bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential and additive effects of platelet-derived chemokines on monocyte arrest on inflamed endothelium under flow conditions
Authors: Baltus Thomas , von Hundelshausen Philipp , Mause Sebastian F , Buhre Wolfgang , Rossaint Rolf , Weber Christian
Published: May 2005

Platelet-derived chemokines, such as regulated on activation, normal T expressed and secreted (RANTES; CC chemokine ligand 5), platelet factor 4 [PF4; CXC chemokine ligand 4 (CXCL4)], and epithelial neutrophil-activating protein 78 (ENA-78; CXCL5), or precursors, such as β-thromboglobulin, which can be processed to neutrophil-activating protein-2 (NAP-2; CXCL7), may play an important role in monocyte recruitment during atherogenesis. Platelets can deposit chemokines on inflamed endothelium; however, little is known about differential or additive effects of platelet chemokines on monocyte arrest. Here, we demonstrate that preincubation of activated human microvascular endothelial cells (HMVECs) with RANTES, PF4, or NAP-2 but not ENA-78 dose-dependently increased surface immobilization and subsequent monocyte arrest in flow. RANTES was the most potent and efficient arrest chemokine. Pretreatment of HMVECs with β-thromboglobulin enhanced monocyte arrest in the presence of cathepsin G generating NAP-2. Combined pretreatment of HMVECs with RANTES and PF4 at suboptimal concentrations synergistically increased arrest, and preincubation with chondroitinase ABC abrogated RANTES- and PF4-induced monocyte arrest. This was associated with reduced expression of chondroitin sulfate, RANTES, and PF4 on the HMVEC surface. Perfusion of HMVECs with platelets known to deposit RANTES and PF4 on the endothelial surface enhanced monocyte arrest, which was inhibited by Met-RANTES, chondroitinase, or a blocking antibody to PF4 but not to ENA-78. The relevance of platelet-derived chemokines was confirmed in adhesion assays with activated whole blood, where Met-RANTES and to a lesser extent, antibodies to PF4 and NAP-2 inhibited arrest of CD14-positive monocytes. Thus, multiple platelet-derived chemokines and processable precursors, which can be presented by specific endothelial proteoglycans, may contribute and cooperate differentially to induce monocyte recruitment.
Signaling through CD16b in human neutrophils involves the Tec family of tyrosine kinases
Authors: Fernandes Maria J G , Lachance Geneviève , Paré Guillaume , Rollet-Labelle Emmanuelle , Naccache Paul H
Published: May 2005

Tec kinases belong to the second largest family of nonreceptor tyrosine kinases. Although these kinases are expressed in myeloid cells, little is known about their implication in neutrophil function. We recently reported the participation of Tec kinases in the responses of human neutrophils to the bacterial peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine via G-coupled protein receptors. In this study, we extended our investigations of Tec kinases to the signaling of the glycosylphosphatidylinositol-linked receptor CD16b, which is highly and specifically expressed in neutrophils. The results obtained indicate that Tec is translocated to the plasma membrane, phosphorylated, and activated upon CD16b cross-linking and that the activation of Tec is inhibited by Src-specific inhibitors as well as by the phosphatidylinositol-3 kinase inhibitor, wortmannin. As no specific inhibitor of Tec exists, the role of Tec kinases was further investigated using a-Cyano-b-hydroxy-b-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a compound known to inhibit Bruton's tyrosine kinase. We show that this compound also inhibits the kinase activity of Tec and provide evidence that the mobilization of intracellular calcium and the tyrosine phosphorylation of phospholipase Cγ2 (PLCγ2) induced upon CD16b engagement are inhibited by LFM-A13. We also show that Tec kinases are important for CD16b-dependent degranulation of neutrophils. In summary, we provide direct evidence for the implication of Tec in CD16b signaling and suggest that Tec kinases are involved in the phosphorylation and activation of PLCγ2 and subsequently, in the mobilization of calcium in human neutrophils.
Cooperation between platelet-derived CD154 and CD4+ T cells for enhanced germinal center formation
Authors: Elzey Bennett D , Grant Julieann F , Sinn Haley W , Nieswandt Bernhard , Waldschmidt Thomas J , Ratliff Timothy L
Published: May 2005

It has been demonstrated previously that platelet-derived CD154 communicates with the adaptive immune compartment, enhancing B and T cell responses in CD154−/− mice. The presence of platelets was also shown to be necessary for optimal production of immunoglobulin G (IgG) in normal C57BL/6 mice. These data led us to hypothesize that platelets perform a sentinel function, quickly relaying activating signals to the adaptive immune compartment. Here, we report that platelet-derived CD154 increases serum IgG levels and germinal center formation under conditions where antigen-specific CD4+ T cell numbers are limiting. We propose that in the physiologic setting where antigen-specific B and T cells are rare, platelets function to enhance signals required for robust adaptive humoral immunity.
Variables that influence decoding and spelling in beginning readers
Authors: Strattman Kathy , Hodson Barbara Williams
Published: May 2005

Performances on tasks of phonemic manipulation, working memory, rapid naming, multisyllable word naming, receptive vocabulary and nonverbal intelligence were compared with decoding and spelling scores for 75 begin-ning readers. Multiple regression analysis revealed that phonemic manipula-tion accounted for the greatest amount of variance for both decoding and spelling. Working memory and receptive vocabulary added additional unique variance for decoding. Multisyllable word naming and rapid naming contri-buted significantly to spelling. The major implication of the results is that phonemic manipulation should be included in an assessment battery for beginning readers.
Last-millennium summer-temperature variations in western Europe based on proxy data
Authors: Guiot J. , Nicault A. , Rathgeber C. , Edouard J. L. , Guibal F. , Pichard G. , Till C.
Published: May 2005

We present a method of multiproxy reconstruction of the climate of Europe during the last millennium. The proxies used comprise long tree-ring width series, grape harvest dates, Greenland ice oxygen isotope series and temperature indices based on historical documents. The proxies are calibrated using gridded April to September mean temperatures for western Europe, i.e., between 10°W and 20°E and between 35°N and 55°N. They are calibrated also using the long instrumental summer temperature series of the Marseilles observatory of Longchamp, which begins in the mid-eighteenth century. The method is a combination of an analogue technique, which is able to deal with missing data, an artificial neural network technique for an optimal non-linear calibration and a bootstrap technique for calculating error bars on the reconstruction. About 70% of the temperature variance is reconstructed. The amplitude of the past temperature variations is particularly well reconstructed, which is important when considering whether the recent temperature trend is or is not within the natural variability It appears that the temperature of the last decade of the twentieth century was reached only 14 times during the last millennium. The reconstruction is discussed with respect to other multiproxy and borehole temperature reconstructions. We conclude that a reconstruction such ours, with a specific regional focus (as opposed to the larger Northern Hemisphere) is more reliable and is in better agreement with borehole results, even allowing for the fact that only a part of the long-term variance is reconstructed. ‘Little Ice Age’ (c. AD 1560-1930) summers were 0.2±0.5°C cooler than the 1961-1990 period. Borehole temperatures indicate a cooling of 0.4°C which falls in the 95% confidence interval of our reconstructions.
Hydrological changes related to the variability of tropical South American climate from the Cabo Frio lagoonal system (Brazil) during the last 5000 years
Authors: Sylvestre Florence , Sifeddine Abdelfettah , Turcq Bruno , Gil Isabelle Martins , Albuquerque Ana Luiza S. , Lallier-Verges Elisabeth , Abrao Jorge
Published: May 2005

From west to east, the Fluminense coastline, composed of two series of lagoons, presents an aridity gradient induced by a local upwelling that is controlled by trade winds coming from the south Atlantic. The physico-chemical conditions of the lagoons are controlled by the duration of the dry season. They are characterized by hypersaline conditions with organic-carbonate sedimentation in the upwelling-influenced area, and by hyposaline conditions with organic-detrital sedimentation out of the upwelling-influenced area. On a core collected in the Brejo do Espinho hypersaline lagoon, diatom analysis supported by sedimentological data revealed a varying high water level from 4500 to 2200 14C yr BP induced by successive freshwater inputs in to the lagoon. Two major dry events occurred during this period, probably related to relative sea-level fluctuations. At 2200 14C yr BP, a drastic change occurred, as indicated by a carbonate nodule, carbonate-dominated sediments and polyto hypersaline diatoms, all suggesting arid conditions. The Brejo do Espinho record suggests that before 2200 14C yr BP, the central part of the Brazilian coast was mostly subjected to south to southeasterly winds and weaker trade winds, whereas after 2200 14C yr BP, trade winds dominated, implying drier conditions at the easternmost part of the Fluminense coastline. These results would also suggest a late Holocene increase in El Ninlo activity (after 2200 14C yr BP), consistent with several El Nifio records from western South America.
Comparison of varve and 14C chronologies from Steel Lake, Minnesota, USA
Authors: Tlan Jian , Brown Thomas A. , Hul Feng Sheng
Published: May 2005

Annually laminated sediments (varves) offer an effective means of acquiring high-quality palaeoenvironmental records. However, the strength of a varve chronology can be compromised by a number of factors, such as missing varves, ambiguous laminations and human counting error. We assess the quality of a varve chronology for the last three millennia from Steel Lake, Minnesota, through comparisons with nine AMS 14C dates on terrestrial plant macrofossils from the same core. These comparisons revealed an overall 8.4% discrepancy, primarily because of missing/uncountable varves within two stratigraphic intervals characterized by low carbonate concentrations and obscure laminations. Application of appropriate correction factors to these two intervals results in excellent agreement between the varve and 14C chronologies. These results, together with other varve studies, demonstrate that an independent age-determination method, such as 14C dating, is usually necessary to verify, and potentially correct, varve chronologies.
Palaeoenvironmental reconstructions using the modern analogue technique: the effects of sample size and decision rules
Authors: Lytle David E. , Wahl Eugene R.
Published: May 2005

Palaeoenvironmental information is often extracted from pollen records using the modem analogue technique (MAT). It is largely unknown how sensitive the MAT is to subsampling-induced variation in pollen assemblages, or to the decision rules used to reconstruct climate and vegetation. We examine these issues in a Monte Carlo framework in which simulated pollen assemblages at eight count sizes were created from four fossil pollen assemblages. Simulated and fossil assemblages are compared with modern data sets at squared chord distance cut-off values between 0.05 and 0.55 to: (1) quantify count-size-induced variation in pollen assemblages, and (2) determine how count-size-induced variation affects analogue selection and climate reconstruction. The effects of sample size and decision rules on vegetation reconstructions are examined using two analogue selection schemes and two levels of minimum required analogues. The results show that decision rules have as much impact on reconstruction precision and accuracy as do large differences in count size. At counts of 150 grains, the best-performing cut-off values yield annual precipitation estimates within 75 mm of those produced by the reference fossil assemblages, and January and July temperature estimates within 0.75C. Counts as low as 150 grains yield vegetation reconstruction accuracies of?90% using the best-case reconstruction rules; the worst-case reconstruction rules may not achieve this accuracy at 1000 grain counts. Although larger count sizes do lead to greater reconstruction precision and accuracy, the results indicate that analyses of the kind presented here can inform count-size decisions and allow significant re-allocation of analytical effort.
Periwinkle (Littorina littorea) intrashell δ18O and δ13C records from the mid-Holocene Limfjord region, Denmark: a new high-resolution palaeoenvironmental proxy approach
Authors: Burmanl Johan , Schmitz Birger
Published: May 2005

Shells of the common intertidal gastropod Littorina littorea both of recent and mid-Holocene origin were analysed along their growth spirals for seasonally induced variations in stable oxygen and carbon isotope compositions. The subfossil specimens are from the Stone Age kitchen midden in Erteb0lle, northern Denmark, dated between 5970 +95 and 5070 + 90 BP. The recent specimens were collected along a west-east salinity gradient within the Limfjord. A Limfjord mixing line of 0.25%, change in 8180 (V-SMOW) for each salinity unit was determined. The recent Littorina periwinkles display a calcite relationship of -0.22%, change in shell 6180 per C change in temperature, as derived from the Littorina equilibrium equation (versus V-PDB): 5180(Littorina) - 8180(water) = 5.250 -0.224T (C). By using this linearity together with maximum (‘winter’) isotopic results, we extracted a Littorina growth stop isotherm equivalent to a temperature of 3.71 C. In order to constrain the climate and salinity in the Limfjord region during the mid-Holocene, we used this regression-derived growth stop isotherm as a boundary condition. The subfossil shells indicate a summer surface-water temperature close to 22 + 1C together with a salinity of 31 +1 PSU. These results suggest a more pronounced water exchange between the central Limfjord and the North Sea during the late Atlantic time, and in terms of temperature they indicate 2-40C warmer conditions than today.
Palaeoecological setting of the western Black Sea area during the last 15000 years
Authors: Atanassova Juliana
Published: May 2005

Analysis of pollen, dinoflagellate cysts and lithology was carried out on ten cores from the western deep Black Sea and combined with radiocarbon dating to reconstruct the vegetation, climate and palaeoecological conditions. All the cores record a consistent sequence of Lateglacial and early Holocene steppe vegetation, which persisted until about 7100-7500 yr BP when Quercus, Corylus, Tilia and other temperate trees expanded, at about the same time as the influx of Mediterranean waters that resulted in sapropel deposition in the deep Black Sea. The sequence implies dry climatic conditions and a low level of the Black Sea during the early Holocene.
Tree-ring based streamfiow reconstruction for Ashley Creek, northeastern Utah: implications for palaeohydrology of the southern Uinta Mountains
Authors: Carson Eric C. , Munroe Jeffrey S.
Published: May 2005

Two ring-width chronologies from Douglas fir (Pseudotsuga menzeisii) and one from pinyon pine (Pinus edulis) were used to reconstruct mean annual discharge of Ashley Creek in the Uinta Mountains, Utah, for the years AD 1637-1970. A backward-elimination multiple linear-regression model identified six statistically significant variables, including annual lags ranging from 1 to +2 years. The final model explains 71% of variability (R2 adjusted for degrees of freedom lost) when regressed against the annual discharges recorded for 1915-72. Statistical analysis of the model reconstruction using the reduction-of-error statistic, the Durbin-Watson statistic and the hypergeometric distri bution all indicate fidelity of the model for reconstructing discharge. The Lilliefors' test indicates that years of extreme discharge (greater than the 90th percentile or less than the 10th percentile) are non-randomly distributed between 1637 and 1970. Persistent years of above-median discharge as well as non-random clustering of years above the 90th percentile occurred from 1692-1704 and 1898-1945. Analysis of the modern gauge data set shows that mean annual discharge on Ashley Creek explains between 81% and 91% of the variations of mean annual discharge on the other main stream in the southern Uinta Mountains, indicating that reconstructed mean annual discharge on Ashley Creek is representative of palaeohydrologic conditions across the south flank of the range. These data suggest that the southern Uinta Mountains experienced persistent below-median discharge for 1741-1897, through the peak of the ‘Little Ice Age’ as identified in numerous surrounding mountain ranges in the Central Rockies. This interpretation agrees with lichenometric evidence for extremely limited ‘Little Ice Age’ glacial activity in the Uintas, indicating that the range experienced unusually warm/dry conditions at this time.
The Younger Dryas episode and the radiocarbon chronologies of the Lake Huleh and Ghab Valley pollen diagrams, Israel and Syria
Authors: Meadows John
Published: May 2005

Pollen diagrams from the former Lake Huleh in Israel and the Ghab Valley in Syria are the most important records of vegetation change in the Levant during the Lateglacial and early Holocene. Environmentally deterministic explanations of the development of agriculture in this region therefore rely on the accuracy of the diagrams radiocarbon chronologies. Radiocarbon results at both sites are subject to large reservoir effects, however: the 14C content of modern water from the Huleh basin implies that the Huleh radiocarbon results require corrections of up to 5500 14C years. A revised chronology of the latest Huleh pollen diagram is proposed. This is consistent with the regional vegetation sequence recorded in eastern Mediterranean marine sediments. The regional sequence also provides the most plausible chronology for the Ghab pollen diagrams.
Histamine-3 receptor antagonists reduce superoxide anion generation and lipid peroxidation in rat brain homogenates
Authors: Badenhorst H E , Maharaj D S , Malan S F , Daya S , van Dyk S
Published: May 2005

Using a cyanide model to induce neurotoxic effects in rat brain homogenates, we examined the neuroprotective properties of three H3 antagonists, namely clobenpropit, thioperamide and impentamine, and compared them to aspirin, a known neuroprotective agent. Superoxide anion levels and malondialdehyde concentration were assessed using the nitroblue tetrazolium and lipid peroxidation assays. Clobenpropit and thioperamide significantly reduced superoxide anion generation and lipid peroxidation. Impentamine reduced lipid peroxidation at all concentrations used, but only reduced superoxide anion generation at a concentration of 1 mM. In the lipid peroxidation assay, all the drugs compared favourably to aspirin. This study demonstrates the potential of these agents to be neuroprotective by exerting antioxidant effects.
Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark
Authors: DalBó Silvia , Jürgensen Sofia , Horst Heros , Ruzza Ângelo Adolfo , Soethe Douglas Nihues , Santos Adair Roberto Soares , Pizzolatti Moacir Geraldo , Ribeiro-do-Valle Rosa Maria
Published: May 2005

The chemical composition of the chromatography 63 subfraction (63SF) from the ethyl acetate soluble fraction of the crude extract of Croton celtidifolius bark presented a high content of total proanthocyanidins (75.0 ± 2.3%). HPLC analysis of 63SF revealed a dimeric profile (e.g. catechin-(4α → 8)-catechin and gallocatechin-(4α → 8)-catechin) and polymeric proanthocyanidins. In pharmacological investigations, 63SF administered intraperitoneally exhibited dose-dependent antinociceptive activity against several chemical stimuli, including the intraperitoneal injection of acetic acid (ID50 (the dose of 63SF which was able to reduce the nociceptive response by 50% relative to the control value) = 0.9 (0.5–1.6)) and the intraplantar injection of capsaicin (ID50 = 13.0 (10.0–17.0)), glutamate (ID50 = 4.0 (2.0–7.0)) and formalin (ID50 first phase = 36.0 (24.0–53.0) and late phase = 11.0 (8.0–14.0)). 63SF administered orally exhibited an antinociceptive effect in the formalin test (ID50 first phase = 125.0 (89.0–177.0) and late phase = 65.0 (33.0–95.0)). In the same test, 63SF was effective when given soon after the first phase, as well as exhibiting therapeutic activity. Furthermore, 63SF was effective in models of thermal nociception including tail-flick and hot-plate tests. When the mice were treated in the neonatal period with capsaicin, the antinociceptive effect of 63SF in the first phase of the formalin test was abolished, but pretreatment with naltrexone did not change the antinociceptive effect of 63SF. Together, these results provide evidence that 63SF exerted a pronounced systemic antinociception against chemical (acetic acid, formalin, glutamate and capsaicin tests) and thermal (hot-plate and tail-flick tests) nociceptive models of pain in mice at a dose that did not interfere with the locomotor activity. The mechanism by which this sub-fraction produced antinociception remains unclear, but it is unlikely to involve the activation of the opioid system. However, unmyelinated C-fibres sensitive to treatment with capsaicin are likely to participate in antinociception caused by 63SF.
Site-specific delivery of anti-inflammatory drugs in the gastrointestinal tract: an in-vitro release model
Authors: Klein Sandra , Stein Jürgen , Dressman Jennifer
Published: May 2005

Mesalazine and budesonide are anti-inflammatory drugs that are used to induce and maintain remission of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis. Both drug substances are intended to act locally at the inflamed sites of the gastrointestinal tract. The therapeutic objective for per oral treatment with these drugs is to achieve a high concentration of the active drug at the sites of inflammation while minimizing systemic absorption. The aim of this study was to develop a test system able to reflect the changing environment that a dosage form incorporating the anti-inflammatory agent is exposed to as it moves through the gastrointestinal tract. The USP dissolution apparatus 3 was used for all experiments. Compendial, as well as biorelevant, media were used to simulate passage through the gastrointestinal tract under various physiological conditions. Different dosage forms of mesalazine (5-aminosalicylic acid, 5-ASA) and budesonide available on the German market were tested. Although all dosage forms were indicated for the same therapeutic objectives, each of the dosage forms exhibited a characteristic release pattern under in-vitro conditions simulating a passage through the fasted-state gastrointestinal tract. Results from this test series indicate that, in the case of various dosage forms of mesalazine and budesonide used for the therapy of Crohn's disease and ulcerative colitis, release patterns as the dosage form moves through the gastrointestinal tract may vary widely. As the various phenotypes of IBD have different requirements in terms of pattern of distribution of the inflamed sites, and because other aspects of gastrointestinal physiology vary within the patient population, the test methods and approach described here should be very useful in designing therapy tailored to the needs of each individual patient.
Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents
Authors: Loftsson Thorsteinn , Thorsteinsson Thorsteinn , Másson Már
Published: May 2005

Quaternary ammonium surfactants, such as benzalkonium chloride and cetylpyridinium chloride, are commonly used as antibacterial agents for disinfectants and for general environmental sanitation, as well as in surfactants, penetration enhancers and preservatives in pharmaceutical and cosmetic formulations. However, these agents are known to cause various side-effects and toxic reactions that are believed to be associated with their chemical stability. Soft analogues of the long-chain quaternary ammonium compounds were synthesized according to the soft drug approach and their physicochemical properties investigated, such as their hydrolytic rate constant, surface activity and lipophilicity. Structure-activity studies showed that the antimicrobial activity of the compounds was strongly influenced by their lipophilicity and chemical stability, the activity increasing with increasing lipophilicity and stability. However, in soft drug design structure-activity relationships are combined with structure-inactivation relationships during the lead optimization. The safety index (SI) of compounds was defined as the hydrolytic rate constant divided by the minimum inhibitory concentration. The SI of the soft antibacterial agents was found to increase with increasing lipophilicity but optimum SI was obtained when their hydrolytic t1/2, at pH 6 and 60°C, was about 11 h. Optimization of the soft antibacterial agents through SI optimization resulted in potent but chemically unstable quaternary ammonium antibacterial agents.
Interaction of baicalin and baicalein with antibiotics in the gastrointestinal tract
Authors: Xing Jie , Chen Xiaoyan , Sun Yuming , Luan Yan , Zhong Dafang
Published: May 2005

To clarify the absorption mechanism of baicalin and to investigate the interaction between baicalin and antibiotics, the pharmacokinetics of baicalin and its aglycone baicalein in normal rats and in antibiotic-treated (with a mixture of neomycin and streptomycin) rats were investigated. A method of liquid chromatography-tandem mass spectrometry with a selected reaction monitoring mode was used to determine the plasma concentrations of baicalin and baicalein. The plasma concentration of total baicalein was determined after treatment of β-glucuronidase/sulfatase. Unpaired Student's t-test was used for statistical comparison. After oral administration of baicalin, the absolute bioavailability of baicalin, based on the AUC of the baicalin parent form, was 2.2 ± 0.2% in normal rats, which decreased to 1.5 ± 0.2% in antibiotic-treated rats. Based on the AUC of total baicalein after enzymatic hydrolysis, the absorption of baicalin was 28.0 ± 5.7%, which significantly decreased to 7.7 ± 1.2% in antibiotic-treated rats. After oral administration of baicalein, the glucuronides/sulfates of baicalein were predominant in plasma. Based on the AUC of total baicalein after enzymatic hydrolysis, the absorption of baicalein was 36.1 ± 4.4% in normal rats, which did not differ markedly from that in antibiotic-treated rats (P > 0.05). The presence of baicalin isomer in plasma after oral administration of baicalin indicated that baicalin was transformed, at least in part, to baicalein before absorption, then to its conjugated metabolites in rats. Aminoglycosides decreased the absorption of baicalin, but not of baicalein, which indicated that antibiotics decreased the decomposition of baicalin to baicalein by inhibiting intestinal flora, and further influenced the absorption, metabolism and efficacy of baicalin. These interactions should be paid attention to in clinical studies when baicalin is administered in combination with antibiotics.
Ecabet sodium raises plasma levels of calcitonin gene-related peptide and substance P in healthy humans
Authors: Katagiri Fumihiko , Inoue Shin , Sato Yuhki , Itoh Hiroki , Takeyama Masaharu
Published: May 2005

Ecabet sodium (ecabet), a cytoprotective drug, produces an increase in mucosal blood flow. One of the gastrointestinal motility regulatory factors has been assumed to be the induction of changes in the levels of peptides (gastrin, somatostatin and motilin) in plasma. On the other hand, recently, capsaicin-sensitive afferent nerves were shown to play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma gastrin-, somatostatin-, motilin-, CGRP- and substance P-like immunoreactive substance (IS) in healthy subjects. Ecabet sodium at a dose of 3.0 g, or placebo, was orally administered in five healthy males. The blood samples were taken before and at 20, 40, 60, 90, 120, 180 and 240 min after administration, subjected to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. Single administration of ecabet caused significant (P < 0.05) increases in plasma CGRP-, substance P- and somatostatin-IS concentration compared with placebo. Ecabet significantly decreased plasma gastrin-IS levels compared with placebo. In this study, we hypothesized that ecabet might stimulate capsaicin-sensitive afferent nerves indirectly and improve mucosal blood flow; this might be a key mechanism underlying its gastroprotective action.
Immuno-stimulating complexes prepared by ethanol injection
Authors: Lendemans Dirk G , Myschik Julia , Hook Sarah , Rades Thomas
Published: May 2005

This study describes the formulation of immuno-stimulating complexes (ISCOMs) utilising the ethanol injection technique. Cholesterol and phosphatidylcholine were dissolved in ethanol and the resulting solution was rapidly injected into a stirred, aqueous solution of the triterpene-saponin mixture Quil-A. The reversed experiment was also carried out by adding the aqueous Quil-A solution to a solution of cholesterol/phosphatidylcholine dissolved in ethanol. This was done by either rapid injection or dropwise addition of the aqueous Quil-A solution. The colloidal dispersions obtained by ethanol injection and reversed addition were compared with formulations obtained by the dialysis and lipid-film hydration methods. In a further experiment, the preparation of ISCOMs from liposomes as precursor structures was investigated. Transmission electron microscopy was used to analyse the resulting colloidal dispersions. Samples were also compared with respect to homogeneity of obtained particle species. The ethanol injection technique led to formation of ISCOMs in high numbers within 2h post formulation. The reversed rapid injection resulted in a similar colloidal dispersion, differing from the former mainly due to the presence of some helical micellar structures. The reversed, dropwise addition led to the formation of helices as the predominant colloidal structure. Of the three previously established methods, only dialysis led to the formation of ISCOMs within 48 h. The lipid-film hydration method and the approach using liposomes as precursor structures did not produce ISCOMs under the conditions and within the time periods investigated. However, it is known that dispersions prepared by the hydration method equilibrate towards ISCOMs after longer storage. Ethanol injection and reversed rapid injection are simple, cost-effective and quick methods to produce ISCOMs.
Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin
Authors: Wang Yi , Cao Jiang , Zeng Su
Published: May 2005

Quercetin, kaempferol, and isorhamnetin were the most important flavonoid constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo flavonols were performed in Caco-2 cell mono-layers. Their apparent permeability in absorptive and secretion directions was determined, and quercetin, kaempferol and isorhamnetin displayed polarized transport, with the Papp,B-A being higher than the Papp,A-B (P < 0.01 for quercetin, P < 0.001 for kaempferol and isorhamnetin, Student's t-test). Bcap37/MDR1 cells, which were transfected with a P-glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were lower than those in parent cells (P < 0.05 for quercetin, P < 0.01 for isorhamnetin, Mann-Whitney U test). The concentrations of the flavonol in transfected cells increased when incubated with the P-gp inhibitor verapamil (P < 0.05 for kaempferol, Mann-Whitney U test). A colorometric assay for ATPase activity was applied to the detection of interaction of flavonol with P-gp. Quercetin and kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase activity (P < 0.05 for isorhamnetin, Mann Whitney U test). The results indicated that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P-gp. The P-gp type efflux pump might limit the bioavailability of Ginkgo flavonols.
Raster scan selective laser melting of the surface layer of a tool steel powder bed
Authors: Childs T H C , Hauser C
Published: May 2005

Square areas, 15 mm × 15 mm in size, have been melted in the surface of powder beds made from H13 tool steel, using a raster-scanning CO2 laser focused to a beam diameter of 0.6 mm. Laser powers from approximately 50 to 150 W and scan speeds from 0.5 to 300 mm/s have been used, at two scan spacings, 0.15 mm and 0.45 mm. The appearances of the layers in the different conditions, dense or porous, have been observed by low-magnification scanning electron microscopy. The masses of the layers have been measured and simulations have been carried out to predict the masses. The variation of mass with scan speed, at a constant laser power, has been found to be much less than might be expected from a constant absorptivity of laser energy into the bed. The simulations suggest that absorptivities range from 0.25 to approximately 1.0 and that, during any one scan, heating of the bed by previous scans must be considered in order even partially to explain the observations. The work is relevant to attempts to build metal parts without supports, by selective laser melting.
Partnership development between product customer and tool and die supplier
Authors: Tang D
Published: May 2005

Generally, the tool and die industry is acting as a tooling supplier for customers' product development. It is widely acknowledged that tool and die suppliers are now more than ever having to improve the cooperation or collaboration level with their customers to gain the tooling market. However, real cooperation or collaboration between product customer and tool and die supplier cannot be achieved before an appropriate partnership is developed. Moreover, the partnership needs to be adaptive to the changing market and requirement levels of customers. The purpose of the present research is to investigate adaptive partnership development between product customer and tool and die supplier through several steps. A set of performance measurements are defined to help the product customer evaluate the capability of tool and die supplier candidates. Different interfaces between product customer and tool and die supplier are analysed. How to develop the right interface structure for adaptive partnership between them is discussed. According to the rational early supplier involvement (ESI) methodology, the adaptive partnership requires the tool and die supplier to justify its role as an active partner along the entire product development process chain, and a decision model is established to specify the ESI partnership between product customer and tool and die supplier. It is suggested that the collaborative partnership be implemented through stronger integration of the tool and die supplier's know-how into the customer's product development process. It is hoped that this research idea can provide comprehensive support for partnership development and management between product customer and tool and die supplier.
Monte Carlo simulation of damaged ship survivability
Authors: Santos T A , Soares C Guedes
Published: May 2005

A probabilistic methodology for assessing damaged ship survivability based on Monte Carlo simulation is proposed. The damage condition is generated using statistical distributions of damage location and extent, derived during a recent research project, coupled to an algorithm that identifies the damaged compartments. Survivability of the ship in each damage condition is evaluated using the formulae recently proposed in Report SLF 46, which are partly based on the static equivalent method and partly on a more conventional approach. The Monte Carlo simulation technique is applied taking into consideration random quantities related to the damage and loading conditions at the time of accident. This methodology is applied to a passenger roll-on roll-off ship, allowing for a direct estimate of the damaged ship survivability in terms of the number of simulated ship capsizes. The effects of changes in the vertical position of the centre of gravity and in the sea state distribution at the moment of accident are also evaluated.
Fracture-mechanics-based analytical prediction of remaining life of tubular T- and Y-joints
Authors: Murthy A R C , Palani G S , Iyer N R
Published: May 2005

This paper presents methodologies for analytical prediction of remaining life of tubular T- and Y-joints by using linear elastic fracture mechanics principles. Bowness and Lee proposed expressions for the computation of the stress intensity factor (SIF) for T-butt plates which can be used for SIF computation of tubular joints and which are also recommended in BS 7910. It is observed from the literature that these expressions have not been used for the remaining life prediction of tubular joints. In this paper, these expressions have been used for analytical prediction of remaining life of tubular T- and Y-joints under constant amplitude loading. The predicted remaining life for T- and Y-joints is found to be in good agreement with those of experimental values reported in the literature. The effect of the degree of bending (DoB) on remaining life has been studied. It is observed from the studies that, the higher the DoB, the longer is the remaining life.
Reliability-based sensitivity analysis of ships
Authors: Downes J , Pu Yongchang
Published: May 2005

Failure of a ship hull girder is a very important failure mode, which is normally catastrophic and has severe consequences. It is of great importance to predict accurately the ultimate strength of a hull girder so that an adequate but not excessive safety margin for this failure can be ensured in the ship design. This study proposes a method for reliability-based analysis of the ultimate strength of a hull girder. The reliability method is interactively integrated with progressive collapse analysis so that the uncertainties in individual random variables relating to the prediction of the ultimate strength of a hull girder can be accurately considered in reliability analysis and that sensitivity factors of these random variables can be probabilistically evaluated. The ultimate strength will be evaluated using a progressive collapse analysis methodology with the appropriate individual element stress-strain curves derived interactively. The method is applied to two example structures and the sensitivities of the reliability to the random variables are presented.
High participation rates are not necessary for cost-effective colorectal cancer screening
Authors: Howard Kirsten , Salkeld Glenn , Irwig Les , Adelstein Barbara-Ann
Published: May 2005

Background: In many countries high participation is an explicit target in screening programmes. The desire for high participation often appears to drive screening policy, although it is increasingly recognized that encouraging high participation may impinge upon the rights of an individual to make an informed choice. One argument offered in support of high participation is that it improves the cost-effectiveness of screening. This is questionable on theoretical grounds, and empirically there are conflicting results. Two recent cost-effectiveness models of faecal occult blood test (FOBT) screening for colorectal cancer (CRC) showed that cost-effectiveness was improved, another showed that cost-effectiveness was worsened and a fourth indicated that cost-effectiveness was unaffected by increasing the participation rate.

Methods: We assessed the extent to which different levels and patterns of participation affect cost-effectiveness, using decision modelling of three CRC screening with FOBT scenarios. We estimate the incremental cost-effectiveness (value for money) ratios for each scenario.

Results: The way in which participation is modelled, particularly assumptions made about the subsequent screening behaviour of non-participants ('if' and 'when' a non-participant attends for subsequent screening), affects the cost-effectiveness estimates for FOBT screening programmes. 100% participation in all screening rounds gives a cost per life year saved (LYS) of US$9705. Cost-effectiveness is worst when people who do not take part in one screening round (initial or subsequent) never take part in any future rounds of screening. Under this scenario, a participation rate of 20% in second and subsequent rounds gives a cost per LYS of US$29,500. Under more realistic assumptions, for example the attendance of even a small proportion of non-participants in subsequent rounds, cost-effectiveness is more favourable and similar to that achieved for full participation: the scenario with a random participation rate of 20% in second and subsequent rounds for both participants and non-participants has a cost per LYS of US$11,270.

Conclusions: Contrary to a commonly held view, high participation in screening programmes is not necessary to achieve cost-effectiveness. Setting high target participation rates in screening programmes does not guarantee cost-effectiveness and may in certain circumstances reduce the cost-effectiveness.
The immunochemical faecal occult blood test leads to higher compliance than the guaiac for colorectal cancer screening programmes: a cluster randomized controlled trial
Authors: Federici Antonio , Rossi Paolo Giorgi , Borgia Piero , Bartolozzi Francesco , Farchi Sara , Gausticchi Gabriella
Published: May 2005

Introduction: We conducted a cluster-randomized trial aimed at assessing the effect of the type of faecal occult blood, guaiac or immunochemical test on screening compliance.

Methods: We sampled 130 general practitioners (GPs) who consented to participate in the trial. We randomly allocated half of them to the guaiac (Hemo-Fec) and half to the immunochemical test (OC-Hemodia). We sampled 2/10 of the GPs' 50–75-year-old patients ( n=7332) and randomly divided this population into half. One half was invited to be screened at the GP's office and the other to the nearest gastroenterology ward. The principal outcome was the percentage of returned tests.

Results: The immunochemical test had a compliance of 35.8% and the guaiac of 30.4% (relative risk [RR] 1.20; 95% confidence interval [CI] 1.02–1.44). The difference was mostly due to a higher probability of returning the sample: 93.8% and 88.6% for immunochemical and guaiac, respectively (RR 1.06; 95% CI 1.02–1.10). The guaiac test had a higher prevalence of positives (10.3% versus 6.3%, RR 0.603; 95% CI 0.433–0.837). There was a higher variability in the results obtained with the guaiac test compared with the immunochemical (F[1, 12] = 16.25; P=0.0017).

Conclusions: Compliance is more likely with the immunochemical than the guaiac test, independent of the provider. Guaiac tests show a higher variability of the results among centres. The successful implementation of a screening programme requires a period of standardization of the test reading in order to avoid unexpected work overload for colonscopy services.
Reaction Pathways and Kinetic Analysis of PVB Thermal Degradation Using TG/FT-IR
Authors: Liau Leo C. K. , Yang Thomas C. K. , Viswanath Dabir S.
Published: May 2005

Poly(vinyl butyral) (PVB) was thermally degraded in a thermogravimetry (TG) in nitrogen atmosphere. Evolving gases during PVB degradation were continuously analyzed with an FT-IR instrument. The main products identified were butyraldehyde, 2-butenal, butanoic acid, acetic acid, 2,5-dihydrofuran, and butanol. The IR spectra of mixture gases were resolved on the basis of the spectrum of pure species. The intensity of IR absorbance for each species was recorded as a function of temperature, and the temperature-dependent quantitative information for each species was calculated and used to evaluate the kinetic parameters. Activation energy and preexponential factors were evaluated for each species under the assumption of a parallel degradation mechanism and first-order kinetics. In addition to this detailed analysis, the polymer weight loss information measured by TG was used to determine the overall kinetic parameters. Results showed that activation energy obtained by both methods was consistent.
Remote Detection of Trichloroethylene in Soil by a Fiber-Optic Infrared Reflectance Probe
Authors: Vohra S. T. , Bucholtz F. , Nau G. M. , Ewing K. J. , Aggarwal I. D.
Published: May 2005

A remote detection method for measuring the infrared reflectance from chlorinated hydrocarbons in soils is demonstrated. The method uses a 12-m-long, field-ruggedized, chalcogenide fiber to transmit IR reflectance data to a remotely located FT-IR spectrometer. Minimum observable signal corresponding to 250 ppm of trichloroethylene (TCE) in sand was measured with the system. Suggestions for improving the threshold detection limit are offered.
Instrumentation and Fundamental Studies on Glow Discharge—Microwave-Induced Plasma (GD-MIP) Tandem Source for Optical Emission Spectrometry
Authors: Duan Yixiang , Li Yimu , Du Zhaohui , Jin Qinhan , Olivares Jose A.
Published: May 2005

Instrumentation and fundamental studies on glow discharge–microwave-induced plasma (GD-MIP) tandem source are described in this paper. Mutual effects among parameters, vacuum pressure, discharge current, voltage, and microwave power are examined with different cathode materials. Sputtering rates with and without microwave boost are measured under various experimental conditions. The experimental results demonstrate that the introduction of a microwave plasma will significantly decrease the sampling rate. A possible mechanism for the more uniform erosion obtained with microwave plasma boosting is suggested and discussed. Excitation temperatures are measured with the line-pair method and Boltzmann plot. A considerable increase in the excitation temperature (from about 3500 to 4200 K by using the line-pair method) is found with the addition of microwave plasma boosting. A comparison of the behavior of glow discharge alone and the GD-MIP tandem source is made. Significant enhancements in signal intensities are observed. The experimental results suggest that the excitation temperature plays an important role in signal enhancement.
Interfacial Events Associated with Case II Diffusion in the Poly(Methylmethacrylate)/CH3OH System
Authors: Drake Phillip A. , Bohn Paul W.
Published: May 2005

Surface plasmon (SP) resonance measurements were used to monitor Case II swelling events in the poly(methylmethacrylate) (PMMA)/CH3OH system on the nanometer-length scale. A simple one-dimensional swelling model effectively correlates measured shifts in SP angular resonance positions to instantaneous film thickness, z, and permeant volume fraction, φ. Swelling motions in continuous polymer films less than 10 nm in thicknesses are easily resolved. Permeant molecules are incorporated at the PMMA interface by a mechanism consistent with a modified Thomas–Windle (TW) model. Temperature differences in sorption kinetics are interpreted in terms of differences in how the elongational viscosity of PMMA depends on temperature. Efflux profiles show evidence of a two-part sample reconstruction process from the rubbery to the glassy state, in which CH3OH leaves the sample rapidly, followed by a slower return of the PMMA chains to their original density. While interfacial swelling motions appear in general form to mirror those of the macroscopic sample surface, measured interfacial penetrant volume fraction values differ from those measured on the macroscopic-length scale in that they exhibit a substantial dependence on sample temperature.