Reactions of cisplatin and oxaliplatin with penicillin G : implications for drug inactivation and biological activity

Determination of the toxicity of compounds toward cancer cells is a frequent procedure in drug discovery. For metal complexes, which are often reactive prodrugs, care has to be taken to consider reactions with components of the cell culture medium that might change the speciation of the metal complex before it is taken up by the cells. Here, we consider possible reactions between the clinical platinum drugs cisplatin and oxaliplatin with penicillin G, an antibiotic added routinely to cell culture media to prevent bacterial contamination. Platinum has a high affinity for ligands with sulfur donors. Penicillin G is an unstable thioether that degrades in a range of pathways. Nuclear magnetic resonance (NMR) and UV–Vis absorption spectroscopic studies show that reactions with cisplatin can occur within minutes to hours at 310 K, but more slowly with oxaliplatin. The identities of the Pt- adducts were investigated by mass spectrometry. The marked effect on cytotoxicity of co-incubation of cisplatin with penicillin G was demonstrated for the HeLa human cervical cancer cell line. These studies highlight the possibility that reactions with penicillin G might influence the cytotoxic activity of metal complexes determined in culture media

Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling

Cyclic adenosine diphosphate (ADP)–ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD+) hydrolysis. We show that v-cADPR (2′cADPR) and v2-cADPR (3′cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2′cADPR-producing TIR domains reveal conformational changes that lead to an active assembly that resembles those of Toll-like receptor adaptor TIR domains. Mutagenesis reveals a conserved tryptophan that is essential for cyclization. We show that 3′cADPR is an activator of ThsA effector proteins from the bacterial antiphage defense system termed Thoeris and a suppressor of plant immunity when produced by the effector HopAM1. Collectively, our results reveal the molecular basis of cADPR isomer production and establish 3′cADPR in bacteria as an antiviral and plant immunity–suppressing signaling molecule

The Indirect Adaptive Feed-Forward Control in Magnetic Bearing Systems for Minimizing Selected Vibration Performance Measures

To attenuate synchronous disturbances in magnetic bearing systems, a number of approaches have been used, including both adaptive feed-forward and feedback approaches. In practice it is generally preferred to use feed-forward techniques as they have less effect on system stability. One method of feed-forward disturbance attenuation that has been proposed is the application of adaptive filtering techniques to minimize the magnitude of the magnetic bearing system error signal. This will be referred to as "indirect" method for synchronous disturbance attenuation

Performance Investigation of a Micro Magnetic Bearing Through Modelling and Simulation

This paper is devoted to the modelling and simulation of a prototype micro magnetic bearing system. A dynamic model for the system is developed and used in simulation for investigating effects of key design parameters. A number of important nonlinearities and dynamics that are usually ignored in simplified linear analysis but are important in the micro bearing system, have been included in the model. Extensive simulation have been carried out, providing valuable information for designing the actuators and control systems. Some testing results of the protoype micro magnetic bearings are also included in the paper

The Direct Method for Adaptive Feed-Forward Vibration Control of Magnetic Bearing Systems

As the actuators of active magnetic bearings (AMB) are open loop unstable a feedback control system is essential for their successful operation and for ensuring good performance. In addition, when rotor systems utilizing AMBs are operated at high speeds there will be synchronous vibrations due to unavoidable rotor mass unbalances, which generate synchronous disturbance forces. These forces and vibrations can often lead to severe problems in rotating machines including collision with the touchdown bearings at high speed and the possible risk of causing damage to the internal parts of the machines. In this paper, a new ''direct" adaptive feedforward algorithm is proposed for minimizing selected vibration performance measures which is based on the filtered-x LMS adaptive filter algorithm. This new adaptive algorithm has been used for adjusting the amplitude and phase of a synchronous signal injected at the summing junction of the bearing feedback control loop. The experimental results reported in this work show the effectiveness of the proposed method

Effects of the Damping Parameters on the Opening and Closing Characteristics of Vent Valves

The main function of the vent valve is to release part of the air at the outlet of the axial compressor to prevent engine surges. The damping parameters have an important effect on the opening and closing characteristics of the vent valve. The control characteristics of each component were obtained by finite element analysis and testing. The overall model of a two-stage partial pressure vent valve was established, and the reliability of the model was verified by testing. The opening and closing characteristics of the damper valve with different damping parameters were obtained by parametric simulation. The results show that there was a pressure mutation point in the middle support pressure and the pressure in the control chamber during operation of the vent valve, which made the valve open and close quickly. The damping hole of the middle shell and the middle nozzle of the support had the greatest influence on the open-close pressure ratio. The damping hole and nozzle of the middle shell had the greatest influence on the opening and closing stability. The results are used to guide the structural design, and the analytical method provides a theoretical basis for research of the same type of valve

A 5-lncRNA Signature Associated with Smoking Predicts the Overall Survival of Patients with Muscle-Invasive Bladder Cancer

Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a P value 15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation

Broadband convolutional scattering characteristics of all dielectric transmission Pancharatnam–Berry geometric phase metasurfaces

In order to obtain the broadband scattering characteristics, we propose a superperiodic cell structure with all-dielectric material to construct Pancharatnam–Berry geometric phase encoding metasurfaces. Because we cannot design or prepare infinitesimal coding unit particles, according to the generalized Snell’s law, we can only obtain discrete scattering angle regulation for the basic coding metasurface sequence. In order to obtain multi-angle scattering characteristics, we introduce the Fourier convolution principle in digital signal processing on the Pancharatnam–Berry geometric phase encoding metasurfaces. By using the addition and subtraction operations on two encoding metasurface sequences, a new encoding metasurface sequence can be obtained with different deflection angle. Fourier convolution operations on the encoding metasurfaces can provide an efficient method in optimizing encoding patterns to achieve continuous scattering beams. The addition and subtraction methods are also applicable to the checkerboard coding mode. The combination of Fourier convolution principle and Pancharatnam–Berry phase coded metasurface in digital signal processing can realize more powerful electromagnetic wave manipulation capability

Patterns and controls of ecosystem service values under different land-use change scenarios in a mining-dominated basin of northern China

Exploring future land use/cover change (LULC) and ecosystem service values (ESV) dynamics is crucial for sustainable development from regional to global scales. However, ESV dynamics is significantly affected by economic development and policy changes, and future projections of ESV are generally characterized by large uncertainties due to complexity in LULC dynamics. Mining activities are supposed to exert significant effects on ESV dynamics, while the patterns and controls of ESV in mining-dominated basins are still less understood, especially under different land-use scenarios. Here, based on multi-source remote sensing data and land-use data in the Fenhe River Basin, we integrated the SD model, Markov model and PLUS model to simulate LULC in the Fenhe River Basin under four scenarios, i.e., the economic development priority (EDP), natural development priority (ND), cultivated land protection priority (CLP), and ecological protection priority (EPP). Based on ESV equivalent coefficient method and geographical detector, we further determined the patterns and controls of ESV. Results showed that construction land and cultivated land were mainly concentrated in the central parts of the basin, and grassland and woodland were concentrated in the edge area of the basin. Over the past two decades, construction land and woodland have experienced significant expansion, while the areas of grasslands and cultivated lands have declined due to mining activities. The high-value and sub-high-value areas of ESV were concentrated in woodland, grassland, reservoir and concentrated water area of mainstream and tributary. The low-value area was mainly located in the gathering area of construction land. The total ESV showed a downward trend with time, and the highest decline in the total ESV under the four land use scenarios was the EDP, while the lowest drop was the EPP. The highest contribution rate of ESV was woodland, which was equivalent to the contribution rate of cultivated land, grassland and water area, totally accounting for 58.54% of the whole ESV. The geographical detector method indicated that distance to the residential area, soil erodibility, distance to the river, soil type and annual average temperature were the main driving factors affecting the spatial patterns of ESV. Our results highlighted the fundamental role of mining activity in affecting LULC characterized by grassland and cultivated land shrinkage, and suggested that mining areas rehabilitation should be given priority in terms of further improving ESV in mining-dominated basins