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Selected AbstractsTHE GEOGRAPHICAL DIMENSIONS OF AL-QA'IDA RHETORICGEOGRAPHICAL REVIEW, Issue 3 2005JOSEPH J. HOBBS ABSTRACT. This article examines the geographical ideology of al-Qa'ida. The central questions are to what extent al-Qa'ida terrorism is motivated by a desire to control geographical space, and how the organization defines that space as place in its communiqués. The study also asks whether al-Qa'ida's geographical rhetoric reveals the nature or locations of future attacks. Principal sources are statements and interviews by and with al-Qa'ida leaders. al-Qa'ida classifies distinctive geographical realms of legitimization, preparation, and action. Its geographical concerns and ambitions are hierarchical and based principally on perceptions of sacred space. The holy places of Mecca, Medina, and Jerusalem are the cornerstones of a greater Islamic holy land that al-Qa'ida seeks to rid of non-Islamic-especially U.S. and "Zionist"-elements and replace with a new caliphate. Terrorism directed principally against American civilians in the United States is one of the main tactics by which al-Qa'ida says it hopes to achieve its goals in geographical space. [source] St Columba and the convention at Druimm Cete: peace and politics at seventh-century IonaEARLY MEDIEVAL EUROPE, Issue 3 2007James E. Fraser Attendance at the ,convention of kings' at Druimm Cete in north-east Ireland is one of the most famous episodes in the career of St Columba or Colum Cille, who died in 597. Discussion of the significance of this shadowy summit, largely informed by unreliable late evidence, has hitherto focused upon what (may have) transpired there between kings based in Ireland and Scotland. The result has been the neglect of the hagiographical dimension of the presentation of Druimm Cete in our principal source, Adomnán's Vita Sancti Columbae, composed c.700. Analysis of this material shows that Adomnán's information about the convention came from his principal source, composed some sixty years earlier. It reveals moreover that Druimm Cete assumed prominence within the Columban dossier in the 640s for what it represented, rather than because of what actually happened there. Once the hagiographical agenda of Vita Sancti Columbae and its principal source is restored to its rightful place in evaluating the text, it emerges that several of its best-known stories , including the story of Columba's ordination of a Scottish king , are much more problematic as witnesses to sixth-century history than is conventionally supposed. As scholars begin to lose their grip upon the historical Columba, however, they grow better able to grasp seventh-century political history in north-east Ireland and Gaelic Scotland. [source] The feeding behavior of Trichogramma brassicae: new evidence for selective ingestion of solid foodENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2000Z.X. Wu Abstract A descriptive study of the feeding behavior and structures of Trichogramma brassicae Bezdenko (Hymenoptera: Trichogrammatidae) was conducted. Based on direct observational and biochemical evidence, larvae feed predominantly on particulate materials, starting ca. 25 h post-oviposition. Feeding lasted for ca. 9 h, at 25±1 °C. During this feeding period the shape of the larvae changed from vermiform to pyriform and then to sacciform, resulting in a ca. 40-fold increase in body size. Larvae used elaborate feeding behaviors as they pulled solid food particles to their oral opening, broke small particles from larger ones, and took the particles into the stomodaeum, which is a powerful pump. In the stomodaeum, peristaltic movement further macerated the particles, which eventually passed through the cardiac valve into the midgut. As indicated by changes in fluorescently labeled casein, digestive enzymes aid in the extra-oral chemical digestion of food. The contents of the gut, during and shortly after feeding, were almost entirely closely packed solid particles. The behavioral activity of feeding larvae centered almost exclusively on processing and ingesting solid food particles. The rapid larval growth is much more plausibly explained by their feeding on the highly concentrated nutrients found in solid foods, rather than the extensive concentration required if dilute liquids were the principal source of nutrients. The implications of these findings for the development of practical artificial diets are discussed. [source] Health care resource utilization in patients with active epilepsyEPILEPSIA, Issue 5 2010Tobias Kurth Summary Purpose:, To evaluate health care resource utilization (HRU) in active epilepsy. Methods:, Thomson-Reuters insurance databases included 14 million persons in 2005,2007. We extracted information for individuals with insurance claims suggestive of epilepsy. Using iterative expert classification, we sorted patients by type of epilepsy. For each type we calculated prevalence and HRU. A distance analysis identified closely similar types, and a principal components analysis revealed dimensions of variation in HRU. Results:, The prevalence of active epilepsy was 3.4 per 1,000. Most common diagnoses among 46,847 patients were generalized convulsive epilepsy (33.3%) and complex partial seizures (24.8%). Patients averaged 10 physician visits per year, 24 diagnostic tests/procedures per year, >30 drug dispensings per year, and <1 emergency room (ER) visit per year, the minority of each of these being related to epilepsy. Female patients generally had more HRU, and HRU increased with age. Patients were hospitalized most frequently for disorders other than epilepsy. HRU was similar for most epilepsy types, excepting grand mal status, epilepsia partialis continua, and infantile spasms. The first principal components of HRU variation was nonepilepsy HRU, followed by components of epilepsy-related medications, other epilepsy/emergency care, and epilepsy visits/diagnostic procedures. Discussion:, The prevalence of active epilepsy in the United States is substantially less than the prevalence of any history of recurrent seizure. Nonepilepsy-related HRU dominated HRU in epilepsy patients and was the principal source of variation. There is a core set of epilepsy diagnoses, the HRU patterns of which are indistinguishable, whereas patients with grand mal status, epilepsia partialis continua, and infantile spasms all have distinct patterns. To provide more specific insights into the economic impact of the condition, studies of HRU in epilepsy should make a distinction about epilepsy-related and unrelated care. [source] International conference on the healthy effect of virgin olive oilEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2005Summary 1Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheime's disease, vascular dementia, cognitive decline, diabetes and cancer. 2Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations. [source] ,Beyond Left and Right': The New Partisan Politics of WelfareGOVERNANCE, Issue 2 2000Fiona Ross The ,new politics of the welfare state,' the term coined by Pierson (1996) to differentiate between the popular politics of welfare expansion and the unpopular politics of retrenchment, emphasizes a number of factors that distinguish countries' capacities to pursue contentious measures and avoid electoral blame. Policy structures, vested interests, and institutions play a prominent role in accounting for cross-national differences in leaders' abilities to diffuse responsibility for divisive initiatives. One important omission from the ,new politics' literature, however, is a discussion of partisan politics. ,Old' conceptualizations of the political right and left are implicitly taken as constants despite radical changes in the governing agenda of many leftist parties over the last decade. Responding to this oversight, Castles (1998) has recently probed the role of parties with respect to aggregate government expenditures, only to concludethat parties do not matter under ,conditions of constraint.' This article contends that parties are relevant to the ,new politics' and that, under specified institutional conditions, their impact is counterintuitive. In some notable cases the left has had more effect inbruising the welfare state than the right. One explanation for these cross-cutting tendencies is that parties not only provide a principal source of political agency, they also serve as strategies, thereby conditioning opportunities for political leadership. By extension, they need to be situatedwithin the ,new politics' constellation of blame-avoidance instruments. [source] Hydrological importance of an unusual hazard in a mountainous basin: flood and landslideHYDROLOGICAL PROCESSES, Issue 14 2006Umesh K. Haritashya Abstract The Bhagirathi River, a proglacial melt water stream of the Gangotri Glacier, is the principal source of the Ganges river system. The upper part of the basin lies in the high altitude region of the Garhwal Himalayas and is extensively covered by glaciers. We provide hydro-meteorological insight into a severe storm that produced unusual high rains in June 2000 in the uppermost part of the Bhagirathi River. This storm was concentrated upstream of Gangotri town and triggered landslides/rockslides at several locations between the glacier snout and Gangotri town. One of the major rockslides blocked the Bhagirathi River at Bhujbas, about 3 km downstream of the Gangotri Glacier snout, creating an artificial lake at this location. High stream flow in the river, generated by rapid runoff response from mountain slopes along with melt runoff from the glacier, quickly increased the level of water stored in the artificial lake. Daily rainfall in this region rarely exceeds 10 mm, while total rainfall during this 6-day storm was 131·5 mm. This unusual rain event occurred during the tourist season in June, consequently trapping a large number of tourists and vendors in this area. Sudden release of stored water generated floods that created havoc downstream of the artificially created lake. This paper presents the hydrological and meteorological information related to such an unusual and devastating event observed in the high altitude region of the Himalayas. Copyright © 2006 John Wiley & Sons, Ltd. [source] Sources of stream sulphate in headwater catchments in Otter Creek Wilderness, West Virginia, USAHYDROLOGICAL PROCESSES, Issue 4 2001Ross D. Fitzhugh Abstract Upland forested catchments in the Appalachian Plateau region receive among the greatest rates of atmospheric sulphur (S) deposition in the eastern USA, although coal mines and S-bearing minerals in bedrock may also contribute to stream acidity in this region. Watershed mass balance and stable S isotopic values (,34S) of sulphate (SO42,) were used to assess the contributions to stream SO42, from atmospheric and lithogenic sources at Yellow Creek (YC), a headwater catchment on the Appalachian Plateau in West Virginia. Oxygen isotopic values (,18O) of water were used to study catchment hydrology. Stream output of SO42, was c. 60% of atmospheric S deposition during a relatively dry year, whereas atmospheric S input was nearly balanced by stream output during a year with above normal amounts of precipitation. The temporal patterns and values of ,34S were similar between bulk precipitation and stream water at two upper elevation sites. At the lowest elevation site, stream ,34S values were similar to bulk precipitation values during the dormant season but were slightly lower than precipitation during the low-flow summer, probably as the result of a greater proportion of stream water being derived from deep hydrological flowpaths that have contacted S-bearing minerals with low ,34S values in coal seams. Stream ,34S values at YC were significantly higher than at Coal Run, a catchment containing abandoned coal prospects and having a greater amount of S-bearing minerals than YC. Results suggested that lithogenic S is a relatively minor source and that atmospheric deposition is the principal source of stream SO42,, and thus stream acidity, at YC. Copyright © 2001 John Wiley & Sons, Ltd. [source] Structure and signaling in polyps of a colonial hydroidINVERTEBRATE BIOLOGY, Issue 1 2004Neil W. Blackstone Abstract. After feeding, polyps of colonial hydroids contract regularly, dispersing food throughout the colony via the gastrovascular fluid. Such contractions may trigger signaling pathways that allow colonies to grow in an adaptive manner, i.e., to initiate development of more polyps in food-rich areas and to suppress polyp development in food-poor areas. In this context, we investigated the structure and potential signaling of the junction between polyps and stolons in colonies of the hydroid Podocoryna carnea. Using transmission electron microscopy, we found that the density of mitochondrion-rich epitheliomuscular cells was low in polyp and stolon tissues except at or near the polyp-stolon junction, where many of these mitochondrion-rich cells occur in ectodermal tissue. In vivo fluorescence microscopy suggests that these mitochondria are a principal source of the metabolic signals of the colony. Both native fluorescence of NAD(P)H and fluorescence from peroxides (visualized with H2DCFDA) co-localize to this region of the polyp. Rhodamine 123 fluorescence suggests that both these metabolic signals emanate from mitochondria. To test whether such metabolic signals may be involved in colony pattern formation, inbred lines of P. carnea were used. Colonies of a runner-like inbred line grow with widely spaced polyps and long stolonal connections, much like wild-type colonies in a food-poor environment. Colonies of a sheet-like inbred line grow with closely spaced polyps and short stolonal connections, similar to wild-type colonies in a food-rich environment. Polyp-stolon junctions in runner-like and sheet-like colonies were imaged for the fluorescence of H2DCFDA. Densitometric analysis of this signal indicates that the mitochondria in epitheliomuscular cells of runner-like polyps emit greater amounts of peroxides. Because peroxides and other reactive oxygen species are frequently intermediaries in metabolic signaling pathways, we suspect that such signaling may indeed occur at polyp-stolon junctions, affecting colony pattern formation in these inbred lines and possibly in hydroid colonies in general. [source] Spatial and temporal variability in host use by Helicoverpa zea as measured by analyses of stable carbon isotope ratios and gossypol residuesJOURNAL OF APPLIED ECOLOGY, Issue 3 2010Graham Head Summary 1.,A high dose/refuge strategy has been adopted in the USA to manage the risk of Bacillus thuringiensis (Bt) resistance in target pests such as the cotton bollworm (CBW), Helicoverpa zea (Boddie) in transgenic Bt cotton Gossypium hirsutum L. Structured refuges, consisting of non-Bt cotton, have been a mandated part of this strategy to produce non-selected insects that are temporally and spatially synchronous with insects from the Bt crop, diluting Bt resistance alleles through mating. However, the bollworm is highly polyphagous and exploits a large number of crop and weedy hosts concurrently with Bt cotton. 2.,A study was carried out in five major US cotton-producing states during 2002 and 2003 using the ratios of 13C to 12C in bollworm moths to estimate the proportions of the population originating from C3 or C4 plants. A separate study measured gossypol residues in moths from four states in 2005 and 2006, enabling the identification of moths whose natal hosts were cotton rather than other C3 hosts. 3.,C4 hosts served as the principal source of bollworm moths from mid-to-late June to early September, depending on the state. Beginning in late August/early September and lasting 1,4 weeks, the majority of moths exhibited isotopic compositions characteristic of C3 hosts. During this period, however, the minimum percentage of moths that developed as larvae on C4 hosts was typically >25%. By mid-September and through October and November, the majority of the bollworm population exhibited C4 isotopic compositions. 4.,Between late June and early August, cotton-derived bollworm moths (moths with gossypol residues) comprised <1% of moths in all states, and remained below this level throughout the season in North Carolina. In other states, cotton-derived moths increased between early August and early September to peak at an average of 19·1% of all moths. 5.,Synthesis and applications.,Data on 13C/12C ratios and gossypol residues in CBW moths were used to assess the importance of structured non-Bt cotton refuges for the management of Bt resistance risk in H. zea. Weekly estimates of bollworm breeding on cotton, C3 plants other than cotton and C4 plants showed that, throughout the season, the majority of bollworm moths caught in pheromone traps adjacent to cotton fields did not develop as larvae on cotton. This result implies that management practices in cotton such as the use of structured cotton refuges will play a relatively minor role , particularly compared with maize Zea mays L. , in managing potential resistance to Bt cotton in populations of the CBW in the US Cotton Belt. [source] Prevalence of enterohaemorrhagic Escherichia coli from serotype O157 and other attaching and effacing Escherichia coli on bovine carcasses in AlgeriaJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006A. Chahed Abstract Aims:, Bovine meat is the principal source of human contamination of attaching and effacing Escherichia coli, including enterohaemorrhagic E. coli O157. The aim was to study the prevalence of these strains on bovine carcasses in Algeria. Methods and Results:, Two-hundred and thirty carcasses were swabbed and analysed by classical microbiological methods for total E. coli counts and for the presence of pathogenic E. coli. The E. coli counts were high, with a 75th percentile of 444·75 CFUs cm,2. For pathogenic E. coli, more than 7% of the tested carcasses were positive for E. coli O157. Eighteen E. coli O157 strains were isolated and typed by multiplex PCR. The main isolated pathotype (78%) was eae+ stx2+ ehxA+. In addition to E. coli O157, other attaching and effacing E. coli (AEEC) were also detected from carcasses by colony hybridization after pre-enrichment and plating on sorbitol MacConkey agar using eae, stx1 and stx2 probes. Thirty carcasses (13%) on the 230 analysed harboured at least one colony positive for one of the tested probes. These positive carcasses were different from those positive for E. coli O157. Sixty-six colonies (2·9%) positive by colony hybridization were isolated. The majority (60·6%) of the positive strains harboured an enteropathogenic E. coli -like pathotype (eae+ stx,). Only three enterohaemorrhagic E. coli (EHEC)-like (eae+ stx1+) colonies were isolated from the same carcass. These strains did not belong to classical EHEC serotypes. Conclusions:, In this study, the global hygiene of the slaughterhouse was low, as indicated by the high level of E. coli count. The prevalence of both E. coli O157 and other AEEC was also high, representing a real hazard for consumers. Significance and Impact of the Study:, This is the first study of this type in Algeria, which indicates that the general hygiene of the slaughterhouse must be improved. [source] Combining mitochondrial DNA sequences and morphological data to infer species boundaries: phylogeography of lanceheaded pitvipers in the Brazilian Atlantic forest, and the status of Bothrops pradoi (Squamata: Serpentes: Viperidae)JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2001G. Puorto Phylogeographic studies using mitochondrial DNA sequence information are frequently used as the principal source of evidence to infer species boundaries. However, a critical analysis of further evidence is essential to test whether different haplotype clades identify different species. We demonstrate a hypothesis-testing approach, using a combination of phylogeographic methods, multivariate morphometrics and matrix association tests, to investigate species boundaries in eastern Brazilian pitvipers conventionally assigned to the species Bothrops leucurus and B. pradoi. Two basal haplotype clades with partly overlapping geographical distributions are identified, which could either represent two partly sympatric species, or multiple haplotypes within one organismal lineage. We use partial Mantel matrix association tests to verify whether generalized morphology, or any of four supposedly diagnostic characters for the two species, show any association with mtDNA variation. Negative results lead to the conclusion that the haplotype clades do not denote independently evolving organismal lineages, and do not constitute separate species under any criterion. [source] Influences of the environment on the endocrine and paracrine fish growth hormone,insulin-like growth factor-I systemJOURNAL OF FISH BIOLOGY, Issue 6 2010M. Reinecke Insulin-like growth factor-I (IGF-I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF-I gene is mainly expressed in the liver that represents the principal source of endocrine IGF-I but also in numerous other organs where the hormone most probably acts in an autocrine,paracrine manner. The primary stimulus for synthesis and release of IGF-I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish ,GH,IGF-I axis'. The GH,IGF-I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF-I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF-I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH,IGF-I research are analysed and future focuses are suggested at the end of the sections. [source] Sources of Dietary Fluoride Intake in 6,7-Year-Old English Children Receiving Optimally, Sub-optimally, and Non-fluoridated waterJOURNAL OF PUBLIC HEALTH DENTISTRY, Issue 4 2006Fatemeh V. Zohouri BSc, RPHNutr Abstract Objectives:Due to increased consumption of pre-packaged drinks, tap water may no longer be the principal source of water intake and consequently fluoride intake. Little is known about the importance of solid foods as fluoride sources and how the relative contribution of foods/drinks to fluoride intake is affected by residing in fluoridated or non-fluoridated areas. This study investigated the relative contributions of different dietary sources to dietary fluoride intake and compared this in children residing in optimally artificially fluoridated, sub-optimally artificially fluoridated, and non-fluoridated areas. Methods:Thirty-three healthy children aged 6 years were recruited from fluoridated and non-fluoridated communities and categorised into three groups based on fluoride content of home tap water: optimally fluoridated (<0.7 mgF/L), sub-optimally fluoridated (>0.3 to <0.7 mgF/L) and non-fluoridated (<0.3 mgF/L) drinking water. A 3-day dietary diary collected dietary information. Samples of foods/drinks consumed were collected and analyzed for fluoride content. Results:Drinks provided 59%, 55% and 32% of dietary fluoride intake in optimally, sub-optimally and non-fluoridated areas respectively. Tap water, fruit squashes and cordials (extremely sweet non-alcoholic fruit flavoured drink concentrates) prepared with tap water, as well as cooked rice, pasta and vegetables were important sources of fluoride in optimally and sub-optimally fluoridated areas. Carbonated soft drinks and bread were the most important contributors to dietary fluoride intake in the non-fluoridated area. Conclusion:The main contributory sources to dietary fluoride differ between fluoridated and non-fluoridated areas. Estimating total fluoride intake from levels of fluoride in tap water alone is unlikely to provide a reliable quantitative measure of intake. Studies monitoring dietary fluoride exposure should consider intake from all foods and drinks. [source] Decreased Proteasome Activity Is Associated With Increased Severity of Liver Pathology and Oxidative Stress in Experimental Alcoholic Liver DiseaseALCOHOLISM, Issue 8 2004Terrence M. Donohue Jr Background: Because of its role in degrading the bulk of intracellular proteins and eliminating damaged proteins, the proteasome is important in maintaining cell viability. Previously, we showed a 35,40% decrease in proteasome peptidase activity when ethanol was administered to rats by intragastric infusion. We hypothesized that this reduction was caused by ethanol-elicited oxidative stress, the degree of which varies depending on the method of ethanol administration. This study examined the relationship of proteasome activity and content with ethanol-induced oxidative stress and the degree of liver injury. Methods: Rats were given ethanol or isocaloric dextrose-containing liquid diets by intragastric infusion for 1 month. The diets contained medium-chain triglycerides (MCT), palm oil (PO), corn oil (CO), or fish oil (FO) as the principal source of fat. Results: Rats given ethanol and MCT exhibited no significant liver pathology, whereas cumulative pathology scores in ethanol-fed rats given PO, CO, or FO were 2.5, 5.4 and 7.0, respectively, indicating that ethanol and FO caused the greatest liver damage. The severity of liver pathology in the last three groups of animals correlated with levels of lipid peroxides and serum 8-isoprostanes. Alpha smooth muscle actin, an indicator of stellate cell activation, was increased relative to controls in the livers of all ethanol-fed rats except FO-fed animals, in which both control and ethanol-fed rats had similar levels of this protein. In livers of CO and FO ethanol-fed rats, proteasome chymotrypsin-like activity was decreased by 55,60%, but there was no quantitative alteration in 20S proteasome subunit content. In contrast, ethanol affected neither proteasome activity nor its content in MCT- and PO-treated animals. Conclusions: Our findings indicate that the severity of liver injury and ethanol-induced oxidative stress is associated with a reduction in proteasome catalysis. [source] Antioxidant and other biological activities of phenols from olives and olive oilMEDICINAL RESEARCH REVIEWS, Issue 1 2002Francesco Visioli Abstract Olive oil is the principal source of fats in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Phenolic compounds, e.g., hydroxytyrosol and oleuropein, in extra-virgin olive oil are responsible for its peculiar pungent taste and for its high stability. Recent findings demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and in vivo, and possess other potent biological activities that could partially account for the observed healthful effects of the Mediterranean diet. © 2001 John Wiley & Sons, Inc. Med Res Rev, 22, No. 1, 65,75, 2002 [source] Metabolism of the major Echinacea alkylamide N -isobutyldodeca-2E,4E,8Z,10Z -tetraenamide by human recombinant cytochrome P450 enzymes and human liver microsomesPHYTOTHERAPY RESEARCH, Issue 8 2010F. Toselli Abstract Echinacea preparations are used for the treatment and prevention of upper respiratory tract infections. The phytochemicals believed responsible for the immunomodulatory properties are the alkylamides found in ethanolic extracts, with one of the most abundant being the N -isobutyldodeca-2E,4E,8Z,10Z -tetraenamide (1). In this study, we evaluated the human cytochrome P450 enzymes involved in the metabolism of this alkylamide using recombinant P450s, human liver microsomes and pure synthetic compound. Epoxidation, N -dealkylation and hydroxylation products were detected, with different relative amounts produced by recombinant P450s and microsomes. The major forms showing activity toward the metabolism of 1 were CYP1A1, CYP1A2 (both producing the same epoxide and N -dealkylation product), CYP2A13 (producing two epoxides), and CYP2D6 (producing two epoxides and an hydroxylated metabolite). Several other forms showed less activity. In incubations with human liver microsomes and selective inhibitors, CYP2E1 was found to be principally responsible for producing the dominant, hydroxylation product, whereas CYP2C9 was the principal source of the epoxides and CYP1A2 was responsible for the dealkylation product. In summary, in this study the relative impacts of the main human xenobiotic-metabolizing cytochrome P450s on the metabolism of a major Echinacea alkylamide have been established and the metabolites formed have been identified. Copyright © 2010 John Wiley & Sons, Ltd. [source] Understanding fire fighting in new product development,THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 5 2001Nelson P. Repenning Despite documented benefits, the processes described in the new product development literature often prove difficult to follow in practice. A principal source of such difficulties is the phenomenon of fire fighting-the unplanned allocation of resources to fix problems discovered late in a product's development cycle. While it has been widely criticized, fire fighting is a common occurrence in many product development organizations. To understand both its existence and persistence, in this article I develop a formal model of fire fighting in a multiproject development environment. The major contributions of this analysis are to suggest that: (1) fire fighting can be a self-reinforeing phenomenon; and (2) multiproject development systems are far more susceptible to this dynamic than is currently appreciated. These insights suggest that many of the current methods for aggregate resource and product portfolio planning, while necessary, are not sufficient to prevent fire fighting and the consequent low performance. [source] Clinical Real-Time Monitoring of Gaseous Microemboli in Pediatric Cardiopulmonary BypassARTIFICIAL ORGANS, Issue 11 2009Shigang Wang Abstract We describe the occurrence and distribution of gaseous microemboli with real-time monitoring in a pediatric cardiopulmonary bypass (CPB) circuit and in the cerebral circulation of patients using the Emboli Detection and Classification (EDAC) system and transcranial Doppler (TCD). Four patients (weights 3.2,13.8 kg) were studied. EDAC monitors were located on the venous line and on the postfilter arterial line to measure gaseous microemboli in the CPB circuit. TCD was used to measure high-intensity transient signals (HITS) in the middle cerebral artery. Before the initiation of CPB, EDAC detected gaseous microemboli in two cases when giving volume through the arterial line. At the initiation of CPB, gross air appeared in the venous line and gaseous microemboli were detected in the arterial line in all patients. EDAC detected a total of 3192,14 699 gaseous microemboli in the arterial line during the whole CPB period, more than 99% of which were smaller than 40 microns. After cessation of CPB, EDAC detected gaseous microemboli in the arterial line in all cases. The TCD detected HITS in two cases (25 and 315), and detected no HITS in two cases. We observed that the venous line acted as a principal source of gaseous microemboli, particularly when using vacuum-assisted venous drainage, and that a significant number of these gaseous microemboli smaller than 40 microns were subsequently transferred to the patient. Using EDAC and TCD together could strengthen the monitoring of gaseous microemboli in the extracorporeal circuit and cerebral circulation. [source] The Role of Mitochondria in the Pathogenesis of Neurodegenerative DiseasesBRAIN PATHOLOGY, Issue 3 2000Giovanni Manfredim MD A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin. Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders. [source] Vitamin D and systemic cancer: is this relevant to malignant melanoma?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2002J.E. Osborne Summary 1,25-dihydroxyvitamin D3[1,25(OH)2D3] is a well-known potent regulator of cell growth and differentiation and there is recent evidence of an effect on cell death, tumour invasion and angiogenesis, which makes it a candidate agent for cancer regulation. The classical synthetic pathway of 1,25(OH)2D3 involves 25- and 1,-hydroxylation of vitamin D3, in the liver and kidney, respectively, of absorbed or skin-synthesized vitamin D3. There is recent focus on the importance in growth control of local metabolism of 1,25(OH)2D3, which is a function of local tissue synthetic hydroxylases and particularly the principal catabolizing enzyme, 24-hydroxylase. The classical signalling pathway of 1,25(OH)2D3 employs the vitamin D nuclear receptor (VDR), which is a transcription factor for 1,25(OH)2D3 target genes. Effects of this pathway include inhibition of cellular growth and invasion. Cytoplasmic signalling pathways are increasingly being recognized, which similarly may regulate growth and differentiation but also apoptosis. 1,25(OH)2D3 has a major inhibitory effect on the G1/S checkpoint of the cell cycle by upregulating the cyclin dependent kinase inhibitors p27 and p21, and by inhibiting cyclin D1. Indirect mechanisms include upregulation of transforming growth factor-, and downregulation of the epidermal growth factor receptor. 1,25(OH)2D3 may induce apoptosis either indirectly through effects on the insulin-like growth receptor and tumour necrosis factor-, or more directly via the Bcl-2 family system, the ceramide pathway, the death receptors (e.g. Fas) and the stress-activated protein kinase pathways (Jun N terminal kinase and p38). Inhibition of tumour invasion and metastasis potential has been demonstrated and mechanisms include inhibition of serine proteinases, metalloproteinases and angiogenesis. The lines of evidence for an effect of vitamin D3 in systemic cancer are the laboratory demonstration of relevant effects on cellular growth, differentiation, apoptosis, malignant cell invasion and metastasis; epidemiological findings of an association of the occurrence and outcome of cancers with derangements of vitamin D3/1,25(OH)2D3 and the association of functional polymorphisms of the VDR with the occurrence of certain cancers. In addition, vitamin D3 analogues are being developed as cancer chemotherapy agents. There is accumulating evidence that the vitamin D3/1,25(OH)2D3/VDR axis is similarly important in malignant melanoma (MM). MM cells express the VDR, and the antiproliferative and prodifferentiation effects of 1,25(OH)2D3 have been shown in cultured melanocytes, MM cells and MM xenografts. Recently, an inhibitory effect on the spread of MM cells has been demonstrated, low serum levels of 1,25(OH)2D3 have been reported in MM patients and the VDR polymorphisms have been shown to be associated with both the occurrence and outcome of MM. The relationship between solar irradiation and MM is more complex than for the systemic cancers. As in other cancers, there is evidence of a protective effect of vitamin D3 in MM, but ultraviolet radiation, which is a principal source of vitamin D3, is mutagenic. Further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. Meanwhile, it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM. [source] Variations of diet composition of Red Deer (Cervus elaphus L.) in EuropeMAMMAL REVIEW, Issue 3-4 2001Claudia Gebert ABSTRACT To define the food resources of Red Deer (Cervus elaphus L.) in Europe and to detect the principal sources of variations in their diet, we reviewed field studies based on stomach content analysis. The study areas were classified into three main habitat groups (mixed-coniferous forest, mixed-deciduous forest, moorland), the food items into 13 plant categories, and we used five seasonal classes (winter, spring, summer, autumn, hunting season) for analysing the data set. For statistical analyses we used correspondence analysis and analysis of variance. Red Deer eat a varied diet comprising at least 145 plant species. The main sources of diet variation were due to habitat, leading us to identify three habitat types characterized by the consumption of a few key species. Clear seasonal variation was observed only for the seed and fruit items which were used mainly during the hunting season. Our results confirm that Red Deer can be classified among the intermediate feeders, with a mixed diet of grass & sedges (29%) and concentrate food items (63%). However, they also show Red Deer to be primarily a concentrate feeder (max. 75%) with no significant seasonal variation between the quantities of grass or sedges and concentrate food in the diet. In the light of these results, we discuss potential competition with other sympatric ungulates (wild and domestic). We suggest that it may be useful to take into account key food resources in modelling population dynamics and in taking management decisions. [source] The UV properties of E+A galaxies: constraints on feedback-driven quenching of star formationMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2007S. Kaviraj ABSTRACT We present the first large-scale study of E+A galaxies that incorporates photometry in the ultraviolet (UV) wavelengths. E+A galaxies are ,post-starburst' systems, with strong Balmer absorption lines indicating significant recent star formation, but without [O ii] and H, emission lines which are characteristic of ongoing star formation. The starburst that creates the E+A galaxy typically takes place within the last Gyr and creates a high fraction (20,60 per cent) of the stellar mass in the remnant over a short time-scale (<0.1 Gyr). We find a tight correlation between the luminosity of our E+A galaxies and the implied star formation rate (SFR) during the starburst. While low-luminosity E+As [M(z) > ,20] exhibit implied SFRs of less than 50 M, yr,1, their luminous counterparts [M(z) < ,22] show SFRs greater than 300 and as high as 2000 M, yr,1, suggesting that luminous and ultra-luminous infrared galaxies in the low-redshift Universe could be the progenitors of massive nearby E+A galaxies. We perform a comprehensive study of the characteristics of the quenching that truncates the starburst in E+A systems. We find that, for galaxies less massive than 1010 M,, the quenching efficiency decreases as the galaxy mass increases. However, for galaxies more massive than 1010 M,, this trend is reversed and the quenching efficiency increases with galaxy mass. Noting that the mass threshold at which this reversal occurs is in excellent agreement with the mass above which active galactic nuclei (AGN) become significantly more abundant in nearby galaxies, we use simple energetic arguments to show that the bimodal behaviour of the quenching efficiency is consistent with AGN and supernovae (SN) being the principal sources of negative feedback above and below M, 1010 M,, respectively. The arguments assume that quenching occurs through the mechanical ejection or dispersal of the gas reservoir and that, in the high-mass regime (M > 1010 M,), the Eddington ratios in this sample of galaxies scale as M,, where 1 < , < 3. Finally, we use our E+A sample to estimate the time it takes for galaxies to migrate from the blue cloud to the red sequence. We find migration times between 1 and 5 Gyr, with a median value of 1.5 Gyr. [source] Effects of crop debris and cultivations on the development of eyespot of wheat caused by Oculimacula spp.ANNALS OF APPLIED BIOLOGY, Issue 3 2010J.F. Jenkyn Results from a series of crop sequence and single-year experiments that tested different straw and cultivation treatments in a total of 11 site,season combinations confirmed previous evidence that the development of eyespot disease in cereals can be decreased by debris in the seed bed even if that debris includes eyespot-infected stem bases, which are the principal sources of primary inoculum. Two of the experiments, which followed non-cereal break crops and tested the effects of crop debris applied after ploughing or tining on eyespot in winter wheat that was artificially inoculated with Oculimacula spp., provided convincing evidence that the effects can be attributed to the debris per se, and not to any associated husbandry practices. There were often larger effects on disease in summer than in spring or on severity than on incidence suggesting that the effects of debris cannot be explained solely by effects on inoculum or initial infection, and that debris has a disease-suppressive effect. [source] An analysis of variability in the manufacturing of dexosomes: Implications for development of an autologous therapy,BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2005Sanjay Patel Abstract Dexosomes are nanometer-size vesicles released by dendritic-cells, possessing much of the cellular machinery required to stimulate an immune response (i.e. MHC Class I and II). The ability of patient-derived dexosomes loaded with tumor antigens to elicit anti-tumor activity is currently being evaluated in clinical trials. Unlike conventional biologics, where variability between lots of product arises mostly from the manufacturing process, an autologous product has inherent variability in the starting material due to heterogeneity in the human population. In an effort to assess the variability arising from the dexosome manufacturing process versus the human starting material, 144 dexosome preparations from normal donors (111) and cancer patients (33) from two Phase I clinical trials were analyzed. A large variability in the quantity of dexosomes (measured as the number of MHC Class II molecules) produced between individual lots was observed (,>,50-fold). An analysis of intra-lot variability shows that the manufacturing process introduces relatively little of this variability. To identify the source(s) of variability arising from the human starting material, distributions of the key parameters involved in dexosome production were established, and a model created. Computer simulations using this model were performed, and compared to the actual data observed. The main conclusion from these simulations is that the number of cells collected per individual and the productivity of these cells of are the principal sources of variability in the production of Class II. The approach described here can be extended to other autologous therapies in general to evaluate control of manufacturing processes. Moreover, this analysis of process variability is directly applicable to production at a commercial scale, since the large scale manufacture of autologous products entails an exact process replication rather than scale-up in volume, as is the case with traditional drugs or biologics. © 2005 Wiley Periodicals, Inc. [source] | |||||||||||||||||||