Identification of TGFβ signaling, p53, and actin stress fibers as targets of LKB1 tumor suppressor activity

Tumorigenesis is a consequence of inactivating mutations of tumor suppressor genes and activating mutations of proto-oncogenes. Most of the mutations compromise cell autonomous and non-autonomous restrains on cell proliferation by modulating kinase signal transduction pathways. LKB1 is a tumor suppressor kinase whose sporadic mutations are frequently found in non-small cell lung cancer and cervical cancer. Germ-line mutations in the LKB1 gene lead to Peutz-Jeghers syndrome with an increased risk of cancer and development of benign gastrointestinal hamartomatous polyps consisting of hyperproliferative epithelia and prominent stromal stalk composed of smooth muscle cell lineage cells. The tumor suppressive function of LKB1 is possibly mediated by 14 identified LKB1 substrate kinases, whose activation is dependent on the LKB1 kinase complex. The aim of my thesis was to identify cell signaling pathways crucial for tumor suppression by LKB1. Re-introduction of LKB1 expression in the melanoma cell line G361 induces cell cycle arrest. Here we demonstrated that restoring the cytoplasmic LKB1 was sufficient to induce the cell cycle arrest in a tumor suppressor p53 dependent manner. To address the role of LKB1 in gastrointestinal tumor suppression, Lkb1 was deleted specifically in SMC lineage in vivo, which was sufficient to cause Peutz-Jeghers syndrome type polyposis. Studies on primary myofibroblasts lacking Lkb1 suggest that the regulation of TGFβ signaling, actin stress fibers and smooth muscle cell lineage differentiation are candidate mechanisms for tumor suppression by LKB1 in the gastrointestinal stroma. Further studies with LKB1 substrate kinase NUAK2 in HeLa cells indicate that NUAK2 is part of a positive feedback loop by which NUAK2 expression promotes actin stress fiber formation and, reciprocally the induction of actin stress fibers promote NUAK2 expression. Findings in this thesis suggest that p53 and TGFβ signaling pathways are potential mediators of tumor suppression by LKB1. An indication of NUAK2 in the promotion of actin stress fibers suggests that NUAK2 is one possible mediator of LKB1 dependent TGFβ signaling and smooth muscle cell lineage differentiation.

Influence of Raman scattering on the cross phase modulation in optical fibers

The effect of Raman scattering on co-propagation of two short optical pulses is considered. The intra pulse Raman scattering causes the self-frequency shift of each pulse. The effect of the inter pulse Raman scattering is to enhance the frequency shift while the stimulated Raman scattering (SRS) term suppresses (enhances) the frequency shift if the center frequency difference between the optical pulses falls to the right (left) of the Raman gain peak. An expression for the frequency shift as a function of the propagation distance is obtained.

Novel synthesis of alpha-SI3N4 fibers

Alpha-Si3N4 fibres have been synthesized by carbothermal reduction and nitridation of pre-oxidized SiO1.7. The fibres were characterized using X-ray diffraction, infrared spectroscopy and electron microscopic techniques. The likely mechanism of reaction has been outlined

Flexural bond strength of masonry using various blocks and mortars

This paper deals with an experimental study on flexural bond strength of masonry using various blocks in combination with different mortars. Flexural bond strength of masonry has been determined by testing stack-bonded prisms using a modified bond wrench test set-up. The effect of mortar composition and strength on the masonry's. flexural bond strength using three types of masonry units (stabilized mud blocks, stabilized soil-sand blocks and burnt brick) has been examined. The effect of the masonry unit's moisture content on flexural bond strength has also been studied. Increases in mortar strength lead to increased flexural bond strength for cement mortar, irrespective of the type of masonry unit. It has been found that combination mortars, such as soil-cement mortar and cement-lime mortar, lead to better bond strength compared to cement mortars. The moisture content of the masonry unit at the time of casting has displayed significant influence on the flexural bond strength of the masonry. It has been found that for each type of masonry unit, an optimum moisture content exists, beyond which the flexural bond strength falls off quickly.

Growth and characterization of single crystal cored fibers of organic nonlinear optical materials

The recent development of several organic materials with large nonlinear susceptibilities, high damage threshold and low melting points encouraged researchers to employ these materials in fiber form to efficiently couple diode laser pumps and obtain enhanced second harmonic generation (SHG). In this paper we report the growth of single crystal cored fibers of 4-nitro-4'-methylbenzylidene aniline, ethoxy methoxy chalcone and (-)2-((alpha) -methylbenzylamino)-5- nitropyridine by inverted Bridgman-Stockbarger technique. The fibers were grown in glass capillaries with varying internal diameters and lengths and were characterized using x-ray and polarizing microscope techniques. The propagation loss at 632.8 nm and 1300 nm were measured and SHG was studied using 1064 nm pump.

Strength characteristics of stone masonry

This paper deals with an experimental investigation on the strength of stone and stone masonry. Granitoid-gneiss is commonly used for masonry construction in India. The compressive strength of stone has been determined through 80 mm size cubes. It has been found that the compressive strength of granitoid-gneiss is greater when the load is parallel to the mineral bands. The compressive strength of stone masonry was studied through masonry prisms using 1:4 and 1:8 cement mortars. These tests have revealed that masonry strength is higher when the load applied is parallel to the mineral bands. The flexural bond strength of stone masonry walls was studied through full-scale tests. Flexural bond strength appears to play a major role in the failure of stone masonry walls.

Stress-strain Curves and Corresponding Structural Parameters in Mulberry and Non-mulberry Silk Fibers

Mulberry fiber (Bivoltine) and non-mulberry fiber (Tassar) were subjected to stress-strain studies and the corresponding samples were examined using wide angle X-ray scattering studies. Here we have two different characteristic stress-strain curves and this has been correlated with changes in crystallite shape ellipsoids in all the fibers. Exclusive crystal structure studies of Tassar fibers show interesting feature of transformation from antiparallel chains to parallel chains.

Properties of lime stabilised steam-cured blocks for masonry

The paper addresses certain issues pertaining to the technology of lime-stabilised steam-cured blocks used for masonry construction. Properties of lime-stabilised steam-cured blocks using expansive soils and tank bed soils have been examined. Influence of parameters like steam curing period, lime content and fly ash content on wet strength of blocks is studied. Steam curing of lime stabilised blocks at 80degreesC for about 20 hours at atmospheric pressure leads to considerably higher strengths when compared with curing under wet cloth at ambient temperatures. Clay-fly ash fractions of the mix control the optimum lime content yielding maximum strength. Long-term strength behaviour of steam-cured blocks has been monitored. The results indicate a favourable lime-clay ratio for stable long-term strength. A small-scale steam cured block production system has been designed and implemented to construct a load bearing masonry structure, thus demonstrating the potential of steam-cured block as a material for masonry construction.

Carbothermal reduction and nitridation reaction of SiOx and preoxidized SiOx: Formation of α-Si3N4 fibers

The chemical composition of amorphous SiOx has been analyzed by oxidation studies and is found to be SiO1.7. SiO1.7 appears to be a monophasic amorphous material on the basis of 29Si nuclear magnetic resonance, high resolution electron microscopy, and comparative behavior of a physical mixture of Si and SiO2. Carbothermal reduction and nitridation reactions have been carried out on amorphous SiO1.7 and on amorphous SiO2 obtained from oxidation of SiO1.7. At 1623 K reactions of SiO1.7 lead exclusively to the formation of Si2N2O, while those of SiO2 lead exclusively to the formation of Si3N4. Formation of copious fibers of α-Si3N4 was observed in the latter reaction. It is suggested that the partial pressure of SiO in equilibrium with reduced SiO1.7 and SiO2 during the reaction is the crucial factor that determines the chemistry of the products. The differences in the structures of SiO2 and SiO1.7 have been considered to be the origin of the differences in the SiO partial pressures of the reduction products formed prior to nitridation. The effect of the ratios, C:SiO1.7 and C:SiO2, in the reaction mixture as well as the effect of the temperature on the course of the reactions have also been investigated.

Carbon Nanotube based Composite Fibers for Strain Sensing, Signal Processing and Computing

Carbon nanotubes dispersed in polymer matrix have been aligned in the form of fibers and interconnects and cured electrically and by UV light. Conductivity and effective semiconductor tunneling against reverse to forward bias field have been designed to have differentiable current-voltage response of each of the fiber/channel. The current-voltage response is a function of the strain applied to the fibers along axial direction. Biaxial and shear strains are correlated by differentiating signals from the aligned fibers/channels. Using a small doping of magnetic nanoparticles in these composite fibers, magneto-resistance properties are realized which are strong enough to use the resulting magnetostriction as a state variable for signal processing and computing. Various basic analog signal processing tasks such as addition, convolution and filtering etc. can be performed. These preliminary study shows promising application of the concept in combined analog-digital computation in carbon nanotube based fibers. Various dynamic effects such as relaxation, electric field dependent nonlinearities and hysteresis on the output signals are studied using experimental data and analytical model.

Hygrothermal durability and failure modes of FRP for marine applications

This article deals with the durability of 2D woven mat carbon/polyester, glass/isopolyester, and gel-coated glass/isopolyester reinforced composites under hygrothermic conditions with regard to marine applications. The test coupons were exposed to 60 degrees C and 70 degrees C at 95% RH for a maximum duration of 100 h. The samples were periodically withdrawn and weighed for moisture absorption and tested for the degradation in the mechanical properties such as ultimate tensile strength, flexural strength, interlaminar shear strength, and Young's modulus and flexural modulus. Carbon/isopolyester-based specimens showed greater stability with respect to degradation in the mechanical properties than the glass/isopolyester/gel coat- and glass/isopolyester-based specimens. Glass/isopolyester exhibited the maximum moisture absorption, whereas the minimum moisture absorption was found in glass/isopolyester/gel coat. Diffusion coefficient (D) was found to be the highest for glass/isopolyester and the lowest for glass/isopolyester/gel coat, based on the Fick's law of diffusion. Diffusion coefficient increases with the increase in temperature for all the specimens. Microstructure study of fractured specimens was carried out using scanning electron microscope to compare matrix/fiber debonding and matrix-degradation of fiber-reinforced polymer composites.

Verification of Masonry Building Code to Flexural Behavior of Cement-Stabilized Soil Block

Most studies involving cement-stabilized soil blocks (CSSB) concern material properties, such as the characteristics of erosion and strength and how the composition of the block affects these properties. Moreover, research has been conducted on the performance of various mortars, investigating their material properties and the tensile bond strength between CSSB units and mortar. In contrast, very little is currently known about CSSB masonry structural behavior. Because structural design codes of traditional masonry buildings were well developed over the past century, many of the same principles may be applicable to CSSB masonry buildings. This paper details the topic of flexural behavior of CSSB masonry walls and whether the Masonry Standards Joint Committee (MSJC) code can be applied to this material for improved safety of such buildings. DOI: 10.1061/(ASCE)MT.1943-5533.0000566. (C) 2013 American Society of Civil Engineers.