Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

Spatio-temporal evolution of the deformation around the Rio-Patras fault (Greece) observed by synthetic aperture radar interferometry from 1993 to 2017

We analysed the ground deformation across two blocks defined by the Rio-Patras fault from 1993 to 2017 using multi-temporal Synthetic Aperture Radar Interferometry (InSAR) techniques. Our main objective was to contribute to the assessment of seismic hazard near the large city of Patras. Multiple data-sets were used, each one covering different temporal periods. Descending and ascending acquisitions, providing different viewing geometries contribute to fully determine the ground displacement in 3D. The data-sets used are from the European Space Agency’s (ESA) European Remote Sensing (ERS), Environmental Satellite (ENVISAT) and SENTINEL-1 as well as German Aerospace Center (DLR) ’s TERRASAR-X missions. Considering ESA’s missions covering both acquisition geometries and long periods, the southern block, showing lack of a sufficient number of scatterers does not allow the displacement characterization. In contrary, the northern block is characterized by a high number of scatterers having values of maximum likehood ranging from ?3.5 to ?4.3 mm year^?1 for ascending geometry and from ?1.6 to ?2.7 mm year^?1 for the descending one. The fact that both geometries show negative values of displacements are consistent with downlift movement and at the same time the quantitative differentiation probably indicates an horizontal component as well.     

On the formation and stability of dislocation patterns—I: One-dimensional considerations

By distinguishing among mobile and immobile dislocations and operating within the framework of continuum mechanics it is possible to derive a set of partial differential equations of the diffusion-reaction type for the evolution of dislocation species. On examining the competition between gradient dependent terms modelling the motion of dislocations and nonlinear terms modelling their interactions, it is shown that stable solutions are possible. The wavelength turns out to be a material property in agreement with observations. The discussion is limited to one dimension, that is to glide of straight dislocations in the slip direction, and the model corresponds physically to the ladder-like structure of persistent slip bands.     

Transplantation for end stage liver disease related to alpha 1 antitrypsin

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.     

Infrared and ultraviolet–visible spectroscopic studies of silica, [(Cp)2ZrCl2] and trimethylaluminum interactions

Infrared and UV–vis studies of metallocene immobilization on silica are reported here. The results have indicated changes in the Zr coordination sphere of metallocene depending on the immobilization route used. The reaction of [(Cp)₂ZrCl₂] with silica formed [(Cp)₂ZrCl]⁺[SiO]⁻ species. The same metallocene, reacting with TMA modified silica, formed monomethylated and dimethylated species by the substitution of chloro for methyl ligands, stabilized on the surface by interaction with “MAO-like” species (methylaluminoxane, MAO). These monomethylated and dimethylated cationic zirconium species are the active centers for the polymerization reaction. Different order of TMA addition in the silica modification step generated surface species of a similar nature, differing in their relative quantities. The highest amount of these active species was obtained when the support was added to the TMA solution rather than adding the TMA solution to the silica support. This was the most significant parameter affecting catalytic activity in ethylene polymerization.     

Dynamic Analysis of Truss‐Beam System

As the manned exploration of space continues, many complex structural components are being developed to construct the orbital platforms that will be used to house communication hardware, personnel, and manufacturing complexes. These components are extremely flexible and complex in their behavior. There is a need for a simple method for determining the dynamic characteristics of these space structures with a minimum of effort. A mathematical model of one of these structural elements, an articulating truss beam, has been developed to predict its dynamic response. Assumptions of the force interaction between the beam elements and the joints have been made for using this model. Algorithms are provided to determine the flexibility matrix of the truss beam for use in the equation of motion. The natural frequencies obtained from using this method are compared with those obtained by the finite element method. An experimental procedure is planned to validate the results from the theoretical method.     

The effect of partial substitution of nb for v on austenite grain size and hardness of a tool steel

In the present work, the composition of H- 13 tool steel was modified with respect to the vanadium content to include an addition of niobium to obtain improved austenite grain size control without altering the tempering response of the steel. Optical metallography and transmission electron microscopy (TEM) observation of extraction replicas showed that the new steel had a smaller austenite grain size and a finer carbide size distribution than the vanadium steel, which indicates a higher potential toughness.     

Optimization techniques for curved path computing

Participating media with an inhomogeneous index of refraction make light follow curved paths. Simulating this in a global illumination environment has usually been neglected due to the complexity of the calculations involved, sacrificing accurate physical simulations for efficient visual results. This paper aims to simulate non-linear media in a more reasonable time than previous works without losing physical correctness. Accuracy is achieved by solving the Eikonal equation of geometrical optics, which describes the path followed by a light beam that traverses a non-linear medium. This equation is used in the context of a photon mapping extension.     

Autoimmune diabetes induced by the beta-cell toxin STZ. Immunity to the 60-kDa heat shock protein and to insulin

Administered at a suitably low dose, the toxin streptozotocin (STZ) can trigger an autoimmune process leading to destruction of the beta-cells of the pancreatic islets. In this study, we examined specific immunological reactions in mice before and during the development of STZ-induced autoimmune diabetes. We now report that the development of spontaneous autoantibodies to insulin can serve as a marker of susceptibility to a low dose of STZ. Susceptible male mice of the C57BL/KsJ strain manifested such anti-insulin antibodies, and resistant female mice did not. Administration of a low dose of STZ (five daily doses each of 30 mg/kg) induced transient hyperglycemia approximately 20-30 days later, which temporarily remitted but was followed by intractable diabetes approximately 2.5 months later. The diabetogenic process triggered by the low dose of STZ was associated with an increase in the level of anti-insulin antibodies bearing the Dana and Micha (DM) idiotype, later followed by the appearance of anti-idiotypic antibodies that peaked before the onset of diabetes. Antibodies and T-cells reactive to hsp60 (heat shock protein) were triggered by the low-dose STZ administration and persisted throughout the period that preceded clinical diabetes. T-cells reactive to the p277 peptide of hsp60 were also observed. Finally, active immunization to hsp60 caused transient hyperglycemia by itself and also aggravated the hyperglycemia induced by low-dose STZ. Thus, autoantibodies to insulin can indicate susceptibility to a toxic trigger of diabetes, and a low dose of a toxin can activate the insulin and hsp60 autoimmunity that has been detected previously in the spontaneous autoimmune diabetes of NOD strain mice.