Sensitivity to chemotherapeutic preparations of anthracycline-resistant strains of murine leukemia P388

P388 leukemia strains resistant to rubomycin and ruboxylnitroxyl derivative of rubomycin were studied for their drug sensitivity. The resistant strains exhibited cross resistance to anthracycline antibiotics, vinca alkaloids, actinomycin D, colchicine. The rubomycin-resistant strain gained significantly higher sensitivity (in comparison with the parent strain and the ruboxyl-resistant strain) to six drugs: cisplatin, sarcolisin, dopan, thiophosphamide, degranol, 6-mercaptopurine. The karyotype of the ruboxyl-resistant cells was characterized by the presence of chromosome with homogeneously straining region (HSR). The alteration of the HSR-location was accompanied by the increase of chemotherapeutical sensitivity of the ruboxylresistant strain to the alkylating agents.     

Characteristics of anthracycline-resistant strains of P388 leukemia

Two strains of P388 murine leukemia with acquired resistance to rubomycin (P388/rm) and its nitroxyl derivative ruboxyl (P388/rx). The rubomycin resistance has been developed by the 14th generation and ruboxyl one-by the 8th generation. The growth kinetic patterns and the cell cycle time of the parent and resistant strains were similar. An increased tumourogenicity of both resistant strains cells was found. The resistance development was accompanied by the appearance of the additional chromosome materials, namely of homogeneously staining region (P388/rx) and of double chromatin bodies (P388/rm). The partial recovery of sensitivity to rubomycin occurred during 36 generations (1 year). Simultaneously the genetic markers have been lost. The recovery of sensitivity to ruboxyl in this period was not observed. The obtained resistant strains possessed the multidrug resistance: the cross resistance of P388/rm and P388/rx to actinomycin D, Vinca alkaloids and colchicine was shown.     

Changes in the chemotherapy sensitivity of leukemia L1210 cells during the development of diazan resistance

L 1210 leukemia strain resistant to diazan (L 1210/D1) was studied for its drug sensitivity in comparison with the parent strain. The resistant strain exhibited significantly higher sensitivity to nine drugs: dopan, sarcolysine, apirazidin, cyclophosphane, 6-mercaptopurine, thiophosphamide, rubomycin, vinblastine and vincristine. L 1210/D1 gained cross resistance to four drugs: 1-(2-chloroethyl)-3-(2, 6-dioxy-3-piperidyl)-1-nitrosourea, methotrexate, 5-fluorouracil and ftorafur. The resistant strain sensitivity remained unchanged (in comparison with the parent strain) to seven drugs: degranol, prospidin, nitrosomethylurea, chlorozotocin, deazauridine, bleomycin and L-asparaginase (crasnitine).     

Ribamidyl (ribavirin) as a modulator of the biological action of arabinosylcytosine and methotrexate

Administration of ribamidyl (Rb) prior to Ara-C to intact mice or mice with implanted tumours enhanced Ara-C toxicity. The growth of tumours (plasmacytoma MOPC-21, adenocarcinoma of the small intestine (strain AKATON), mammary adenocarcinoma 755 (Ca 755) resistant to Ara-C or Rb was inhibited after coadministration of these drugs. The augmentation of toxic and antitumour effects of Ara-C by Rb is similar to the described effect of high doses of thymidine. This is in accordance with the enhancement of the intracellular pool of thymidine phosphates under the action of Rb. The toxicity of methotrexate in vivo was increased by coadministration with Rb. This effect may be connected with a decrease in purine precursors pool under the action of Rb.     

Achieving Outstanding Mechanical Performance in Reinforced Elastomeric Composite Fibers Using Large Sheets of Graphene Oxide

A simple fiber spinning method used to fabricate elastomeric composite fibers with outstanding mechanical performance is demonstrated. By taking advantage of the large size of as‐prepared graphene oxide sheets (in the order of tens of micrometers) and their liquid crystalline behavior, elastomeric composite fibers with outstanding low strain properties have been fabricated without compromising their high strain properties. For example, the modulus and yield stress of the parent elastomer improved by 80‐ and 40‐fold, respectively, while maintaining the high extensibility of ～400% strain inherent to the parent elastomer. This outstanding mechanical performance was shown to be dependent upon the GO sheet size. Insights into how both the GO sheet size dimension and dispersion parameters influence the mechanical behavior at various applied strains are discussed.     

Role of intracellular pH in the development of resistance of leukemic cells to antineoplastic drugs

Intracellular pH (pHi) of mouse lymphoid leukemia P388 cells was measured at the wavelength of 518 and 570 nm of fluorescein: pHi of rubomycin-sensitive P388 cells was higher than pHi of the cells resistant to this antitumour antibiotic (6.98 +/- 0.04 and 6.63 +/- 0.03, respectively, P less than 0.001). The role of pHi is established during induction of the resistance of tumour cells to the antitumour drugs.     

Effect of 1,2-dimethylhydrazine on the estrous cycle in different strains of mice

CBA, C3HA, C57Bl, Balb/c and DBA female mice received 20 subcutaneous weekly injections of 1,2-dimethylhydrazine in the dose of 8 mg/kg body weight. Estrous cycles were studied in vaginal smears taken 5, 10, 15 and 20 weeks after the 1st DMH injection. In CBA strain susceptible to DMH induction of uterine sarcomas a persistent estrus was observed in 50% of mice after 5 to 10 DMH injections. In C3HA, C57B1, Balb/c and DBA strains resistant to the DNH induction of uterine sarcomas persistent estrus was not observed; the majority of these mice retained a normal estrus cycle. Persistent diestrus which was absent in susceptible CBA mice was found in these resistant strains. No CBA females with a normal estrous cycle were observed after the beginning of DMH treatment. The differences in the estrous cycle found in the mouse strains treated with DMH may partly explain the observed strain differences in the susceptibility to the DMH induction of uterine sarcomas.     

Study of the biotransformation of various antineoplastic agents using the Ames test

The Ames test on indicator bacteria S. typhimurium TA 1950 and TA 100 and the differential spectrophotometry have shown that cytochrome P-450-dependent monooxygenases of mammalian liver participate in the metabolism of antitumour drugs (cyclophosphamide, thiophosphamide) and of nitrosomorpholine (promutagen). Data concerning prospidin indicate that microsomal liver enzymes either induce no metabolic transformations of this preparation or the formed metabolites possess the mutagenic activity similar to that of the parent compound.     

Dealloying in Individual Nanoparticles and Thin Film Grains: A Bragg Coherent Diffractive Imaging Study

Dealloying is a process whereby selective dissolution results in a porous, strained structure often with new properties. The process is of both intrinsic and applied interest, and recently has been used to make highly active catalysts. The porosity has been studied using electron microscopy while the dealloying‐induced strain has been studied at the ensemble level using X‐ray diffraction. Despite the importance of local, for example, at the individual particle or grain level, strain in controlling the properties of the dealloyed material, it remains unresolved due to the difficulty of imaging 3D strain distributions with nanometer resolution in reactive environments. This information could play an integral role in understanding and controlling lattice strain for a variety of applications. Here, 3D strain distributions in individual nanoparticles and thin film grains in silver–gold alloys undergoing nitric acid‐induced dealloying are imaged by Bragg coherent diffractive imaging. Particles exhibit dramatic changes in their local strains due to dealloying but grains do not. The average lattice in both grains and particles contracts during dealloying. In general, the results reveal significant dealloying‐induced strain heterogeneity at the nanoscale in both isolated and extended samples, which may be utilized to develop advanced nanostructures for a variety of important applications.     

Residual elongations of submarine optical-fiber cable laid on the sea bottom

Fiber elongations during laying and residual fiber-elongation strain after laying of submarine optical-fiber cables have been reported. The fiber elongations have been measured by the optical-pulse-delay method. It has been found that the residual fiber-elongation strains are closely related to cable slack and the cable tension at the sea bottom. Therefore, the residual strains can be minimized by controlling the slack and the tension. The relation between necessary proof-test strain and allowed residual strain has also been mentioned. If the proof-test strain is 1 percent, the allowed residual strain due to laying becomes 0.26 percent.     

Comparative analysis of the sensitivity to natural killers and macrophages of 3-methylcholanthrene-induced tumors in mice

The sensitivity of 3 primary and 13 continuous tumour cell cultures 11 of which were induced with 20-methylcholanthrene to natural killer cells and cytotoxic macrophages has been tested. It is shown that the sensitivity of target cells varies markedly to both types of effector cells and that the level of susceptibility correlates with transplantability of tumour cells but not with their growth rate in syngeneic animals. Cells with high or zero transplantable capacity proved to be resistant, while cells with intermediate transplantability were sensitive to nonspecific immunity effector cells.     

2D Percolation Design with Conductive Microparticles for Low‐Strain Detection in a Stretchable Sensor

Although a variety of stretchable strain sensors based on electrical percolation have been reported, stretchable sensors detecting low strains have been rarely demonstrated. This is because large stretchability of a strain sensor conflicts with high strain resolution at low strains. Here, the electrical percolation into 2D is confined and a strain sensor that is highly sensitive at low strains and simultaneously highly stretchable is presented. The 2D confinement of the electrical percolation is accomplished by a close‐packed monolayer assembly of conductive microparticles (MPs) on an elastomer substrate. The current profiles of the MP monolayer at low strains are in situ visualized using conductive atomic force microscopy. When the lattice of the MP monolayer is aligned vertically to the strain direction, the resistance is highly sensitive to low‐strain deformations (ε = 0 – 0.05), but the sensor has reasonable stretchability (ε = 0.3). The simultaneous achievement of the high sensitivity at low strains and the reasonable stretchability is explained by the relationship between the strain‐dependent current profile and the relative position changes of the MPs. A high‐precision pulse sensor clearly showing the representative peaks is demonstrated.     

Dual‐Targeting to Cancer Cells and M2 Macrophages via Biomimetic Delivery of Mannosylated Albumin Nanoparticles for Drug‐Resistant Cancer Therapy

Multidrug resistance (MDR) is an issue that is not only related to cancer cells but also associated with the tumor microenvironments. MDR involves the complicated cancer cellular events and the crosstalk between cancer cells and their surroundings. Ideally, an effective system against MDR cancer should take dual action on both cancer cells and tumor microenvironments. The authors find that both the drug‐resistant colon cancer cells and the protumor M2 macrophages highly express two nutrient transporters, i.e., secreted protein acidic and rich in cysteine (SPARC) and mannose receptors (MR). By targeting SPARC and MR, a system can act on both cancer cells and M2 macrophages. Herein the authors develop a mannosylated albumin nanoparticles with coencapsulation of different drugs, i.e., disulfiram/copper complex (DSF/Cu) and regorafenib (Rego). The results show that combination therapy of DSF/Cu and Rego efficiently inhibits the growth of drug‐resistant colon tumor, and the combination has not been reported yet for use in anticancer treatment. The system significantly improves the treatment outcomes in the animal model bearing drug‐resistant tumors. The therapeutic mechanisms involve enhanced apoptosis, upregulation of intracellular ROS, anti‐angiogenesis, and tumor‐associated macrophage “re‐education.” This strategy is characterized by dual targeting to and the simultaneous action on cancer cells and M2 macrophages, with biomimetic codelivery of a novel drug combination.     

Cytogenetic characteristics of the leukemia L1210 strain in the development of drug resistance

The dose and schedule dependent resistance occurred at the 17th (L1210/D1) and 27th (L1210/D2) generations during leukemia L1210 transplantation by the cells treated with suboptimal diazane doses. With growth of the resistance to diazane the selection of modal cell class with 39 chromosomes took place while in the parent leukemia line the modal cell class consists of the cells with 40 chromosomes. No reliable differences were observed in G-banded karyotypes between the resistant subline L1210/D1 and the parent line L1210. When the resistant sublines were transplanted without supporting the diazane doses no restoration of the leukemic cells sensitivity to the drug was observed (the time of observation for L1210/D1 was 92 transplantation generations and for L1210/D2-48 generations). The changed number chromosome characteristics remained the same in this case.     

Electronic packaging solder joint reliablity assessment with a mechanics-based StrainGage methodology

It is essential to understand solder joint strains to improve package reliability. However, it is often difficult to measure the true solder joint strains directly. Strain gages have been increasingly used by component suppliers and original equipment manufacturers (OEMs) to indicate package mechanical stress levels. One of the most used strain gage locations is on the component side, right next to the package corner. A concern with this location alone is that the strain gages mounted close to the package pick up the local stress concentration near the package edges or corners. In this paper, appropriate strain gage locations are suggested based on mechanics principles and finite element simulation results. An analytical methodology is developed to determine the solder joint deformations from strain gage readings at various locations. This paper also proposes a new strain matching criterion. Most OEMs have been using maximum principal strain to match stress levels and define critical strain limits. A problem with maximum principal strain is that it does not indicate the direction along which the maximum bending occurs. Experimental data demonstrates that the new strain criterion has much better correlation to solder joint failure than maximum principal strains in various bend modes. The conclusions apply to any strain gage mounting metrology on packages attached to printed circuit boards.     

Real-time regularized ultrasound elastography

This paper introduces two real-time elastography techniques based on analytic minimization (AM) of regularized cost functions. The first method (1D AM) produces axial strain and integer lateral displacement, while the second method (2D AM) produces both axial and lateral strains. The cost functions incorporate similarity of radio-frequency (RF) data intensity and displacement continuity, making both AM methods robust to small decorrelations present throughout the image. We also exploit techniques from robust statistics to make the methods resistant to large local decorrelations. We further introduce Kalman filtering for calculating the strain field from the displacement field given by the AM methods. Simulation and phantom experiments show that both methods generate strain images with high SNR, CNR and resolution. Both methods work for strains as high as 10% and run in real-time. We also present in vivo patient trials of ablation monitoring. An implementation of the 2D AM method as well as phantom and clinical RF-data can be downloaded.     

Effect of surface lipopolysaccharide on the nature of membrane vesicles liberated from the Gram-negative bacterium Pseudomonas aeruginosa

Membrane vesicles (MVs) were isolated from three isogenic lipopolysaccharide (LPS) mutants derived from the Gram-negative bacterium Pseudomonas aeruginosa PAO1 and compared with the parent strain. Parent cells possessed serotype 05 (A+B+) LPS whereas the three mutants contained A+B-, A-B+ and A-B-. The MVs from the mutants contained their expected phenotypic LPS and varied in size, especially A-B- MVs. Mass and total protein differences were also noted. When the parent and mutant cells were treated with the outer membrane-perturbing antibiotic gentamicin, all cells produced 3-5 times more MVs and these had great variation in size, mass and total protein. It is concluded that the type of cellular LPS affects both the natural and gentamicin-induced development of MVs.     

不锈钢部件失效分析中的EBSD应用

本文利用EBSD和EDS对不锈钢部件的点腐蚀进行了失效分析。通过EBSD对样品弯曲部位沿横断面的应变及织构的分析发现,部件在加工过程中造成了局部的织构变化,弯曲部位内表面主要是铜织构。由于铜织构致使部件表面由非密排面组成,因此导致AISI304L不锈钢部件在弯曲内表面出现点腐蚀。     

Mechanisms of deformation in high-ductility Ce-containing Sn-Ag-Cu solder alloys

Rare-earth-containing Pb-free solders have gained widespread attention due to their superior ductility relative to conventional Pb-free alloys. Our previous work has shown that new Ce-based alloys are also extremely oxidation resistant compared to La or Y-containing alloys. In this paper, we report on a mechanism-based model for the large increases in ductility with small addition of rare-earth element to Sn-3.9Ag-0.7Cu. The mechanisms of ductility enhancement by Ce were observed in a scanning electron microscope, in interrupted shear-tests, where CeSn₃ particles served as microscopic fracture and void nucleation sites. Micro-mechanical modeling using the finite-element method was used to examine the plastic strain field in solder affected by the particles. The concentrated deformation band was seen to be disturbed by the particles, resulting in a more uniform deformation pattern with reduced strains and thus enhanced ductility of the lap-sheared joint.