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Calcified aortic valve stenosis (CAVS) is caused by calcium buildup and tissue thickening that impede the blood flow from left ventricle (LV) to aorta. In recent years, CAVS has become one of the most common cardiovascular diseases. Therefore, it is necessary to study the mechanics of aortic valve (AV) caused by calcification. In this paper, based on a previous idealized AV model, the hybrid immersed boundary/finite element method (IB/FE) is used to study AV dynamics and hemodynamic performance under normal and calcified conditions. The computational CAVS model is realized by dividing the AV leaflets into a calcified region and a healthy region, and each is described by a specific constitutive equation. Our results show that calcification can significantly affect AV dynamics. For example, the elasticity and mobility of the leaflets decrease due to calcification, leading to a smaller opening area with a high forward jet flow across the valve. The calcified valve also experiences an increase in local stress and strain. The increased loading due to AV stenosis further leads to a significant increase in left ventricular energy loss and transvalvular pressure gradients. The model predicted hemodynamic parameters are in general consistent with the risk classification of AV stenosis in the clinic. Therefore, mathematical models of AV with calcification have the potential to deepen our understanding of AV stenosis-induced ventricular dysfunction and facilitate the development of computational engineering-assisted medical diagnosis in AV related diseases.

The manual identification and segmentation of intracranial aneurysms (IAs) involved in the 3D reconstruction procedure are labor-intensive and prone to human errors. To meet the demands for routine clinical management and large cohort studies of IAs, fast and accurate patient-specific IA reconstruction becomes a research Frontier. In this study, a deep-learning-based framework for IA identification and segmentation was developed, and the impacts of image pre-processing and convolutional neural network (CNN) architectures on the framework's performance were investigated. Three-dimensional (3D) segmentation-dedicated architectures, including 3D UNet, VNet, and 3D Res-UNet were evaluated. The dataset used in this study included 101 sets of anonymized cranial computed tomography angiography (CTA) images with 140 IA cases. After the labeling and image pre-processing, a training set and test set containing 112 and 28 IA lesions were used to train and evaluate the convolutional neural network mentioned above. The performances of three convolutional neural networks were compared in terms of training performance, segmentation performance, and segmentation efficiency using multiple quantitative metrics. All the convolutional neural networks showed a non-zero voxel-wise recall (V-Recall) at the case level. Among them, 3D UNet exhibited a better overall segmentation performance under the relatively small sample size. The automatic segmentation results based on 3D UNet reached an average V-Recall of 0.797 ± 0.140 (3.5% and 17.3% higher than that of VNet and 3D Res-UNet), as well as an average dice similarity coefficient (DSC) of 0.818 ± 0.100, which was 4.1%, and 11.7% higher than VNet and 3D Res-UNet. Moreover, the average Hausdorff distance (HD) of the 3D UNet was 3.323 ± 3.212 voxels, which was 8.3% and 17.3% lower than that of VNet and 3D Res-UNet. The three-dimensional deviation analysis results also showed that the segmentations of 3D UNet had the smallest deviation with a max distance of +1.4760/-2.3854 mm, an average distance of 0.3480 mm, a standard deviation (STD) of 0.5978 mm, a root mean square (RMS) of 0.7269 mm. In addition, the average segmentation time (AST) of the 3D UNet was 0.053s, equal to that of 3D Res-UNet and 8.62% shorter than VNet. The results from this study suggested that the proposed deep learning framework integrated with 3D UNet can provide fast and accurate IA identification and segmentation. Published version This research was funded by the National Natural Science Foundation of China (NSFC) (12272289, 12271440).

Previous research has shown that people are more averse to uncertainty caused by conflicting but precise information (conflictive uncertainty) than uncertainty caused by consistent but imprecise information (ambiguous uncertainty), which is termed conflict aversion (Cabantous 2007; Cabantous et al, 2011; Smithson, 1999). A pilot study showed that source credibility was likely to be the mediator between information conflict and aversion to conflictive uncertainty. In this first study (https://archive.org/details/osf-registrations-83ker-v1), we found evidence about the effect of source credibility on people's aversion to uncertainty. However, we didn't find evidence for conflict aversion. We suspect that this absence of evidence of conflict aversion can be due to sampling error. Thus, this is a direct replication of the first study.

The forced binary choice question, certainty equivalent, and matching probability are three common measures of preferences in decision making research. However, little is known about their convergent validity. A low convergent validity may make the conclusion inconsistent and incomparable across different studies. Therefore, it is important to verify the convergent validity of measures. This study uses these three measures (forced binary choice question, certainty equivalent, and matching probability) to measure people's attitudes towards two different uncertain choices (ambiguous choice, and conflictive choice).

The forced binary choice question, certainty equivalent, and matching probability are three common measures of preferences in decision making research. However, little is known about their convergent validity. A low convergent validity may make the conclusion inconsistent and incomparable across different studies. Therefore, it is important to verify the convergent validity of measures. This study uses these three measures (forced binary choice question, certainty equivalent, and matching probability) to measure people's attitudes towards two different uncertain choices (ambiguous choice, and conflictive choice).

Previous research has shown that people are more averse to uncertainty caused by conflicting but precise information (conflictive uncertainty) than uncertainty caused by consistent but imprecise information (ambiguous uncertainty), which is termed conflict aversion (Cabantous 2007; Cabantous et al, 2011; Smithson, 1999). A pilot study showed that information credibility was likely to be the mediator between information conflict and aversion to conflictive uncertainty. In this first study (https://archive.org/details/osf-registrations-83ker-v1), we found evidence about the effect of information credibility on people's aversion to uncertainty. However, we didn't find evidence for conflict aversion. The comparative ignorance hypothesis may explain why (Fox & Tversky, 1995). The first study is a between-subjects design where participants only face one kind of uncertainty. In contrast, participants in previous studies are exposed to both kinds of uncertainty, which may create a comparison between them (Cabantous 2007; Cabantous et al, 2011; Smithson, 1999). When comparing both kinds of uncertainty, the relatively low credibility of conflicting but precise information could motivate participants to show aversion to conflictive uncertainty. When the comparison disappears, people may have similar attitudes toward ambiguous and conflictive uncertainty. However, we are not sure about other possibilities, because the first study also differs in covered scenarios and presentation of conflictive uncertainty from previous studies (Cabantous 2007; Cabantous et al, 2011; Smithson, 1999). Therefore, this study will replicate the first study except that the type of uncertainty is manipulated within-subjects. It aims to test whether people will show conflict aversion when presenting with both kinds of uncertainty in the same scenarios and presentations.

Previous research has shown that people are more averse to uncertainty caused by conflicting but precise information (conflictive uncertainty) than uncertainty caused by consistent but imprecise information (ambiguous uncertainty), which is termed conflict aversion (Cabantous 2007; Cabantous et al, 2011; Smithson, 1999). A pilot study showed that information credibility was likely to be the mediator between information conflict and aversion to conflictive uncertainty. Here, information conflict refers to the inconsistency between information which makes them unable to be true at the same time, while information credibility refers to the subjective perception of the truthiness of the information. The aversion to uncertainty is measured by matching probability. Higher matching probability stands for less aversion, vice versa. This study aims to test this mediation relationship by intervening in the information credibility. The intervention is to manipulate the source credibility. Source credibility represents the extent to which audience members perceive a communicator as someone whose words or interpretations they would benefit from believing. The research question is: Can the change in information credibility (e.g., by increasing or decreasing the source credibility) influence people’s perceived degree of uncertainty and behavioral aversion towards conflictive uncertainty?

Due to high ramping rates on the Booster Ring (BRing), which is the key part of the high-intensity heavy-ion accelerator facility (HIAF) complex at the Institute of Modern Physics (IMP), thin-wall vacuum chambers are required for all magnets to maintain the eddy currents at a tolerable level. A novel thin-wall vacuum chamber supported by ceramic rings was discussed and evaluated for the HIAF at the IMP to reduce the manufacturing cost, reduce the difficulty, shorten the production cycle, and improve the quality. Because the beam coupling impedance aspects are highly important for beam stability, several approaches were used to evaluate the impedance on the ceramics-loaded tube. In this article, we describe the results from the single- and two-wire bench measurements and the numerical simulations. The simulated and measured impedance results are consistent with each other. Several effective methods to mitigate the impedance were proposed and investigated in detail. According to the simulation and measurement results of the beam coupling impedance mitigation, this novel ceramic-ring copper-coated thin-wall vacuum chamber structure will be considered for application to the HIAF project with the highest priority.

Supplemental material, sj-docx-1-mac-10.1177_00202940221089501 for Estimation and simulation for route choice proportion in multi-period urban rail transit control systems by Yiyuan Yang, Ranran Sun, Peiyue Wang, Yang Yi and Guangyu Zhu in Measurement and Control

We consider the problem of sequential multiple hypothesis testing with nontrivial data collection cost. This problem appears, for example, when conducting biological experiments to identify differentially expressed genes in a disease process. This work builds on the generalized $α$-investing framework that enables control of the false discovery rate in a sequential testing setting. We make a theoretical analysis of the long term asymptotic behavior of $α$-wealth which motivates a consideration of sample size in the $α$-investing decision rule. Posing the testing process as a game with nature, we construct a decision rule that optimizes the expected return (ERO) of $α$-wealth and provides an optimal sample size for the test. Empirical results show that a cost-aware ERO decision rule correctly rejects more false null hypotheses than other methods. We extend cost-aware ERO investing to finite-horizon testing which enables the decision rule to allocate samples across many tests. Finally, empirical tests on real data sets from biological experiments show that cost-aware ERO produces actionable decisions to conduct tests at optimal sample sizes., 12 pages, 4 figures, 5 tables

Supplemental material, sj-docx-1-mac-10.1177_00202940221089501 for Estimation and simulation for route choice proportion in multi-period urban rail transit control systems by Yiyuan Yang, Ranran Sun, Peiyue Wang, Yang Yi and Guangyu Zhu in Measurement and Control

A novel type of perforated travelling wave pick-up/kicker structure was developed for CSRe stochastic cooling which was originally proposed by F. Caspers at CERN. The simulated and measured results of shunt impedance of the slotted travelling wave pickup electrode are in reasonable agreement. In December 2015 stochastic cooling of heavy ions was successfully applied for the first time at the CSRe storage ring of IMP in Lanzhou, China. During four days of commissioning, transverse and longitudinal cooling could be observed. Both the time-of-flight and the notch filter methods were used for longitudinal cooling. The measured cooling rates are presented.

A noninvasive Ionization profile monitor (IPM) consisting of micro-channel plates, a phosphor screen and the optical-signal acquisition has been developed at the cooling storage ring of Heavy Ion Research Facility in Lanzhou (HIRFL-CSR). It makes the real-time profile measurements for the transverse beam cooling and orbit oscillation possible and efficient. This paper firstly describes all the IPM design criterions including the theoretical signal yield calculation, the space charge field and initial momentum evaluation, and the electrostatic field distortion simulation as well. In order to investigate the IPM performance, the beam profile measurements are done with different high voltage settings. Subsequently, some valuable beam experiments about the transverse electron cooling and orbit oscillation study are also presented. In the end, fast turn-by-turn profile measurements for the emittance blow-up research in a synchrotron are discussed. In cooperation with the newly deployed emittance instruments at the HIRFL-CSR injector, the IPM shows great prospects for the injection mismatch study, and potential values for the tune, dispersion and chromaticity measurements as well.

The transverse broadband impedances of major components in the BRing (booster ring) of HIAF (High Intensity Heavy-ion Accelerator Facility) are estimated using the analytical formulas or the wakefield solver in the CST Studio Suite. At low frequency, the transverse broadband impedance model of BRing is ${Z}_{1}^{H}(\ensuremath{\omega})=\ensuremath{-}417.14i\text{ }\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}(\mathrm{horizontal})$ and ${Z}_{1}^{V}(\ensuremath{\omega})=\ensuremath{-}530.19i\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}(\mathrm{vertical})$, which are larger than the threshold impedance for the transverse mode-coupling instability. The ceramic rings in the vacuum chamber are the primary source of impedance. With a goal of mitigating the instability by reducing the impedance of ceramic rings, a high conductivity coating is discussed in detail. In addition, a prototype of ceramic rings-loaded thin-wall vacuum chamber is manufactured and the impedance measurements are performed. When ceramic rings are coated by $2\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$-copper, the CST simulation and experiment results show that the transverse broadband impedance of ceramic rings-loaded thin-wall vacuum chamber can be reduced from ${Z}_{1}^{H}(\ensuremath{\omega})=\ensuremath{-}291.69i\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$ and ${Z}_{1}^{V}(\ensuremath{\omega})=\ensuremath{-}352.37i\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$ to ${Z}_{1}^{H}(\ensuremath{\omega})=\ensuremath{-}46.16i\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$ and ${Z}_{1}^{V}(\ensuremath{\omega})=\ensuremath{-}64.56i\text{ }\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$. Furthermore, in this case the transverse broadband impedance model of BRing is reduced by more than 50% to ${Z}_{1}^{H}(\ensuremath{\omega})=\ensuremath{-}171.61i\text{ }\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$ and ${Z}_{1}^{V}(\ensuremath{\omega})=\ensuremath{-}242.38i\text{ }\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}/\mathrm{m}$.

By regulating the order of monomer addition, four kinds of copolymer polyimides (PIs) were prepared using diethylene glycol dimethyl ether (DEGDE) and N, N-dimethylacetamide (DMAc) as the solvents. The molecular weights of polyamide acids (PAAs) ranged from 3.8 × 105 to 9.2 × 105. All of the films displayed high glass transition temperatures ( Tgs) ranging from 313°C to 346°C. The polymer films show excellent thermal stabilities with 5% weight loss at temperatures of 505–524°C and char yields at 800°C were as high as 55% under nitrogen. The peel strengths of flexible copper (Cu) clads were in the range from 0.337 N cm−1 to 0.598 N cm−1. Compared to the molecular weight and peel strength of fresh PAA, those of PAAs prepared using DMAc significantly decreased after storage for 3 months at 0°C. However, when DEGDE was used as the solvent, the molecular weights of the PAAs and the thermal properties of the PIs were maintained after long storage time.

The High Intensity heavy-ion Accelerator Facility (HIAF) is under construction. The lattice of HIAF/BRing is the same for both heavy ion beams and proton beam. Since the proton beam will cross the transition energy during acceleration, a γt jump scheme with maximum Δ γt of 2 is designed to reduce the growth of momentum spread and influence of collective effects near transition. The broadband impedance of the ceramic-lined rings in the vacuum chamber has been significantly reduced by a 2 μm-copper coating. Thus, the impedance model has been updated for analyzing collective effects in the BRing. The longitudinal collective effects can be compensated by the multi-harmonic feedforward system. The transition energy crossing point should be optimized to reduce the bunch oscillations after transitions. In both two transverse planes, the normalized emittance growth given by the Simulation Platform for Collective Instabilities (CISP) are stopped by the broadband impedance near transition and there is no obvious transverse collective instability, which is quite different from the Vlasov results. More researches will be performed to find out the reason.

Polyimide (PI)@copper (Cu) composite nano particles have been successfully synthesized from poly(amic acid) triethylamine salts (PAAS) and Cu(II) ions via a one-step high-temperature induction/imidization route. The formation of PI@Cu nano particles has been investigated by the stoichiometric ratio of PAAS and Cu ion. The resulting products, formed stable shell-core structures, exhibited the uniform core-size and thick shell layer. Additionally, the multi-layer structure, Ag@PI@Cu, was successfully prepared via a post process of PI@Cu nanoparticles. The morphology of the formed “Sunflower-mode” structure, with the pistil of Cu, the sunflower seed of PI, and the petal of Ag, was also characterized by SEM and TEM. Both electrical resistivity and thermal conductivity of nano particles were measured. The coefficient of heat conduction of Ag@PI@Cu is even 255 times, 754 times, 3081 times, and 1310 times as large as PI@Cu in 50 °C, 100 °C, 150 °C, and 200 °C, respectively. The resistance of both nano particles is that the result of RsPI@Cu and RsAg@PI@Cu is 11.0*109 Ω and 0.11 Ω, respectively, and also the difference between them is more than 1012.

The development, performance, and testing of the longitudinal bunch shape monitor, namely, the Fast Faraday Cup (FFC), are presented in this paper. The FFC is an invasive instrument controlled by a stepper motor, and its principle of operation is based on a strip line structure. The longitudinal bunch shape was determined by sampling a small part of the beam hitting the strip line through a 1-mm hole. The rise time of the detector reached 24 ps. To accommodate experiments that utilize high-intensity beams, the materials of the bunch shape monitor were chosen to sustain high temperatures. Water cooling was also integrated in the detector system to enhance heat transfer and prevent thermal damage. We also present an analysis of the heating caused by the beam. The bunch shape monitor has been installed and commissioned at the China ADS proton LINAC Injector II.

Recently, soil contamination by heavy metals in farmland has become a severe problem. In this study, a novel assessment method of heavy metal pollution based on reactive heavy metals (RHMs) was introduced. RHMs showed strong correlation with soil profile and land use, distinctly different from the variation of total heavy metals. According to modified geoaccumulation and Hakanson index, farmlands in study area were certainly polluted by various heavy metals, but had low ecological risk. RHMs were greatly influenced by soil properties such as nitrogen, phosphorus, organic matter (OM), pH, moisture content, cation exchange capacity (CEC), electrical conductivity, inorganic anion, and soil texture. Freundlich-type empirical models were developed by combining pH, OM, CEC, total phosphorus, and clay for sufficiently robust and accurate prediction of RHM contents in farmland. The absolute principal component score with multiple linear regression (APCS-MLR) model was used to quantify sources of RHMs in farmland. Agricultural production (water-fertilizer management practice and fertilizer/pesticide use) was the major influence on RHMs with contributions greater than 50% for Fe, Cu, Zn, Pb, and As. Industrial activity, traffic emission, and soil erosion should be also given special attentions because of their great influence on soil RHM contents.

The category of rational mixed Hodge-Tate structures is a mixed Tate category. So thanks to the Tannakian formalism, it is equivalent to the category of finite dimensional graded comodules over a graded commutative Hopf algebra H over Q. Since the category has homological dimension 1, the Hopf algebra H is isomorphic to the commutative graded Hopf algebra provided by the tensor algebra of the graded vector space given by the direct sum of the groups C/Q(n) over n>0. However this isomorphism is not natural in any sense, e.g. does not work in families. We give a natural explicit construction of the Hopf algebra H. Generalizing this, we define a Hopf dg-algebra related to any dg-algebra R over a field k, equipped with an invertible line k(1). When R is the sheaf of algebras given by the holomorphic de Rham complex of a complex manifold X, and the line is Q(1), the related Hopf dg-algebra describes a dg-model of the derived category of variations of Hodge-Tate structures on X. Its cobar complex provides a dg-model for the rational Deligne cohomology of X. We consider a variant of our construction which starts from Fontaine's crystalline / semi-stable period rings and produces graded / dg Hopf algebras, which we relate to the p-adic Hodge theory., Dedicated to Alexander Beilinson, for his 60th birthday. Version 4 is a major revision: the p-adic part in Section 5 is new. To appear in the special volume of Selecta Mathematica

Multi-parameter one-sided hypothesis test problems arise naturally in many applications. We are particularly interested in effective tests for monitoring multiple quality indices in forestry products. Our search reveals that there are many effective statistical methods in the literature for normal data, and that they can easily be adapted for non-normal data. We find that the beautiful likelihood ratio test is unsatisfactory, because in order to control the size, it must cope with the least favorable distributions at the cost of power. In this paper, we find a novel way to slightly ease the size control, obtaining a much more powerful test. Simulation confirms that the new test retains good control of the type I error and is markedly more powerful than the likelihood ratio test as well as many competitors based on normal data. The new method performs well in the context of monitoring multiple quality indices.

For a bunched beam, the signals on pickups are coherent, providing a signal power proportional to the square of the number of particles. For a coasting beam the individual particle signals have a random phase; therefore, the overall signal is proportional to the particle number N. As a consequence, Schottky signals are often relatively weak and have to compete with many noise sources. For a small number of particles, the S/N is always a problem. To achieve a high signal-to-noise ratio and better temporal resolution, which could yield important physical information about fast processes, a resonant pickup was developed at GSI (Nolden et al., 2011 [1] ), and a similar device is now installed in the CSRe [2] at IMP. This device will be used for nuclear mass and lifetime measurement, as well as other uses. The final goal of the pickup is to detect single particles. In Dec 2012, we performed an experiment with a 112Sn50+ beam with an energy of 253 MeV/u, and the single particle sensitivity of the pickup was successfully confirmed. This paper presents hardware measurements of the pickup as well as beam measurements.

The terminal equipment costs associated with electronic multiplexing can comprise of a dominating percentage of the total network costs in today's backbone wavelength-division-multiplexed (WDM) synchronous optical network (SONET) ring networks. The deployment of wavelength add-drop multiplexers (WADM) allows certain wavelengths to optically bypass the nodes without being electronically terminated, thus can effectively reduce the total equipment costs if connections and channels are appropriately assigned in traffic grooming. This paper presents a series of wavelength assignment algorithms with the objective to optimize the number of required wavelengths and SONET add-drop multiplexers in both unidirectional and bi-directional rings under an arbitrary grooming factor. In our analysis, we have considered both uniform and non-uniform all-to-all network traffic. As a simple model for realistic traffic pattern, a special case of non-uniform traffic, distance-dependent traffic is analyzed in detail. Significant ADM savings are reported for different traffic scenarios using our proposed algorithms.

Beam Position Monitors (BPMs) for the low-beta beam of the Chinese Accelerator Driven Subcritical system (CADS) Proton linac are of the capacitive pick-up type. They provide higher output signals than that of the inductive type. This paper will describe the design and tests of the capacitive BPM system for the low-beta proton linac, including the pick-ups, the test bench and the read-out electronics. The tests done with an actual proton beam show a good agreement between the measurements and the simulations in the time domain.

An accelerator-driven subcritical system (ADS) project was launched in China in 2011, aiming to design and build an ADS demonstration facility with the capability of more than 1000 MW thermal power. The driver linac is defined to be a 10 mA current of high energy protons at 1.5 GeV in continuous wave operation mode. To meet the extremely high power and intense beam accelerator requirements, non-interceptive monitors for the beam transverse profile are required for this proton linac. Taking advantage of the residual gas as active material, the Beam Induced Fluorescence (BIF) monitor exploits gas-excited fluorescence in the visible spectrum region for transverse profile measurements. The advantages of this non-intercepting method are that nothing is installed in the vacuum pipe, component design is compact and there is no need for expensive signal processing electronics. Beam experiments have been performed under constant beam conditions. The helium spectrum has been verified with different optical filters, showing that a proper optical band-pass filter covering 400–500 nm is necessary for fluorescence experiments with helium. By changing gas pressure, it is shown that gas pressure is proportional to the signal amplitude but has no influence on detected profile width. Finally, a comparison experiment between the BIF monitor and a wire scanner shows that the detected profile width results of both methods agree well.

Cisplatin is a widely used anticancer drug that acts by binding DNA and causing the formation of intrastrand and interstrand (ICL) crosslinks, but the precise downstream effects of the latter damage are not well understood. In this study, we investigated the influence of cisplatin ICLs on synthetic nucleosomes that were platinated in a site-specific manner in vitro and on gene transcription in live mammalian cells. Nucleosome core particles that we constructed contained site-specific cisplatin 5′-d(G*pC)/5′-d(G*pC) ICLs, where the asterisk denotes the platinated nucleoside, to examine the influence of platinum lesions on the dynamic behavior of nucleosomes in solution. A cisplatin ICL, but not a 1,2-d(GpG) crosslink, significantly inhibited ATP-independent histone octamer-DNA sliding. We also used a novel linearization-recircularization strategy described here to synthesize mammalian expression vectors containing site-specific cisplatin ICLs. Plasmid vectors were tested in live mammalian cells to study the transcription inhibition effects of cisplatin ICLs in the context of two different repair backgrounds. Cisplatin ICLs inhibit transcription as effectively as 1,2-d(GpG) crosslinks. We determined that nucleotide excision repair plays a key role in the removal of cisplatin ICLs, acting in a replication-independent fashion. We also found that loss of mismatch repair function dramatically attenuates the transcription inhibition effects by cisplatin ICLs but not 1,2-d(GpG) intrastrand crosslinks. Our results revealed the unique properties of cisplatin ICLs on nucleosome mobility and on transcription, and they defined how these adducts act in a manner completely different from that used for cisplatin 1,2-d(GpG) crosslinks. These new findings provide direct support for a role of ICLs in the pharmacologic activities of cisplatin, despite the lower frequency of their formation., National Cancer Institute (U.S.) (Grant CA034992)

Resistance of tumor cells to platinum anticancer agents poses a major problem in cancer chemotherapy. One of the mechanisms associated with platinum-based drug resistance is the enhanced capacity of the cell to carry out nucleotide excision repair (NER) on platinum-damaged DNA. Endonucleases XPF and XPG are critical components of NER, responsible for excising the damaged DNA strand to remove the DNA lesion. Here, we investigated possible consequences of down-regulation of XPF and XPG gene expression in osteosarcoma cancer cells (U2OS) and the impact on cellular transcription and DNA repair. We further evaluated the sensitivity of such cells toward the platinum anticancer drugs cisplatin and oxaliplatin., National Cancer Institute (U.S.) (Grant Number CA034992.), National University of Singapore., German Academic Exchange Service (DAAD)