Osteosarcoma (OS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to ...aggressive phenotype and metastasis. The proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined. To link metastatic propensity to a hypoxia-induced proteotype, we compared the protein profiles of two isogenic canine OS cell lines, POS (low metastatic) and HMPOS (highly metastatic), under normoxia and hypoxia. Label-free shotgun proteomics was applied to comprehensively characterize the hypoxia-responsive proteome profiles in the OS cell phenotypes. Hypothesis-driven parallel reaction monitoring was used to validate the differential proteins observed in the shotgun data and to monitor proteins of which we expected to exhibit hypoxia responsiveness, but which were absent in the label-free shotgun data. We established a "distance" score (|z
- z
|), and "sensitivity" score (|z
- z
) to quantitatively evaluate the proteome shifts exhibited by OS cells in response to hypoxia. Evaluation of the sensitivity scores for the proteome shifts observed and principal component analysis of the hypoxia-responsive proteins indicated that both cell types acquire a proteome that supports a Warburg phenotype with enhanced cell migration and proliferation characteristics. Cell migration and glucose uptake assays combined with protein function inhibitor studies provided further support that hypoxia-driven adaption of pathways associated with glycolytic metabolism, collagen biosynthesis and remodeling, redox regulation and immunomodulatory proteins typify a proteotype associated with an aggressive cancer cell phenotype. Our findings further suggest that proteins involved in collagen remodeling and immune editing may warrant further evaluation as potential targets for anti-metastatic treatment strategies in osteosarcoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The reliability and stability of the seal at the fuel-supply end of a rocket-engine turbopump are important factors in determining safety. Conventional single-stage floating rings used for the ...isolation-sealing of cryogenic media are highly susceptible to operational instability during startup and shutdown, which places demands on the seals’ structure, size, and material properties. In this study, a two-stage floating-ring isolation seal with a non-slotted main sealing surface was designed using a tangential air-intake mode. Based on the full-size three-dimensional finite-volume model, the leakage characteristics of the floating ring during operation were calculated, taking into account the effect of the “inlet effect” on the seal’s performance. Combining the temperature and pressure distributions of the sealing system under cryogenic operating conditions, calculated using a numerical simulation, a reliability analysis of various inlet directions and two kinds of floating-ring schemes was carried out on a self-constructed service-performance test bench. The results indicate that the main wear location of the non-slotted floating ring occurs on the auxiliary sealing surface, with stable working performance. When the inlet direction and spindle-rotation direction are the same, this is more conducive to ensuring the stability of seal performance in practical applications. The results of the current research are instructive for designing floating-ring isolation seals for turbine pumps.
A high-neutron yield platform imploded by a thin shell target is generally built to probe nuclear science problems, and it has the advantages of high neutron yield, ultrashort fusion time, micro ...fusion zone, isotropic and monoenergetic neutron. Some analytical models have been proposed to interpret exploding-pusher target implosion driven by a long wavelength laser, whereas they are imperfect for a 0.35 μm laser implosion experiment. When using the 0.35 μm laser, the shell is ablated and accelerated to high implosion velocity governed by Newton’s law, ablation acceleration and quasi-adiabatic compression models are suitable to explain the implosion of a laser direct-drive thin shell target. The new analytical model scales bang time, ion temperature and neutron yield for large variations in laser power, target radius, shell thickness, and fuel pressure. The predicted results of the analytical model are in agreement with experimental data on the Shenguang-III prototype laser facility, 100 kJ laser facility, Omega, and NIF, it demonstrates that the analytical model benefits the understanding of experiment performance and optimizing the target design of high neutron yield implosion.
Two neutron time-of-flight (nToF) detectors have been employed to measure the neutron time-of-flight spectrum in different lines-of-sight, i.e., at the equator plane and the south pole, on ...Shenguang-III (SG-III) laser facility. The contribution of scattered neutrons has been calculated with the Monte Carlo code JMCT for each nToF detector. The results show that the scattered neutron spectrum is dominated by neutrons scattered on materials in the experiment hall, including the vacuum chamber. The shape of the scattered neutron spectrum depends on the view line, which has been observed with nToF detectors located in the experiment hall of the SG-III laser facility. A method based on the convolution of the calculated neutron time-of-flight spectrum and the instrument response function has been developed for the ion temperature determination. The calculated neutron spectra with the contribution of scattered neutrons can fit the measured results. No obvious ion temperature anisotropy has been observed on the SG-III laser facility at present.
Coronary microvascular dysfunction (MVD) is a syndrome of abnormal regulation of vascular tone, particularly during increased metabolic demand. While there are several risk factors for MVD, some of ...which are similar to those for coronary artery disease (CAD), the cause of MVD is not understood. We hypothesized that MVD in symptomatic non-elderly subjects would be characterized by specific lipidomic profiles. Subjects (n = 20) aged 35–60 years and referred for computed tomography coronary angiography (CTA) for chest pain but who lacked obstructive CAD (>50% stenosis), underwent quantitative regadenoson stress-rest myocardial contrast echocardiography (MCE) perfusion imaging for MVD assessment. The presence of MVD defined by kinetic analysis of MCE data was correlated with lipidomic profiles in plasma measured by liquid chromatography and high-resolution mass spectrometry. Nine of twenty subjects had evidence of MVD, defined by reduced hyperemic perfusion versus other subjects (beta-value 1.62 ± 0.44 vs. 2.63 ± 0.99 s−1, p = 0.009). Neither the presence of high-risk but non-obstructive CAD on CTA, nor CAD risk factors were different for those with versus without MVD. Lipidomic analysis revealed that patients with MVD had lower concentrations of long-carbon chain triacylglycerols and diacylglycerols, and higher concentrations of short-chain triacylglycerols. The diacylglycerol containing stearic and linoleic acid classified all participants correctly. We conclude that specific lipidomic plasma profiles occur in MVD involving saturated long-chain fatty acid-containing acylglycerols that are distinctly different from those in non-obstructive CAD. These patterns could be used to better characterize the pathobiology and potential treatments for this condition.
A series of biodegradable polyesters have been prepared from sebacic acid (SA), glycol (Go) and glycerol (Ge) through a two-step process. First the linear prepolymers were prepared from SA and Go, ...then crosslinked polyesters were obtained from the prepolymer and Ge with different molar ratios. The resulting samples were characterized by Fourier Transform Infrared Spectrum (FTIR), X-ray Photoelectron Spectroscopy (XPS), and Differential Scanning Calorimetry (DSC). Dynamic Contact Angle tests (DCA) and mechanical tests were also investigated. The enzymatic degradation studies were performed at 37
°C in phosphate buffer solution with porcine pancreas lipase. The resultant polyesters were transparent, flexible, insoluble in organic solvents, and the surfaces of the polyesters were hydrophilic. Young’s modulus, tensile strength, glass transition temperature (
T
g) and the degree of enzymatic degradation increased with increasing the content of Ge. It was also worth noticing that the surface content of –COOC– groups was a key factor in the enzymatic degradability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The neutron time-of-flight (nTOF) detector, which is based on bibenzyl, an organic crystal scintillator with low afterglow, is used to diagnose the fuel areal density of target capsules by measuring ...the down-scattered neutron ratio. This paper presents a method for calibrating the sensitivity of bibenzyl scintillation detectors to 1–5 MeV down-scattered neutrons. The distributions of detector sensitivity are analyzed using the Monte-Carlo method. The analysis shows that most light output of neutrons below 5 MeV comes from recoil protons. Therefore, the sensitivity of the back-scattered neutron can be calculated with the 2.45 MeV neutron sensitivity and the relative responses of the 1–5 MeV protons. These responses are calibrated using a deuterium-deuterium implosion neutron source at a 100-kJ laser facility and a monoenergetic proton beam at a Van de Graaf accelerator, respectively. The total uncertainty of the calibration for 1–5 MeV neutron sensitivity ranges from 5% to 9%. This calibration method provides accurate measurements for the broad-spectrum neutron sensitivity of scintillation detectors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In recent years, quantitative proteomic research attracts great attention because of the urgent needs in biological and clinical research, such as biomarker discovery and verification. Currently, ...mass spectrometry (MS) based bottom up strategy has become the method of choice for proteomic quantification. In this strategy, the amount of proteins is determined by quantifying the corresponding proteolytic peptides of the proteins, therefore highly efficient and complete protein digestion is crucial for achieving accurate quantification results. However, the digestion efficiency and completeness obtained using conventional free protease digestion is not satisfactory for highly complex proteomic samples. In this work, we developed a new type of immobilized trypsin using hairy noncross-linked polymer chains hybrid magnetic nanoparticle as the matrix aiming at ultra fast, highly efficient proteomic digestion and facile 18O labeling for absolution protein quantification. The hybrid nanoparticle is synthesized by in situ growth of hairy polymer chains from the magnetic nanoparticle surface using surface initiated atom transfer radical polymerization technique. The flexible noncross-linked polymer chains not only provide large amount of binding sites but also work as scaffolds to support three-dimensional trypsin immobilization which leads to increased loading amount and improved accessibility of the immobilized trypsin. For complex proteomic samples, obviously increased digestion efficiency and completeness was demonstrated by 27.2% and 40.8% increase in the number of identified proteins and peptides as well as remarkably reduced undigested proteins residues compared with that obtained using conventional free trypsin digestion. The successful application in absolute protein quantification of enolase from Thermoanaerobacter tengcongensis protein extracts using 18O labeling and MRM strategy further demonstrated the potential of this hybrid nanoparticle immobilized trypsin for high throughput proteome quantification.
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IJS, KILJ, NUK, PNG, UL, UM
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