Oxidised phospholipid regulation of toll-like receptor signalling

Toll-like receptors (TLRs) serve to initiate inflammatory signalling in response to the detection of conserved microbial molecules or products of host tissue damage. Recent evidence suggests that TLR-signalling plays a considerable role in a number of inflammatory diseases, including atherosclerosis and arthritis. Agents which modulate TLR-signalling are, therefore, receiving interest in terms of their potential to modify inflammatory disease processes. One such family of molecules, the oxidised phospholipids (OxPLs), which are formed as a result of inflammatory events and accumulate at sites of chronic inflammation, have been shown to modulate TLR-signalling in both in vitro and in vivo systems. As the interaction between OxPLs and TLRs may play a significant role in chronic inflammatory disease processes, consideration is given in this review to the potential role of OxPLs in the regulation of TLR-signalling.

Studies of phospholipid oxidation by electrospray mass spectrometry: from analysis in cells to biological effects

The oxidation of lipids is important in many pathological conditions and lipid peroxidation products such as 4-hydroxynonenal (HNE) and other aldehydes are commonly measured as biomarkers of oxidative stress. However, it is often useful to complement this with analysis of the original oxidized phospholipid. Electrospray mass spectrometry (ESMS) provides an informative method for detecting oxidative alterations to phospholipids, and has been used to investigate oxidative damage to cells, and low-density lipoprotein, as well as for the analysis of oxidized phosphatidylcholines present in atherosclerotic plaque material. There is increasing evidence that intact oxidized phospholipids have biological effects; in particular, oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycerophosphocholine (PAPC) have been found to cause inflammatory responses, which could be potentially important in the progression of atherosclerosis. The effects of chlorohydrin derivatives of lipids have been much less studied, but it is clear that free fatty acid chlorohydrins and phosphatidylcholine chlorohydrins are toxic to cells at concentrations above 10 micromolar, a range comparable to that of HNE and oxidized PAPC. There is some evidence that chlorohydrins have biological effects that may be relevant to atherosclerosis, but further work is needed to elucidate their pro-inflammatory properties, and to understand the mechanisms and balance of biological effects that could result from oxidation of complex mixtures of lipids in a pathophysiological situation.

Biosynthesis and analysis of plant oxylipins

The term oxylipin is applied to the generation of oxygenated products of polyunsaturated fatty acids that can arise either through non-enzymatic or enzymatic processes generating a complex array of products, including alcohols, aldehydes, ketones, acids and hydrocarbon gases. The biosynthetic origin of these products has revealed an array of enzymes involved in their formation and more recently a radical pathway. These include lipoxygenases and α-dioxygenase that insert both oxygen atoms in to the acyl chain to initiate the pathways, to specialised P450 monooxygenases that are responsible for their downstream processing. This latter group include enzymes at the branch points such as allene oxide synthase, leading to jasmonate signalling, hydroperoxide lyase, responsible for generating pathogen/pest defensive volatiles and divinyl ether synthases and peroxygenases involved in the formation of antimicrobial compounds. The complexity of the products generated raises significant challenges for their rapid identification and quantification using metabolic screening methods. Here the current developments in oxylipin metabolism are reviewed together with the emerging technologies required to expand this important field of research that underpins advances in plant-pest/pathogen interactions.

The Notion of Model in Software Engineering

Милослав A. Средков - Понятията модел и моделиране се използват толкова интензивно в много дисциплини, че е трудно да им се придаде конретно значение. Дори в Софтуерните технологии, разбирането на тези понятия силно зависи от контекста. Ние смятаме, че това допринася за неконсистентността между подходите за моделиране там. В тази статия посочваме някои от произтичащите проблеми, както и важността да има подходяща дефиниция, съчетана с подходящи инструменти. Преглеждаме по-общите дефиниции на модел отвъд границите на Софтуерните технологии. Минаваме през моделирането на различни вторични продукти на процесите от Софтуерните технологии. Накрая представяме нашата визия относно използването на такава обща основа за наша полза.

Properties of the Bellman Gamma Distribution

2000 Mathematics Subject Classification: 62H10.

Model Mining and Efficient Verification of Software Product Lines

Software product line modeling aims at capturing a set of software products in an economic yet meaningful way. We introduce a class of variability models that capture the sharing between the software artifacts forming the products of a software product line (SPL) in a hierarchical fashion, in terms of commonalities and orthogonalities. Such models are useful when analyzing and verifying all products of an SPL, since they provide a scheme for divide-and-conquer-style decomposition of the analysis or verification problem at hand. We define an abstract class of SPLs for which variability models can be constructed that are optimal w.r.t. the chosen representation of sharing. We show how the constructed models can be fed into a previously developed algorithmic technique for compositional verification of control-flow temporal safety properties, so that the properties to be verified are iteratively decomposed into simpler ones over orthogonal parts of the SPL, and are not re-verified over the shared parts. We provide tool support for our technique, and evaluate our tool on a small but realistic SPL of cash desks.

Motivations for servitization:the impact of product complexity

Purpose – The purpose of this paper is to identify the commonalities and differences in manufacturers’ motivations to servitise. Design/methodology/approach – UK study based on interviews with 40 managers in 25 companies in 12 sectors. Using the concept of product complexity, sectors were grouped using the Complex Products and Systems (CoPS) typology: non-complex products, complex products and systems. Findings – Motivations to servitise were categorised as competitive, demand based (i.e. derived from the customer) or economic. Motivations to servitise vary according to product complexity, although cost savings and improved service quality appear important demand-based motivations for all manufacturers. Non-complex product manufacturers also focus on services to help product differentiation. For CoPS manufacturers, both risk reduction and developing a new revenue stream were important motivations. For uniquely complex product manufacturers, stabilising revenue and increased profitability were strong motivations. For uniquely systems manufacturers, customers sought business transformation, whilst new service business models were also identified. Research limitations/implications – Using the CoPS typology, this study delineates motivations to servitise by sector. The findings show varying motivations to servitise as product complexity increases, although some motivational commonality existed across all groups. Manufacturers may have products of differing complexity within their portfolio. To overcome this limitation the unit of analysis was the strategic business unit. Practical implications – Managers can reflect on and benchmark their motivation for, and opportunities from, servitisation, by considering product complexity. Originality/value – The first study to categorise servitisation motivations by product complexity. Identifying that some customers of systems manufacturers seek business transformation through outsourcing.

Town and Countryside in early modern Hungary The Case of Sopron, c. 1500-1800

The town of Sopron (Ödenburg) is situated near the western border of Hungary at the junction of major routes of commerce, no further than 70 km from Vienna. As early as in 1291 the town had become a chartered town or free royal town, which meant the most fully-fledged municipial autonomy in this period. The town was subordinated only to the king and could represent itself in parliament from 1445. The surrounding seigniorial towns and villages often lodged an appeal with the Town Court due to its wide legal autonomy. The inhabitants of seigniorial towns and the villagers could have been under the necessity of going to the town, and the legal proceedings they experienced in Sopron may have meant a model pattern for them. The seigniorial town (oppidum) is a settlement under the landlord's authority, with limited legal privileges, concentrated mostly on agricultural production and on the exchange of products of its immediate hinterland. Sopron as a county town was gradually becoming significant during the early modern period. The county (megye) was not only the unit of administration in Hungary, but that of the autonomy of nobility, too. The importance of Sopron as a county town attracted many noblemen dwelling in Sopron county to the town. The county was one of the most densely populated in the 15-18th c., at the beginning of the 18th c., for example, the density was 32 person/km2 and it rose more than 40 p/km2 by the end of the century. The population of Sopron was approximately 3500-3700 in the middle of the 15th c., and due to the decline during the later decades some 3000 persons lived in the town in the early 16th c. According to the first national census the population of Sopron was 12600 in 1784-87. These data place Sopron at the high level of Hungarian urban hierarchy in this period. This paper will explore two significant aspects of the relation between the town and its countryside: the problems of mutual economic dependence and the role of Sopron as a centre of culture.

Reactions of singlet oxygen and singlet oxygen mimics with dicyclopropylethylenes: Comparison of reactivity and mechanisms

An extensive study of the reaction pathways of 1,1-dicyclopropyl ethylene, cis- and trans- 1,2-dicyclopropylethylenes has been undertaken with different electrophiles 4-methyl-1,2,4-triazoline-3,5-dione (MTAD), tetracyanoethylene (TCNE), and singlet oxygen $\rm(\sp1O\sb2).$ Comparison of reactivity and reaction mechanisms among the electrophiles is investigated. Singlet oxygen exhibits significantly lower reactivity compared to the other electrophiles. MTAD and TCNE react with dicyclopropylethylenes to produce predominantly $\sp{\prime\prime}2+2\sp{\prime\prime}$ adducts and a small amount of the "ene" adducts. The $\sp{\prime\prime}2+2\sp{\prime\prime}$ is the major product presumably because of the high activation energy leading to the highly strained "ene" products. Solvent trapping studies provide strong evidence of a "stepwise" mechanism, involving a zwitterionic or aziridinium imide as an intermediate from the study of the reactions products of dicyclopropylethylenes and MTAD. ^

Sequence analysis of complementary DNAs encoding C3 in the nurse shark ({\it Ginglymostoma cirratum\/})

Mammalian C3 is a pivotal complement protein, encoded for by a single gene. In some vertebrate species multiple C3 isoforms are products of different C3 genes. The goal of this study was to determine whether multiple genes encode for shark C3. A protocol was developed for the isolation of mRNA from shark blood for the isolation of C3 cDNA clones. RT-PCR amplification of mRNA, using sense (GCGEQNM) and antisense (TWLTAYV) primers encoding conserved regions of human C3, yielded 21 clones. The C3-like clones isolated shared 97% similarity with each other and 40% similarity to human C3. RACE-PCR amplification of shark liver RNA, using gene specific primers, yielded products ranging from 1800bp to 3000bp. Deduced amino acid sequence, corresponding to 408bp of the 1800bp fragment, was obtained which showed 51% similarity to human C3. These results suggest that nurse shark C3 might be encoded for by more than one gene. ^

Health beliefs and health care options of disparate black communities in the United States

According to the 1999 U.S. Census, there were approximately thirty-three million African Americans and approximately 1.8 million non-Hispanic black immigrants in the United States. The 1997 U.S. Census estimated that there were as many as 554,000 foreign-born Haitians and 505,000 foreign-born Jamaicans living in the United States, mainly residing in Florida and New York. The U.S. Census claims that blacks are one of the largest emerging ethnic groups in America constituting at least twelve percent of this country's population. Because of this increase, their specific health beliefs and health care options are increasingly nationally significant. ^ In the present intra-black and inter-ethnic study, two hundred seventy African Americans, Haitian immigrants, and Jamaican immigrants residing in South Florida were quantitatively and qualitatively surveyed in order to investigate their health beliefs and health care options. According to the reviewed literature, the three black ethnic groups researched in this study have not been compared or contrasted before in relation to these beliefs and health care choices. ^ As was discovered by the present research, differing health beliefs and health care options were the cultural products of the ethnic differences of the researched communities. It was expected that differing health beliefs among the researched black groups might indicate disparate patterns of health care utilization of either western or non-western models. Additionally, it was projected that by investigating the health beliefs and the health care options of these emerging black ethnic groups, western health care providers in the United States could become better versed in medically servicing growing ethnically-disparate black populations. The study yielded results about the researched groups that supported major findings in the reviewed literature. The data were reported and examined, and theoretical generalizations from the data were discussed. The most important of these findings was that, within a race, health beliefs and health care options were determined by specific ethno-cultural variables dependent on national origins. ^

Occurrence and environmental fate of Irgarol 1051, a new antifouling agent

The purpose of this study is to characterize the degradation products of Irgarol 1051(2-methylthio-4-tertbutylamino-6-cyclopropylamino- s-triazine), a compound recently developed for use as an antifouling agent on boat hulls. The photolytic fate of this compound in different natural waters will be used in the development of a monitoring program designed to survey the occurrence of this compound and its degradation products in South Florida marinas, the Miami River and surrounding coastal areas. ^ The transformation of Irgarol 1051 and degradation rate constants were characterized in a photo-reactor under simulated natural conditions. The degradation pathway in the UVB-UVA region (300nm to 350nm) closely resembled the transformations under natural conditions in the pond, showing that both direct photolysis and the presence of natural sensitizers play an important role in the abiotic transformation of this compound. Irgarol 1051 has an average environmental half-life of 10 days in surface waters. Average concentrations from samples around Biscayne Bay and the Miami River increased from 1–5 ng/L during 1999 and increased to between 28 and 38 ng/L in 2001, respectively. Irgarol concentrations showed a strong correlation with concentrations of its major transformation product, M1, from samples collected as part of the study ([M1]/[Irgarol] = 0.247, R2 = 0.9165, n = 125). ^

Mechanistic studies on the advanced oxidation and photochemical transformation of cyanotoxins (microcystins)

The increased occurrence of cyanobacteria (blue-green algae) blooms and the production of associated cyanotoxins have presented a threat to drinking water sources. Among the most common types of cyanotoxins found in potable water are microcystins (MCs), a family of cyclic heptapeptides containing substrates. MCs are strongly hepatotoxic and known to initiate tumor promoting activity. The presence of sub-lethal doses of MCs in drinking water is implicated as one of the key risk factors for an unusually high occurrence of primary liver cancer. ^ A variety of traditional water treatment methods have been attempted for the removal of cyanotoxins, but with limited success. Advanced Oxidation Technologies (AOTs) are attractive alternatives to traditional water treatments. We have demonstrated ultrasonic irradiation and UV/H2O2 lead to the degradation of cyanotoxins in drinking water. These studies demonstrate AOTs can effectively degrade MCs and their associated toxicity is dramatically reduced. We have conducted detailed studies of different degradation pathways of MCs and conclude that the hydroxyl radical is responsible for a significant fraction of the observed degradation. Results indicate preliminary products of the sonolysis of MCs are due to the hydroxyl radical attack on the benzene ring and substitution and cleavage of the diene of the Adda peptide residue. AOTs are attractive methods for treatment of cyanotoxins in potable water supplies. ^ The photochemical transformation of MCs is important in the environmental degradation of MCs. Previous studies implicated singlet oxygen as a primary oxidant in the photochemical transformation of MCs. Our results indicate that singlet oxygen predominantly leads to degradation of the phycocyanin, pigments of blue green algae, hence reducing the degradation of MCs. The predominant process involves isomerization of the diene (6E to 6Z) in the Adda side chain via photosensitized isomerization involving the photoexcited phycocyanin. Our results indicate that photosensitized processes play a key role in the environmental fate and elimination of MCs in the natural waters. ^

The development of optimized high performance liquid chromatography systems for the analysis of improvised explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

The problematics of mestizaje in the Indigenist Peruvian novels of "Yawar Fiesta" (1941) by Jose Maria Arguedas, "El mundo es ancho y ajeno" (1941) by Ciro Algeria, and "Los rios profundos" (1958) by Jose Maria Arguedas

This study was a critical reassessment of the problematics of mestizaje in three representative texts pertaining to the Indigenist Peruvian narrative: Yawar Fiesta (1941) by José María Arguedas; El mundo es ancho y ajeno (1941) by Ciro Alegría; and Los ríos profundos (1958) by José María Arguedas. As this investigation demonstrated, Alegría's and Arguedas' writings went beyond the reach of Indianism and orthodox Indigenism, which were prevalent during the first decades of the twentieth century, to emphasize, the values of the Indian peasantry as well as those of the mestizo and mestiza: the products of Indian and white unions, who were also considered representatives of the Peruvian culture. ^ The first chapter traced the historical process of mestizaje and demonstrated how the discursive practice of this mestizaje was expressed in the Indigenist Peruvian narrative. The chronological organization of the chapters in this dissertation paralleled the evolution of this narrative.^ The relevance of my research lies on the important contribution it makes to the field of Indigenist literature, by seeing mestizaje as both a reconstruction and a reinterpretation of the idea of nation, identity and cultural interchange. In Alegría's and Arguedas' novels, the Indigenous reality was not only seen as an isolated phenomenon, but also as the dichotomy of European versus Indian values. As a result, Indigenist narrative presented a true and all encompassing world; therefore, Alegría's and Arguedas' narrative deepened our understanding of the aspects of a multicultural society.^ In order to accomplish this analysis, research was conducted in areas such as history, languages, ethnology, ethnography, anthropology, folklore, religion, and syncretism. My study was based on works such as Antonio Cornejo Polar's heterogeneous literatures, Mijail Bajtín's conception of dialogism and polyphony, Benedict Anderson's Imagined Communities, Angel Rama's notion of transculturation, Homi Bhabha's liminal space, Walter Ong's study of orality and literacy, and Julia Kristeva's theory of abjection, among others.^