X射线干涉光刻光束线关键光学元件热-结构耦合分析

为了保证上海光源X射线干涉光刻光束线的稳定性,减小热变形对实验结果的影响,对X射线干涉光刻光束线的3个关键光学元件——偏转镜、聚焦镜和精密四刀狭缝进行热-结构耦合分析。首先,计算偏转镜、聚焦镜和精密四刀狭缝所承载的功率密度;然后,建立其有限元模型;最后,获得光学元件的温度场和热变形的结果。结果表明,偏转镜和聚焦镜采用间接水冷方式可有效抑制热变形,冷却后的最大面形误差分别为7.2μrad和9.2μrad。精密四刀狭缝未冷却时,刀片组件温度介于271.56~273.27℃,刀口热变形为0.19 mm,直线导轨热变形为0.08 mm;经过铜辫子冷却后,刀片组件温度降至22.24~23.94℃,刀口热变形降至0.2μm,直线导轨热变形降至0.1μm;采用影像法和接触探头法测试后,刀口直线度、平行度和重复精度均满足技术要求。偏转镜、聚焦镜和精密四刀狭缝的热变形通过间接水冷和铜辫子的冷却方式可以得到很大程度的抑制,进而保证光斑质量。     

Experimental optimization of power-function-shaped drive pulse for stick-slip piezo actuators

Motion of a stick-slip piezo actuator is generally controlled by the parameters related to its mechanical design and characteristics of the driving pulses applied to piezoceramic shear plates. The goal of the proposed optimization method is to find the driving pulse parameters leading to the fastest and the most reliable actuator operation. In the paper the method is tested on a rotary stick-slip piezo actuating system utilized in an atomic force microscope.The optimization is based on the measurement of the actuator response to driving pulses of different shapes and repetition frequencies at various load forces. To provide it, a computer controlled testing system generating the driving pulses, and detecting and recording the corresponding angular motion response of the actuator by a position sensitive photo detector (PSPD) in real time has been developed. To better understand and interpret the experimental results, supportive methods based on a simple analytical model and numerical simulations were used as well.In this way the shapes of the single driving pulses and values of the load force providing the biggest actuator steps were determined. Generally, the maximal steps were achieved for such a combination of the pulse shapes and load forces providing high velocities at the end of the sticking mode of the actuator motion and, at the same time, lower decelerations during the slipping mode.As for the multiple driving pulses, the pulse shapes and values of repetition frequency ensuring the sticking mode of the actuator motion during the pulse rise time together with the maximum average angular rotor velocity were specified. In this way the effective and stable operation conditions of the actuator were provided.In principle, the presented method can be applied for the testing and optimization of any linear or angular stick-slip actuator.     

Coupling in situ experiments and modeling – Opportunities for data fusion,machine learning,and discovery of emergent behavior

This paper reviews recent studies, that not only includes both experiments and modeling components, but celebrates a close coupling between these techniques, in order to provide insights into the plasticity and failure of polycrystalline metals. Examples are provided of studies across multiple-scales, including, but not limited to, density functional theory combined with atom probe tomography, molecular dynamics combined with in situ transmission electron miscopy, discrete dislocation dynamics combined with nanopillars experiments, crystal plasticity combined with digital image correlation, and crystal plasticity combined with in situ high energy X-ray diffraction. The close synergy between in situ experiments and modeling provides new opportunities for model calibration, verification, and validation, by providing direct means of comparison, thus removing aspects of epistemic uncertainty in the approach. Further, data fusion between in situ experimental and model-based data, along with data driven approaches, provides a paradigm shift for determining the emergent behavior of deformation and failure, which is the foundation that underpins the mechanical behavior of polycrystalline materials.     

Thermoplastic and low dielectric constants polyimides based on BPADA-BAPP

ABSTRACT

The thermoplastic and low dielectric constants polyimides were introduced. The polyimides were prepared by pyromellitic dianhydride (PMDA) or 4,4?-(4,4?-Isopropylidenediphenoxy)diphthalic anhydride (BPADA) as anhydride monomer and 4,4?-oxydianiline (ODA) or 2,2-bis(4-(4-aminephenoxy)phenyl)propane (BAPP) as amine monomer. The polyimides were well characterized by FT-IR, thermogravimetric analysis, dynamic thermomechanical analysis, dielectric measurement, and tensile test. The dielectric constants were 2.32–2.95 compared with 3.10 of ODA-PMDA polyimide, while partly polyimides were thermoplastic. The results indicated anhydride monomers, containing lateral methyl groups, made polyimides become thermoplastic. The results of molecular simulations via Materials Studio also proved this conclusion.     

Analysis of Cerebrospinal Fluid Extracellular Vesicles by Proximity Extension Assay: A Comparative Study of Four Isolation Kits

There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood–brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson’s correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

The roles of conceptual modelling in improving construction simulation studies: A comprehensive review

The conceptual modelling phase of simulation studies has proven to be effective in enhancing the impact of simulation modelling in different domains. However, this simulation phase did not receive much attention in the construction simulation domain. The objective of this paper is to identify the roles that conceptual modelling can play in advancing the engagement, accuracy, and adoption (among other things) of discrete-event simulation studies in construction. In this paper, a Systematic Literature Review (SLR) is conducted, which involves a comprehensive search of databases and researchers’ profiles to identify journal papers, conference articles, books, and theses that have reported the benefits of conceptual modelling for discrete-event simulation studies. The review resulted in 82 documents that were published from 2000 to 2020. Results indicate that the benefits of conceptual modelling include facilitating communications between stakeholders, capturing sufficient information for the simulation model, improving the quality of simulation models, guiding other simulation modelling activities, and facilitating verification and validation of simulation models. By linking these benefits to the current research agenda in construction simulation, this paper shows the significance and potential of the conceptual modelling phase to enhance the impact of discrete-event simulation studies in construction.     

CFD Modeling of Active Volume Creation in a Non‐Newtonian Fluid Agitated by Submerged Recirculating Jets

Computational fluid dynamics (CFD) models were employed to investigate flow conditions inside a model reactor in which yield stress non‐Newtonian liquid is mobilized using submerged recirculating jets. The simulation results agree well with the experimental results of active volume in the reactor obtained using flow visualization by the authors in a previous study. The models developed are capable of predicting a critical jet velocity (v_c) that determines the extent of active volume obtained due to jet mixing. The v_c values are influenced both by the rheological properties of the liquid and the nozzle orientation. The liquid with higher effective viscosity leads to higher v_c for a downward facing injection nozzle. However, an upward facing injection nozzle along with a downward facing suction nozzle generates enhanced complementary flow fields which overcome the rheological constraints of the liquid and lead to lower v_c.     

Soret and Dufour effects between two rectangular plane walls with heat source/sink

This study addresses the thermo‐diffusion and the diffusion‐thermo phenomena in a semi‐infinite absorbent channel whose walls are contracting/expanding, with heat source/sink effects. The governing partial differential equations with suitable boundary conditions are transformed to a system of dimensionless ordinary differential equations. An analytic solution of the problem has been found using a technique called homotopy analysis method (HAM). HAM gives consistently valid answers to the problem over an extensive variety of parameters and also provides better accuracy. To validate the analytical results, a comparison has been presented with a numerical solution calculated by using the parallel shooting method. The effects of dimensionless parameters, that is, deformation parameter, Reynolds number, Soret and Dufour numbers, and heat source/sink parameter on the expressions of velocity, temperature, and concentration profiles are analyzed graphically to understand the physics of the deformable channel. It has been noted that the velocity across the channel is higher for the expanding channel, as compared to that for the contracting channel. Also the Soret and Dufour number increases the temperature of the fluid, and decreases the concentration. The temperature profile has an increasing behavior in the case of heat source, and a decreasing behavior in the case of heat sink.