A multi-fidelity deep operator network (DeepONet) for fusing simulation and monitoring data: Application to real-time settlement prediction during tunnel construction

Ground settlement prediction during the process of mechanized tunneling is of paramount importance and remains a challenging research topic. Typically, two paradigms are existing: a physics-driven approach utilizing process-oriented computational simulation models for the tunnel-soil interaction and the settlement prediction, and a data-driven approach employing machine learning techniques to establish mappings between influencing factors and the ground settlement. To integrate the advantages of both approaches and to assimilate the data from different sources, we propose a multi-fidelity deep operator network (DeepONet) framework, leveraging the recently developed operator learning methods. The presented framework comprises of two components: a low-fidelity subnet that captures the fundamental ground settlement patterns obtained from finite element simulations, and a high-fidelity subnet that learns the nonlinear correlation between numerical models and real engineering monitoring data. A pre-processing strategy for causality is adopted to consider the spatio-temporal characteristics of the settlement during tunnel excavation. Transfer learning is utilized to reduce the training cost for the low-fidelity subnet. The results show that the proposed method can effectively capture the physical information provided by the numerical simulations and accurately fit measured data as well. Remarkably, even with very limited noisy monitoring data, the proposed model can achieve rapid, accurate, and robust predictions of the full-field ground settlement in real-time during mechanized tunnel excavation

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ¹H molecular diffusion NMR and ¹⁹F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ¹H molecular diffusion nuclear magnetic resonance (NMR) and ¹⁹F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ¹⁹F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Ispitivanje antioksidativne aktivnosti in vitro polipeptida meduze (Rhopilema esculentum)

Jellyfish gelatin was hydrolyzed by different proteases to obtain antioxidative polypeptides. The gelatin hydrolysate obtained by progressive hydrolysis using trypsin and Properase E exhibited the highest hydrolysis degree and antioxidant activity. Three series of gelatin polypeptides (SCP1, SCP2 and SCP3) were obtained by ultrafiltrating the gelatin hydrolysate through molecular mass cut-off membranes of 10, 6 and 2 kDa, respectively. Amino acid composition analysis showed that SCP3 had the highest total hydrophobic amino acid content. The in vitro antioxidant tests demonstrated that SCP2 had the strongest hydroxyl radical and hydrogen peroxide scavenging activities and metal chelating ability, while SCP3 showed the highest reducing power, antioxidant activity in linoleic acid emulsion system and superoxide anion radical scavenging activity. The results support the feasibility of jellyfish gelatin as a natural antioxidant polypeptide provider, and enzymatic hydrolysis and ultrafiltration could be potent future processing technologies to utilize the abundant jellyfish resource.Hidrolizom želatine iz meduze pomoću različitih proteaza dobiveni su polipeptidi antioksidativnih svojstava. Najveći stupanj hidrolize i najbolja antioksidativna svojstva imao je hidrolizat dobiven progresivnom hidrolizom pomoću tripsina i Properase E. Ultrafiltracijom hidrolizata kroz membrane (10, 6 i 2 kDa) dobivene su tri serije polipeptida želatine: SCP1, SCP2 i SCP3. Analizom aminokiselinskoga sastava ustanovljeno je da SCP3 ima najveći ukupni udio hidrofobnih aminokiselina. Antioksidativni testovi in vitro pokazali su da SCP2 ima najveću sposobnost uklanjanja hidroksilnih radikala i vodikova peroksida te keliranja metala, a SCP3 najveću redukcijsku moć, najbolju antioksidativnu aktivnost u emulzijskom sustavu linoleinske kiseline te sposobnost uklanjanja superoksidnih aniona. Rezultati potvrđuju da se želatina iz meduze može upotrijebiti kao izvor prirodnih antioksidativnih polipeptida, a enzimska hidroliza i ultrafiltracija kao postupci prerade za njezino iskorištavanje

Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator.

BackgroundAmyloid-β (Aβ) 42 has been implicated as the initiating molecule in the pathogenesis of Alzheimer's disease (AD); thus, therapeutic strategies that target Aβ42 are of great interest. γ-Secretase modulators (GSMs) are small molecules that selectively decrease Aβ42. We have previously reported that many acidic steroids are GSMs with potencies ranging in the low to mid micromolar concentration with 5β-cholanic acid being the most potent steroid identified GSM with half maximal effective concentration (EC50) of 5.7 μM.ResultsWe find that the endogenous cholesterol metabolite, 3β-hydroxy-5-cholestenoic acid (CA), is a steroid GSM with enhanced potency (EC50 of 250 nM) relative to 5β-cholanic acid. CA i) is found in human plasma at ~100-300 nM concentrations ii) has the typical acidic GSM signature of decreasing Aβ42 and increasing Aβ38 levels iii) is active in in vitro γ-secretase assay iv) is made in the brain. To test if CA acts as an endogenous GSM, we used Cyp27a1 knockout (Cyp27a1-/-) and Cyp7b1 knockout (Cyp7b1-/-) mice to investigate if manipulation of cholesterol metabolism pathways relevant to CA formation would affect brain Aβ42 levels. Our data show that Cyp27a1-/- had increased brain Aβ42, whereas Cyp7b1-/- mice had decreased brain Aβ42 levels; however, peripheral dosing of up to 100 mg/kg CA did not affect brain Aβ levels. Structure-activity relationship (SAR) studies with multiple known and novel CA analogs studies failed to reveal CA analogs with increased potency.ConclusionThese data suggest that CA may act as an endogenous GSM within the brain. Although it is conceptually attractive to try and increase the levels of CA in the brain for prevention of AD, our data suggest that this will not be easily accomplished

A Tunable Two-impurity Kondo system in an atomic point contact

Two magnetic atoms, one attached to the tip of a Scanning Tunneling Microscope (STM) and one adsorbed on a metal surface, each constituting a Kondo system, have been proposed as one of the simplest conceivable systems potentially exhibiting quantum critical behaviour. We have succeeded in implementing this concept experimentally for cobalt dimers clamped between an STM tip and a gold surface. Control of the tip-sample distance with sub-picometer resolution allows us to tune the interaction between the two cobalt atoms with unprecedented precision. Electronic transport measurements on this two-impurity Kondo system reveal a rich physical scenario which is governed by a crossover from local Kondo screening to non-local singlet formation due to antiferromagnetic coupling as a function of separation of the cobalt atoms.Comment: 22 pages, 5 figure

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

A Comprehensive Research on Antibiotic Resistance Genes in Microbiota of Aquatic Animals

The occurrence of antibiotic resistance genes (ARGs) as emerging contaminants is of continued concern for human health. Antibiotics used in aquaculture have promoted the evolution and spread of ARGs. This study aimed to investigate the occurrence of 37 ARGs conferring resistance to six classes of antibiotics in 94 aquatic animals from five cities in southeast coast of China. The results showed that floR, sulII, sulI, strB, strA, aadA, and tetS were identified as the prominent ARGs with the high detection frequencies ranging from 30.9 to 51.1% in total samples. Then relative expression amount of seven prominent ARGs quantified by qPCR, ranging from 0.003 to 0.065. The tetS was the most abundant ARG among the seven ARGs. Though aadA was the second highest detection frequency of ARGs, it was the lowest expression amount ARG. The occurrences and abundances of ARGs in freshwater aquatic animals were greater than those in marine, reflecting the discrepancy of cultivation pattern between the freshwater and marine aquaculture. Shanghai was considered as the most prevalent site with 16 ARGs, and Ningbo merely contained 9 ARGs without of β-lactam ARGs and quinolone ARGs, showing variations of ARGs with geographical location. Eight kinds of sulfonamides and one chloramphenicol residues were further measured in samples from Shanghai. Interestingly, no target antibiotics were found, but sulfonamides resistance genes (sulI, sulII) and chloramphenicol resistance genes (floR) persisted at aquatic animals in the absence of selection pressure. Our research firstly shows comprehensive information on the ARGs in skin microbiota of aquatic animals, which could provide useful information and a new insight for better understanding on the ARGs dissemination in aquatic animals