (neoadjuvant + adjuvant) treatment of resectable NSCLC remains uncertain. We conducted a comprehensive analysis of its antitumor efficacy and adverse effects (AEs) by pooling data from the KEYNOTE-671, NADIM II, and AEGEAN clinical trials.MethodsFor eligible studies, we searched seven databases. The randomized controlled trials (RCTs) pertaining to the comparative analysis of combination neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy (PIO) versus perioperative placebo (PP) were included. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints encompassed drug responses, AEs, and surgical outcomes.ResultsThree RCTs (KEYNOTE-671, NADIM II, and AEGEAN) were included in the final analysis. PIO group (neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy) exhibited superior efficacy in OS (hazard ratio [HR]: 0.63 [0.49-0.81]), EFS (HR: 0.61 [0.52, 0.72]), objective response rate (risk ratio [RR]: 2.21 [1.91, 2.54]), pathological complete response (RR: 4.36 [3.04, 6.25]), major pathological response (RR: 2.79 [2.25, 3.46]), R0 resection rate (RR: 1.13 [1.00, 1.26]) and rate of adjuvant treatment (RR: 1.08 [1.01, 1.15]) compared with PP group (neoadjuvant platinum-based chemotherapy plus perioperative placebo). In the subgroup analysis, EFS tended to favor the PIO group in almost all subgroups. BMI (>25), T stage (IV), N stage (N1-N2) and pathological response (with pathological complete response) were favorable factors in the PIO group. In the safety assessment, the PIO group exhibited higher rates of serious AEs (28.96% vs. 23.51%) and AEs leading to treatment discontinuation (12.84% vs. 5.81%). Meanwhile, although total adverse events, grade 3-5 adverse events, and fatal adverse events tended to favor the PP group, the differences were not statistically significant.ConclusionPIO appears to be superior to PP for resectable stage II-III NSCLC, demonstrating enhanced survival and pathological responses. However, its elevated adverse event (AE) rate warrants careful consideration.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023487475

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30x. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.Peer reviewe

NonDL_models_clean

Python file used to perform classification with non-RNN models

Anisotropic flow and the valence quark skeleton of hadrons

Abstract We study transverse momentum anisotropies, in particular, the elliptic flow v 2 due to the interference effect sourced by valence quarks in high-energy hadron-hadron collisions. Our main formula is derived as the high-energy (eikonal) limit of the impact-parameter dependent cross section in quantum field theory, which agrees with that in terms of the impact parameter in the classical picture. As a quantitative assessment of the interference effect, we calculate v 2 in the azimuthal distribution of gluons at a comprehensive coverage of the impact parameter and the transverse momentum in high-energy pion-pion collisions. In a broad range of the impact parameter, a sizable amount of v 2, comparable with that produced due to saturated dense gluons or final-state interactions, is found to develop. This is in contrast with similar studies in heavy-ion collisions using classical color charge distributions in which such a contribution from geometric correlations was found to be small and has, hence, been ignored in recent studies. In our calculations, the valence sector of the pion wave function is obtained numerically from the Basis Light-Front Quantization, a non-perturbative light-front Hamiltonian approach. And our formalism is generic and can be applied to other small collision systems like proton-proton collisions

Modeling the Effects of Spatial Variability of Irrigation Parameters on Border Irrigation Performance at a Field Scale

The interaction between surface and subsurface water flows plays an important role in surface irrigation systems. This interaction can effectively be simulated by the physical-based models, which have been developed on the basis of the numerical solutions to the Saint-Venant and Richards’ equations. Meanwhile, the spatial variability of field physical properties (such as soil properties, surface micro-topography, and unit discharge) affects the interaction between surface and subsurface water flows and decreases the accuracy of simulating surface irrigation events at large scales. In this study, a new numerical methodology is developed based on the physical-based model of surface irrigation and the Monte Carlo simulation method to improve the modeling accuracy of surface irrigation performance at a field scale. In the proposed numerical methodology, soil properties, unit discharge, surface micro-topography, roughness, border length, and the cutoff time for the unit discharge are used as the stochastic parameters of the physical-based model, while field slope is assumed as the constant value because of the same field tillage and management conditions at a field scale. Monte Carlo simulation is used to obtain the stochastic parameter sample combinations of the physical-based model to represent the spatial variability of field physical properties. The updated stochastic simulation model of surface micro-topography, which is developed to model the spatial distribution of surface elevation differences (SED), is used to obtain the surface micro-topography samples at a field scale. Compared with the distributed-parameter modelling methodology and the field experimental data, the proposed numerical methodology presents the better simulation performance