Sephin1 selectively inhibits a protein phosphatase to prevent two protein misfolding diseases in mice. The reversible phosphorylation of proteins controls virtually all aspects of cell and organismal function. Targeting phosphorylation offers a broad range of therapeutic opportunities, and kinases have become important therapeutic targets. Phosphatases should be as attractive as kinases as therapeutic targets, but in fact they are more challenging. Das et al. identified a small molecule, Sephin1, that is a specific inhibitor targeting a regulatory subunit of protein phosphatase 1. Sephin1 binds and inhibits PPP1R15A, but not the related regulatory phosphatase PPP1R15B. Sephin1 prolonged a stress-induced, phosphorylation-dependent signaling pathway to prevent the pathological defects in mouse models of two unrelated protein-misfolding diseases Charcot-Marie-Tooth 1B and amyotrophic lateral sclerosis. I. Das, A. Krzyzosiak, K. Schneider, L. Wrabetz, M. D'Antonio, N. Barry, A. Sigurdardottir, A. Bertolotti, Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science 348, 239–242 (2015). [Abstract] [Full Text]


The aim of this article is to revisit disasters as materially enlivened events. The sociology of disasters has usually rested upon two assumptions. First, that disasters are phenomena circumscribed in time and space. They are geographically situated and time-specific, thus their effects can be controlled and compared. And second, that the main actors involved in disasters are humans and institutions, the basic units of sociological research and theory. These principles, taken together, help in converting disaster into objects for cultural inquiry, but at the expense of diluting their material surplus. Based on the work of Tim Ingold, and drawing on the case of the Aznalcóllar ecological disaster in Doñana, one of the most damaging environmental disasters in the history of Spain, we propose to define disasters as meshworks in order to fully grasp the vibrant ontology of disasters. More specifically, by focusing on the role played by migratory birds in the enacting of the disaster, we argue that disasters are dynamic realities, difficult to localize and always distributed along disparate scales and actors. Moreover, disasters have a dual reality, unfolding actually and virtually at once – and therefore comprising a form of cosmopolitics rather than conforming to classical political imaginations. Finally, our larger point is to take disasters as opportunities to rethink our ways of living together.


Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.


Compiled by specialists from the University of Durham Department of East Asian Studies, this new reference work contains approximately 1500 entries covering Chinese civilisation from Peking Man to the present day. Subjects include history, politics, art, archaeology, literature, etc. The Dictionary is intended for students, teachers and researchers, and will also be of interest to the general reader. Entries provide factual information and contain suggestions for further reading. Chinese terms are in pinyin romanisation and characters are given for the subject headings. A name index and comprehensive cross-reference system make this an easy to use, multi-purpose guide to the student of Chinese in the broadest sense.


Predictions that invasive alien plants would use significant
amounts of water were a major factor in the establishment of South
Africa'sWorking forWater programme, which aims to protect water
resources by clearing these plants. The predictions were made
by combining the results of hydrological experiments, conducted
to assess the effects of afforestation with alien trees on water
resources, with an ecological understanding of the spread and
establishment of invasive trees. The forecasts were then scaled up
to arrive at national estimates of the corresponding water consumption.
This paper reviews the approaches that have been used to
estimate these consequences at different scales. We propose a
framework for assessing the process of knowledge generation, and
review the approaches used in South Africa at each level of the
framework, the current level of understanding arising from the use
of these methods, and significant gaps in understanding. The
framework has four levels: fundamental observations from which a
detailed understanding of biophysical processes can be developed;
applied or predictive research from which an understanding
of processes can be scaled up to predict generic outcomes; integrative
research where a predictive understanding of hydrology
can be combined with information from other disciplines to place
the outcomes in a wider context; and research on management support,
such that the information can be used to improve management
and policy decisions.We conclude that much knowledge exists, but
that there are also significant gaps in understanding, and challenges
associated with scaling up and down to make appropriate
predictions. This is especially true at the management support
level, where very different kinds of uncertainties operate in the
same comparative framework. Existing knowledge needs also to
be used more effectively, to help prioritize clearing operations by
targeting areas in terms of water-related benefits.


This paper treats estimation of the Wigner-Ville spectrum (WVS) of Gaussian continuous-time stochastic processes using Cohen's class of time-frequency representations of random signals. We study the minimum mean square error estimation kernel for locally stationary processes in Silverman's sense, and two modifications where we first allow chirp multiplication and then allow nonnegative linear combinations of covariances of the first kind. We also treat the equivalent multitaper estimation formulation and the associated problem of eigenvalue-eigenfunction decomposition of a certain Hermitian function. For a certain family of locally stationary processes which parametrizes the transition from stationarity to nonstationarity, the optimal windows are approximately dilated Hermite functions. We determine the optimal coefficients and the dilation factor for these functions as a function of the process family parameter


Variable interaction between the Bw4 epitope of HLA-B and the polymorphic KIR3DL1/S1 system of inhibitory and activating NK cell receptors diversifies the development, repertoire formation, and response of human NK cells. KIR3DL1*004, a common KIR3DL1 allotype, in combination with Bw4+ HLA-B, slows progression of HIV infection to AIDS. Analysis in this study of KIR3DL1*004 membrane traffic in NK cells shows this allotype is largely misfolded but stably retained in the endoplasmic reticulum, where it binds to the chaperone calreticulin and does not induce the unfolded protein response. A small fraction of KIR3DL1*004 folds correctly and leaves the endoplasmic reticulum to be expressed on the surface of primary NK and transfected NKL cells, in a form that can be triggered to inhibit NK cell activation and secretion of IFN-γ. Consistent with this small proportion of correctly folded molecules, trace amounts of MHC class I coimmunoprecipitated with KIR3DL1*004. There was no indication of any extensive intracellular interaction between unfolded KIR3DL1*004 and cognate Bw4+ HLA-B. A similarly limited interaction of Bw4 with KIR3DL1*002, when both were expressed by the same cell, was observed despite the efficient folding of KIR3DL1*002 and its abundance on the NK cell surface. Several positions of polymorphism modulate KIR3DL1 abundance at the cell surface, differences that do not necessarily correlate with the potency of allotype function. In this context, our results suggest the possibility that the effect of Bw4+ HLA-B and KIR3DL1*004 in slowing progression to AIDS is mediated by interaction of Bw4+ HLA-B with the small fraction of cell surface KIR3DL1*004.


We present new numerical cosmological solutions of the Einstein Field Equations. The spacetime is spherically symmetric with a source of dust and radiation approximated as a perfect fluid. The dust and radiation are necessarily non-comoving due to the inhomogeneity of the spacetime. Such a model can be used to investigate non-linear general relativistic effects present during decoupling or big-bang nucleosynthesis, as well as for investigating void models of dark energy with isocurvature degrees of freedom. We describe the full evolution of the spacetime as well as the redshift and luminosity distance for a central observer. After demonstrating accuracy of the code, we consider a few example models, and demonstrate the sensitivity of the late time model to the degree of inhomogeneity of the initial radiation contrast.


In 1973 progress report for the experimental study of the structure of nuclei and the interactions of intermediate energy particles.


This work is the result of an ended research about the Spanish foreign language teaching for specific purposes, that contains a proposal of theoretic methodological model based on interactive communicative tasks for speaking skills development in the students academic discourse, who are preparing as future professionals of Physical Culture. The model is derived of the dialectical materialistic interpretations of the interaction and the communication from diverse dimensions (philosophical, psychological, sociological, pedagogic and linguistic) and it constitutes a theoretical contribution. In making of this work were used procedures and research techniques like oral records that facilitated to know the students' interlanguage and it was directed to check in what measure a correct use of the language was made. The contribution to Spanish's teaching as a foreign language for professional goals in the physical culture area, reflected in this work, precise the components of the teaching learning process and the teachers' and students' functions in an interactive process. It allows the students to express their ideas with correction and property making use of the scientific style and transactional functions of the language to be able to define, to describe, to argue, to synthesize, to narrate, to debate, among others. The making of a tasks program used in Spanish's teaching as foreign language, constitutes the practical contribution of the research carried out, as well as the application of the model in other courses of foreign languages for professional goals. The work in general sense is a professional experience directed to solve educational problems, particularly those related with the abilities of the Physical Culture professional of the country and the institution in question, where its results were applied during several courses.


Background— Impulsive behavior in humans predicts the onset of drinking during adolescence and alcohol use disorders (AUDs) in adulthood. It is also possible, however, that heavy drinking may increase impulsive behavior by affecting the development of brain areas that support behavioral control or through other associated mechanisms. This study examined whether drinking heavily during adolescence is related to changes in impulsive behavior with a specific focus on how the association differs across individuals, contingent on the developmental course of their impulsiveness. Method— Data came from a sample of boys ( N =503) who were followed annually from approximate age 8 to age 18 and again at approximate age 24/25. Heavy drinking was defined as experiencing a blood alcohol concentration (BAC) level of .08% or higher. At each assessment, the parent and child each reported whether the child was impulsive. Results— First, group-based trajectory analysis was used to identify four groups differing in the level and slopes of their trajectories of impulsive behavior from age 9 to age 17: low (13.9%), early adolescence-limited (18.7%), moderate (60.8%) and high (6.6%). These trajectory groups differed in their prevalence of any heavy drinking, peak BACs, and rates of alcohol dependence in adolescence and AUD in early adulthood, with the less impulsive groups being lower on these measures than the more impulsive groups. Heavy drinking was then entered into the model as a time-varying covariate; this measure was lagged so that the results represent change in impulsive behavior the year following heavy drinking. Among boys on the moderate trajectory, those who drank heavily were rated as significantly more impulsive the following year compared to those who did not drink heavily. Conclusions— The association between heavy drinking and impulsive behavior may depend on earlier levels of impulsive behavior with those who are moderately impulsive appearing to be at greatest risk for increased impulsive behavior following heavy drinking. Further research is needed to clarify this association.


Most of the current swarm model studies and applications try to mimic the collective behaviors of social animals, such as birds and ants. The studies seek to solve tasks similar to patterns and behaviors exhibited in those animal colonies. In this research, we demonstrated that the swarm model is also the major collaboration and organization model of Open Source Software (OSS) developer communities. OSS developers swarm together and spend their time attempting to achieve their relatively simple goals, while their contributions emerged as a collection of useful and sophisticated functionality that can compete with commercial software. The results discovered in this research will be helpful in demonstrating that the swarm model can not only be considered as a feasible approach to classical optimization problems, but can also be applied to constructing highly sophisticated systems.


Before the age of Industrial Revolution, the great Asian civilisations - whether located in the Middle East, India, South-East Asia, or the Far East - constituted areas not only of high culture but also of advanced economic development. They were the First World of human societies. This 1985 book examines one of the driving forces of that historical period: the long chain of oceanic trade which stretched from the South China Sea to the eastern Mediterranean. It also looks at the natural complement of the seaborne commerce, its counterpart in the caravan trade. Its main achievement is to show how socially determined demand derived from cultural habits and interpretations operated through the medium of market forces and relative prices. It points out the unique and limiting features of Asian commercial capitalism, and shows how the contribution of Asian merchants was valued universally, in reality if not legally and formally. Professor Chaudhuri's book, based on more than twenty years' research and reflection on pre-modern trade and civilisations, was a landmark in the analysis and interpretation of Asia's historical position and development.


In some diamond-based semiconducting devices, large variations of doping level are required over short distances. Tools to determine doping level and defects distribution should therefore be developed. The present contribution shows the capabilities of electron microscopy in this field. Focused ion beam (FIB-dual beam) cross section preparations allowed evaluating doping level in highly boron doped sample with doping transition down to some nm by diffraction contrast mode of transmission electron microscopy (CTEM) and by high angle annular dark field mode of scanning transmission electron microscopy (HAADF-STEM). The sensibility of the latter is around 1019cm-3 and, thus, cathodoluminescence (CL) is required for lower doping levels. Cross sectional analysis on FIB prepared lamella allowed to separate the epilayer behaviour from that of the substrate. Mid-gap centers involving boron, hydrogen and, for some peaks, also nitrogen are revealed. sp2 bonds are also present in the grown epilayer. These transitions make difficult the observation of excitonic recombinations in the cross section configuration.


Borrelia burgdorferi sensu lato, a tick-borne spirochete, is the causative agent of Lyme disease, the most prevalent vector-borne disease in Europe and United States. However, the incidence of this disease is variable and the clinical picture depends on the pathogen species. The infectivity of Ixodes ticks with Borrelia, was 46 % and 35 % in 2000 and 2001 in Latvia, respectively, and 14 % in 2002 in Lithuania, assessed by nested polymerase chain reaction (PCR) amplifi cation of the plasmid OspA gene fragment of Borrelia. PCR-restriction fragment length polymorphism (RFLP) analysis of the 16S-23S (rrs-rrlA) rRNA intergenic spacer was used for typing of Borrelia directly in ticks. Species-specifi c primers and subsequent sequences analysis were used as another approach for Borrelia species typing. All three clinically relevant B. burgdorferi sensu lato genospecies (B. afzelii, B. garinii, B. burgdorferi sensu stricto) were detected in the ticks collected in Latvia. The same result was obtained earlier in Estonia. B. valaisiana, a possible infectious agent of Lyme borreliosis, was detected only in Latvia. Only B. afzelii and B. garinii species were detected in ticks from Lithuania. Different subspecies were also identifi ed. This study demonstrates the predominance of the genospecies B. afzelii in all three Baltic countries, and the circulation of different B. burgdorferi sensu lato subspecies in the environment. This knowledge might have a signifi cant importance for monitoring of Lyme disease in Europe.


William Gunn (1800-1868), police magistrate and Superintendent of Prisoners' Barracks, was born in Newry, Ireland, son of Lieut. William Gunn and Margaret (Wilson). After service in the British army, he came to Tasmania in 1822 and received a grant of land in the Sorell district, called by Gunn "Bourbon" after his regiment He served as Superintendent of Prisoners' Barracks in Hobart from 1826 1850 and Launceston 1850 -1859 and remained Police Magistrate in Launceston until his death in 1868. On moving to Launceston he acquired Glen Dhu as his main residence. In 1829 William Gunn married at Sorell Frances Hannah (Fanny) Arndell. They had three sons, including William, Ronald Thomas and James Arndell, and 6 daughters, including Margaret who married in 1852 Frank Allison (see A2) and Frances (Fanny jr.) and Isabel (Issie). Gunn was an elder of St Andrews Church, Hobart, and later of Chalmers Church, Launceston.
In 1830 William's brother, Ronald Campbell Gunn (1808-1881) settled in Tasmania.
William Gunn's wife's sister, Elizabeth Emily (Arndell), was married to another Sorell land holder, James Gordon of Forcett, who she married in 1814. James Gordon (1779-1842), born at Forcett, Yorkshire, England, son of John Gordon steward of the Stanwyck estate, had emigrated to Sydney as a merchant in 1806. In 1814 he was appointed Naval Officer in Hobart and granted land at Sorell and the following year he resigned his appointment to develop his property. In 1828 he succeeded his nephew, John Lakeland, as Superintendent of Convicts and in 1829 he was appointed Police Magistrate at Launceston but his delay in making his financial returns led to suspicion of fraud. In 1835 he retired to look after his property and the children of John Lakeland who were his wards. He was involved in a debt dispute with William Gunn, who after Gordon's death brought a law suit against his widow.
John Lakeland (d.1828) arrived in Tasmania in 1814 or 1815. He served as Superintendent of Convicts until his death in 1828 and was granted land at Pittwater. He married Mary Louisa Arndell (d.1835),sister of Emily Elizabeth Arndell who was married to Lakeland's uncle, James Gordon. They had 2 sons, James Gordon and John Thomas, and 2 daughters, Emily Elizabeth and Louisa. John Lakeland appointed his uncle James Gordon and his brother-in-law William Gunn as executors and trustees of his will and guardian of his children. His widow, Mary, married Thomas H. White, the farm manager, in 1831 against the wishes of the trustees owing to some scandalous rumours about White's intentions and moral character.


Chapter 1 reviews the copper- and palladium-mediated aryl-N bond formations used in the synthesis of biological active compounds. Examples using the palladium-catalysed Buchwald-Hartwig method, the copper-mediated Ullmann-Goldberg method and the Cham-Lan method were compared concerning their reaction conditions, their scope for a wide spectra of substituent and functional groups and their scale-up prospects. The discussed examples show that palladium-catalysed reactions are favoured for large scale applications and tolerate sterical demanding substituents on the coupling partners better than Cham-Lan conditions. Cham-Lan N-arylations are particular mild and do not require the addition of ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald-Hartwig-type reactions have been used in intramolecular reactions giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C-N bond formation in the course of a total synthesis or drug synthesis.

Chapters 2, 3 and 4 deal with the modulation of the membrane located ABC-transporter ABCG2, which is an effective tool for the treatment of multi-drug resistant cancer cells. Starting from the recently discovered tariquidar-derived selective ABCG2 modulator (lead structure), in chapter 2 different fluorescent labelled ABCG2 modulators were synthesised. The modified modulators show emission in the red part of the spectrum and reveal quantum yields up to
31.2 %. Moderate potency was obtained by the replacement of the tetrahydroisoquinoline part of the tariquidar-derived lead-structure by a pyrylium label. All synthesised derivatives showed selectivity for ABCG2 over ABCB1. Studies at the physiological expressed ABCG2 concentrations on rat brain capillaries revealed that the parent lead structure is also influencing the rat ABCG2 transporter, confirming the results of previous in vitro experiments with MCF-7/Topo cells and Hoechst 33342 as substrate. Due to lower affinity of the fluorescent labelled compounds, this could not be proven for the fluorescent modulators.
Chapter 3 shows structural variations of the lead structure to improve the drug-like properties and the potency. Incubation in mouse plasma proved the stability of the ester functionality, but one of the peptide bonds was cleaved, also if N-methylated. Structural changes of different parts of the molecule decreased the potency only moderately as long as there was no negative charge introduced under physiological conditions. The phenylbenzamide group turned out to be essential for the interaction with the transporter.
Chapter 4 discribes photochromic tariquidar-derived compounds as potential ABCG2 modulators which may be useful as tool in mechanistic investigation. The synthetic approach was focused on the replacement of characteristic structural moieties of a potent and selective ABCG2 inhibitor by photochromic dithienylethenes. Photochemical properties, thermostability, cycle performance, photostationary state and photostability at assay conditions are suitable for all four compounds for pharmacological in vitro investigations.

Chapter 5 reports the synthesis of secondary amines containing two carbon stereocentres in both alpha-positions. These are typical substructure of ACE inhibitors and other biological active compounds. The stereoselective synthesis was aspired in different approaches, but industrial applications still mostly apply the separation of diastereomers. Here, two synthetic methods, a SN2 reaction and an oxazolidine mediated reaction sequence, were compared concerning their selectivity. The oxazolidine intermediate-mediated amine formation gave only one entantiomer for the substituted secondary amine. The synthesised compounds showed weak or no cytotoxicity. Selected compounds were tested as inhibitors of ACE-2, but revealed no biological activity.


Objective—Dendritic cells (DCs) have recently been found in atherosclerosis-predisposed regions of arteries and have been proposed to be causal in atherosclerosis. The chemokine receptor CX3CR1 is associated with arterial injury and atherosclerosis. We sought to determine whether a link exists between arterial DC accumulation, CX3CR1, and atherosclerosis. Methods and Results—Mouse aortas were isolated and subjected to en face immunofluorescence analysis. We found that DCs were located predominantly in the intimal regions of arterial branch points and curvatures. Consistent with the increased accumulation of intimal DCs in aged and ApoE−/− aortas compared with young WT aortas (P=0.004 and 0.05, respectively), the incidence of atherosclerosis was 88.9% for aged WT and 100% for ApoE−/− mice compared with 0% for young WT mice. CX3CR1 was expressed on intimal DCs and DC numbers were decreased in CX3CR1-deficient aortas of young, aged, and ApoE−/− mice (P=0.0008, 0.013, and 0.0099). The reduced DC accumulation in CX3CR1-deficiency was also correlated with decreased atherosclerosis in these animals. Conclusions—The accumulation of intimal DC increases in aged and ApoE−/− aortas and correlates with the generation of atherosclerosis. CX3CR1-deficiency impairs the accumulation of DC in the aortic wall and markedly reduces the atherosclerotic burden.


Millions of slide presentations are being authored and delivered with computer software every day. Yet much of the computer's power for these tasks remains untapped. Existing interaction techniques leave presenters wrestling with limited size computer displays to get meaningful overviews of their work. Without these overviews, they have trouble finding patterns in their data and experimenting with alternate organizations. They also have difficulty communicating the structure of large or complex talks to the audience and keeping the audience oriented during unexpected transitions between ideas. A natural solution is Zoomable User Interfaces (ZUIs) since they offer the capability to view information at multiple levels of detail and smoothly transition between ideas. This work presents two ZUIs, Niagara and CounterPoint, for authoring and delivering slide presentations.
Niagara is a ZUI workspace for authoring presentation content with techniques to improve authoring in the zoomable environment. Empirical evaluations of ZUI-based authoring tools revealed performance improvements and subjective preferences over folder-based interfaces for organization tasks. Users were 30% faster with ZUIs than with folders in completing a simplified shape organization task. Some classes of users were also faster with ZUIs than with folders in completing a text-based organization task. Users performing both tasks exhibited a strong preference for ZUIs over folders.
CounterPoint provides a number of features to simplify the creation and delivery of ZUI presentations. The effects of these presentations on the audience were evaluated in a controlled comparison of presentations with slides only, slides with spatial layouts, and slides with spatial layouts and animation. The study revealed a strong subjective preference and higher ratings of organization for presentations with spatial layout.
Feedback was also gathered from presenters who used CounterPoint to deliver over 100 real-world presentations. They indicated that CounterPoint helped them communicate overviews and multi-level presentation structures. More experienced CounterPoint presenters also found that CounterPoint helped them keep the audience oriented when navigating the presentation in response to audience feedback.


This paper was initiated by a question of Eisenbud who asked whether the entries of the matrices in a minimal free resolution of a monomial ideal (which, after a suitable choice of bases, are monomials) divide the least common multiple of the generators of the ideal. We will see that this is indeed the case, and prove it by lifting the multigraded resolution of an ideal, or more generally of a multigraded module, keeping track of how the shifts 'deform'' in such a lifting; see Theorem 2·1 and Corollary 2·2.


A freshwater Indian air breathing catfish, Clarias batrachus was subjected to low (3.75 mg/L) and high (18.75 mg/L) sub lethal dose of lead nitrate for short (24, 48 and 96 hours) and long term (15, 30 and 45 days) treatment to study serum biochemical features. All the variations were more dependent on the dose in comparison to the duration. At the end of the experiment, serum glucose, serum cholesterol and serum urea levels raised (p<0.05) in both the concentrations of lead exposed fish when compared to controlled one. Conversely, the serum protein level decreased (p<0.05) in the lead exposed groups in comparison to the control group. These changes are indicative of stress imposed on the fish by lead and could be used as biomarkers of lead poisoning.


Democracy is not just about free and fair elections. It requires at least some minimal substantial guarantees, such as freedom of speech and freedom of assembly, that formulate and enable free choice of autonomous and equal agents. These notions are well founded in Israeli constitutional law, but in recent years it seems that this basic understanding of the democratic process is weakening, especially as reflected in the actions of the Knesset. Several recent examples of Knesset legislation processes suggest that Israeli democratic culture is being eroded, as some of democracy's fundamental notions are abandoned in favor of national-chauvinism and intolerance.


The reflection properties of pressed polytetrafluoroethylene powder have been under investigation by the Radiometric Physics Division at the National Bureau of Standards for the past five years. This material has a great potential use, both as a standard of diffuse reflectance and as a coating for integrating spheres for applications in reflectance spectrophotometry and other signal-averaging devices. It possesses certain physical and optical properties that make it ideal for use in these applications. Techniques are given for preparing reflection standards and coating integrating spheres with the pressed powder. The effects of powder density and thickness on its reflectance are reported, and observations of possible problems with fluorescence that are due to the presence of contaminants in the powder are discussed. The absolute reflectance (6°/hemispherical reflectance factor relative to a perfect diffuser) is reported for the spectral range of 200–2500 nm. The directional/hemispherical reflectance factor relative to 6°/hemispherical reflectance is given for several wavelengths in the ultraviolet and visible spectrum and for angles of incidence between 5 and 75°. The bidirectional reflectance factor is reported for 300, 600, and 1500 nm at angles of incidence of −10, −30, −50, and −70° and at viewing angles at 10° intervals from −80 to +80°.


A series of synthetic oligomers (based on the thermosensitive polymer poly(N-isopropylacrylamide) and carbohydrate polymers (including hyaluronic acid, carboxymethyl cellulose, dextran, and methylcellulose) were functionalized with hydrazide or aldehyde functional groups and mixed using a double-barreled syringe to create in situ gelling, hydrazone-cross-linked hydrogels. By mixing different numbers and ratios of different reactive oligomer or polymer precursors, covalently cross-linked hydrogel networks comprised of different polymeric components are produced by simple mixing of reactive components, without the need for any intermediate chemistries (e.g., grafting). In this way, hydrogels with defined swelling, degradation, phase transition, drug binding, and mechanical properties can be produced with properties intermediate to those of the mixture of reactive precursor polymers selected. When this modular mixing approach is used, one property can (in many cases) be selectively modified while keeping other properties constant, providing a highly adaptable method of engineering injectable, rapidly gelling hydrogels for potential in vivo applications.


During the short photoperiod of winter, some short-lived rodents repress reproduction and other non-essential functions, while others continue to reproduce. The capacity to reproduce during short photoperiod or to repress reproduction is genetically variable, signaling a potential microevolutionary lifehistory tradeoff. Previous results linked this variation to the location and abundance of immunoreactive (IR) gonadotropin releasing hormone (GnRH) neurons in male white-footed mice (Peromyscus leucopus). Independently, previous results also found differences in food intake in males linked to genetic variation in the same population. In this study we tested for the relationship between food intake and the number of IR-GnRH neurons in females. The experiment used three selected lines of P. leucopus derived from a wild population. The three lines were, respectively, reproductively inhibited in short photoperiod (R line), reproductive in short photoperiod and therefore non-responsive to photoperiod (NR), and a control line not deliberately under selection. We performed immunostaining and counted the number of IR-GnRH neurons in one anterior and three preoptic brain sections. We tested for variation in the number of GnRH neurons in female P. leucopus and compared food intake, reproductive development and the interaction of all three. We found a significant difference in food intake among lines, with the NR mice eating 20 percent more than the R mice. The difference in food intake is consistent with a microevolutionary lifehistory tradeoff, similar to previous findings in males, but smaller in magnitude. There was no significant difference in the number of IR-GnRH neurons among lines. There was no correlation between the number of IR-GnRH neurons and the other measures. This suggests either a need for additional testing for females or that there is an actual difference in the number of IR-GnRH neurons between males and females.


The community radio sector in Australia is under-funded and under-resourced. Many of the 270-plus stations in Australia (CBAA 2012) struggle to maintain long-term viability and manage their day-to-day financial operations. Practitioners in the sector use a range of strategies to attract funding; however, there are no magic formulas for keeping their heads above water. Approximately 10 per cent of funding comes from government grants (Forde at al 2002: 98–99), most of which are one-off grants for specific projects. If the value of a community radio station could be determined, then surely it would be easier to attract funding from government or other sources. In this paper I examine the concept of value in the context of the community radio station. I explain why the assessment of value is important. Since the value of community radio is a divergent and contested theoretical terrain, a clearer understanding of value would most likely enable stations to attract more funding. I explore the notion of value in relation to community radio through four theoretical lenses. The first lens is the lens of definitions, where the value of community radio can be determined by how it is defined. As a medium, community radio can sit under various umbrella "alternative media"–type definitions. The definitions can also be entwined with notions of value, obfuscating the theoretical territory. The second lens is the lens of oppositional power. Community radio as a type of alternative media has long been associated with "oppositional" stances to mainstream media themes. The value of this oppositional power is questionable and may be overstated. The third lens is the lens of social power. Community radio as alternative media has the potential to empower participants personally or politically. The fourth lens is the lens of participation in media production, where community radio encourages participation in media content production and administration.


Nice guidelines recommend psychological treatment (cognitive–behavioural therapy, involving major elements of exposure and response prevention) as the first-line treatment for obsessive compulsive–disorder (Ocd). in this contribution, the theory and practice of integrated cognitive–behavioural therapy is described. The use of normalizing strategies and re-appraisal of beliefs motivating compulsive behaviour are emphasized as ways of enabling patients to choose to change. developments in terms of dissemination and delivery are considered.


Historically, ring tests have been performed to determine the time for concrete or mortar specimens to crack under restrained shrinkage. When the concrete or mortar ring deforms due to shrinkage, the steel ring restrains the material and tensile stresses are induced. Stress development cannot be monitored for test setups in which the degree of restraint is so high that no measurable deformation occurs in the steel as the material shrinks. Such test setups have provided qualitative evaluations and have not enabled a simple procedure to be established to routinely quantify the restrained shrinkage characteristics of the materials. In this study, an instrumented ring setup is used to quantify the restrained shrinkage behavior of concrete and mortar. The setup provides a high degree of restraint while still allowing sufficient strain in the steel as the material shrinks. It is shown with the ring setup that the cracking potential of concrete or mortar under restrained shrinkage can be classified on the basis of either how long it takes the material to crack or the rate of stress development in the material. The testing and analysis procedure provides a rational basis for assessing the relative performance of concrete or mortar mixtures when subjected to shrinkage under restraint. A simple procedure is also developed for a preliminary assessment of cracking potential using standard values of drying shrinkage and modulus of elasticity obtained at seven days after initiation of drying.


The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.


Theoretical studies on image formation in a confocal scanning microscope with optical fibers as the transmission medium are reported. Theoretical analyses show that this new kind of microscope can be considered a coherent imaging system, even for finite fiber spot size. Based on these studies the coherent transfer functions in both in-focus and defocused cases are derived and calculated. The axial coherent transfer functions are also obtained, and, furthermore, the optical-sectioning property of the microscope system is investigated with the consideration of the image formation of a perfect-reflection planar object and a point object.


As a lawyer, it is a privilege to contribute to this Festschrift in honour of Professor Doctor Johan Buitendag. His entire career has been a quest for the truth. In the process, he has fearlessly rejected political agendas based on the Bible, and has inspired countless students in their quest to serve God in a practical and humane manner. His published research as well as the output of his doctoral students, both present and past, bear witness to a life dedicated to the search for knowledge in the service of God. He has also assisted substantially in placing South African theological research on the international map. In a sense, this article which deals with the protection of the right to a fair trial of an accused, also acknowledges Johan Buitendag's quest for justice for all South Africans, whatever their creed, gender, race or standing. The subject of my article demonstrates my own quest to promote the constitutional right of an accused to a fair trial, a right that should not be subject to inordinate pressure by the media, and which gives priority to the right of an accused to be presumed innocent: an accused who may frequently suffer loneliness and a sense of rejection. Related to that it is, of course, always important to bear in mind that freedom of expression is at the heart of our democracy. A balance has, accordingly, to be struck between the competing rights.


This paper presents our on-going project on performance evaluation of the major existing solutions based on server- side access control for SYN-flooding distributed denial- of-service attacks using a real network system. Although many solutions have been proposed and implemented, there is no formal performance study that measures and compares the solutions based on server-side access control. The successful connection rate of the existing solutions was measured, compared and analyzed using an experiment test bed developed by LINUX-based PCs. We have tested SYN-cookie, Random Drop and the unmodified TCP in various conditions. We also simulated different types of legitimate clients in the end-to-end signal propagation delay to evaluate the fairness in connections. The results of our experiments showed that SYN-cookie resulted in the perfect (i.e., 100%) connection rate in all the experiments and configurations. Regardless of the length of the end-to-end delay, the connection rate of the unmodified TCP dropped to below 5% for a low request rate of 50 requests per second or more. Random Drop was more effective in improving connection rate than the unmodified TCP if the end-to-end delay was short or when the TCP backlog queue size was increased to more then 300 slots. KEY WORDS Network security, access control, denial-of-service attacks, TCP SYN-flood attacks, flash crowd


In 1774 Mexico City leaders created the Mexico City Poor House - the centrepiece of a bold experiment intended to eliminate poverty and impose a new work ethic on former beggars by establishing a forcible internment policy for some and putting others to work. In "Containing the Poor" Silvia Marina Arrom tells the saga of this ill-fated plan, showing how the asylum functioned primarily to educate white orphans instead of suppressing mendicancy and exerting control over the multiracial community for whom it was designed. For a nation that had traditionally regarded the needy as having the undisputed right to receive alms and whose affluent citizens felt duty-bound to dispense them, the experiment was doomed from the start, explains Arrom. She uses deep archival research to reveal that - much to policymakers' dismay - the Poor House became an orphanage largely because the government had underestimated the embeddedness of this moral economy of begging. While tracing the course of an eventful century that also saw colonialism give way to republicanism in Mexico, Arrom links the Poor House's transformation with other societal factors as well, such as Mexican women's increasing impact on social welfare policies. With poverty, begging, and homelessness still rampant in much of Latin America today, this study of changing approaches to social welfare will be particularly valuable to student and scholars of Mexican and Latin American society and history, as well as those engaged in the study of social and welfare policy.


Given the theatrical extremities of Harry Potter's birth, early childhood and treatment, we could expect some similarities between Charles Dickens' Victorian waif, Oliver Twist, and the boy wizard, to the point that we might reasonably trace Harry's origins to his literary predecessor. However, while such an attempt might uncover places where Rowling's creation in some ways faces similar circumstances as Dickens', for the most part, Rowling gives a backstory and characterization to Harry which diverge so greatly from Oliver and his workhouse experiences that other similarities seem largely superficial. Instead, if we seek to find the influence of Oliver Twist, we find the most convincing comparison not with the protagonist of Rowling's series but with the villain, for in Tom Riddle, the boy who will become Lord Voldemort, we find the true inheritor of the Dickensian model.


Retinal projection is required for xR applications that can deliver immersive visual experience throughout the day. If general-purpose retinal projection methods can be realized at a low cost, not only could the image be displayed on the retina using less energy, but there is also the possibility of cutting off the weight of projection unit itself from the AR goggles. Several retinal projection methods have been previously proposed; however, as the lenses and iris of the eyeball are in front of the retina, which is a limitation of the eyeball, the proposal of retinal projection is generally fraught with narrow viewing angles and small eyebox problems. In this short technical report, we introduce ideas and samples of an optical system for solving the common problems of retinal projection by using the metamaterial mirror (plane symmetric transfer optical system). Using this projection method, the designing of retinal projection can becomes easy, and if appropriate optics are available, it would be possible to construct an optical system that allows the quick follow-up of retinal projection hardware.


In this paper, we propose an effective face completion algorithm using a deep generative model. Different from well-studied background completion, the face completion task is more challenging as it often requires to generate semantically new pixels for the missing key components (e.g., eyes and mouths) that contain large appearance variations. Unlike existing nonparametric algorithms that search for patches to synthesize, our algorithm directly generates contents for missing regions based on a neural network. The model is trained with a combination of a reconstruction loss, two adversarial losses and a semantic parsing loss, which ensures pixel faithfulness and local-global contents consistency. With extensive experimental results, we demonstrate qualitatively and quantitatively that our model is able to deal with a large area of missing pixels in arbitrary shapes and generate realistic face completion results.


In this paper is we attempt to construct and validate a typology of innovation strategies among family SMEs applying the Miles and Snow's configurational model. We also try to extend the scope of the model testing the fit between entrepreneurial, managerial and governance characteristics and innovative posture of the firm. Research has been carried out on a representative sample of small and medium family firms of the Italian region Friuli Venezia Giulia. Results indicate that significant differences in the mentioned contextual variables exist among different strategic typologies of family firms, however some questions remain unanswered and more effort is needed to develop the configurational approach in the field of family business.


Synthetic fatliquors are useful as a fatliquoring agent, flotation agent and emulsifying agent in a wide range of industrial applications such as leather, pharmacy and farm chemicals. These fatliquors remain recalcitrant to natural biota in existing treatment plants. In the present study, the isolated microaerophilic Serratia sp. HA1 strain CSMB3 is capable of utilizing structurally different fatliquors as the sole substrate for their growth under microaerobic conditions. Degradation of vegetable fatliquors was observed from 95 to 97% in terms of lipids, with the production of lipase at 72 h. Degradation of synthetic fatliquors was observed in terms of chemical oxygen demand from 85% to a minimum of 25%. It is in the order of sulfited/sulfated fatliquors > sulfochlorinated fatliquors > chlorinated fatliquors. A thin layer chromatography chromatogram confirmed the degradation of non polar fatliquor to polar compounds. Production of the red pigment prodigiosin in synthetic fatliquors enhanced the growth of the isolate. Fourier transform infrared spectroscopy (FTIR) confirmed the bioremediation of sulfochlorinated fatliquor into lipids and fatty acids and gas chromatography-mass spectrometry (GC-MS) results confirmed that alcohols and esters are the final end products. Thus the isolated strain CSMB3 may be used in the treatment of wastewaters containing vegetable and synthetic fatliquors.


Aerospace vehicles are subject to broadband, sometimes severe, vibroacoustic and structure-borne excitations of various origin, which can danger the availment of the payload on board and the electronic equipment, and consequently the unsuccess of the entire mission. It is therefore important for the modern industry the development of analytical and numerical tools that can accurately predict the vibroacoustic response within structures of various geometries and subject to a combination of vibroacoustic excitations in order to mitigate unwanted phenomena able to compromise the whole mission. Nowadays, A lot of research has been conducted on the correctly modelling of wave propagation characteristics within representing the reactivity of the structure in noise field. As sake of simplicity, we will deal a simple test, coupled plate-cavity, where numerical modeling techniques risen are tipically based on deterministic approaches. The plate structure is often modeled by the finite element method and the Kirchhoff/Mindlin are mostly assumed to describe the through-the-thickness variation of the resultant displacement field. These simple assumptions of modeling the plate clearly reduce the required computational effort, but can also introduce huge errors in the prediction of the plate dynamic response and consequently affect the sorrounding acoustic pressure field, where noise is risen. In this work, a powerful notation has been used: Carrera's Unified Formulation, whose permits to obtain a wide class of refined plate theories (LW) with a unique formulation, providing an optimal element to completely describe the complex risen effects due to plate layouts and for higher frequency ranges. This work was conducted through the use of Actran Software, in order to conduct research in Vibro-Acoustic field. Structural Vibroacoustic interaction is modeled and analyzed using the finite element method coupling (interfaces), to solve the structure-acoustic coupled interaction for the noise radiation problem in a plate cavity system. The important keywords are the complete understanding of the generation of noise, its radiation in operating structure and the mitigation of the negative effect in order to improve the functionality of the system. Structures are generally characterized by the use of composite materials of various configurations/complexity in term of thicknesses, as well as geometries. Acoustic load and high frequency vibration can strictly and disadvantageously affect structures that represents a significant issue in spacecraft structures. Because of the extensive geometric complexity of structures, the usage of Finite Element (FE) modelling is frequently inevitable within the aerospace industry. The use of such models is limited mainly because of the immensity computation time required for calculations.


Cryogenic treatment has been acknowledged by some as means of extending tool life of many cutting tool materials, thus improving productivity significantly. However real mechanisms which guarantee better tool performance are still dubious. This implies the need of further investigations in order to control the technique more significantly. Studies on cryogenically treated HSS tools show microstructural changes in material that can influence tool lives. However little research has been done on other cutting tool materials. Cryogenic treatment of carbides has yet to be extensively studied. This work aims to study the effect of cryogenic treatment on M2 and S400 as well as Carbide inserts of SNMS120408 and SNMG120412MP grades. The tools were cryo-treated for 24 hours. The flank wear tests, sliding wear tests and hardness tests were conducted. In the process of ascertaining these findings, it was shown in this study that in flank wear tests cryogenically treated tool showed an increase in tool life. However in sliding wear test, weight loss in case of cryogenically treated tools was found to be more indicating the fact that the tool becomes more brittle after cryogenic treatment due to transformation of retained austenite to martensite as well as due to carbide refinement. Microstructural analysis and SEM analysis were done to support the results obtained. Performance of cryogenically treated tools largely depends upon the cutting conditions. Hence design of experiment (DOE) was employed to study the effect of cutting parameters on tool wear and tool life equations were developed illustrating the significant factors that affect performance of cryogenically treated tools.


Objective: to elaborate the methods of treatment for the patients with diabetic retinopathy (DR) by means of both conventional treatment (medical or surgical) and preparations with extracted fetal stem cells (FSCs) in suspensions containing stem cells of fetal liver, brain and fetal eye.
Materials and methods: A comparative study was conducted on 15 patients with diabetic retinopathy including 7 women and 8 men aged from 27 to 61 years. All patients were administered conventional treatment, laser coagulation and, only over 6 months following the latter, FSCs suspensions containing cells separated from human embryonic tissues of fetal liver, brain and fetal eye were used for treatment of the patients under study.
Results: Authors proved effectiveness and safety of treatment using FSCs in patients suffering from DR. Based on the study we recorded improvements of glycemic and lipids profile as well as overall ophthalmology status among the patients.
Conclusion: FSCs use in complex treatment of patients with DR stabilizes disease compensation, can improve laboratory values and ophthalmology status.


The study examined two low-cost point-of-use water treatment systems developed in respect of bacterial and particulate removal when exposed to surface water for three months. Bacterial removal efficiency was estimated using E. coli and fecal coliforms, while particulate reduction efficiency was estimated by determining turbidity and total suspended solids (TSS). The systems investigated were the Gift of Water System (GWS) made in USA and the Drip Filter System (DFS) Model-JW-PD-1-70 made in South Africa. The study included seasonal water quality changes. Both systems recorded 100% bacterial removal throughout the study. Although results show that DFS was slightly better in terms of particulate reduction, both systems removed large proportions of particles from the water. On average TSS removals were 89% and 95%, while turbidity removals were 87% and 94%, by GWS and DFS respectively. The treated water from the two systems compared well with good quality tap water supplied to Stellenbosch University. The results show that both systems can treat the poor quality water used to meet the SANS 241 and WHO guidelines with respect to bacterial and suspended solids content.


Mountains Beyond Mountains tells the story of Dr. Paul Farmer, founder of the international NGO Partners in Health, as he works to heal disease and fight poverty in some of the most underserved communities in the world. Farmer, a Harvard-trained physician and public health icon, believes that all people should have access not only to basic, but to top-of-the-line medical resources and technology, regardless of their financial means. The book follows Farmer and his colleagues around the world as they work to save lives and build healthier communities in Haiti, Russia, Peru and right here in North America.


Abstract Objective. This study compared the prehospital motor component subscale of the Glasgow Coma Scale (mGCS) to the prehospital total GCS (tGCS) score for its ability to predict the need for intubation, survival to hospital discharge, and neurosurgical intervention in trauma patients. Methods. This is a retrospective analysis of an urban level 1 trauma registry. All trauma patients presenting to the trauma center emergency department via emergency medical services from July 2008 through June 2010 were included. The area under the receiver operating characteristics curve (AUC) analysis was used to compare the predictive ability of the prehospital mGCS to tGCS for three outcomes: intubation, survival to hospital discharge, and neurosurgical intervention. Two subgroups (patients with injury severity score [ISS] ≥ 16 and traumatic brain injury [TBI] [head abbreviated injury score (AIS) ≥ 3]) were analyzed. An a priori statistically significant absolute difference of 0.050 in AUC between mGCS and tGCS for these clinical outcomes was used as a clinically significant difference. Multiple imputation was used for missing prehospital GCS data. Results. There were 9,816 patients, of which 4% were intubated, 3.8% had neurosurgical intervention, and 97.1% survived to hospital discharge. The absolute difference in AUC (prehospital tGCS minus mGCS) for all cases was statistically significant for all three outcomes but did not reach the clinical significance threshold: survival = 0.010 (95% CI: 0.002–0.018), intubation = 0.018 (95% CI: 0.011–0.024), and neurosurgical intervention = 0.019 (95% CI: 0.007–0.029). The difference in AUC between tGCS and mGCS for the subgroups ISS ≥ 16 (n = 1,151) and TBI (n = 1,165) did not reach clinical significance for the three outcomes. The discriminatory ability of the prehospital mGCS was good for survival (AUC: all patients = 0.89, ISS ≥ 16 = 0.84, traumatic brain injury = 0.86) excellent for intubation (AUC: all patients = 0.95, ISS ≥ 16 = 0.91, traumatic brain injury = 0.91), and poor for neurosurgical intervention (AUC: all patients = 0.67, ISS ≥ 16 = 0.57, traumatic brain injury = 0.60). Conclusion. The prehospital mGCS appears have good discriminatory power and is equivalent to the prehospital tGCS for predicting intubation and survival to hospital discharge in this trauma population as a whole, those with ISS ≥ 16, or TBI.


Lifelogging is the ambient, continuous digital recording of a person's everyday activities for a variety of possible applications. Much of the work to date in lifelogging has focused on developing sensors, capturing information, processing it into events and then supporting event-based access to the lifelog for applications like memory recall, behaviour analysis or similar. With the recent arrival of aggregating platforms such as Apple's HealthKit, Microsoft's HealthVault and Google's Fit, we are now able to collect and aggregate data from lifelog sensors, to centralize the management of data and in particular to search for and detect patterns of usage for individuals and across populations. In this paper, we present a framework that detects both low-level and high-level periodicity in lifelog data, detecting hidden patterns of which users would not otherwise be aware. We detect periodicities of time series using a combination of correlograms and periodograms, using various signal processing algorithms. Periodicity detection in lifelogs is particularly challenging because the lifelog data itself is not always continuous and can have gaps as users may use their lifelog devices intermittingly. To illustrate that periodicity can be detected from such data, we apply periodicity detection on three lifelog datasets with varying levels of completeness and accuracy.


"Investigations on effects of Xenon application time on cerebral outcome following cardiopulmonary bypass with cerebral air embolism in the rat"

Cerebral air embolism (CAE) is thought to be one of the risk factors for adverse cerebral outcome following cardiac surgery with cardiopulmonary bypass (CPB). Neurologic and neurocognitive deficits after cardiac surgery remain a common and severe complication, alleviating patients´ quality of life for years. Providing neuroprotective properties and cardiovascular stability Xenon may also improve cerebral outcome after cardiac surgery with CPB. However, Xenon`s disposition to expand air bubbles could possibly be a disadvantage for its use in combination with CPB, as such air bubbles can be detected during CPB. In this study Xenon was administered before (group XEv), during (group XEw) or after CPB (group XEn) to investigate differential effects of application time on cerebral outcome after CPB with cerebral air embolism in a rat model.
50 male Sprague-Dawley rats (BW: 330-390 g) were assigned to five groups of ten animals each. Control group (Ko) animals were neither exposed to CPB nor received Xenon. The CPB-groups such as Xenon before CPB, Xenon during CPB, Xenon after CPB and no Xenon (kXE) were anesthetized with isofluran, intubated and ventilated with 2.0-2.5 Vol % isoflurane in 50 % oxygen. The right superficial epigastric artery and vein, the right external jugular vein and the sacral artery were cannulated for blood sampling, application of drugs, invasive blood pressure monitoring as well as inflow and return connection to the CPB circuit. A catheter was inserted into the right internal carotid artery and ten repetitively administered air emboli of 0.3 µl each were applicated. After completion of surgery all animals received an additional basic intravenous anesthesia (continuous infusion of midazolam, fentanyl and atracurium) which was maintained until the end of operation (60 min after CPB). Rats subjected to Xenon before CPB were ventilated with Xenon (56 % Xenon, 5 % N2, 34 % O2 and 5 % CO2) applied for 60 minutes before connection to CPB. The Xenon during CPB group received the above mentioned Xenon gas mixture through the oxygenator for 90 minutes during CPB. Xenon after CPB animals were treated in the same fashion but inhaled Xenon for 60 minutes after CPB and no Xenon animals continously received an oxygen-air-mixture (61 % N2, 34 % O2 und 5 % CO2). Emerging from anesthesia the rats recovered by being placed in an oxygen-enriched environment. Animals underwent standardized functional neurologic testing on the 1st-4th, 8th, 12th, 16th and 21st postoperative days. Beginning with the 4th postoperative day cognitive performance as well as behaviour was ascertained up to the 21st postoperative day using the modified hole-board test. All neurologic, cognitive and behavioural testing was performed by a investigator blinded to treatment. After testing on the 21st postoperative day the rats were killed by exsanguination in deep isofluran anesthesia and subjected to in situ brain fixation with formaline. Brains were removed in total, were serially cut and stained with hematoxylin and eosin for further histological evaluation determining maximal infarction size and infarction volume.
This is the first investigative study on the effects of different Xenon application times, that is before, during and after CPB in combination with CAE. The occurrence of CAE is more likely during CPB in contrast to before and after CPB where CAE are rarer. In this setting rats showed short-time sensomotoric and long-term cognitive and behavioural changes which was confirmed by histopathological results. The significant worse outcome of animals treated with Xenon after CPB is of profound relevance discussing the safety of Xenon`s use associated with CPB. Interestingly rats subjected to CPB without Xenon achieved no better results neither at cognitive and behavioural testing nor at histopathological evaluation. Knowledge about the pathophysiology of CAE remains sparse and further investigation in this direction would be of high importance in trying to explain the results of this study.


Decision Altitude: Incident Report uses the medium of photography to examine the physical and psychological experience of skydiving. Images of falling skydivers are captured using a pin-hole camera and printed using a photo-etching process. The means of capture and output are selected to highlight the performative nature and physicality of photography. Thresholds of light, the body, space, and time are collapsed into the images as the physical limitation of gravity, the impermanence of the body and the medium of photography are explored.


Humans involuntarily tend to infer parts of the conversation from lip movements when the speech is absent or corrupted by external noise. In this work, we explore the task of lip to speech synthesis, i.e., learning to generate natural speech given only the lip movements of a speaker. Acknowledging the importance of contextual and speaker-specific cues for accurate lip-reading, we take a different path from existing works. We focus on learning accurate lip sequences to speech mappings for individual speakers in unconstrained, large vocabulary settings. To this end, we collect and release a large-scale benchmark dataset, the first of its kind, specifically to train and evaluate the single-speaker lip to speech task in natural settings. We propose a novel approach with key design choices to achieve accurate, natural lip to speech synthesis in such unconstrained scenarios for the first time. Extensive evaluation using quantitative, qualitative metrics and human evaluation shows that our method is four times more intelligible than previous works in this space.


One of the ways to improve the quality of math and natural science education is to develop the pedagogical community of STEM education. On the one hand, according to the forecasts, an increase in the number of students and teachers is expected by an average of 20 % in both Russia and worldwide. On the other hand, there is definitely some specificity in the pedagogical community as compared with any other labor collective, since the pedagogical community develops alongside with the student one. In this perspective, the age heterogeneity of the teaching staff is of particular relevance. Consequently, the key point in the management of math and natural science education is the analysis of the age structure of STEM educators. The following subjects are taken to conduct a further analysis of STEM education: mathematics, handicraft, physics, biology, and chemistry. Accordingly, the purpose of the article is to analyze and forecast the heterogeneous development of the age structure of STEM teachers. The authors of the article justify the necessity for changes in the personnel policy on the basis of the assessment of the capacity of the teaching staff of STEM education in schools of the European part of Russia. The leading research approach is the method of the normal and natural distribution of age groups in the structure of the STEM education pedagogical community. As a result of a study conducted in 569 schools of the European part of Russia in 2016–2018, the authors of the article have found out the following: the average age of STEM school teachers in the European part of Russia is 6.8 years higher than the average age of teachers in Russia; there is a significant shortage of STEM teachers aged under 35; the average rate of the teaching load of a STEM school teacher in an academic subject is 0.72, but the load is distributed very unevenly, math teachers having the highest teaching load. The theoretical significance of the research lies in its contribution to the development of scientific ideas concerning the age heterogeneity of STEM school teachers. The research results can be used in building development trajectories of STEM education teaching staff by implementing a series of managerial and organizational measures to achieve the normal state of the age structure of teachers.


Giant Hogweed is a poisonous invasive weed in Latvia that poses significant threat to biodiversity and human health. Local residents are afraid and have very special concerns about the safety of their children because the plant causes phytophotodermatitis (severe burns), painful blistering, permanent scarring and blindness when the sap of the plant comes in contact with the human body and is exposed to sunlight. This study utilizes public participation GIS (PPGIS) involving Latvian high school students as data collectors to monitor the geographic distribution of Giant Hogweed in Northeast Latvia. This paper also explores challenges with implementing such a public program, how to maximize participation, and how participation impacts environmental awareness of participants. In this study we also assessed the accuracy of PPGIS-collected data and how the utilization of such data impacts mapping and monitoring of Giant Hogweed in the study area. Results indicate that this PPGIS program is effective in facilitating data collection for monitoring Giant Hogweed in Latvia. Tested methods of increasing participation have proven largely unsuccessful to date. Statistical analyses of survey responses indicate participation had a marked effect on sensitivity towards environmental issues. Accuracy assessments indicate that quality of point data collected by participants is sufficient for mapping and for use as ground verification.


—This paper highlights the role of digital forensics in the enterprise information architecture. It presents a framework for embedding digital forensics analysis techniques at various stages of corporate information and communication technologies (ICT) lifecycle. A set of best practices for the corporate ICT security policy is also outlined to keep the operational costs of digital forensics at the optimal level. It also presents a detailed analysis of the risks to the competitive-edge of the companies that will not employ the forensics solutions to protect their business interests. This work also provides a high-level roadmap for the adaption of digital forensics in the emerging core business technologies such as cloud computing and virtualization infrastructures.


This thesis studies the use of data dependent structures in cryptography. Since the introduction of RC5 by Rivest in 1994, which relied heavily on data-dependent rotations for its security [1], these structures have gained interest in cryptography. During the Advanced Encryption Standard selection process two candidate ciphers, RC6 and MARS, relied on data-dependent structures. -- The thesis focuses on CIKS-1, a cipher introduced in the Journal of Cryptography in 2002 [2], that relies mainly on data-dependent permutations for its security. Due to its reliance on these permutations, this cipher is chosen as a basis for the study of data-dependent structures in cryptographic algorithms. -- The first attack on CIKS-1 presented is a chosen plaintext attack which exploits the lack of change in the Hamming weight of the data as it is enciphered. The research shows that there is a class of weak keys with low weight that can be detected when the input weight is constrained. An attack on a 6 round reduced version of the cipher is outlined that can reduce the search space of the first round subkey to within a weight of two from the weight of the actual key. This attack is experimentally shown to work when the subkey weights are around six or less with a total time complexity for the attack of 2⁵² encryption operations. -- The second attack presented is a variant of classical differential cryptanalysis. Instead of focusing on the exact bit difference of the two inputs that make up the differential, the attack instead focuses on the difference in their weights. An experimental attack on a three-round reduced version of the cipher is presented using this technique which can retrieve the last round subkey of CIKS 1 with a data complexity of approximately 2³⁵ plaintext/ciphertext pairs and time complexity of approximately 2³⁵ encryption operations plus 2⁶⁸ partial decryption operations. It is also shown that this can theoretically be extended to the whole cipher with a total data complexity of 2⁵¹ plaintext/ciphertext pairs and time complexity of approximately 2⁵² encryption operations plus 2⁸⁴ partial decryption operations. -- Despite the weaknesses discovered in CIKS 1, there is potentially some merit in using data dependent permutations in ciphers. Therefore, the implementation of CIKS-1 in software is investigated. The cipher was originally designed to be fast in hardware and contains many operations that work at the bit level, which are inefficient to implement in software. A software version of the cipher is presented which uses bitslicing, effectively parallelizing the cipher on a single processor. This version experimentally shows a speed up of approximately 175 times over a more straight forward implementation using arrays of elements to hold individual bits.


Camptothecin and taxol are secondary metabolites found, respectively, in the wood bark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the United States. The compounds were isolated guided by bioassay on various extracts and chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry, and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; camptothecin uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication. Taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. Camptothecin and analogues singly or combined with cisplatin show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.


Ceramide levels are elevated in mantle cell lymphoma (MCL) cells following treatment with cannabinoids. Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R(+)-methanandamide (R-MA). We further interfered with the conversion of ceramide into sphingolipids that promote cell growth. Treatment with R-MA led to increased levels of ceramide species C16, C18, C24, and C24:1 and transcriptional induction of ceramide synthases (CerS) 3 and 6. The effects were attenuated using SR141716A, which has high affinity to cannabinoid receptor 1 (CB1). The CB1-mediated induction of CerS3 and CerS6 mRNA was confirmed using Win-55,212-2. Simultaneous silencing of CerS3 and CerS6 using small interfering RNA abrogated the R-MA-induced accumulation of C16 and C24. Inhibition of either of the enzymes serine palmitoyl transferase, CerS, and dihydroceramide desaturase within the de novo ceramide pathway reversed ceramide accumulation and cell death induced by R-MA treatment. To enhance the cytotoxic effect R-MA, sphingosine kinase-1 and glucosylceramide synthase, enzymes that convert ceramide to the pro-proliferative sphingolipids sphingosine-1-phospate and glucosylceramide, respectively, were inhibited. Suppression of either enzyme using inhibitors or small interfering RNA potentiated the decreased viability, induction of cell death, and ceramide accumulation induced by R-MA treatment. Our findings suggest that R-MA induces cell death in MCL via CB1-mediated up-regulation of the de novo ceramide synthesis pathway. Furthermore, this is the first study were the cytotoxic effect of a cannabinoid is enhanced by modulation of ceramide metabolism. (Mol Cancer Res 2009;7(7):1086–98)


Background and Objectives. Health communication is a critical aspect of care for both providers and recipients having a direct influence on engagement and outcomes. Communicating which in this context includes talking and listening in order to share information or support young women to understand their DSD can be difficult especially since the topic area is sensitive. Methods. In this qualitative study thirteen young women (aged 14–19 years) with a disorder of sex development who engaged with health care professionals were purposively recruited between 2011 and 2012 from three specialist centres across the United Kingdom. The young women either were interviewed or completed a diary about their experiences of communication with a range of health care professionals. An interpretative phenomenological approach was used to analyse these data. Results. By analysis of data the young women were able to clearly articulate the qualities and skills health professional needed in relation to communication. Two main categories focused on the duty in which professionals have to share information and their role in supporting young women to manage this information. Discussion and Conclusion. The study results revealed that these young women with a DSD expected to meet skilled professionals who could recognise the emotional aspects of dialogues in the short and longer term.


On 4–7 May this year, Melbourne will host the World Congress of Cardiology, a tribute to the high international regard in which Australian cardiology research and practice are held. Australia's achievements in cardiology are considerable, with well substantiated claims for the invention of the world's fi rst cardiac pacemaker in the 1920s1 and the establishment of the fi rst coronary care unit in the 1960s.2 Discoveries made early in the careers of distinguished Australian cardiac investigators, such as Philip Barter on the role of transfer proteins in high-density lipoprotein (HDL) cholesterol metabolism, and Murray Esler on the role of the sympathetic nervous system in blood pressure control, have led to extensive clinical testing of modifi ers of HDL cholesterol3 and renal denervation as a potential major advance in the treatment of hypertension.4 Both these developments are the subject of active current controversy and ongoing clinical trials to clarify their roles in the treatment of dyslipidaemia and hypertension. They are inspiring examples of how decades of dedicated basic research can open up new and unexpected pathways for clinical progress. Australia's impressive collaborative capability for largescale, nationally inclusive clinical projects has been demonstrated by the LIPID and ANBP2 study groups, with their respective major practice-changing trials of statin therapy after acute coronary syndromes5 and comparisons of antihypertensive therapies.6 The recent national ACACIA and CONCORDANCE registries and the binational SNAPSHOT audit of acute coronary syndromes confi rm a strong Australian appetite for collaborative cardiovascular research.7 The theme of the 2014 World Congress is global health, with a stated aim to reduce premature deaths from cardiovascular disease globally by 25% by 2025. Perhaps the most important Australian contribution to global cardiovascular health may come from an examination of our dramatic, if uneven, decline in the rate of cardiovascular disease since the 1960s. The Australian statistics in this regard are particularly impressive: rates of premature cardiovascular death have declined to less than a third of the level in the late 1960s; non-fatal myocardial infarction and stroke have declined; and survival after a coronary event has improved.8 The role of health promotion bodies such as the Heart Foundation has been an important key to this success. Although changes towards a lower-fat Australian diet have no doubt contributed, the current ready access to highenergy foods and a high prevalence of obesity remain concerning. With 28.3% of the adult population being obese, Australia already ranks among the top three most obese nations in the world and is growing fatter faster than almost any other nation.9 On the other hand, Australia's decline in rates of adult smoking has been impressive and continues.10 Innovative and persistent campaigns from public health advocates such as Simon Chapman have stimulated effective community support and government action on tobacco control.11 Australia's world-leading introduction of plain packaging laws will almost certainly see the trend to limit smoking continue. However, Australia's decline in coronary mortality, while impressive, is unevenly shared throughout the community. It may have slowed in younger age groups, and obesity trends may reverse some of the decline. Importantly, the Indigenous population continues to have excessively high rates of cardiovascular disease and has not shared in the improvements in cardiovascular health.12 We have much to be proud of in a vigorous basic cardiovascular research effort that can translate to major clinical improvements. We need to balance our basic research effort with clinical and population research. A fruitful Australian contribution to reducing the global burden of cardiovascular disease may be a critical analysis of what we are doing right, where we are not succeeding and how we can maximise the trends seen in Australia. We can then assess whether lessons learned here are applicable in other countries.


Optimization problems with cardinality constraints are very difficult mathematical programs which are typically solved by global techniques from discrete optimization. Here we introduce a mixed-integer formulation whose standard relaxation still has the same solutions (in the sense of global minima) as the underlying cardinality-constrained problem; the relation between the local minima is also discussed in detail. Since our reformulation is a minimization problem in continuous variables, it allows us to apply ideas from that field to cardinality-constrained problems. Here, in particular, we therefore also derive suitable stationarity conditions and suggest an appropriate regularization method for the solution of optimization problems with cardinality constraints. This regularization method is shown to be globally convergent to a Mordukhovich-stationary point. Extensive numerical results are given to illustrate the behavior of this method.


In this paper, we examine the economic viability of two new energy technologies when implemented in the US Southwest. The first technology of interest is a long distance high voltage direct current (HVDC) transmission link between Texas and Southern California that is constructed using a so-called "nanowire" technology. The second technology is grid-connected photovoltaic solar power. We investigate the potential value of these technologies by examining how profitable they would likely have been if they had been available in 2003.


This paper explores how the temporal disjunction established in the production of narrative affords a way of managing the tension between competing demands for accountability in settings where the issue of cultural difference features as a participant concern. Specifically, in speculating upon the nature of cultural variation and cross-cultural contact, interview participants employ narrative accounts to manage the tension between the demand to formulate their concerns in an impartial and unprejudiced fashion on the one hand while displaying an appreciation of and sensitivity to cultural difference on the other. Such interactional work is considered for its theoretical significance to recent developments in discursive psychology. The deployment of narrative is therefore examined for how it relates to the situated production of social scientific investigation itself as a form of social activity in which speakers manage the reflexive implications of their own participation in an undertaking where knowledge of cultural difference is worked up as the outcome of the situated activity in which they are engaged.{Narrative, Discursive Psychology, Culture, Identity, Reflexivity)


OBJECTIVE
The objective was to determine the incidence of bladder stones in patients with spinal cord injury (SCI) and to assess if catheter encrustation or positive urinary culture of Proteus mirabilis is predictive of bladder stones.

BACKGROUND
Bladder stones are common urological complication in those with SCI managed with indwelling urinary catheter. Detection and removal of bladder stones are important to prevent possible further complications.

DESIGN
This was a prospective cohort study.

MATERIALS AND METHODS
Ultrasound scan was performed in persons with SCI seen from 1st January to 31st December 2009 who had indwelling urethral catheter for at least 3-month post-injury. Indwelling urethral catheters were examined for encrustation at the time of removal, urine culture taken specifically for P. mirabilis and ultrasound scan done to detect bladder stones.

RESULTS
There were 89 patients with spinal cord injury and 68 (76.4%) patients were evaluated during the review period. Twenty-nine (42.6%) patients had bladder stones and 22 (32.3%) patients had catheter encrustation. Of the 22 patients with catheter encrustation, 19 (86.3%) also had bladder stones. Forty-six (67.6%) patients had no catheter encrustation. Of these, 7 (14.7%) were found to have bladder stones. Thirty-seven (38.2%) urine cultures were positive for P. mirabilis. Of these 37 (54.4%) patients, 27 also had bladder stones. Catheter encrustation (P = 0.004) and a positive urine culture of P. mirabilis (P = 0.007) in patients with indwelling urinary catheter is highly predictive of the presence of bladder stone.

CONCLUSIONS
This study shows that a large number of SCI patients have an indwelling urethral catheter and suggests that ultrasound scan for the presence of stone should be schedule in a catheterized SCI patient if catheter encrustation or a positive urine culture of P. mirabilis is noted.


To aid in forest management, various approaches using Geographic Information Systems (GIS) have been used to identify the spatial distributions of relative slope instability. This study presents a systematic evaluation of three common slope instability modeling approaches applied in the Blue Ridge Mountains of Virginia. The modeling approaches include the Qualitative Map Combination, Bivariate Statistical Analysis, and the Shallow Landsliding Stability (SHALSTAB) model. Historically, the qualitative nature of the first model has led to the use of more quantitative statistical models and more deterministic physically-based models such as SHALSTAB. Although numerous studies have been performed utilizing each approach in various regions of the world, only a few comparisons of these approaches have been done in order to assess whether the quantitative and deterministic models result in better identification of instability. The goal of this study is to provide an assessment of relative model behavior and error potential in order to ascertain which model may be the most effective at identifying slope instability in a forest management context. The models are developed using both 10-meter and 30-meter elevation data and outputs are standardized and classified into instability classes (e.g. low instability → high instability). The outputs are compared with cross-tabulation tables based on the area (m) assigned to each instability class and validated using known locations of debris flows. In addition, an assessment of the effects of varying source data (i.e. 10-meter vs. 30-meter) is performed. Among all models and using either resolution data, the Qualitative Map Combination correctly identifies the most debris flows. In addition, the Qualitative Map Combination is the best model in terms of correctly identifying debris flows while minimizing the classification of high instability in areas not affected by debris flows. The statistical model only performs well when using 10-meter data while SHALSTAB only performs well using 30-meter data. Overall, 30-meter elevation data predicts the location of debris flows better than 10-meter data due to the inclusion of more area into higher instability classes. Of the models, the statistical approach is the least sensitive to variations in source elevation data.


A sizeable proportion of structures with Z′ = 2 are thought to exhibit pseudosymmetry, but establishing the extent of the deviation from true symmetry is problematic. By considering both the conformational similarity between the independent molecules and the way in which they are related in space, assessment of the pseudosymmetry of a structure becomes possible. A method of matching two groups of atoms where both these factors are quantified using CRYSTALS [Betteridge, Carruthers, Cooper, Prout & Watkin (2003). J. Appl. Cryst. 36, 1487] is described.


Background The purpose of this study is to determine whether elderly subjects with severe brain atrophy, which is associated with neurodegeneration and difficulty swallowing (dysphagia), are more susceptible to lower respiratory tract infections (LRTI), including pneumonia. Methods The severity of brain atrophy was assessed by computed tomography in 51 nursing home residents aged 60–96 years. The incidence of LRTI, defined by body temperature ≥ 38.0°C, presence of two or more respiratory symptoms, and use of antibiotics, was determined over 4 years. The incidence of LRTI was compared according to the severity and type of brain atrophy. Results The incidence rate ratio of LRTI was significantly higher (odds ratio 4.60, 95% confidence interval 1.18–17.93, fully adjusted P = 0.028) and the time to the first episode of LRTI was significantly shorter (log-rank test, P = 0.019) in subjects with severe brain atrophy in any lobe. Frontal and parietal lobe atrophy was associated with a significantly increased risk of LRTI, while temporal lobe atrophy, ventricular dilatation, and diffuse white matter lesions did not influence the risk of LRTI. Conclusion Elderly subjects with severe brain atrophy are more susceptible to LRTI, possibly as a result of neurodegeneration causing dysphagia and silent aspiration. Assessing the severity of brain atrophy might be useful to identify subjects at increased risk of respiratory infections in a prospective manner.


Recent developments in seismic attributes and seismic facies classification techniques have greatly enhanced the capability of interpreters to delineate and characterize features that are not prominent in conventional 3D seismic amplitude volumes. The use of appropriate seismic attributes that quantify the characteristics of different geologic facies can accelerate and partially automate the interpretation process. Self-organizing maps (SOMs) are a popular seismic facies classification tool that extract similar patterns embedded with multiple seismic attribute volumes. By preserving the distance in the input data space into the SOM latent space, the internal relation among data vectors on an SOM facies map is better presented, resulting in a more reliable classification. We have determined the effectiveness of the modified algorithm by applying it to a turbidite system in Canterbury Basin, offshore New Zealand. By incorporating seismic attributes and distance-preserving SOM classification, we were able to observe architectural elements that are overlooked when using a conventional seismic amplitude volume for interpretation.


ABSTRACT We conducted a regional seismic intensity survey in northern Chile following the 1 April 2014 M  8.2 Iquique earthquake to document the level of damage caused by the earthquake and tsunami. We observed very limited damage at the 204 sites surveyed. The modified Mercalli intensities (MMIs) reached a maximum value of VI adjacent to the earthquake rupture plane. The contours of our MMI map are similar in shape to the contour maps of peak ground acceleration (PGA) and peak ground velocity (PGV). A comparison of our seismic intensities with the recorded PGA and PGV values reveals that our MMI values are one to two units lower than predicted by ground‐motion intensity conversion equations (GMICEs). We propose that this is due to the well‐engineered buildings and moderate levels of high‐frequency (0.5–5 Hz) ground shaking experienced during this earthquake. Whether existing GMICEs consistently overpredict seismic intensities for large subduction‐zone earthquakes deserves further study.


The Ah receptor (AHR) is directly involved in the regulation of both innate and adaptive immunity. However, these activities are poorly understood at the level of gene regulation. The chemokine (c-c motif) ligand 20 (CCL20) plays a nonredundant role in the chemoattraction of C-C motif receptor 6 expressing cells (eg, T cells and others). A survey of promoter regions of chemokine genes revealed that there are several putative dioxin responsive elements in the mouse Ccl20 promoter. The addition of an AHR agonist along with lipopolysaccharide (LPS) to cultured primary peritoneal macrophages results in synergistic induction of both Ccl20 mRNA and protein, compared with each compound alone. Through the use of macrophage cultures derived from Ahr(-) (/) (-) and Ahr(nls/nls) mice, it was established that expression of the AHR and its ability to translocate into the nucleus are necessary for AHR ligand-mediated synergistic induction of Ccl20. Gel shift analysis determined that a potent tandem AHR binding site ~3.1 kb upstream from the transcriptional start site can efficiently bind the AHR/ARNT (aryl hydrocarbon receptor/AHR nuclear translocator) heterodimer upon activation with a number of AHR agonists. Furthermore, studies reveal that LPS increases AHR levels on the Ccl20 promoter while decreasing HDAC1 occupancy. The level of Ccl20 constitutive expression in the colon is greatly attenuated in Ahr(-) (/) (-) mice. These studies suggest that the presence of AHR ligands during localized inflammation may augment chemokine expression, thus participating in the overall response to pathogens.


The aim of this research was to formulate a novel biodegradable, biocompatible cationic microparticle vector for the delivery of DNA vaccines. The work builds upon previous research by Singh et al which described the adsorption of DNA to the surface of poly (D,L-lactide-co-glycolide) (PLG) microparticles stabilised with the surfactant cetyltrimethyl ammonium bromide (CT AB). This work demonstrated the induction of antibody and cellular immune responses to HIV proteins encoded on plasmid DNA adsorbed to the particle surface in mice, guinea pigs and non-human primates (Singh et aI, 2000; O'Hagan et aI, 2001). However, the use of surfactants in microparticle formulations for human vaccination is undesirable due to long term safety issues. Therefore, the present research aim was to develop an adsorbed DNA vaccine with enhanced potency and increased safety compared to CTAB stabilised PLG microparticles (PLG/CTAB) by replacement of the surfactant CTAB with an alternative cationic agent. The cationic polymers chitosan and poly (N- vinylpyrrolidone/2-dimethylaminoethyl methacrylate), dimethyl sulfate quaternary (PVP-PDAEMA) were investigated as alternative stabilisers to CTAB. From a variety of initial formulations, the most promising vector(s) for DNA vaccination were selected based on physicochemical data (chapter 3) and in vitro DNA loading and release characteristics (chapter 4). The chosen formulation(s) were analysed in greater depth (chapters 3 and 4), and gene expression was assessed by in vitro cell transfection studies using 293T kidney epithelial and C2C12 myoblast non-phagocytic cell lines (chapter 5). The cytotoxicity of the microparticles and their constituents were also evaluated in vitro (chapter 5). Stability and suitability of the formulation(s) for commercial production were assessed by cryopreparation and lyophilisation studies (chapters 3 and 4). Gene expression levels in cells of the immune response were evaluated by microparticle transfection of the dendritic cell (DC) line 2.4 and primary bone marrow derived DCs (chapter 6). In vivo, mice were injected i.m. with the formulations deemed most promising on the basis of in vitro studies and humoral and cellular immune responses were evaluated (chapter 6).