Localized heating of droplets on an electrowetting-on-dielectric (EWOD) chip has been implemented and shown to accelerate trypsin digestion reaction rates, sample drying, and matrix crystallization ...for matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Achieving this involved extending the functionality of previous EWOD droplet-based techniques by developing a multifunctional electrode with closed-loop temperature control, while minimizing overall system complexity and addressing challenges associated with rapid evaporation. For the EWOD chip design, we discuss the performance of multifunctional surface electrodes for actuation, localized Joule heating, and thermistic temperature sensing. Furthermore, a hydrophilic pattern is formed in the multifunctional electrode to control the location of an evaporating droplet on the electrode. To demonstrate the capabilities and limitations of this technique, we performed three experiments and measured the results using MALDI-MS: (i) insulin disulfide reductions in dithiothreitol (DTT) over a range of heater temperatures (22−70 °C) to show how reaction rates can be affected by thermal control, (ii) insulin disulfide reductions at 130 °C in dimethyl sulfoxide (DMSO) to demonstrate a reaction in a high boiling point solvent, and (iii) tryptic digestions of cytochrome c at 22 and 40 °C to show that heated droplets can yield reasonably higher peptide sequence coverage than unheated droplets. Although they do not decouple the effects of changing temperatures and concentrations, these experiments verified that thermal cycling by EWOD electrodes accelerates reaction rates in liquid droplets in air.
We develop a tractable model of realization utility that studies the role of reference-dependent S-shaped preferences in a dynamic investment setting with reinvestment. Our model generates both ...voluntarily realized gains and losses. It makes specific predictions about the volume of gains and losses, the holding periods, and the sizes of both realized and paper gains and losses that can be calibrated to a variety of statistics, including Odean's measure of the disposition effect. Our model also predicts several anomalies, including, among others, the flattening of the capital market line and a negative price for idiosyncratic risk.
To make a molecular design of efficient indoline dyes, fluorescence lifetimes should be longer than ca. 0.8 ns in chloroform, in addition to suitable HOMO and LUMO levels and bathochromic UV-vis ...absorption bands.
Nuclear magnetic resonance (NMR) spectroscopy has provided a unique opportunity to study the characteristic smectic-A to chiral nematic phase transition in a dimesogenic liquid crystal (“KI-5S”). The ...order parameters in the liquid crystalline phases were obtained from the 2H NMR quadrupole splitting and 13C NMR chemical shift measurements, manifesting a first-order smectic-nematic phase transition.
•NMR employed to study smectic-chiral nematic phase transition in a dimesogenic liquid crystal.•Temperature-dependent smectic order parameter obtained by 2H NMR quadrupole splitting.•Order parameters in different phases obtained from 13C NMR chemical shifts.
Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs.
Here we evaluated the ...benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial).
Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD.
We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.
•Nine hundred metastatic urothelial carcinoma patients from the IMvigor211 phase III trial were treated with atezolizumab versus chemotherapy.•A total of 4489 organ-specific measurements were made: 1544 measurements in the lymph, 999 in the lung, 691 in the liver, and 559 locoregionally.•Longer treatment effect was observed in the lung (P value = 0.043) and liver (P = 0.001) lesions under atezolizumab compared to chemotherapy.•Those with a 10-mm growth of liver lesion had their instantaneous risk of death increased by 12%, compared to 5% in the lung.•Treatment effect on overall survival could be predicted based on early organ-specific tumor data 6 months after last patient inclusion.
People homozygous for mutations in the Niemann-Pick type C1 (NPC1) gene have physiological defects, including excess accumulation of intracellular cholesterol and other lipids, that lead to drastic ...neural and liver degeneration. The NPC1 multipass transmembrane protein is resident in late endosomes and lysosomes, but its functions are unknown. We find that organelles containing functional NPC1-fluorescent protein fusions undergo dramatic movements, some in association with extending strands of endoplasmic reticulum. In NPC1 mutant cells the NPC1-bearing organelles that normally move at high speed between perinuclear regions and the periphery of the cell are largely absent. Pulse-chase experiments with dialkylindocarbocyanine low-density lipoprotein showed that NPC1 organelles function late in the endocytic pathway; NPC1 protein may aid the partitioning of endocytic and lysosomal compartments. The close connection between NPC1 and the drug U18666A, which causes NPC1-like organelle defects, was established by rescuing drug-treated cells with overproduced NPC1. U18666A inhibits outward movements of NPC1 organelles, trapping membranes and cholesterol in perinuclear organelles similar to those in NPC1 mutant cells, even when cells are grown in lipoprotein-depleted serum. We conclude that NPC1 protein promotes the creation and/or movement of particular late endosomes, which rapidly transport materials to and from the cell periphery.
A novel electromagnetic bandgap (EBG) power plane etched with multiring complementary split ring resonators (CSRRs) is proposed for effectively suppressing simultaneous switching noise. Its ...equivalent circuit model is derived for predicting its bandwidth numerically. The measured insertion losses, i.e., S21-parameters of the two fabricated samples agree well with the simulated ones obtained by using the commercial software HFSS, respectively. It is shown that –40 dB suppression is achieved over an ultrawideband from 600 MHz to 13.26 GHz, when the two-ring CSRRs EBG power plane is used. While for four-ring CSRRs EBG case, the suppression level can be extended to –60 dB. Comparative studies are also performed on the signal integrity of a pair of differential transmission lines over L-bridge EBG with and without CSRRs, respectively, and similar performance is achieved.
Purpose
The purpose of this study was to investigate the differences in resistance training adaptation on muscle oxygenation between young and elderly subjects. Groups of eleven trained young, ...untrained young, trained elderly, and untrained elderly (UTE) were recruited.
Methods
Muscle oxygenation of the vastus lateralis muscle during 20 % maximal voluntary isometric contraction was observed using near-infrared spectroscopy. The oxygen saturation (SpO
2
) kinetics in the contraction and recovery phases was modeled with a tangential model to extract ΔSpO
2
and inflection time (IF). The median frequencies of SpO
2
data representing the change of tissue oxygenation oscillation were compared.
Results
The ΔSpO
2
values for the trained groups (12.00 ± 7.86 %) were significantly higher than those for the untrained groups (5.91 ± 4.36 %,
P
< 0.05), and those for the young groups (11.63 ± 7.52 %) were significantly higher than those for the older groups (6.29 ± 4.70 %,
P
< 0.05). In the recovery phase, the IF was significantly longer for the elderly groups (10.32 ± 4.39 s,
P
< 0.05) than that for the young groups (6.31 ± 3.69 s). The median frequency of tissue oxygenation oscillation was significantly lower for the TE group (0.41 ± 0.12 Hz,
P
< 0.05) than that for the UTE group (0.57 ± 0.13 Hz).
Conclusions
The increased ΔSpO
2
in trained groups during muscle contraction may be due to lower microvascular O
2
pressure. The lower median frequency for the TE group indicates that tissue oxygenation oscillation significantly trended toward low-frequency oscillation, possibly resulting from the enhancement of vascular function.
Global warming will have direct impacts on regional water resources by accelerating the hydrological cycle. Hydrological simulation is an important approach to studying climate change impacts. In ...this paper, a snowmelt-based water balance model (SWBM) was used to simulate the effect of climate change on runoff in the Kuye River catchment of the Loess Plateau, China. Results indicated that the SWBM is suitable for simulating monthly discharge into arid catchments. The response of runoff in the Kuye River catchment to climate change is nonlinear, and runoff is more sensitive to changes in precipitation than to changes in temperature. The projections indicated that the Kuye River catchment would undergo more flooding in the 2020s, and global warming would probably shorten the main flood season in the catchment, with greater discharge occurring in August. Although projected changes in annual runoff are uncertain, the possibilities of regional water shortages and regional flooding are essential issues that need to be fully considered.
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