Supra-nutritional selenium supplementation has emerged as an attractive new approach to intervene in a range of human cancers, in particular prostate cancer. However, scanty information is currently ...available on molecular mechanisms underlying selenium's anticancer action. The tumor suppressor p53 plays an important role in preventing transformation by transcriptional regulation of a range of genes that are involved in vital cell functions such as DNA repair, cell cycle arrest, and induction of apoptosis. Here we report that incubation of LNCaP human prostate cancer cells (p53 +/+) with a natural form of selenium triggers rapid transcriptional activation of p53, and up-regulation of the expression of p53-target genes as well as induction of miR-34 class of microRNAs. Moreover, blocking p53 function by transfection of cells with a dominant-negative, mutated p53 gene, or by siRNA, significantly reduced selenium-induced expression of p53-target genes and induction of apoptosis. Since majority of the early-stage human prostate cancers bear functional p53 gene (p53+/+), our findings indicate that the anticancer action of selenium may involve transactivation of p53 as a potential mechanism, and suggest that selenite may be useful not only for prevention but also for treatment of human prostate cancer.
Pathways mediated by p53 and Rb are frequently altered in aggressive human cancers, including prostate carcinoma. To test directly the roles of p53 and Rb in prostate carcinogenesis, we have ...conditionally inactivated these genes in the prostate epithelium of the mouse. Inactivation of either p53 or Rb leads to prostatic intraepithelial neoplasia developing from the luminal epithelium by 600 days of age. In contrast, inactivation of both genes results in rapidly developing (median survival, 226 days) carcinomas showing both luminal epithelial and neuroendocrine differentiation. The resulting neoplasms are highly metastatic, resistant to androgen depletion from the early stage of development, and marked with multiple gene expression signatures commonly found in human prostate carcinomas. Interestingly, gains at 4qC3 and 4qD2.2 and loss at 14qA2-qD2 have been consistently found by comparative genomic hybridization. These loci contain such human cancer-related genes as Nfib, L-myc, and Nkx3.1, respectively. Our studies show a critical role for p53 and Rb deficiency in prostate carcinogenesis and identify likely secondary genetic alterations. The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis of human prostate cancer.
The mass production of metallic components requires high agility in the working process conditioned by the necessity of building details of different shapes and sizes. Changing the size of the ...components theoretically influences the thermal dissipation capability of the same, which could lead to a change in their structure and mechanical properties. This is particularly important when aluminum alloys are concerned. For this reason, two Al5356 single-track specimens were built using the same technological conditions of layer deposition by varying only their geometrical size. In all cases, the specimens were wire and arc additively manufactured (WAAM) using a process based on gas metal arc welding (GMAW) in the cold arc pulse mode (CAP). The structure of both specimens was studied and defects along their surfaces were detected in the form of micro-pores and micro-cracks. A high concentration of undissolved Mg particles was also detected, along with some standalone Si particles. Uniformity in the build-up process was achieved, which led to the formation of nearly identical structures in the specimens. Subsequently, the resultant mechanical properties were also highly comparable. This indicates that the geometry-related variation in thermal conditions has an insignificant influence on the component’s structure and properties.
The aim of the study is the formalization of the balance method with respect to the determination of the ecological and economic efficiency of the use of land resources. During the research, the ...following methods were used: statistical-economic, monographic, balance, computational and constructive. In the sphere of environmental protection, there is usually uncertainty about benefits and uncertainty about costs. Therefore, at the moment, further formalization of the assessment of the processes taking place in the system of interaction between man and land in the process of agricultural production is required. When analyzing the effectiveness of the use of agricultural land, it is important to determine not only economic, but also environmental and economic components. The ecological component of land use can be measured on the strength of the amount of prevented environmental damage applied to soil fertility, and the magnitude of the ecological effect that is created when carrying out measures to reproduce soil fertility. As the studies show, cultivating agricultural crops causes a negative balance of nutrients in the soil, and the calculation of environmental and economic efficiency indicates the need not only for joint application of organic and mineral fertilizers in optimal parameters, but also for finding alternative ways of ensuring reproduction of soil fertility.
The sigmoidal tuning curve that maximizes the mutual information for a Poisson neuron, or population of Poisson neurons, is obtained. The optimal tuning curve is found to have a discrete structure ...that results in a quantization of the input signal. The number of quantization levels undergoes a hierarchy of phase transitions as the length of the coding window is varied. We postulate, using the mammalian auditory system as an example, that the presence of a subpopulation structure within a neural population is consistent with an optimal neural code.
Currently, the technology of microelectromechanical systems is widely used in the development of high-frequency and ultrahigh-frequency devices. The most important requirements for modern and ...advanced devices of the ultra-high-frequency range are the reduction of weight and size characteristics, power consumption with an increase in their functionality, operating frequency and level of integration. Radio frequency microelectromechanical switches are developed using the technology of the manufacture of CMOS-integrated circuits. Integrated radio frequency control circuits require low control voltages, the high ratio of losses to the isolation in the open and closed condition, high performance and reliability. This review is devoted to the analytical approach based on the knowledge of materials, basic performance indices and mechanisms of failure, which can be used in the development of radio-frequency microelectromechanical switches.
Scientific literature is a source of the most reliable and comprehensive knowledge about molecular interaction networks. Formalization of this knowledge is necessary for computational analysis and is ...achieved by automatic fact extraction using various text-mining algorithms. Most of these techniques suffer from high false positive rates and redundancy of the extracted information. The extracted facts form a large network with no pathways defined.
We describe the methodology for automatic curation of Biological Association Networks (BANs) derived by a natural language processing technology called Medscan. The curated data is used for automatic pathway reconstruction. The algorithm for the reconstruction of signaling pathways is also described and validated by comparison with manually curated pathways and tissue-specific gene expression profiles.
Biological Association Networks extracted by MedScan technology contain sufficient information for constructing thousands of mammalian signaling pathways for multiple tissues. The automatically curated MedScan data is adequate for automatic generation of good quality signaling networks. The automatically generated Regulome pathways and manually curated pathways used for their validation are available free in the ResNetCore database from Ariadne Genomics, Inc. 1. The pathways can be viewed and analyzed through the use of a free demo version of PathwayStudio software. The Medscan technology is also available for evaluation using the free demo version of PathwayStudio software.
The low-frequency component of the distortions caused by both the atmospheric turbulence and the behavior of the telescope itself has been studied. A corrector for the position of the center of the ...star image has been developed and is being used in front of the high-resolution Echelle spectrograph on the 6 m telescope of the Special Astrophysical Observatory, Russian Academy of Sciences. To speed up the calculations and to increase the bandwidth, a laser beam angular stabilization system based on an FPGA platform is considered. The system consists of two tip-tilt mirrors and two quadrant photodiodes. The FPGA analyzes the signals from the photodiodes, calculates and then applies the voltages to the piezo-driven tip-tilt mirrors to minimize the displacement of the beam on the photodiodes. The stabilization system was developed as a part of the adaptive optical system to improve the efficiency of the high-resolution Echelle spectrograph.
Multicolor nonlinear microscopy of living tissue using two- and three-photon-excited intrinsic fluorescence combined with second harmonic generation by supermolecular structures produces images with ...the resolution and detail of standard histology without the use of exogenous stains. Imaging of intrinsic indicators within tissue, such as nicotinamide adenine dinucleotide, retinol, indoleamines, and collagen provides crucial information for physiology and pathology. The efficient application of multiphoton microscopy to intrinsic imaging requires knowledge of the nonlinear optical properties of specific cell and tissue components. Here we compile and demonstrate applications involving a range of intrinsic molecules and molecular assemblies that enable direct visualization of tissue morphology, cell metabolism, and disease states such as Alzheimer's disease and cancer.
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