Genetic changes are hallmarks of cancer development involving the activation and/or inactivation of oncogenes and tumour suppressor genes, respectively. In non-melanoma skin cancer (NMSC) development, the initiation of genetic mutations results from exposure to solar ultraviolet radiation. Non-melanoma skin cancers are comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Several related cutaneous lesions also exist, of which solar keratoses (SK) are widely accepted as a precursor dysplasia to SCC development. The study of recurrent genetic changes present within NMSC and SK should help reveal causative mutations in skin cancer development. Such analysis could also elucidate links in the genetic similarity of these dysplasia. The rapid screening of numerical changes in DNA sequence copy number throughout the entire genome has been made possible by the advent of comparative genomic hybridisation (CGH). This technique enables the identification of net gains and loss of genetic material within a tumour DNA sample. Chromosomal regions of recurrent gain or loss identify loci containing putative oncogenes and tumour suppressor genes, respectively with potential roles in NMSC tumourigenesis. Used in conjunction with tissue microdissection and universal degenerate PCR techniques this can enable the elucidation of aberrations in small histologically distinct regions of tumour. Such a technique can utilize archival material such as paraffin embedded tissue, which is the major source of neoplastic material available for cancer research. This study used the CGH technique to investigate aberrations in BCC, SCC and SK samples. The screening of copy number abnormalities (CNAs) in BCC revealed that although these tumours were close to diploid and generally genetically stable, they did contain several recurrent aberrations. The loss of genetic material at 9q was identified in a third of BCC tumours studied. This is characteristic of inactivation of the PTCH tumour suppressor gene, a known attribute in some sporadic BCC development. Validation of this loss was performed via loss of heterozygosity, demonstrating good concordance with the CGH data. In addition the over-representation of the 6p chromosome arm was revealed in 47% of biopsies. This novel CNA is also commonly observed in other cutaneous neoplasias, including Merkel cell carcinoma and malignant melanoma. This suggests a possible common mechanism in development and or promotion in these cutaneous dysplasias, the mechanisms of which have yet to be clearly defined. In contrast to BCC, numerical genetic aberrations in SCC and SK were much more frequent. Several regions of recurrent gain were commonly shared between both dysplasias including gain of 3q, 4p, 5p, 8q, 9q, 14q, 17p, 17q and 20q. Common chromosomal regions of loss included 3p, 8p, 9p, 11p, 13q and 17p. In addition loss of chromosome 18 was significantly observed in SCC in comparison to SK, a possible defining event in SK progression to SCC. The identification of shared genetic aberrations suggests a clonal and genetic relationship between the two lesions. This information further supports the notion for re-classification of SK to an SCC in situ or superficial SCC. Finally, the CNAs detected have been similarly observed in other squamous cell-derived tumours, for example cervical and head and neck SCC. This provides further evidence to common mechanisms involved in the initiation, development and progression of SCC neoplasia. This study has identified a number of recurrent chromosomal regions, some of which are novel in NMSC development. The further delineation of these loci should provide additional evidence of their significance and degree of involvement in NMSC tumourigenesis. The identification of the cancer-causing genes mapped to these loci will further demarcate the genetic mechanisms of BCC and SCC progression. An understanding of the events involved in skin cancer formation and progression should shed additional light on molecular targets for diagnostics, management and therapeutic treatment.

科学研究費補助金 研究種目:基盤研究(B)(2) 課題番号:07455279 研究代表者:森永 正彦 研究期間:1995-1996年度

No description available.

The dependence of flow stress of body centered cubic metals on variables such as strain rate, temperature, strain and microstructural is a research area of continued interest. Recently, there has been renewed interest in deformation of fine grained BCC metals, which display characteristics that are different from their coarse-grained counterparts. Deformation mechanisms, strain-rate and temperature dependence, and strain hardening characteristics of fine-grained BCC metals are not well understood. The aim of this thesis is to understand the effect of strain-rate, temperature, strain and microstructure (i.e., grain size) on the mechanical response of poly¬crystalline tantalum. Among the topics addressed were constitutive modeling of flow stress, understanding the microstructural origins of strain hardening, and characterizing the effect of severe plastic deformation (SPD) on microstructure and mechanical properties. Rolling and equal-channel angular pressing (ECAP) were among the processing techniques employed. Mechanical testing was conducted over a range of temperatures and strain rates, and this was supported by a slew of microscopic characterization methods. It was found that the strain hardening response depends on microstructural evolution at different strain rates. Results indicate that the same thermally activated mechanisms operate in both as-received and processed material and this was found to be the overcoming of Peierls barriers via a double-kink mechanism. Lastly, it was found that the low strain rate sensitivity of SPD processed material was not due to fine grain size, but instead due to high internals stresses.

No description available.

PhD (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology. / High levels of pollutants in water are found to have poisonous effects on human health. Due to increasing awareness about the environment and strict environmental regulations, wastewater treatment has become a very important aspect of research. Thus, this makes the adsorption of pollutants an urgent matter. The aim of this research was to investigate the adsorption capacity of black cumin seeds in the removal of cobalt-Co(II), nickel-Ni(II), copper-(II), chromium-Cr(VI), lead-Pb(II), and methylene blue (MB) dye from aqueous solution. In this research work the black cumin seeds were reacted with sodium hydroxide (NaOH), hydrochloric acid (HCl), phosphoric acid (H3PO4), potassium permanganate (KMnO4) and sulfuric acid (H2SO4). Thereafter it was carbonized at 200 and 300 °C and functionalized with magnetite-sucrose nanoparticles and further carbonized at 600 °C to improve the adsorption capacity of the materials towards different pollutants. The seeds were characterized by scanning electron microscopy (SEM), thermogravimetric analyser (TGA), X-ray diffractometer (XRD), Brunauer, Emmett and Teller (BET) and Fourier transformed infrared (FTIR) spectroscopy. The SEM images showed that the surface morphology of the treated adsorbents was more porous and had cavities more than the starting material. The TGA profile showed a major weight loss between 198-487 °C which was due to disintegration of cellulose, lignin and hemicellulose. The XRD spectra of adsorbents showed broad peaks at 2θ value of 21° associated crystalline lignocellulose content. FTIR results showed that the adsorbents had functional groups such as hydroxyl (-OH), carboxyl (-COOH), amide (-NH) and carbonyl (-C=O). The BET surface area of pristine black cumin seeds was 2.7 m2/g and increased after treatment with KMnO4 and H3PO4 to 10.1 and 9.3 m2/g respectively. The surface area of the carbon black cumin seeds was 11.67 m2/g whilst the activation of carbon from black cumin seeds with 10 and 20% H2SO4 gave the surface area of 20.14 and 21.54 m2/g respectively. The seeds activated with 20% H2SO4 showed larger pore width of 7.13 nm compared to 6.81 and 3.78 nm after treatment with 10% H2SO4 and carbon black cumin seeds respectively. The results show that there is an increase in surface area and pore size for both 10 and 20% H2SO4 in comparison with carbon black cumin seeds. The adsorption of Co(II), Ni(II), Cu(II), Cr(VI) and Pb(II) and MB in the solution was investigated by studying the effect of initial concentration, contact time, temperature and pH. The batch adsorption experiments were conducted using different ion solution concentrations of 20, 40, 60, 80 and 100 mg/L, contact time was determined at intervals of 1, 5, 10, 15, 20, 30, 60, 90 and 120 min, while temperature was studied at 298, 303, 313, 333 and 353 K. On the other hand, the effect of pH on all solutions was studied at pH 1, 3,5,7 and 9. The results showed that the acid treated black cumin seeds (AT-BCS) and base treated black cumin seeds (BT-BCS) were successfully used for quaternary adsorption study of Cu(II), Co(II), Pb(II) and Ni(II) ions from aqueous solution. The results for the adsorbents indicated that the BT-BCS adsorbed more metals than AT-BCS and the UT-BCS. The maximum capacity for BT-BCS was 190.7 mg/g for Cu(II) whilst AT-BCS and UT-BCS showed capacities of 180.1 and 135 mg/g respectively for Pb(II). The uptake of Cr(VI) and Cd(II) ions onto pristine black seeds (PBS), KMnO4 black seeds (KMBS) and H3PO4 black seeds (H3BS) treated adsorbents showed that the trend for Cr(VI) ions was KMBS>H3BS>PBS with capacities of 16.12, 15.98 and 10.15 mg/g respectively. Meanwhile the adsorption of Cd(II) ions showed maximum capacities of 19.15, 19.09 and 16.80 mg/g for KMBS, H3BS and PBS respectively. Carbon from black cumin (CBC) seeds was modified with 10 % and 20 % sulfuric acid (H2SO4) then carbonized at 200 °C to obtain the activated adsorbents of ACBC-10 and ACBC-20. The new adsorbents were used for the adsorption of Cd(II) and methylene blue (MB). The adsorbents maximum trend for Cd(II) was ACBC-10>ACBC-20>CBC meanwhile the trend for methylene blue (MB) dye was ACBC-20>ACBC-10>CBC. The overall capacities showed that the prepared materials adsorbed more MB dye (16.42 mg/g) than Cd(II) ions (13.65 mg/g). The preparation of carbon from black cumin seeds (BCC) and activation with 10 and 20 % sulfuric acid (H2SO4) at 300 °C to obtain new adsorbents namely (BCAC-10) and (BCAC-20) respectively was used for the adsorption of Pb(II) ions and MB dye from aqueous solution. The maximum adsorption of Pb(II) ions was 17.19, 17.71 and 17.98 mg/g onto BCC, BCAC-10 and BCAC-20 respectively. Whilst for MB dye it was 11.63, 12.71 and 16.85 mg/g onto BCC, BCAC-10 and BCAC-20 respectively. The utilization of pristine Nigella Sativa (PNS) and magnetite-sucrose functionalized Nigella Sativa (FNS) seeds as the adsorbents for the uptake of Cr(VI) and Pb(II) ions from synthetic wastewater revealed that the maximum adsorption capacities for Cr(VI) were 15.6 and 13.0 mg/g onto PNS and FNS composites respectively at pH 1. On the hand, the maximum sorption capacities for Pb(II) ions were 39.7 and 37.9 mg/g onto PNS and FNS respectively at pH 5. The sorption study of Cr(VI), Cd(II) ions and MB dye by pristine Nigella Sativa (PNS) seeds, defatted and carbonized Nigella Sativa seeds from aqueous solution was investigated. The PNS seeds were treated using acetone (then named ANS) and N,N dimethylformamide (named DNS). The defatted ANS and DNS adsorbents were carbonized at 600 °C and named CANS and CDNS. The results of pristine, defatted and carbonized seeds maximum capacities were compared with each other and found that CANS had highest adsorption capacity of 99.82 mg/g for MB, 96.89 mg/g for Cd(II) and 87.44 mg/g for Cr(VI) followed by CDNS with 93.90, 73.91 and 65.38 mg/g for MB, Cd(II) and Cr(VI) respectively. ANS capacities were 58.44, 45.28 and 48.96 mg/g whilst DNS capacities were 48.19, 32.69 and 34.65 mg/g for MB, Cd and Cr(VI) respectively. PNS had the lowest sorption capacities at 43.88, 36.01 and 19.84 mg/g for MB, Cd and Cr(VI) respectively. Therefore, this makes black cumin seeds a promising material for use in wastewater treatment to mitigate metal ions and dye pollution.

<div>Decades of scaling in semiconductor technology has resulted in a drastic reduction in the cost and size of unit computing. This has enabled computing capabilities in small form factor wearable and implantable devices. These devices communicate with each other to form a network around the body, commonly known as the Wireless Body Area Network (WBAN). Radio wave transmission over air is the commonly used method of communication among these devices. However, the human body can be used as the communication medium by utilizing its electrical conductivity property. This has given rise to Human Body Communication (HBC), which provides higher energy efficiency and enhanced security compared to over the air radio wave communication enabling applications like remote health monitoring, secure authentication. In this thesis we characterize the human body channel characteristics at low frequencies, utilize the insight obtained from the channel characterization to build high energy-efficiency, interference-robust circuits and demonstrate the security and selectivity aspect of HBC through a Common Off the Shelf (COTS) component-based system. First, we characterize the response of the human body channel in the 10KHz1MHz frequency range with wearable transmitter/ receiver to study the feasibility of using it as a broadband communication channel. Voltage mode measurements with capacitive termination show almost at-band response in this frequency range, establishing the body as a broadband channel. The body channel response is also measured across different interaction scenario between two wearable devices and a wearable and a computer. A bio-physical model of the HBC channel is developed to explain the measurement results and the wide discrepancies found in previous studies.We analyze the safety aspect of different type of HBC by carrying out theoretical circuit and FEM based simulations. A study is carried out among multiple subjects to assess the effect of HBC on the vital parameters of a subject. A statistical analysis of the results shows no signicant change in the vital parameters before and during HBC transmission, validating the theoretical simulations showing >!000x safety margin compared to the established ICNIRP guidelines. Next, an HBC transceiver is built utilizing the wire-like, broadband human body channel to enable high energy efficiency. The transceiver also provides robustness to ambient interference picked up by the human body through integration followed by periodic sampling. The transceiver achieves 6.3pJ/bit energy effciency while operating at a maximum data rate of 30Mbps, while providing -30dB interference tolerant operation. Finally, a COTS based HBC prototype is developed, which utilizes low frequency operation to enable selective and physically secure communication strictly during touch for Human Computer Interaction (HCI) between two wearable devices for the rst time. A thorough study of the effect of different parameters such as environment, posture, subject variation, on the channel loss has also been characterized to build a robust HBC system working across different use cases. Applications such as secure authentication (e.g. opening a door, pairing a smart device) and information exchange (e.g. payment, image, medical data, personal profile transfer) through touch is demonstrated to show the impact of HBC in enabling new human-machine interaction modalities.</div>

Transition Metal (TM) silicides are potential materials for different high temperature applications due to their high melting points and chemical stability at elevated temperatures. In the present work, the possible use of Gr (VIB) disilicides: MoSi2 and CrSi2 for high temperature structural application and thermopower generation respectively are investigated. Literature reports on MoSi2 indicate this material to have excellent mechanical and thermal behaviors at temperatures greater than 1273 K. The major problems limiting its use are the low temperature brittleness and oxidation at intermediate temperatures and form the scope of this work. Also, CrSi2 is reported to be a narrow band gap semiconductor. Its feasibility as a thermoelectric material for power generation is investigated. The first chapter briefly summarizes the literature on MoSi2 and CrSi2 relevant to structural and thermoelectric applications respectively. Based on the available literature, the scope of further work is discussed. The second chapter describes the methods of synthesis employed for these materials and the characterization techniques adopted. Some experimental setups like thermal conductivity and hot pressing unit that were fabricated as part of the work are described in detail. The thermal conductivity apparatus is based on the principle of parallel heat flow technique. It allows accurate measurement of K and S in the temperature range 300-700 K. The induction based hot-pressing unit allows compaction of polycrystalline powders to near theoretical densities thereby allowing quantitative evaluation of the physical properties. In the third chapter, an understanding of ductility/brittleness based of electron charge density distribution is attempted. The electron charge density in Tin and simple metals (BCC and FCC) is analyzed using Bader’s Atoms in Molecule (AIM) theory. Also the relevant surface and dislocation energies in these materials are calculated according to the Rice Model. It is found that the electron densities at the critical points correlate in a simple way with the relevant stacking fault and surface energetics. Based on these results, a ductility parameter (DM odel) based on electron charge distribution, to predict the effects of chemical substitutions on ductility/brittleness in materials is proposed. In the fourth chapter, possible elements to impart ductility in MoSi2 are identified based on the DM odel values. Calculations indicate, Nb, Ta, Al, Mg and Ga to be suitable candidates for improving ductility in MoSi2. Also oxidation studies based on present experiments and reported literature data reveal, Al to improve the intermediate temperature (773-873 K) oxidation behavior. Thus to simultaneously improve the low temperature ductility and oxidation resistance, Nb and Al were identified as suitable candidates. In the fifth chapter, the experimental data of Nb and Al co-substituted MoSi2 samples are reported. Oxidation studies carried out by thermogravimetry show improved oxidation resistance in Nb and Al co-substituted samples compared to pure MoSi2 in the temperature range of 773-873 K. Mechanical characterization was carried out for (Mo0.99Nb0.01)(Si0.96Al0.04)2 co-substituted composition. Compression testing at room temperature show plastic deformation at low strain rates (10−3 /sec). Indentation experiments show a reduction in the hardness and stiffness compared to pure MoSi2. There is also an increase in the fracture toughness (K1C ) value with the fracture modes being predominantly transgranular. The sixth chapter describes the structural, thermal and transport properties of CrSi2. Structural refinement was carried out by Rietveld method and the positional, thermal parameters and occupancy were fixed. Thermo-gravimetric analysis shows oxidation resistance in powdered samples upto 1000 K. Thermal expansion (α) studies reveal anisotropy in the α values with an unusual decrease in the average αV values between 500 and 600 K. Measurements of electrical resistivity and seebeck coefficient indicate a degenerate semiconducting behavior. Electronic band structure calculations indicate a narrow indirect band gap (EG) material with EG~0.35 eV. Thermal conductivity (K) measurements show a decrease in K value with increasing temperature. Calculation of the thermoelectric figure of merit (ZT) show a maximum value of 0.18 at 800 K for the temperature range studied. Based on an analysis of the experimental and theoretical results, it is identified that further improvements in ZT of CrSi2 may be possible by reducing the lattice thermal conductivity and optimization of the carrier concentration. In chapter seven, the effect of particle size on ZT of CrSi2 is studied. Nano powders of CrSi2 were prepared by mechanical milling. Contamination is found to be a major problem during milling and the different milling parameters (milling speed, atmosphere, dispersant etc) were optimized to minimize contamination. The milled powders were further hot pressed to achieve high densities in a short duration thereby minimizing the grain growth. It is observed that the lattice thermal conductivity is reduced significantly with decreasing grain size. Measurements of ZT show a maximum value of 0.20 in the milled sample compared to 0.14 in arc melted CrSi2 at 600 K. In chapter eight the effect of chemical substitutions on ZT of CrSi2 is studied. Mn substitutions in Cr site were carried out to study the effect of atomic mass on lattice thermal conductivity (KP ). Al substitutions in Si site were carried out to tune the Fermi level. Results of Mn substitution show a large decrease in KP but also a reduction in the thermoelectric power factor (S2σ). The maximum ZT observed in the Mn substituted samples was 0.12 at 600 K. Al substitution results in an increase in the thermoelectric power factor and a subsequent increase in ZT. The maximum ZT observed was 0.27 at 700 K for 10% substitution of Al in Si site. The work reported in the thesis has been carried out by the candidate as a part of the Ph.D. training programme at Materials Research Centre, Indian Institute of Science, Bangalore, India. He hopes that this work would constitute a worthwhile contribution towards (a) basic understanding of ductility/brittleness in materials and understanding the effects of chemical substitutions, (b) Suitability of chemically substituted MoSi2 to overcome the problems of low temperature brittleness and oxidation. (c) Development of CrSi2 as a high temperature thermoelectric material.

The mechanical behavior of structural materials used in nuclear applications is significantly degraded as a result of irradiation, typically characterized by an increase in yield stress, localization of inelastic deformation along narrow dislocation channels, and considerably reduced strains to failure. Further, creep rates are accelerated under irradiation. These changes in mechanical properties can be traced back to the irradiated microstructure which shows the formation of a large number of material defects, e.g., point defect clusters, dislocation loops, and complex dislocation networks. Interaction of dislocations with the irradiation-induced defects governs the mechanical behavior of irradiated metals. However, the mechanical properties are seldom systematically correlated to the underlying irradiated microstructure. Further, the current state of modeling of deformation behavior is mostly phenomenological and typically does not incorporate the effects of microstructure or defect densities. The present research develops a continuum constitutive crystal plasticity framework to model the mechanical behavior and deformed microstructure of bcc ferritic/martensitic steels exposed to irradiation. Physically-based constitutive models for various plasticity-induced dislocation migration processes such as climb and cross-slip are developed. We have also developed models for the interaction of dislocations with the irradiation-induced defects. A rate theory based approach is used to model the evolution of point defects generated due to irradiation, and coupled to the mechanical behavior. A void nucleation and growth based damage framework is also developed to model failure initiation in these irradiated materials. The framework is used to simulate the following major features of inelastic deformation in bcc ferritic/martensitic steels: irradiation hardening, flow localization due to dislocation channel formation, failure initiation at the interfaces of these dislocation channels and grain boundaries, irradiation creep deformation, and temperature-dependent non-Schmid yield behavior. Model results are compared to available experimental data. This framework represents the state-of-the-art in constitutive modeling of the deformation behavior of irradiated materials.

Le développement à grande échelle des projets de véhicules électriques à pile àcombustible nécessite le déploiement d’infrastructures de transport et de stockaged’Hydrogène gazeux. La conception de ces structures et la sélection des matériaux nécessitede s’affranchir des risques liés à la fragilisation par l’Hydrogène des alliages métalliques. Cephénomène est bien décrit depuis plusieurs décennies, mais les mécanismes élémentaires àl’origine de ce mode d’endommagement restent controversés, notamment par manque demodèles quantitatifs. Plus précisément, le rôle de la déformation (micro-)plastique en pointede défaut sur le piégeage et l’endommagement par l’hydrogène, s’il est bien démontréexpérimentalement dans de nombreux systèmes, reste mal pris en compte dans les modèlesmicro-mécaniques. Le centre SMS de l’ENSM.SE a proposé des approches originales demodélisation des interactions hydrogène – dislocations, qui ont pu être validéesexpérimentalement dans des matériaux modèles de structure cubique à faces centrées. Cette thèsese propose d’appliquer une démarche semblable dans des alliages de structure cubiquecentrée. On mettra en oeuvre des essais de déformation sur des matériaux modèles pré-chargésen hydrogène, des modèles semi-analytiques et des observations des structures de déformationen microscopie électronique à transmission. / The development of electrical vehicles powered by hydrogen fuel cells requires the large scaledeployment of hydrogen storage and transport infrastructures. This in turn requires theassessment of the sensitivity of structural materials to hydrogen embrittlement phenomena.These damage modes, while being well described experimentally for since several decades,are still highly debated when it comes to elementary physical processes, mainly because of thelack of quantitative models for these elementary processes. More precisely, the role of the(micro-)plasticity developing at the tip of structural defects, while being well establishedexperimentally, is still poorly accounted for in the available micro-mechanical models. TheScience of Materials and Structures division of ENSM.SE already proposed originalmodelling approaches for hydrogen – dislocation interactions, that have been experimentallyvalidated in face-centred cubic materials. This project aims at applying the same type ofapproach to body-centred cubic metals. This will be achieved by means ofdeformation tests on hydrogen-charged model body centred cubic alloys, investigations of thedislocation microstructures by transmission electron microscopy and the development ofsemi-analytical models of hydrogen-dislocation interactions.