Thermal stability of the ���cave��� mineral ardealite Ca2(HPO4)(SO4)���4H2O

Thermogravimetry combined with evolved gas mass spectrometry has been used to characterise the mineral ardealite and to ascertain the thermal stability of this ���cave��� mineral. The mineral ardealite Ca2(HPO4)(SO4)���4H2O is formed through the reaction of calcite with bat guano. The mineral shows disorder and the composition varies depending on the origin of the mineral. Thermal analysis shows that the mineral starts to decompose over the temperature range 100 to 150��C with some loss of water. The critical temperature for water loss is around 215��C and above this temperature the mineral structure is altered. It is concluded that the mineral starts to decompose at 125��C, with all waters of hydration being lost after 226��C. Some loss of sulphate occurs over a broad temperature range centred upon 565��C. The final decomposition temperature is 823��C with loss of the sulphate and phosphate anions.

Cyclin-dependent kinase-mediated phosphorylation of RBP1 and pRb promotes their dissociation to mediate release of the SAP30��mSin3��HDAC transcriptional repressor complex

Eukaryotic cell cycle progression is mediated by phosphorylation of protein substrates by cyclin-dependent kinases (CDKs). A critical substrate of CDKs is the product of the retinoblastoma tumor suppressor gene, pRb, which inhibits G1-S phase cell cycle progression by binding and repressing E2F transcription factors. CDK-mediated phosphorylation of pRb alleviates this inhibitory effect to promote G1-S phase cell cycle progression. pRb represses transcription by binding to the E2F transactivation domain and recruiting the mSin3��histone deacetylase (HDAC) transcriptional repressor complex via the retinoblastoma-binding protein 1 (RBP1). RBP1 binds to the pocket region of pRb via an LXCXE motif and to the SAP30 subunit of the mSin3��HDAC complex and, thus, acts as a bridging protein in this multisubunit complex. In the present study we identified RBP1 as a novel CDK substrate. RBP1 is phosphorylated by CDK2 on serines 864 and 1007, which are N- and C-terminal to the LXCXE motif, respectively. CDK2-mediated phosphorylation of RBP1 or pRb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation. Consistent with these findings, RBP1 phosphorylation is increased during progression from G 1 into S-phase, with a concurrent decrease in its association with pRb in MCF-7 breast cancer cells. These studies provide new mechanistic insights into CDK-mediated regulation of the pRb tumor suppressor during cell cycle progression, demonstrating that CDK-mediated phosphorylation of both RBP1 and pRb induces their dissociation to mediate release of the mSin3��HDAC transcriptional repressor complex from pRb to alleviate transcriptional repression of E2F.

Machine vision toolbox for MATLAB, release 3 [Software]

The Toolbox, combined with MATLAB �� and a modern workstation computer, is a useful and convenient environment for investigation of machine vision algorithms. For modest image sizes the processing rate can be sufficiently ``real-time'' to allow for closed-loop control. Focus of attention methods such as dynamic windowing (not provided) can be used to increase the processing rate. With input from a firewire or web camera (support provided) and output to a robot (not provided) it would be possible to implement a visual servo system entirely in MATLAB. Provides many functions that are useful in machine vision and vision-based control. Useful for photometry, photogrammetry, colorimetry. It includes over 100 functions spanning operations such as image file reading and writing, acquisition, display, filtering, blob, point and line feature extraction, mathematical morphology, homographies, visual Jacobians, camera calibration and color space conversion.

Robotics toolbox for MATLAB, release 9 [Software]

The ninth release of the Toolbox, represents over fifteen years of development and a substantial level of maturity. This version captures a large number of changes and extensions generated over the last two years which support my new book ���Robotics, Vision & Control���. The Toolbox has always provided many functions that are useful for the study and simulation of classical arm-type robotics, for example such things as kinematics, dynamics, and trajectory generation. The Toolbox is based on a very general method of representing the kinematics and dynamics of serial-link manipulators. These parameters are encapsulated in MATLAB �� objects - robot objects can be created by the user for any serial-link manipulator and a number of examples are provided for well know robots such as the Puma 560 and the Stanford arm amongst others. The Toolbox also provides functions for manipulating and converting between datatypes such as vectors, homogeneous transformations and unit-quaternions which are necessary to represent 3-dimensional position and orientation. This ninth release of the Toolbox has been significantly extended to support mobile robots. For ground robots the Toolbox includes standard path planning algorithms (bug, distance transform, D*, PRM), kinodynamic planning (RRT), localization (EKF, particle filter), map building (EKF) and simultaneous localization and mapping (EKF), and a Simulink model a of non-holonomic vehicle. The Toolbox also including a detailed Simulink model for a quadcopter flying robot.

Effort-release public-key encryption from cryptographic puzzles

Timed-release cryptography addresses the problem of ���sending messages into the future���: information is encrypted so that it can only be decrypted after a certain amount of time, either (a) with the help of a trusted third party time server, or (b) after a party performs the required number of sequential operations. We generalise the latter case to what we call effort-release public key encryption (ER-PKE), where only the party holding the private key corresponding to the public key can decrypt, and only after performing a certain amount of computation which may or may not be parallelisable. Effort-release PKE generalises both the sequential-operation-based timed-release encryption of Rivest, Shamir, and Wagner, and also the encapsulated key escrow techniques of Bellare and Goldwasser. We give a generic construction for ER-PKE based on the use of moderately hard computational problems called puzzles. Our approach extends the KEM/DEM framework for public key encryption by introducing a difficulty notion for KEMs which results in effort-release PKE. When the puzzle used in our generic construction is non-parallelisable, we recover timed-release cryptography, with the addition that only the designated receiver (in the public key setting) can decrypt.

Ca2+ regulates the Drosophila Stoned-A and Stoned-B proteins interaction with the C2B domain of Synaptotagmin-1.

The dicistronic Drosophila stoned gene is involved in exocytosis and/or endocytosis of synaptic vesicles. Mutations in either stonedA or stonedB cause a severe disruption of neurotransmission in fruit flies. Previous studies have shown that the coiled-coil domain of the Stoned-A and the ��-homology domain of the Stoned-B protein can interact with the C2B domain of Synaptotagmin-1. However, very little is known about the mechanism of interaction between the Stoned proteins and the C2B domain of Synaptotagmin-1. Here we report that these interactions are increased in the presence of Ca(2+). The Ca(2+)-dependent interaction between the ��-homology domain of Stoned-B and C2B domain of Synaptotagmin-1 is affected by phospholipids. The C-terminal region of the C2B domain, including the tryptophan-containing motif, and the Ca(2+) binding loop region that modulate the Ca(2+)-dependent oligomerization, regulates the binding of the Stoned-A and Stoned-B proteins to the C2B domain. Stoned-B, but not Stoned-A, interacts with the Ca(2+)-binding loop region of C2B domain. The results indicate that Ca(2+)-induced self-association of the C2B domain regulates the binding of both Stoned-A and Stoned-B proteins to Synaptotagmin-1. The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles.

A vibrational spectroscopic study of the phosphate mineral zanazziite - Ca2(MgFe2+)(MgFe2+Al)4Be4(PO4)6���6(H2O)

Zanazziite is the magnesium member of a complex beryllium calcium phosphate mineral group named roscherite. The studied samples were collected from the Ponte do Piau�� mine, located in Itinga, Minas Gerais. The mineral was studied by electron microprobe, Raman and infrared spectroscopy. The chemical formula can be expressed as Ca2.00(Mg3.15,Fe0.78,Mn0.16,Zn0.01,Al0.26,Ca0.14)Be4.00(PO4)6.09(OH)4.00���5.69(H2O) and shows an intermediate member of the zanazziite���greinfeinstenite series, with predominance of zanazziite member. The molecular structure of the mineral zanazziite has been determined using a combination of Raman and infrared spectroscopy. A very intense Raman band at 970 cm���1 is assigned to the phosphate symmetric stretching mode whilst the Raman bands at 1007, 1047, 1064 and 1096 cm���1 are attributed to the phosphate antisymmetric stretching mode. The infrared spectrum is broad and the antisymmetric stretching bands are prominent. Raman bands at 559, 568, 589 cm���1 are assigned to the ��4 out of plane bending modes of the PO4 and HPO4 units. The observation of multiple bands supports the concept that the symmetry of the phosphate unit in the zanazziite structure is reduced in symmetry. Raman bands at 3437 and 3447 cm���1 are attributed to the OH stretching vibrations; Raman bands at 3098 and 3256 are attributed to water stretching vibrations. The width and complexity of the infrared spectral profile in contrast to the well resolved Raman spectra, proves that the pegmatitic phosphates are better studied with Raman spectroscopy.

An influenza virus inspired polymer system for the timed release of siRNA

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.

Mathematical modelling of controlled drug release from polymer micro-spheres : incorporating the effects of swelling, diffusion and dissolution via moving boundary problems

Controlled drug delivery is a key topic in modern pharmacotherapy, where controlled drug delivery devices are required to prolong the period of release, maintain a constant release rate, or release the drug with a predetermined release profile. In the pharmaceutical industry, the development process of a controlled drug delivery device may be facilitated enormously by the mathematical modelling of drug release mechanisms, directly decreasing the number of necessary experiments. Such mathematical modelling is difficult because several mechanisms are involved during the drug release process. The main drug release mechanisms of a controlled release device are based on the device���s physiochemical properties, and include diffusion, swelling and erosion. In this thesis, four controlled drug delivery models are investigated. These four models selectively involve the solvent penetration into the polymeric device, the swelling of the polymer, the polymer erosion and the drug diffusion out of the device but all share two common key features. The first is that the solvent penetration into the polymer causes the transition of the polymer from a glassy state into a rubbery state. The interface between the two states of the polymer is modelled as a moving boundary and the speed of this interface is governed by a kinetic law. The second feature is that drug diffusion only happens in the rubbery region of the polymer, with a nonlinear diffusion coefficient which is dependent on the concentration of solvent. These models are analysed by using both formal asymptotics and numerical computation, where front-fixing methods and the method of lines with finite difference approximations are used to solve these models numerically. This numerical scheme is conservative, accurate and easily implemented to the moving boundary problems and is thoroughly explained in Section 3.2. From the small time asymptotic analysis in Sections 5.3.1, 6.3.1 and 7.2.1, these models exhibit the non-Fickian behaviour referred to as Case II diffusion, and an initial constant rate of drug release which is appealing to the pharmaceutical industry because this indicates zeroorder release. The numerical results of the models qualitatively confirms the experimental behaviour identified in the literature. The knowledge obtained from investigating these models can help to develop more complex multi-layered drug delivery devices in order to achieve sophisticated drug release profiles. A multi-layer matrix tablet, which consists of a number of polymer layers designed to provide sustainable and constant drug release or bimodal drug release, is also discussed in this research. The moving boundary problem describing the solvent penetration into the polymer also arises in melting and freezing problems which have been modelled as the classical onephase Stefan problem. The classical one-phase Stefan problem has unrealistic singularities existed in the problem at the complete melting time. Hence we investigate the effect of including the kinetic undercooling to the melting problem and this problem is called the one-phase Stefan problem with kinetic undercooling. Interestingly we discover the unrealistic singularities existed in the classical one-phase Stefan problem at the complete melting time are regularised and also find out the small time behaviour of the one-phase Stefan problem with kinetic undercooling is different to the classical one-phase Stefan problem from the small time asymptotic analysis in Section 3.3. In the case of melting very small particles, it is known that surface tension effects are important. The effect of including the surface tension to the melting problem for nanoparticles (no kinetic undercooling) has been investigated in the past, however the one-phase Stefan problem with surface tension exhibits finite-time blow-up. Therefore we investigate the effect of including both the surface tension and kinetic undercooling to the melting problem for nanoparticles and find out the the solution continues to exist until complete melting. The investigation of including kinetic undercooling and surface tension to the melting problems reveals more insight into the regularisations of unphysical singularities in the classical one-phase Stefan problem. This investigation gives a better understanding of melting a particle, and contributes to the current body of knowledge related to melting and freezing due to heat conduction.

Infrared and Raman spectroscopic characterization of the phosphate mineral fairfieldite ��� Ca2(Mn2+,Fe2+)2(PO4)2��2(H2O)

Raman spectroscopy complimented with infrared spectroscopy has been used to determine the molecular structure of the phosphate mineral fairfieldite. The Raman phosphate (PO4)3- stretching region shows strong differences between the fairfieldite phosphate minerals which is attributed to the cation substitution for calcium in the structure. In the infrared spectra complexity exists with multiple (PO4)2- antisymmetric stretching vibrations observed, indicating a reduction of the tetrahedral symmetry. This loss of degeneracy is also reflected in the bending modes. Strong Raman bands around 600 cm-1 are assigned to v4 phosphate bending modes. Multiple bands in the 400���450 cm-1 region assigned to m2 phosphate bending modes provide further evidence of symmetry reduction of the phosphate anion. Three broadbands for fairfieldite are found at 3040, 3139 and 3271 cm-1 and are assigned to OH stretching bands. By using a Libowitzky empirical equation hydrogen bond distances of 2.658 and 2.730 A are estimated. Vibrational spectroscopy enables aspects of the molecular structure of the fairfieldite to be ascertained.

Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 ��g/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 ��g/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.

Fluorescence detection of plant extracts that affect neuronal voltage-gated Ca2+ channels

Structurally novel compounds able to block voltage-gated Ca2+ channels (VGCCs) are currently being sought for the development of new drugs directed at neurological disorders. Fluorescence techniques have recently been developed to facilitate the analysis of VGCC blockers in a multi-well format. By utilising the small cell lung carcinoma cell line, NCI-H146, we were able to detect changes in intracellular Ca2+ concentration ([Ca2+]i) using a fluorescence microplate reader. NCI-H146 cells have characteristics resembling those of neuronal cells and express multiple VGCC subtypes, including those of the L-, N- and P-type. We found that K+-depolarisation of fluo-3 loaded NCI-H146 cells causes a rapid and transient increase in fluorescence, which was readily detected in a 96-well plate. Extracts of Australian plants, including those used traditionally as headache or pain treatments, were tested in this study to identify those affecting Ca2+ influx following membrane depolarisation of NCI-H146 cells. We found that E. bignoniiflora, A. symphyocarpa and E. vespertilio caused dose-dependent inhibition of K+-depolarised Ca2+ influx, with IC50 values calculated to be 234, 548 and 209 ��g/ml, respectively. This data suggests an effect of these extracts on the function of VGCCs in these cells. Furthermore, we found similar effects using a fluorescence laser imaging plate reader (FLIPR) that allows simultaneous measurement of real-time fluorescence in a multi-well plate. Our results indicate that the dichloromethane extract of E. bignoniiflora and the methanolic extract of E. vespertilio show considerable promise as antagonists of neuronal VGCCs. Further analysis is required to characterise the function of the bioactive constituents in these extracts and determine their selectivity on VGCC subtypes.

Modulation of in vitro platelet 5-HT release by species of Erythrina and Cymbopogon

Extracts of Australian plants were screened to detect constituents affecting adenosine di-phosphate (ADP) induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of four tested plants including, Eremophila gilesii, Erythrina vespertilio, Cymbopogon ambiguus, and Santalum acuminatum, were found to cause significant inhibition of platelet 5-HT release. Inhibition levels ranged from 56-98%, and was not due to the non-specific effects of protein binding tannins. These extracts, and those we have previously identified as being active, were examined further to determine if they affect epinephrine (EPN), arachidonic acid (A.A) or collagen stimulated platelet aggregation and 5-HT release. Among those extracts investigated, we found that both the methanolic extract of E. vespertilio and the dichloromethane (DCM) extract of C. ambiguus were most potent and caused significant inhibition of platelet activation induced by EPN, A.A and to a lesser extent by collagen. Inhibition of ADP induced platelet 5-HT release by both of these extracts, was dose-dependent, with IC50 values for E. vespertilio and C. ambiguus estimated to be 20.4 microl (1.855 mg/ml) and 8.34 microl (0.758 mg/ml), respectively. Overall, C. ambiguus exhibited most activity and also caused dose-dependent inhibition of A.A induced platelet activation. These results indicate that inhibition may occur specifically at a site within the A.A pathway, and suggest the presence of a cyclo-oxygenase inhibitor. Both E. vespertilio and C. ambiguus are reported to be traditional headache treatments, with the present study providing evidence that they affect 5-HT release.

Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments

To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action.

Quantification of ebullitive and diffusive methane release to atmosphere from a water storage

Accurately quantifying total freshwater storage methane release to atmosphere requires the spatial���temporal measurement of both diffusive and ebullitive emissions. Existing floating chamber techniques provide localised assessment of methane flux, however, significant errors can arise when weighting and extrapolation to the entire storage, particularly when ebullition is significant. An improved technique has been developed that compliments traditional chamber based experiments to quantify the storage-scale release of methane gas to atmosphere through ebullition using the measurements from an Optical Methane Detector (OMD) and a robotic boat. This provides a conservative estimate of the methane emission rate from ebullition along with the bubble volume distribution. It also georeferences the area of ebullition activity across entire storages at short temporal scales. An assessment on Little Nerang Dam in Queensland, Australia, demonstrated whole storage methane release significantly differed spatially and throughout the day. Total methane emission estimates showed a potential 32-fold variation in whole-of-dam rates depending on the measurement and extrapolation method and time of day used. The combined chamber and OMD technique showed that 1.8���7.0% of the surface area of Little Nerang Dam is accounting for up to 97% of total methane release to atmosphere throughout the day. Additionally, over 95% of detectable ebullition occurred in depths less than 12 m during the day and 6 m at night. This difference in spatial and temporal methane release rate distribution highlights the need to monitor significant regions of, if not the entire, water storage in order to provide an accurate estimate of ebullition rates and their contribution to annual methane emissions.