Base modified peptidic nucleic acids: synthesis and crystallographic analysis of intermediates

Peptidic Nucleic Acids (PNAs) are achiral, uncharged nucleic add mimetics, with a novel backbone composed of N-(2-aminoethyl)glycine units attached to the DNA bases through carboxymethylene linkers. With the aim of extending and improving upon the molecular recognition properties of PNAs, the aim of this work was to synthesjse PNA building block intermediates containing a series of substituted purine bases for subsequent use in automated PNA synthesis. Four purine bases: 2,6~diaminopurine (D), isoGuanine (isoG), xanthine (X) and hypoxanthine (H) were identified for incorporation into PNAs targeted to DNA, with the promise of increased hybrid stability over extended pH ranges together with improvements over the use of adenine (A) in duplex formation, and cytosine (C) in triplex formation. A reliable, high-yielding synthesis of the PNA backbone component N -('2- butyloxycarbonyl-aminoethyl)glycinate ethyl ester was establishecl. The precursor N~(2-butyloxycarbonyl)amino acetonitrile was crystallised and analysed by X-ray crystallography for the first time. An excellent refinement (R = 0.0276) was attained for this structure, allowing comparisons with known analogues. Although chemical synthesis of pure, fully-characterised PNA monomers was not achieved, chemical synthesis of PNA building blocks composed of diaminopurine, xanthine and hypoxanthine was completely successful. In parallel, a second objective of this work was to characterise and evaluate novel crystalline intermediates, which formed a new series of substituted purine bases, generated by attaching alkyl substituents at the N9 or N7 sites of purine bases. Crystallographic analysis was undertaken to probe the regiochemistry of isomers, and to reveal interesting structural features of the new series of similarly-substituted purine bases. The attainment of the versatile synthetic intermediate 2,6-dichloro~9- (carboxymethyl)purine ethyl ester, and its homologous regioisomers 6-chloro~9- (carboxymethyl)purine ethyl ester and 6-chloro-7-(carboxymethyl)purine ethyl ester, necessitated the use of X-ray crystallographic analysis for unambiguous structural assignment. Successful refinement of the disordered 2,6-diamino-9-(carboxymethyl) purine ethyl ester allowed comparison with the reported structure of the adenine analogue, ethyl adenin-9-yl acetate. Replacement of the chloro moieties with amino, azido and methoxy groups expanded the internal angles at their point of attachment to the purine ring. Crystallographic analysis played a pivotal role towards confirming the identity of the peralkylated hypoxanthine derivative diethyl 6-oxo-6,7-dihydro-3H-purlne~3,7~djacetate, where two ethyl side chains were found to attach at N3 and N7,

The compressive creep and load relaxation properties of a series of high aluminium zinc-based alloys

A new family of commercial zinc alloys designated as ZA8, ZA12, and ZA27 and high damping capacity alloys including Cosmal and Supercosmal and aluminium alloy LM25 were investigated for compressive creep and load relaxation behaviour under a series of temperatures and stresses. A compressive creep machine was designed to test the sand cast hollow cylindrical test specimens of these alloys. For each compressive creep experiment the variation of creep strain was presented in the form of graphs plotted as percentage of creep strain () versus time in seconds (s). In all cases, the curves showed the same general form of the creep curve, i.e. a primary creep stage, followed by a linear steady-state region (secondary creep). In general, it was observed that alloy ZA8 had the least primary creep among the commercial zinc-based alloys and ZA27 the greatest. The extent of primary creep increased with aluminium content to that of ZA27 then declined to Supercosmal. The overall creep strength of ZA27 was generally less than ZA8 and ZA12 but it showed better creep strength than ZA8 and ZA12 at high temperature and high stress. In high damping capacity alloys, Supercosmal had less primary creep and longer secondary creep regions and also had the lowest minimum creep rate among all the tested alloys. LM25 exhibited almost no creep at maximum temperature and stress used in this research work. Total creep elongation was shown to be well correlated using an empirical equation. Stress exponent and activation energies were calculated and found to be consistent with the creep mechanism of dislocation climb. The primary α and β phases in the as-cast structures decomposed to lamellar phases on cooling, with some particulates at dendrite edges and grain boundaries. Further breakdown into particulate bodies occurred during creep testing, and zinc bands developed at the highest test temperature of 160°C. The results of load relaxation testing showed that initially load loss proceeded rapidly and then deminished gradually with time. Load loss increased with temperature and almost all the curves approximated to a logarithmic decay of preload with time. ZA alloys exhibited almost the same load loss at lower temperature, but at 120°C ZA27 improved its relative performance with the passage of time. High damping capacity alloys and LM25 had much better resistance to load loss than ZA alloys and LM25 was found to be the best against load loss among these alloys. A preliminary equation was derived to correlate the retained load with time and temperature.

The effects of metallurgical variables on the mechanical properties of high-chromium cast irons

The.use of high-chromium cast irons for abrasive wear resistance is restricted due to their poor fracture toughness properties. An.attempt was made to improve the fracture characteristics by altering the distribution, size and.shape of the eutectic carbide phase without sacrificing their excellent wear resistance. This was achieved by additions of molybdenum or tungsten followed by high temperature heat treatments. The absence of these alloying elements or replacement of them with vanadium or manganese did not show any significant effect and the continuous eutectic carbide morphology remained the same after application of high temperature heat treatments. The fracture characteristics of the alloys with these metallurgical variables were evaluated for both sharp-cracks and blunt notches. The results were used in conjunction with metallographic and fractographic observations to establish possible failure mechanisms. The fracture mechanism of the austenitic alloys was found to be controlled not only by the volume percent but was also greatly influenced by the size and distribution of the eutectic carbides. On the other hand, the fracture mechanism of martensitic alloys was independent of the eutectic carbide morphology. The uniformity of the secondary carbide precipitation during hardening heat treatments was shown to be a reason for consistant fracture toughness results being obtained with this series of alloys although their eutectic carbide morphologies were different. The collected data were applied to a model which incorporated the microstructural parameters and correlated them with the experimentally obtained valid stress intensity factors. The stress intensity coefficients of different short-bar fracture toughness test specimens were evaluated from analytical and experimental compliance studies. The.validity and applicability of this non-standard testing technique for determination of the fracture toughness of high-chromium cast irons were investigated. The results obtained correlated well with the valid results obtained from standard fracture toughness tests.

Using organoclay to promote morphology refinement and co-continuity in high-density polyethylene/polyamide 6 blends - Effect of filler content and polymer matrix composition

We investigate the gradual changes of the microstructure of two blends of high-density polyethylene (HDPE) and polyamide 6 (PA6) at opposite composition filled with increasing amounts of an organomodified clay. The filler locates preferentially inside the polyamide phase, bringing about radical alterations in the micron-scale arrangement of the polymer phases. When the host polyamide represents the major constituent, a sudden reduction of the average sizes of the polyethylene droplets was observed upon addition of even low amounts of organoclay. A morphology refinement was also noticed at low filler contents when the particles distributes inside the minor phase. In this case, however, keep increasing the organoclay content eventually results in a high degree of PA6 phase continuity. Rheological analyses reveal that the filler loading at which the polyamide assembles in a continuous network corresponds to the critical threshold for its rheological transition from a liquid- to a gel-like behaviour, which is indicative of the structuring of the filler inside the host PA6. On the basis of this finding, a schematic mechanism is proposed in which the role of the filler in driving the space arrangement of the polymer phases is discussed. Finally, we show that the synergism between the reinforcing action of the filler and its ability to affect the blend microstructure can be exploited in order to enhance relevant technological properties of the materials, such as their high temperature structural integrity.

Effect of calcium source on structure and properties of sol-gel derived bioactive glasses

The aim was to determine the most effective calcium precursor for synthesis of sol-gel hybrids and for improving homogeneity of sol-gel bioactive glasses. Sol-gel derived bioactive calcium silicate glasses are one of the most promising materials for bone regeneration. Inorganic/organic hybrid materials, which are synthesized by incorporating a polymer into the sol-gel process, have also recently been produced to improve toughness. Calcium nitrate is conventionally used as the calcium source, but it has several disadvantages. Calcium nitrate causes inhomogeneity by forming calcium-rich regions, and it requires high temperature treatment (>400 C) for calcium to be incorporated into the silicate network. Nitrates are also toxic and need to be burnt off. Calcium nitrate therefore cannot be used in the synthesis of hybrids as the highest temperature used in the process is typically 40-60 C. Therefore, a different precursor is needed that can incorporate calcium into the silica network and enhance the homogeneity of the glasses at low (room) temperature. In this work, calcium methoxyethoxide (CME) was used to synthesize sol-gel bioactive glasses with a range of final processing temperatures from 60 to 800 C. Comparison is made between the use of CME and calcium chloride and calcium nitrate. Using advanced probe techniques, the temperature at which Ca is incorporated into the network was identified for 70S30C (70 mol % SiO, 30 mol % CaO) for each of the calcium precursors. When CaCl was used, the Ca did not seem to enter the network at any of the temperatures used. In contrast, Ca from CME entered the silica network at room temperature, as confirmed by X-ray diffraction, Si magic angle spinning nuclear magnetic resonance spectroscopy, and dissolution studies. CME should be used in preference to calcium salts for hybrid synthesis and may improve homogeneity of sol-gel glasses.

Annealing and temperature coefficient study of type IA fibre Bragg gratings inscribed under strain and no strain - Implications to optical fibre component reliability

The annealing properties of Type IA Bragg gratings are investigated and compared with Type I and Type IIA Bragg gratings. The transmission properties (mean and modulated wavelength components) of gratings held at predetermined temperatures are recorded from which decay characteristics are inferred. Our data show critical results concerning the high temperature stability of Type IA gratings, as they undergo a drastic initial decay at 100°C, with a consequent mean index change that is severely reduced at this temperature However, the modulated index change of IA gratings remains stable at lower annealing temperatures of 80°C, and the mean index change decays at a comparable rate to Type I gratings at 80°C. Extending this work to include the thermal decay of Type IA gratings inscribed under strain shows that the application of strain quite dramatically transforms the temperature characteristics of the Type IA grating, modifying the temperature coefficient and annealing curves, with the grating showing a remarkable improvement in high temperature stability, leading to a robust grating that can survive temperatures exceeding 180°C. Under conditions of inscription under strain it is found that the temperature coefficient increases, but is maintained at a value considerably different to the Type I grating. Therefore, the combination of Type I and IA (strained) gratings make it possible to decouple temperature and strain over larger temperature excursions.

Room-temperature operation of widely tunable loss filter

A widely tunable and room-temperature operationable loss filter based on a long-period fibre grating (LPFG) fabricated in a B/Ge codoped fibre is reported. The filter exhibits extremely high temperature sensitivity. A maximum spectral shift of -48.1 nm from 10 to 40°C is achieved, corresponding to a thermal tuning efficiency of 1.6nm/°C. This value is increased by more than one order of magnitude compared with the LPFGs fabricated in standard telecom fibre, and even twice that of a LPFG with sensitivity enhanced by a special polymer.

Highly sensitive temperature and strain sensors based on all-fiber 45°-TFG Lyot filter

We demonstrate highly sensitive temperature and strain sensors based on an all-fiber Lyot filter structure, which is formed by concatenating two 45°-TFGs (tilted fiber gratings) with a PM fiber cavity. The experiment results show the all-fiber 45°-TFG Lyot filter has very high sensitivity to strain and temperature. The 45°-TFG Lyot filters of two different cavity lengths (18cm and 40 cm) have been evaluated for temperature sensing by heating a section of the cavity from 10°C to 50°C. The experiment results have shown remarkably high temperature sensitivities of 0.616nm/°C for 18cm and 0.31nm/°C for 40cm long cavity filter, respectively. The 18cm long cavity filter has been subjected to strain variations up to around 550μ ε and the filter has exhibited strain sensitivities of 0.02499nm/μ ε and 0.012nm/μ ε for two straining situations, where its cavity middle section of 18cm and 9cm were stretched, respectively. © 2012 SPIE.

Sensitivity-enhanced fiber optic temperature sensor with strain response suppression

A temperature sensor based on a multimode-singlemode-multimode (MSM) fiber structure has been proposed and experimentally demonstrated. By utilizing the interference between fiber core and cladding modes, temperature measurement is exploited by monitoring the selected resonant dips shift of the transmission spectrum. A high temperature sensitivity of 50.65 pm/ºC is achieved at a certain resonant dip, accompanied by a suppressed strain sensitivity of only 0.587 pm/με. The sensor reveals the advantages of easy fabrication and interrogation, low cost and small axial strain response. © 2013 Elsevier Inc. All rights reserved.

The effects of material variations in high value manufacturing industries

It has never been easy for manufacturing companies to understand their confidence level in terms of how accurate and to what degree of flexibility parts can be made. This brings uncertainty in finding the most suitable manufacturing method as well as in controlling their product and process verification systems. The aim of this research is to develop a system for capturing the company’s knowledge and expertise and then reflect it into an MRP (Manufacturing Resource Planning) system. A key activity here is measuring manufacturing and machining capabilities to a reasonable confidence level. For this purpose an in-line control measurement system is introduced to the company. Using SPC (Statistical Process Control) not only helps to predict the trend in manufacturing of parts but also minimises the human error in measurement. Gauge R&R (Repeatability and Reproducibility) study identifies problems in measurement systems. Measurement is like any other process in terms of variability. Reducing this variation via an automated machine probing system helps to avoid defects in future products.Developments in aerospace, nuclear, oil and gas industries demand materials with high performance and high temperature resistance under corrosive and oxidising environments. Superalloys were developed in the latter half of the 20th century as high strength materials for such purposes. For the same characteristics superalloys are considered as difficult-to-cut alloys when it comes to formation and machining. Furthermore due to the sensitivity of superalloy applications, in many cases they should be manufactured with tight tolerances. In addition superalloys, specifically Nickel based, have unique features such as low thermal conductivity due to having a high amount of Nickel in their material composition. This causes a high surface temperature on the work-piece at the machining stage which leads to deformation in the final product.Like every process, the material variations have a significant impact on machining quality. The main cause of variations can originate from chemical composition and mechanical hardness. The non-uniform distribution of metal elements is a major source of variation in metallurgical structures. Different heat treatment standards are designed for processing the material to the desired hardness levels based on application. In order to take corrective actions, a study on the material aspects of superalloys has been conducted. In this study samples from different batches of material have been analysed. This involved material preparation for microscopy analysis, and the effect of chemical compositions on hardness (before and after heat treatment). Some of the results are discussed and presented in this paper.

Viscosity of aged bio-oils from fast pyrolysis of beech wood and miscanthus:shear rate and temperature dependence

The viscosity of four aged bio-oil samples was measured experimentally at various shear rates and temperatures using a rotational viscometer. The experimental bio-oils were derived from fast pyrolysis of beech wood at 450, 500, and 550 °C and Miscanthus at 500 °C (in this work, they were named as BW1, BW2, BW3, and MXG) in a bubbling fluidized bed reactor. The viscosity of all bio-oils was kept constant at various shear rates at the same temperature, which indicated that they were Newtonian fluids. The viscosity of bio-oils was strongly dependent upon the temperature, and with the increase of the temperature from 30 to 80 °C, the viscosity of BW1, BW2, BW3, and MXG decreased by 90.7, 93.3, 92.6, and 90.2%, respectively. The Arrhenius viscosity model, which has been commonly used to represent the temperature dependence of the viscosity of many fluids, did not fit the viscosity-temperature experimental data of all bio-oils very well, especially in the low- and high-temperature regions. For comparison, the Williams-Landel-Ferry (WLF) model was also used. The results showed that the WLF model gave a very good description of the viscosity-temperature relationship of each bio-oil with very small residuals and the BW3 bio-oil had the strongest viscosity-temperature dependence.