The Stability Analysis of Foundation Pit Under Seepage State Based on Plaxis Software

The stability of excavation engineering is closely related to groundwater, so it is important to study the impact of seepage flow on the stability of foundation pit. The work is based on the percolation theory and principles of strength reduction. The computation were done with use of the Plaxis software. There were studied simulations which included the seepage state and simulations which didn\u27t include this effect. In order to studythe influence of seepage on the stability of foundation pit, there was computed the stability coefficient by using the strength. The results show that, when the seepage stability was not considered, the coefficient is 30% larger than when considering the seepage. Therefore, when designing and calculating the excavation, the seepage should be considered when checking stability if there is groundwater

Rephasing Ion Packets in the Orbitrap Mass Analyzer to Improve Resolution and Peak Shape

A method is described to improve resolution and peak shape in the Orbitrap under certain experimental conditions. In these experiments, an asymmetric anharmonic axial potential was first produced in the Orbitrap by detuning the voltage on the compensator electrode, which results in broad and multiply split mass spectral peaks. An AC waveform applied to the outer electrode, 180° out of phase with ion axial motion and resonant with the frequency of ion axial motion, caused ions of a given m/z to be de-excited to the equator (z = 0) and then immediately re-excited. This process, termed “rephasing,” leaves the ion packet with a narrower axial spatial extent and frequency distribution. For example, when the Orbitrap axial potential is thus anharmonically de-tuned, a resolution of 124,000 to 171,000 is obtained, a 2- to 3-fold improvement over the resolution of 40,000 to 60,000 without rephasing, at 10 ng/μL reserpine concentration. Such a rephasing capability may ultimately prove useful in implementing tandem mass spectrometry (MS/MS) in the Orbitrap, bringing the Orbitrap\u27s high mass accuracy and resolution to bear on both the precursor and product ions in the same MS/MS scan and making available the collision energy regime of the Orbitrap, ∼1500 eV

Rephasing Ion Packets in the Orbitrap Mass Analyzer to Improve Resolution and Peak Shape

A method is described to improve resolution and peak shape in the Orbitrap under certain experimental conditions. In these experiments, an asymmetric anharmonic axial potential was first produced in the Orbitrap by detuning the voltage on the compensator electrode, which results in broad and multiply split mass spectral peaks. An AC waveform applied to the outer electrode, 180° out of phase with ion axial motion and resonant with the frequency of ion axial motion, caused ions of a given m/z to be de-excited to the equator (z = 0) and then immediately re-excited. This process, termed “rephasing,” leaves the ion packet with a narrower axial spatial extent and frequency distribution. For example, when the Orbitrap axial potential is thus anharmonically de-tuned, a resolution of 124,000 to 171,000 is obtained, a 2- to 3-fold improvement over the resolution of 40,000 to 60,000 without rephasing, at 10 ng/μL reserpine concentration. Such a rephasing capability may ultimately prove useful in implementing tandem mass spectrometry (MS/MS) in the Orbitrap, bringing the Orbitrap\u27s high mass accuracy and resolution to bear on both the precursor and product ions in the same MS/MS scan and making available the collision energy regime of the Orbitrap, ∼1500 eV

Supermultiplexed optical imaging and barcoding with engineered polyynes

Optical multiplexing has a large impact in photonics, the life sciences and biomedicine. However, current technology is limited by a 'multiplexing ceiling' from existing optical materials. Here we engineered a class of polyyne-based materials for optical supermultiplexing. We achieved 20 distinct Raman frequencies, as 'Carbon rainbow', through rational engineering of conjugation length, bond-selective isotope doping and end-capping substitution of polyynes. With further probe functionalization, we demonstrated ten-color organelle imaging in individual living cells with high specificity, sensitivity and photostability. Moreover, we realized optical data storage and identification by combinatorial barcoding, yielding to our knowledge the largest number of distinct spectral barcodes to date. Therefore, these polyynes hold great promise in live-cell imaging and sorting as well as in high-throughput diagnostics and screening

Formation of Maillard Reaction Products in Heat-Treated Torreya grandis cv. Merrilli Seed Oil and Their Effects on Two Analytical Methods for the Determination of Total Phenolics

The occurrence of Maillard reaction in heated Torreya grandis cv. Merrilli seed oil was verified by detecting browning index and the contents of the Maillard reaction products (MRPs) 3-deoxyglucosone, methylglyoxal and 5-(hydroxymethyl)furfural, and the effects of the MRPs on the quantification of total phenolics using the Folin-Ciocalteu and Fast Blue BB assays were explored. The Folin-Ciocalteu assay showed that the content of total phenolics in the oil increased after treatment at 150 ℃ for 90 to 120 min, while the Fast Blue BB assay showed the opposite result. It was also observed that the absorbance of the oil at a wavelength of 294 nm increased after long-term low-temperature or high-temperature heat treatment. 3-Deoxyglucosone (0.21–0.47 μg/g) and 5-(hydroxymethyl)furfural (0.06–0.40 μg/g) were detected only in the 150 ℃ treated oil, while methylglyoxal (0.67–1.73 μg/g) existed in both oil samples. In the Folin-Ciocalteu assay, the absorbance at a wavelength of 765 nm of 3-deoxyglucosone and methylglyoxal linearly increased with an increase in their concentrations, and the decreasing order of the absorbance of the MRPs at the same concentration was 3-deoxyglucosone > methylglyoxal > 5-(hydroxymethyl)furfural. In the presence of 3-deoxyglucosone, the Folin-Ciocalteu result was greater than the actual value, and the degree of interference was not related to the content of total phenolics in samples, but instead was positively correlated with the concentration of 3-deoxyglucosone. In the Fast Blue BB assay, there was no significant difference in absorbance at 420 nm among the three MRPs. For food matrices prone to the formation of 3-deoxyglucosone and methylglyoxal during processing, the Fast Blue BB assay can be selected instead of the Folin-Ciocalteu assay to mitigate the interferences from the two substances in the quantification of total phenolics

Metabolic features of orbital adipose tissue in patients with thyroid eye disease

BackgroundThyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients.MethodThe OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis.ResultsIn our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5′-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies.ConclusionThe findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery

Profiling target engagement and cellular uptake of cRGD-decorated clinical-stage core-crosslinked polymeric micelles

Polymeric micelles are increasingly explored for tumor-targeted drug delivery. CriPec® technology enables the generation of core-crosslinked polymeric micelles (CCPMs) based on thermosensitive (mPEG-b-pHPMAmLacn) block copolymers, with high drug loading capacity, tailorable size, and controlled drug release kinetics. In this study, we decorated clinical-stage CCPM with the αvβ3 integrin-targeted cyclic arginine-glycine-aspartic acid (cRGD) peptide, which is one of the most well-known active targeting ligands evaluated preclinically and clinically. Using a panel of cell lines with different expression levels of the αvβ3 integrin receptor and exploring both static and dynamic incubation conditions, we studied the benefit of decorating CCPM with different densities of cRGD. We show that incubation time and temperature, as well as the expression levels of αvβ3 integrin by target cells, positively influence cRGD-CCPM uptake, as demonstated by immunofluorescence staining and fluorescence microscopy. We demonstrate that even very low decoration densities (i.e., 1 mol % cRGD) result in increased engagement and uptake by target cells as compared to peptide-free control CCPM, and that high cRGD decoration densities do not result in a proportional increase in internalization. In this context, it should be kept in mind that a more extensive presence of targeting ligands on the surface of nanomedicines may affect their pharmacokinetic and biodistribution profile. Thus, we suggest a relatively low cRGD decoration density as most suitable for in vivo application

Orthogonal Covalent Entrapment of Cargo into Biodegradable Polymeric Micelles via Native Chemical Ligation

Polymeric micelles (PMs) are promising platforms for enhanced tissue targeting of entrapped therapeutic agents. Strategies to circumvent premature release of entrapped drugs include cross-linking of the micellar core as well as covalent attachment of the drug cargo. The chemistry employed to obtain cross-linked micelles needs to be mild to also allow entrapment of fragile molecules, such as certain peptides, proteins, oligonucleotides, and fluorescent dyes. Native chemical ligation (NCL) is a mild bio-orthogonal reaction between a N-terminal cysteine residue and a thioester that proceeds under physiological conditions. Here, we designed a trifunctional cross-linker containing two cysteine residues for the micelle core-cross-linking reaction and an azide residue for ring-strained alkyne conjugation of fluorescent dyes. We applied this approach to thermosensitive methoxypolyethylene glycol-b-N-(2-hydroxypropyl)methacrylamide-lactate (mPEG-b-HPMAmLacn) based block copolymers of a core-cross-linked polymeric micelle (CCPM) system by attaching thioester residues (using ethyl thioglycolate-succinic anhydride, ETSA) for NCL cross-linking with the trifunctional cross-linker under physiological conditions. By use of mild copper-free click chemistry, we coupled fluorescent dyes, Sulfo.Cy5 and BODIPY, to the core via the azide residue present on the cross-linker by triazole ring formation. In addition, we employed a recently developed cycloheptyne strain promoted click reagent (TMTHSI, CliCr) in comparison to the frequently employed cyclooctyne derivative (DBCO), both achieving successful dye entrapment. The size of the resulting CCPMs could be tuned between 50 and 100 nm by varying the molecular weight of the thermosensitive block and ETSA content. In vitro cell experiments showed successful internalization of the dye entrapped CCPMs, which did not affect cell viability up to a polymer concentration of 2 mg/mL in PC3 cells. These fluorescent dye entrapped CCPMs can be applied in diagnostic imaging and the chemistry developed in this study serves as a steppingstone toward covalently entrapped fragile drug compounds with tunable release in CCPMs

Supermultiplexed optical imaging and barcoding with engineered polyynes

Optical multiplexing has a large impact in photonics, the life sciences and biomedicine. However, current technology is limited by a 'multiplexing ceiling' from existing optical materials. Here we engineered a class of polyyne-based materials for optical supermultiplexing. We achieved 20 distinct Raman frequencies, as 'Carbon rainbow', through rational engineering of conjugation length, bond-selective isotope doping and end-capping substitution of polyynes. With further probe functionalization, we demonstrated ten-color organelle imaging in individual living cells with high specificity, sensitivity and photostability. Moreover, we realized optical data storage and identification by combinatorial barcoding, yielding to our knowledge the largest number of distinct spectral barcodes to date. Therefore, these polyynes hold great promise in live-cell imaging and sorting as well as in high-throughput diagnostics and screening

Performance characteristics and resonant AC dipolar excitation for ion motion control in the Orbitrap mass analyzer

This thesis describes the prototype form of a powerful mass spectrometer, the Orbitrap, based on a new type of mass analyzer invented by Makarov. Features of the Orbitrap at its present stage of development include high mass resolution (up to 150,000), high mass accuracy (2-5 ppm), a mass/charge range of at least 6000, and a dynamic range greater than 103. Applications based on electrospray ionization are described, including characterization of transition-metal complexes, oligosaccharides, drugs, peptides, and proteins. Use is also made of the high-resolution capabilities of the Orbitrap to confirm the presence of metaclusters of serine octamers in ESI mass spectra and to perform H/D exchange experiments on these ions in the storage quadrupole. Desorption electrospray ionization (DESI) is implemented on the Orbitrap mass spectrometer. The ion source is described and applications which utilize the high resolution capabilities of the Orbitrap are emphasized, including the characterization of peptides and active ingredients in pharmaceutical tablets. Measurements are made in less than 1 second at a resolution of 60,000. The implications of the data for the mechanisms of DESI ionization are discussed. Besides presenting performance characteristics and applications, this thesis demonstrates capabilities to control ion motion in the Orbitrap mass analyzer using resonant ac dipolar waveforms. A dipolar ac signal applied to the split outer electrode of the Orbitrap at the axial resonance frequency causes excitation of ion axial motion and either eventual ion ejection from the trap, if applied in phase with ion motion, or de-excitation, if applied 180° out of phase. Both de-excitation and excitation may be achieved mass-selectively. Degradation of resolution and mass accuracy due to space charge either in the storage quadrupole or during ion injection can be recovered by application of dipolar ac excitation. Rephasing of the ion population after long trapping times in the Orbitrap has been demonstrated and such a capability offers the potential to achieve tandem mass spectrometry in the Orbitrap. Attempts to accomplish tandem mass spectrometry in the Orbitrap by surface-induced dissociation, using collision with the outer electrode of the Orbitrap, were not successful; these experiments are also described