Calcium-41 (t(1/2) = 10(5) years) can be used after a single dose to follow calcium metabolism over a subject's lifetime. The aims of this study were to expand a (41)Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance for the design and interpretation of (41)Ca studies. Forty-two women >5 years post-menopause were given (41)Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ~5 years while subjects were free living. Urinary (41)Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (n = 13), studied previously in a 3-week balance and full kinetic study with (45)Ca, agreed with those using (41)Ca methodology. Thus, rates of bone resorption can be estimated from (41)Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation. 相似文献
We present a simple analytic formalism to explain the unique resonance phenomenon in subwavelength high-contrast gratings (HCG). We show that the resonances are due to strong coupling between two surface-normal waveguide array modes resulting from abrupt and large index contrast. Simple expression for HCG quality factor is derived that agrees with spectral-fitting approaches reported in literature. 相似文献
Rocket‐like vesicles formed are composed of poly(acrylic aicd) (PMAA )/poly(ethylene glycol) (PEG) complex coated hollow silica spheres, and the structure and composition of the vesicles are characterized using TGA, 1H NMR, FTIR, and TEM. Although only one‐third of EG units of PEG brushes grafted to hollow silica spheres form the complex with PMAA via hydrogen bonding, the first “booster” layer composed of PMAA/PEG complex can provide secure encapsulation of model compound calcein blue under an acidic condition. The second “booster” layer composed of PEG brushes can be formed by changing acidic pH to 7.4 through the disassociation of the PMAA/PEG complex. A higher molecular weight PMAA exhibits a faster disassembly due to the formation of a looser PMAA/PEG complex on the surfaces of hollow silica spheres.
Employing a quartz crystal microbalance (QCM) as a MHz-viscoelastic sensor requires extracting information from higher harmonics beyond the Sauerbrey limit, which can be problematic for rubbery polymer films that are highly dissipative because of the onset of anharmonic side bands and film resonance. Data analysis for QCM can frequently obscure the underlying physics or involve approximations that tend to break down at higher harmonics. In this study, modern computational tools are leveraged to solve a continuum physics model for the QCM's acoustic shear wave propagation through a polymer film with zero approximations, retaining the physical intuition of how the experimental signal connects to the shear modulus of the material. The resulting set of three coupled equations are solved numerically to fit experimental data for the resonance frequency Δfn and dissipation ΔΓn shifts as a function of harmonic number n, over an extended harmonic range approaching film resonance. This allows the frequency-dependent modulus of polymer films at MHz frequencies, modeled as linear on a log–log scale, to be determined for rubbery polybutadiene (PB) and polydimethylsiloxane (PDMS) films, showing excellent agreement with time–temperature shifted rheometry data from the literature. 相似文献
The synthesis of a zwitterionic Pd(II) complex supported by an anionic bis(phosphino)borate ligand, Ph(2)B(CH(2)PPh(2))(2) (abbreviated as [Ph(2)BP(2)]), is reported. The new complex, [Ph(2)BP(2)]PdMe(THF), is active for CO and ethylene copolymerization. The copolymerization activity and polyketone molecular weight for the neutral, zwitterionic system are compared with those for the cationic systems [R(2)E(CH(2)PPh(2))(2)PdMe(THF)][B(C(6)F(5))(4)] where ER(2) = SiPh(2) and CH(2). Surprisingly, the more electron rich zwitterionic system is a catalyst of activity comparable to that of the more conventional cationic systems. 相似文献
We consider a class of continuous non-linear systems defined by the ordinary differential equation x = f(x, t) + g(x, t)u, where u is an unknown input representing noise or disturbances. The object is to estimate states and parameters in these systems by means of a fixed number of discrete observations yi = h(x(ti), ti) + vi, 1 ? i ? m, where the vi represents unknown errors in the measurements yi. No statistical assumptions are made concerning the nature of the unknown input u or the unknown measurement errors vi. A weighted least squares criterion is defined as a measure of the optimal estimate. A result concerning the existence of solutions of the differential equation which minimize the criterion is presented. The necessary conditions for an optimal estimate, a set of Euler-Lagrange equations and multi-point discontinuous non-linear boundary conditions, are given. The multi-point problem is converted to an equivalent continuous two-point boundary value problem of larger dimension in the case in which the observations are assumed to be linear functions of the state. A pair of equivalent quasilinearization algorithms is defined for the two-point system and the multi-point system. Quadratic convergence for these algorithms is proved. 相似文献
It has been proposed that the clinical accuracy of distortion product otoacoustic emissions (DPOAEs) is affected by the interaction of distortion and reflection sources contributing to the response. This study evaluated changes in dichotomous-decision test performance and threshold-prediction accuracy when DPOAE source contribution was controlled. Data were obtained from 205 normal and impaired ears with L(2) ranging from 0 to 80 dB SPL and f(2)=2 and 4 kHz. Data were collected for control conditions (no suppressor, f(3)) and with f(3) presented at three levels that previously had been shown to reduce the reflection-source contribution. The results indicated that controlling source contribution with a suppressor did not improve diagnostic accuracy (as reflected by relative operating characteristic curve area) and frequently resulted in poorer test performance compared to control conditions. Likewise, correlations between DPOAE and behavioral thresholds were not strengthened when using the suppressors to control source contribution. While improvements in test accuracy were observed for a subset of subjects (normal ears with the smallest DPOAEs and impaired ears with the largest DPOAEs), the lack of improvement for the larger, unselected subject group suggests that DPOAEs should be recorded in the clinic without attempting to control the source contribution with a suppressor. 相似文献
We report the design and synthesis of a series of new 5-chloropyridinyl esters of salicylic acid, ibuprofen, indomethacin, and related aromatic carboxylic acids for evaluation against SARS-CoV-2 3CL protease enzyme. These ester derivatives were synthesized using EDC in the presence of DMAP to provide various esters in good to excellent yields. Compounds are stable and purified by silica gel chromatography and characterized using 1H-NMR, 13C-NMR, and mass spectral analysis. These synthetic derivatives were evaluated in our in vitro SARS-CoV-2 3CLpro inhibition assay using authentic SARS-CoV-2 3CLpro enzyme. Compounds were also evaluated in our in vitro antiviral assay using quantitative VeroE6 cell-based assay with RNAqPCR. A number of compounds exhibited potent SARS-CoV-2 3CLpro inhibitory activity and antiviral activity. Compound 9a was the most potent inhibitor, with an enzyme IC50 value of 160 nM. Compound 13b exhibited an enzyme IC50 value of 4.9 µM. However, it exhibited a potent antiviral EC50 value of 24 µM in VeroE6 cells. Remdesivir, an RdRp inhibitor, exhibited an antiviral EC50 value of 2.4 µM in the same assay. We assessed the mode of inhibition using mass spectral analysis which suggested the formation of a covalent bond with the enzyme. To obtain molecular insight, we have created a model of compound 9a bound to SARS-CoV-2 3CLpro in the active site. 相似文献
Statins have displayed significant, although heterogeneous, anti-tumour activity in breast cancer disease progression and recurrence. They offer promise as a class of drugs, normally used for cardiovascular disease control, that could have a significant impact on the treatment of cancer. Understanding their mode of action and accurately assessing their efficacy on live cancer cells is an important and significant challenge. Stimulated Raman scattering (SRS) microscopy is a powerful, label-free imaging technique that can rapidly characterise the biochemical responses of live cell populations following drug treatment. Here, we demonstrate multi-wavelength SRS imaging together with spectral phasor analysis to characterise a panel of breast cancer cell lines (MCF-7, SK-BR-3 and MDA-MB-231 cells) treated with two clinically relevant statins, atorvastatin and rosuvastatin. Label-free SRS imaging within the high wavenumber region of the Raman spectrum (2800–3050 cm−1) revealed the lipid droplet distribution throughout populations of live breast cancer cells using biocompatible imaging conditions. A spectral phasor analysis of the hyperspectral dataset enables rapid differentiation of discrete cellular compartments based on their intrinsic SRS characteristics. Applying the spectral phasor method to studying statin treated cells identified a lipid accumulating phenotype in cell populations which displayed the lowest sensitivity to statin treatment, whilst a weaker lipid accumulating phenotype was associated with a potent reduction in cell viability. This study provides an insight into potential resistance mechanisms of specific cancer cells towards treatment with statins. Label-free SRS imaging provides a novel and innovative technique for phenotypic assessment of drug-induced effects across different cellular populations and enables effective analysis of drug–cell interactions at the subcellular scale.Stimulated Raman scattering microscopy with spectral phasor analysis provides a label-free approach for phenotypic evaluation of drug-induced effects.相似文献