TAMI-43. HYPOXIC REGULATION OF GLIOBLASTOMA TUMOR GROWTH THROUGH L(3)MBTL1

Glioblastoma (GBM) is the deadliest and most common of all primary brain tumors. Drosophila brain tumor models have uncovered signaling pathways regulating tumor growth that are highly conserved in GBM. Our search for a novel tumor suppressor using Drosophila led to Lethal (3) malignant brain tumor [l(3)mbt], temperature-sensitive mutants of which cause neuroepithelial tumor-like overproliferation in optic lobes. dL(3)MBT and its human orthologs L3MBTL1-L3MBTL4 all harbor Malignant Brain Tumor (MBT) domains that recognize methylated lysines on histone tails. Like dL(3)MBT, hL(3)MBTL1 acts as a chromatin compaction factor that represses transcription and inhibits cytokinesis in GBM cell lines. The highly hypoxic tumor microenvironment (TME) in GBM drives its progression, recurrence, and therapeutic resistance. However, it remains unclear if L(3)MBTL1 is regulated by TME cues to promote GBM growth. Based on this knowledge gap and our preliminary data, we hypothesize that hypoxia directly regulates L(3)MBTL1 in favor of GBM growth. Analysis of TCGA data for IDH-wildtype gliomas revealed that L3MBTL1 gene expression is downregulated in GBM, which are necrotic and severely hypoxic, compared to histologic grade 2/3 gliomas, which do not contain necrosis, indicating that hypoxia could potentially suppress L3MBTL1 to enhance glioma progression. TCGA data also revealed a number of HIF pathway and hypoxia-inducible genes strongly correlating with L3MBTL1 expression, including HIF1a and VHL. Using patient-derived GBM neurosphere cultures, we exposed glioma cells to hypoxia (1% O2 for 24hrs) and found that L3MBTL1 protein levels were suppressed compared to normoxia (21%). Under these same conditions, we found more rapid cell proliferation under hypoxia. Exploration of hypoxic TME regulation of the novel tumor suppressor L3MBTL1 in glioma progression has the potential to uncover novel mechanisms involving epigenetic modulation and potentially new therapeutic strategies.

Experiment Investigation On Concrete With Partial Replacement Of Cement By Cow Dung Ash

Experimental investigations were carried out to study the cow dung ash on the strength of concrete. Cement was partially replaced with four percentages (5%, 10%, 15%, 20%) of cow dung ash by weight in M20 grade concrete mix. Test performed on the concrete mix are compressive strength, splitting tensile strength and workability. The compressive strengths of the concrete specimens were determined at 7 and 28 days respectively. The tests were performed on the moulds of size (150mm x150mm x150mm).Workability test is done using compaction factor apparatus. Workability Test shows that workability of concrete decreases as percentage of cow dung ash increases in concrete mix. When compared to normal concrete the concrete containing 10% of CDA has 17% increase in compressive strength and 15% increase in Tensile Strength. The Compressive Strength and Tensile strength tends to decrease after 10%. Thus 10% replacement of cement by CDA gives satisfactory result.

Multiple Regression and Modified Faust Equation on Well Logging Data in Application to Seismic Procedures: Polish Outer Carpathians Case Study

An appropriate velocity model from well logs is a key issue in the processing and interpretation of seismic data. In a deep borehole located in the central part of the Polish Outer Carpathians, the sonic measurements were inadequate for seismic purposes due to the poor quality of data and gaps in the logging. Multiple regression (MR) and a modified Faust equation were proposed to model the velocity log. MR estimated the P-wave slowness as a dependent variable on the basis of sets of various logs as independent variables. The solutions were verified by the interval velocity from Check Shots (CS) and by the convergence of synthetic seismograms and the real seismic traces. MR proved to be an effective method when a set of other logs was available. The modified Faust method allowed computation of P-wave velocity based on the shallow resistivity logs, depth, and compaction factor. Faust coefficients were determined according to the lithology and stratigraphy divisions and were calibrated with the use of the velocity previously determined in the MR analysis. The modified Faust equation may be applied in nearby old wells with limited logging data, particularly with no sonic logs, where MR could not be successfully applied.

Uniaxial compression mechanical properties and damage constitutive model of limestone under osmotic pressure

To study the influence of osmotic pressure on the uniaxial compression mechanical properties of limestone, uniaxial compression tests were carried out on limestone specimens under different osmotic water pressure. The test results show that with the increase of osmotic pressure, the closure strain, yield strain and peak strain of limestone gradually increase, while the closure stress, yield stress, peak stress and elastic modulus gradually decrease. To describe the stress-strain response of limestone during uniaxial compression failure, the concepts of compaction factor and osmotic pressure influencing factor were proposed, and a constitutive model of rock compaction stage was established by integrating the relationship between the compaction factor and osmotic pressure influencing factor and the tangent modulus of compaction section. On this basis, combining the continuum damage mechanics theory, and assuming that the rock micro-unit strength obeys the compound power function distribution, a constitutive model reflecting the uniaxial compression mechanical properties of rock under osmotic pressure was established by the statistical method. The rationality of the model was verified using the results of the uniaxial compression test of limestone under different osmotic pressures. The results show that the test results under different osmotic pressures are in good agreement with the theoretical curves, and the model in this paper can reflect the stress-strain response of limestone before its failure under different osmotic pressures.

Effects of Granite Sourced from Selected Locations in Ogbomoso, Nigeria on the Properties of Concrete

Aggregates constitute 60 – 80% of total concrete constituents. The characteristics of concrete may be affected by the sources from which the aggregate was obtained. The effects of granite sourced from four selected locations within Ogbomoso, Nigeria; on the fresh and hardened properties of concrete were investigated. The granites were obtained from: Asafa (80 4.681 N and 40 20.781 E), Ola-jesu (80 13.591 N and 40 10.11 E), Igbo-ile (80 4.681 N and 40 19.571 E) and Apasu (80 14.961 N and 40 10.051 E). Sieve analysis, specific gravity, moisture content, Aggregate Crushing Value (ACV) and Aggregate Impact Value (AIV) of the granites were determined. The aggregates were used to produce concrete of two different mix ratio-1:2:4 and 1:3:6. Slump and compaction factor tests were carried out on fresh concrete and compressive strength, splitting tensile strength and water absorption on hardened concrete. The results indicated that granite obtained from Asafa and Ola-jesu exhibited improved characteristics over those sourced from Igbo-ile and Apasu and are more suitable for use in producing high-quality concrete.

Alpha-buckets in High Energy Electron Storage Rings (Review of Existing Experiments and Feasibility Studies for Future Developments)

Electron storage rings operating at high energies have proven to be invaluable source of synchrotron radiation. Two and even three simultaneous beams of particles have been observed at different light source facilities worldwide. So called alpha-buckets were studied at Metrological Light Source (MLS) in Berlin (Germany), SOLEIL facility in France, DIAMOND light source in UK, NSLS ring in Brookhaven (USA). It is widely recognized that alpha buckets are general phenomena which is not restricted to a certain storage ring. However, earlier measurements showed essential limitations on parameters of alpha-buckets, strong dependence on high order (sextupole and octupoles) magnetic field imperfections and associated fast decay of electron current as well as reduced life time. Also a rising relevance of high order non-linear longitudinal beam dynamics is associated with new generation of diffraction limited light sources (DLSR) approaches, which all suffer nonlinear momentum compaction factor. A large variety of future generation electron synchrotrons require a comprehensive investigation of the physical processes involved into the operation of such rings. In this paper, we present review of high order non-linear longitudinal beam dynamics based on the longitudinal equations of motion and Hamiltonian expanded to a high order of the momentum compaction factor. Roots of the third order equation with a free term are derived in a form suitable for analytical estimations. The momentum independent term of orbit lengthening due to particle transverse excursions is estimated and taken into account. The results from simulations were benchmarked against existing experiments at the Karlsruhe Research Accelerator (KARA), SOLEIL and MLS rings. Parameters of three simultaneous beams and alpha buckets at MLS and SOLEIL have been reproduced with high accuracy. General conditions for stable operation of alpha buckets are presented. Based on analytical formulas and computer simulations, studies of longitudinal motion at KARA have been performed with an objective to estimate feasibility of filling and storing of beam in α-buckets. A Computer model was used to describe the behavior and dynamics of simultaneous beams in the KARA storage ring.

Review of manufacturers'recommendations on technological capabilities of ejectable excavator vibroplates assessment during soil compaction

Introduction. Add-on compactors for excavators (ACE hereinafter) are replaceable working equipment for excavators. They are used for soil compaction after the backfill of trenches, wells, foundation cavities and other “narrow spaces” of construction, as well as soil compaction at slopes of embankments and excavations.In practical use of ACE, builders face two challenges:to justify the choice of an ACE for soil compaction under given conditions determined by the soil type and moisture, layer thickness, and the required compaction factor; to determine the time required to compact soil with an ACE at a single point positional compaction to ensure the required compaction factor of a given type of soil in a layer of required thickness.The problems above require the information regarding technological capabilities of ACEs in different technological situations of soil compaction. The assessment of such technological capabilities of ACEs, at the same time, should take into account the ongoing transition to a new regulatory framework in Russia in the field of assessment indicators for the results of soil compaction in construction.Materials and methods. ACE technological capabilities review was conducted based on the information provided on the official websites of the largest Russian and foreign ACE manufacturers and suppliers.Conclusion. The analysis of information provided by ACE manufacturers and suppliers showed that most of that information is technical specifications of ACEs and excavators. There is almost no information on technological capabilities of ACEs. At the same time, ACE manufacturers and suppliers use ambiguous terminology (for example, “compaction volume”) in the assessment of technological capabilities.Practical value. Lack of information on technological capabilities of ACEs in various technological situations of soil compaction leads to errors in selection of an ACE model and its operation time during single point positional soil compaction, which increases the risk of under compaction and reduced service life of constructed objects. To solve this problem, the Construction and Road-Building Machinery Department of Yaroslavl State Technical University is developing a methodology for calculating the results of soil compaction with an ACE in different technological situations.

METHOD OF DEVELOPMENT OF TECHNOLOGY FOR THE DEVICE OF ROAD STRUCTURES USING ASPHALT GRANULATE

Statement of the problem. The currently used waste (asphalt granulate) for milling non-rigid pavements differs in its characteristics from hot and cold asphalt concrete mixtures as well as crushed stone. The used fleet of machines for compacting the material layer is characterized by a wide range of roller weights and roller parameters, which affects the compaction effect. Ensuring the quality of compaction depends on the compliance of the technological modes of the mechanized link of machines with the properties of the materials used. It is necessary to develop a technology for the device of layers using asphalt granulate and taking into account its properties, thickness, as well as the parameters of compaction machines. Results. The method of development of technology for the device of road structures in the reconstruction and repairs of highways with the use of asphalt granulate is considered. Based on experimental studies the dependence between the load and the deformation of the layer of material, deformation and compaction factor and the values of the angles of contact of the roller with the surface layer of the compacted material is identified with regard to its granulometric composition and thickness of the stacked layer. The simulation results are presented of the interaction of the roller rink with the sealing material obtained analytical dependence for the calculation of stresses in the contact zone of the roller with the material allowing one to set the parameters of the rollers depending on the properties of asphalt granulate.Conclusions. An analytical dependence is obtained for calculating the stresses in the contact zone of the roller with the asphalt granulate layer, which allows one to assign the parameters of the rollers depending on the properties of the material being laid. The suggested method for developing the technology of layer arrangement using asphalt granulate enables the required quality of compaction taking into account the properties of the material, the thickness of the layer to be laid and the parameters of compacted machines.