bluuebunny/crossref_metadata_2025 huggingface dataset:
NOD2/CARD15 Gene Polymorphisms in Crohn’s Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls
Authors: Vind Ida , Vieira Ana , Hougs Lotte , Tavares Lourdes , Riis Lene , Skytt Andersen Paal , Locht Henning , Freitas Joao , Monteiro Estela , Christensen Ib Jarle , Munkholm Pia
Published: September 2005

Background: A North-South gradient in Crohn’s disease (CD) implying a higher incidence in northern Europe compared to southern Europe has been established. Aims: To investigate whether there is a difference between Denmark and Portugal in the frequency of CARD15 mutations in CD patients compared to a healthy background population and to compare genotype-phenotype relations in the two countries. Methods: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. Results: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates in Danish patients were significantly different (p = 0.02) compared with Danish controls, no difference (p = 0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p = 0.03) using the Mantel-Haenszel test. No difference in evolution of phenotypes and the CARD15 status in CD was found during follow-up between the two matched populations. Ileal disease correlated to high occurrence of CARD15. Conclusion: No North-South gradient regarding occurrence of CARD15 was revealed. Although a trend towards more mutations in the Portuguese controls was seen, a relationship between CD and CARD15 mutations was observed in both countries.
Cell Surface Membrane Antigen Phenotype of Human Gastrointestinal Mast Cells
Authors: Krauth Maria-Theresa , Majlesi Yasamin , Florian Stefan , Böhm Alexandra , Hauswirth Alexander W. , Ghannadan Minoo , Wimazal Friedrich , Raderer Markus , Wrba Friedrich , Valent Peter
Published: September 2005

Background: Mast cells (MC) are important effector cells of allergic and inflammatory reactions in diverse organs. These cells interact with a number of other immune cells and structural cells in the tissues as well as with proinflammatory mediators and cytokines. The various interactions are considered to be mediated through distinct cell surface membrane receptors on MC. Methods:In the present study, we have established the cell surface membrane phenotype of human gastrointestinal MC (HGMC) using a panel of monoclonal antibodies and indirect immunofluorescence staining techniques. Results: HGMC were found to react with antibodies against CD29, CD33, CD44, CD45, CD47, CD54, CD55, CD58, CD63, CD117, CD147, CD151, CD172a, and CD203c. By contrast, HGMC did not express detectable amounts of CD1, CD2, CD4, CD5, CD14, CD15, CD16, CD22, CD24, CD25, CD26, CD27, CD28, CD31, CD32, CD34, CD35, CD88, or CD116. The α-chain of the IL-3 receptor (CD123) was detectable neither in resting HGMC nor in HGMC exposed to stem cell factor and interleukin-4. Conclusions: HGMC express a unique profile of surface antigens including the receptor for mast cell growth factor, adhesion-related molecules, and activation-linked membrane antigens.
A Single Exposure to Organic Dust of Non-Naïve Non-Exposed Volunteers Induces Long-Lasting Symptoms of Endotoxin Tolerance
Authors: Hoffmann Hans Jürgen , Iversen Martin , Sigsgaard Torben , Omland Øyvind , Takai Hisamitsu , Bonefeld-Jørgensen Eva , Seedorf Jens , Dahl Ronald
Published: September 2005

Background: Work with occupational levels of organic dust is associated with a chronic inflammatory response that must somehow be controlled. Endotoxin tolerance has previously been described in vitro and animal studies as a mechanism that modifies the threshold at which response occurs. Objective: We investigated the response of non-naïve, currently non-exposed persons to a single exposure of organic dust in a swine confinement building. Methods: We exposed 16 non-naïve persons in a swine confinement building with low-to-moderate representative levels of organic dust and characterized their acute immune response. Results: Under work-like 3-hour exposure conditions, non-naïve volunteers developed an inflammatory response documented by an increase in interleukin-6 (IL-6) in bronchoalveolar lavage (BAL) from 3.1 to 6.1 pg/ml and visual indices of bronchial inflammation. Similarly, serum IL-6 increased with a peak 3 h after exposure. Tumor necrosis factor (TNF)-α was not detected in BAL, and serum TNF-α was reduced from 3.7 pg/ml at baseline to less than 2 pg/ml within 3 h after exposure, and remained decreased until 2 weeks after exposure. This is a cardinal marker for immune suppression which was confirmed by other markers: reduction in HLA-DR expression on alveolar macrophages and CD14 expression on blood monocytes. Conclusion: We report findings that suggest that long-lasting endotoxin tolerance and immune suppression may be induced by a brief exposure to organic dust concentrations in the medium-low range of occupational levels.
Anomalous Subjective Experience among First-Admitted Schizophrenia Spectrum Patients: Empirical Investigation
Authors: Parnas Josef , Handest Peter , Jansson Lennart , Sæbye Ditte
Published: September 2005

Our research group has for several years conducted philosophically informed, phenomenological-empirical studies of morbid alterations of conscious experience (subjectivity) in schizophrenia (Sz) and its spectrum of disorders. Some of these experiential alterations constitute, in our view, the vulnerability markers to Sz – indicators that are intrinsic to this disorder and which were historically considered as constituting the phenotypic anchor of the very concept and the diagnostic validity of Sz spectrum disorders. In a more pragmatic clinical context, these indicators, considered here as symptoms, may be potentially effective for early differential diagnosis. In this study, 151 consecutive first-admitted patients (with bipolar, melancholic and organic patients excluded) diagnosed according to the ICD-10, were evaluated on a number of expressive and experiential psychopathological dimensions, with special emphasis on the experiences of perplexity, disorders of self-awareness, perceptual disorders and anomalous bodily experiences. The a priori scales derived from the item pool of a slightly modified OPCRIT and BSABS were used for analyses. Sz and schizotypal disorder scored equally on the subjective dimensions, suggesting a basic phenomenological affinity of these disorders. In contrast, anomalies of subjective experience were clearly more pronounced among the patients within, as compared to those outside the Sz spectrum.
Is There Evidence in the EEG for Increased Epileptiform Activity in ICD-10 Acute and Transient Psychotic Disorder?
Authors: Röttig Stephan , Pillmann Frank , Blöink Raffaela , Haring Annette , Marneros Andreas
Published: September 2005

Background: The aim of this study was to examine whether there is electroencephalographic evidence for an increased epileptiform activity in the EEG of ICD-10 acute and transient psychotic disorders (ATPD; F23) as a hint for a closer relationship to epilepsy. Methods: We analyzed the EEGs of 39 inpatients with ATPD, comparing them with ‘positive’ schizophrenic and bipolar schizoaffective controls matched for age and gender. The evaluation was performed visually and qualitatively using a rating scale of demonstrated reliability. Results: We found no indication of an increased incidence of epileptiform discharges in ATPD compared with ‘positive’ schizophrenic and bipolar schizoaffective controls. Conclusion: The hypothesis of a relationship between ATPD and epilepsy could not be confirmed by EEG findings.
Effects of Estrogen Treatment on Expression of Brain-Derived Neurotrophic Factor and cAMP Response Element-Binding Protein Expression and Phosphorylation in Rat Amygdaloid and Hippocampal Structures
Authors: Zhou Jin , Zhang Huaibo , Cohen Rochelle S. , Pandey Subhash C.
Published: September 2005

Clinical studies indicate an effect of estrogen (E2) on affect and cognition, which may be mediated by the cAMP response element-binding protein (CREB) pathway and CREB-related gene target brain-derived neurotrophic factor (BDNF). We investigated the effect of E2 on CREB expression and phosphorylation and BDNF expression in the amygdala and hippocampus, areas involved in emotional processing. Ovariectomized rats were given 10 µg 17β-estradiol or vehicle for 14 days and expression of components of the CREB signaling pathway, i.e., CREB, phosphorylated CREB (pCREB), and BDNF in amygdala and hippocampus were investigated using immunogold labeling. Levels of BDNF mRNA were determined by in situ reverse-transcriptase polymerase chain reaction. We also examined the effect of E2 on calcium/calmodulin kinase (CaMK IV) immunolabeling in the hippocampus. E2 increased immunolabeling and mRNA levels of BDNF in the medial and basomedial amygdala and CA1 and CA3 regions of the hippocampus, but not in any other amygdaloid or hippocampal regions examined. E2 increased immunolabeling of CREB and pCREB in the medial and basomedial, but not central or basolateral amygdala. E2 also increased CaMK IV and pCREB immunolabeling in the CA1 and CA3 regions, but not CA2 region or dentate gyrus, of the hippocampus. There was no change in immunolabeling of CREB in any hippocampal region. These data identify a signaling pathway through which E2 increases BDNF expression that may underlie some actions of E2 on affective behavior and indicate neuroanatomical heterogeneity in the E2 effect within the amygdala and hippocampus.
Sweet’s Syndrome – An Extraintestinal Manifestation in Inflammatory Bowel Disease
Authors: Ytting Henriette , Vind Ida , Bang Didi , Munkholm Pia
Published: September 2005

Background/Aims: Sweet’s syndrome (SS) is a severe dermatosis that may be an extraintestinal manifestation of inflammatory bowel disease (IBD). Worldwide, 35 cases of SS associated with IBD have been reported. We present the first case of severe, recurrent SS in combination with amebic infection and ulcerative colitis complicated with multiple other extraintestinal manifestations. Methods: Disease course was monitored by serum YKL-40 and C-reactive protein (CRP), white blood cell count, albumin and the Simple Clinical Colitis Activity Index (SSCAI). The amebic infection was diagnosed by direct microscopy of wet mount scrapings sampled by repetitive sigmoidoscopies. Results: The patient was diagnosed with left-sided ulcerative colitis and SS combined with extraintestinal manifestations: arthropathies, iridocyclitis and erythema nodosum. Cysts of Entamoeba histolytica were detected in the stools in two separate periods of time. Serum YKL-40 increased prior to CRP and correlated with disease activity, SCCAI, CRP, white blood cell count and inversely with serum albumin. Conclusion: This case gives further support for SS being an extraintestinal manifestation of ulcerative colitis. YKL-40 may be useful in monitoring the disease course of IBD.
Population-Based Screening for Family History of End-Stage Renal Disease among Incident Dialysis Patients
Authors: Freedman Barry I. , Volkova Nataliya V. , Satko Scott G. , Krisher Jenna , Jurkovitz Claudine , Soucie J. Michael , McClellan William M.
Published: September 2005

Background: We determined the familial aggregation of end-stage renal disease (ESRD) in a large, population-based sample of incident ESRD cases to assess the feasibility of developing a targeted screening and prevention program directed at members of families at high risk for kidney disease. Methods: Between January 1, 1995, and December 31, 2003, incident dialysis patients in ESRD Network 6 facilities were asked to complete a voluntary questionnaire on family history (FH) of ESRD. Cases with ESRD attributed to Mendelian diseases or urologic causes were excluded. FH was considered present if first- or second-degree relatives had ESRD. De-identified FH data were collated with demographic data at dialysis initiation. Results: More than 46% of eligible patients (25,883/55,929) provided FH information and 22.8% (5,901/25,883) of these reported having a FH of ESRD. FH of ESRD was positively associated with female gender, earlier age at ESRD onset, and primary cause of ESRD, and negatively associated with white race. FH associations with age, race, gender, and primary cause of renal failure remained statistically significant after simultaneous adjustment in a multivariate logistic regression model. Conclusions: Approximately23% of incident dialysis patients have close relatives with ESRD. Far more are likely to have relatives with clinically silent proteinuria or chronic kidney disease (CKD), both risk factors for future cardiovascular events and ESRD. Physicians caring for patients with CKD should be aware of the marked familial aggregation of ESRD and consider focusing screening efforts on high-risk family members in an attempt to slow the exponential growth rate of kidney disease.
Relaciones intergrupales, valores, identidad social y prejuicio en España después del atentado terrorista del 11 de Marzo
Authors: Techio Elza-M. , Calderón-Prada Alicia
Published: September 2005

A partir de una comparación entre dos muestras de vascos, una evaluada antes de los atentados del 11-M en Madrid y otra después, se observó que la violencia colectiva refuerza los valores de seguridad y poder, y la identidad social endogrupal; aunque disminuye la identificación con españoles y aumenta la identificación con árabes/musulmanes. Se discute el efecto de la saliencia de la identidad social a través de la identificación con exogrupos amenazados por otro exogrupo. En España, se constató que la percepción de amenaza se asocia a un prejuicio y discriminación hacia árabes/musulmanes. El valor colectivista de seguridad se relacionó a niveles personales y colectivos, mientras que el valor jerárquico de poder sólo se asoció a nivel personal. En conclusión, existe evidencia parcial de que la violencia colectiva del 11-M reforzó los valores colectivistas jerárquicos, aunque no el prejuicio y la discriminación hacia los árabes; sin embargo, estos valores junto a la percepción de amenaza sí actuaron como reforzadores del prejuicio y discriminación hacia árabes y musulmanes.
Control social subjetivo y valores culturales: estudio transcultural experimental sobre el efecto oveja negra y un estudio de campo sobre el 11-M
Authors: Mendoza Roberto , Páez Darío , Marques José , Techio Elza-M. , Espinosa Agustín
Published: September 2005

Un estudio experimental en seis naciones y regiones confirma la tendencia a sobre-valorar a los miembros del endogrupo que realizan conductas normativas así como la tendencia paralela a devaluar más fuertemente a los miembros del endogrupo nacional que no cumplen con una norma altruista—en comparación con personas de un exogrupo o efecto Oveja Negra (EON). Las personas más en desacuerdo con valores de Poder y creencias de Dominación y más de acuerdo con valores de Benevolencia tienden a mostrar EON debido a que atribuyen más la conducta a causas internas. Sujetos más de acuerdo con valores de Conformidad de Schwartz y creencias autoritarias de la escala RWA de Altmeyer tienden a evaluar mejor al sujeto normativo del endogrupo. El estudio de campo muestra que la tendencia central de los sujetos fue a valorar con la misma negatividad a un colaborador endo que exogrupal con el atentado del 11-M. Las personas que respondieron con un estilo EON se caracterizan por menores creencias de dominación social medidas por la escala SDO de Sidanius et al. y autoritarias (menor RWA) y más valores de Benevolencia. Se concluye que el EON caracteriza a personas igualitarias y cohesivas, individualistas horizontales y cooperativos, mientras que el favoritismo endogrupal caracteriza más a sujetos que viven en contextos culturales colectivistas y jerárquicos, de creencias más conservadoras.
Flow over Heated Terrain. Part II: Generation of Convective Precipitation
Authors: Tucker Donna F. , Crook N. Andrew
Published: September 2005

Previous studies have shown that thunderstorms in the Rocky Mountain region have preferred areas in which to form. There has been some indication that these areas depend on the midtropospheric wind direction. A nonhydrostatic model with a terrain-following horizontal grid is employed to investigate the initiation of precipitating convection over heated topography. Horizontally homogeneous meteorological conditions with no directional shear in the vertical wind profile are used.

The numerical simulations indicate that precipitating convection was more likely to be generated downwind of ridges than upwind of them. Initiation of these storms was more likely downwind of ridges with their long axis parallel to the wind direction than downwind of ridges with their long axis perpendicular to the wind direction. In Part I of this study it was shown that heating-induced convergence is larger downwind of a ridge with its longer axis parallel to the wind direction. For the orographic configuration of the Rocky Mountains, total precipitation is maximized for southerly and northwesterly winds. Slower wind speeds are more likely and faster wind speeds are less likely to produce convective storms. Soundings with larger instability are more likely to produce convection. The soundings with a greater temperature lapse rate produce more initiation locations, and soundings with greater moisture produce greater amounts of precipitation.

Even though a number of assumptions were made for this study, the authors believe the results explain a significant amount of the observed variability in the initiation locations of precipitating convection in the Rocky Mountains during the summer. Because of the theoretical basis for this work, detailed in Part I of this study, the authors believe it should explain convective initiation in other mountainous areas that are subject to strong solar heating.
Cyclogenesis off the African Coast: The Case of Cindy in August 1999
Authors: Sall Saïdou Moustapha , Sauvageot Henri
Published: September 2005

Using radar data from Dakar (Sengal), National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalyses, outgoing longwave radiation provided by the National Oceanic and Atmospheric Administration (NOAA) Television Infrared Observation Satellite (TIROS) satellite series as well as data from the National Hurricane Center (NHC), a cyclogenesis process leading to the birth of a tropical cyclone from a Sahelian mesoscale convective system (MCS) off the African coast of Senegal is described. The cause of this evolution seems to be the coincidence of the MCS with an easterly wave over a warm sea, the presence of a wide area of precipitable water vapor, strong convergence in the low and midtropospheric layers, and an easterly vertical shear of the zonal wind. As a result, a dynamically well organized convective system built up and the system rapidly strengthened. Before moving away from the African coast of Senegal, this perturbation, which became the tropical cyclone “Cindy,” caused the wreck of more than a hundred fishing pirogues and the deaths of many fishermen because of the suddenness and speed of the phenomenon.
The Interaction of Supertyphoon Maemi (2003) with a Warm Ocean Eddy
Authors: Lin I-I. , Wu Chun-Chieh , Emanuel Kerry A. , Lee I-Huan , Wu Chau-Ron , Pun Iam-Fei
Published: September 2005

Understanding the interaction of ocean eddies with tropical cyclones is critical for improving the understanding and prediction of the tropical cyclone intensity change. Here an investigation is presented of the interaction between Supertyphoon Maemi, the most intense tropical cyclone in 2003, and a warm ocean eddy in the western North Pacific. In September 2003, Maemi passed directly over a prominent (700 km × 500 km) warm ocean eddy when passing over the 22°N eddy-rich zone in the northwest Pacific Ocean. Analyses of satellite altimetry and the best-track data from the Joint Typhoon Warning Center show that during the 36 h of the Maemi–eddy encounter, Maemi’s intensity (in 1-min sustained wind) shot up from 41 m s−1 to its peak of 77 m s−1. Maemi subsequently devastated the southern Korean peninsula. Based on results from the Coupled Hurricane Intensity Prediction System and satellite microwave sea surface temperature observations, it is suggested that the warm eddies act as an effective insulator between typhoons and the deeper ocean cold water. The typhoon’s self-induced sea surface temperature cooling is suppressed owing to the presence of the thicker upper-ocean mixed layer in the warm eddy, which prevents the deeper cold water from being entrained into the upper-ocean mixed layer. As simulated using the Coupled Hurricane Intensity Prediction System, the incorporation of the eddy information yields an evident improvement on Maemi’s intensity evolution, with its peak intensity increased by one category and maintained at category-5 strength for a longer period (36 h) of time. Without the presence of the warm ocean eddy, the intensification is less rapid. This study can serve as a starting point in the largely speculative and unexplored field of typhoon–warm ocean eddy interaction in the western North Pacific. Given the abundance of ocean eddies and intense typhoons in the western North Pacific, these results highlight the importance of a systematic and in-depth investigation of the interaction between typhoons and western North Pacific eddies.
All quiet in Dubuque
Authors: McLure Jason
Published: September 2005

McLure monitored the American media for the BJR and reports: "In West Virginia, Charleston Gazette columnist Don Surber took issue with those who blamed the London attacks on the Iraq war. 'Those who say Britain was attacked for liberating Iraq get it only half-right, which means completely wrong,' he wrote. 'The terrorists want to break the British will. If anything, the British doubled their resolve.' Those sentiments were echoed in the opinion columns of many regional newspapers located in the heart of the country - what America's coastal elitists refer to derisively as 'flyover land'. 'What if the terrorist attackers in London a few days ago had been able to use biological, chemical or nuclear weapons, killing many, many more people than were viciously and tragically murdered?' wondered Tennessee's Chattanooga Times Free Press. 'How can anyone suggest U.S. retreat or surrender? Our only acceptable option is to defeat our terrorist enemies.'"
Swimming (weakly) against the tide
Authors: Wilby Peter
Published: September 2005

Wilby edited the New Statesman for almost exactly seven years from 1998 to 2005 and writes: "I was the longest-serving occupant of that chair since Kingsley Martin, to whose record 29 years I never aspired. Martin took the view that 'an editor's paper should be his mistress' and, like him, I 'ate, drank and slept' with the New Statesman." He concludes: "My goal was to make the New Statesman a witty, readable, confident and ground-breaking paper of the Left. I believe I partially succeeded in those aims. I did not succeed as much as I had hoped - or, more precisely, did not succeed in convincing enough readers of my achievement - because I was swimming against the tide, and I was not, as it proved, a strong enough swimmer."
Mr Deedes takes a gamble
Authors: Hagerty Bill
Published: September 2005

The Hon. Jeremy Deedes, son of venerable Daily Telegraph journalist Lord (Bill) Deedes has twice retired from the group - well, almost. He was recalled to captain what looked a badly holed ship after Hollinger and Lord Black went to war over alleged unauthorised payments. Having overseen the sale of the papers to the Barclay Brothers, he retired again, only to be retained as non-executive vice-chairman. Now he's become chairman of the proposed new gambling paper, The Sportsman. In an exclusive interview, Deedes talks about the Telegraph, tabloids, the future of newspapers, Richard Desmond and much, much more. You can bet that gambling's on the agenda, too.
Disability: lessons to be learnt
Authors: Page Lloyd
Published: September 2005

The writer, who has slight learning difficulties, demands better representation of people like himself throughout the media and writes: "People with a learning disability are excluded from many parts of the media. I don't see people with a learning disability reading the news. I don't see people with a learning disability on soaps or games shows. When I do see people with a learning disability, it is often as negative stereotypes, such as mongols or the mentally handicapped. I would like to see people with a learning disability in a positive light. I would to see people with a learning disability represented in the same way as everybody else."
Hey! Let's start a magazine
Authors: Doyle Terence
Published: September 2005

Most journalists harbour a dream. They either want to write a novel or satisfy proprietorial longing by owning a newspaper or magazine. One such budding entrepreneur tells a cautionary tale about launching a movie magazine, observing along the way: "Disaster: through no fault of his own, my partner lost his principal marketing contract and could not devote time to the magazine. Certainly he did not monitor Ad Man as planned and, a few weeks later, I discovered that he had done nothing and disappeared off the face of the earth. By now I had commissioned everyone and much material was already in and being processed with the help of a former journalist colleague, so I simply worked harder, remembering that film projects were often thus fraught... The important thing was to hold your nerve. Things would be all right on the night."
It's cricket, but is it journalism?
Authors: Hagerty Bill
Published: September 2005

BBC Test Match Special team members Jonathan Agnew, Henry Blofeld and producer Peter Baxter discuss their unique form of cricket reporting during the most dramatic season in recent memory. His contribution to the radio coverage is a performance, says Agnew - "But it's a journalistic performance - for all the messing around, you've got to get it right... You've got to be absolutely focussed."
Sacha Guitry, National Portraiture and the Artist's Hand
Authors: Margulies Ivone
Published: September 2005

Sacha Guitry is known for his witty farces and flamboyant historical film pageants. This study examines his documentary films and their function as archive and display case of French genius: Ceux de chez nous (1915; 1952), a home movie showing among others Rodin, Anatole France and Andre Antoine, and MCDXXIX–MCMXLII De Jeanne d’Arc à Philippe Pétain (1943–4), a film consisting of an anonymous hand turning the pages of a book (of the same title), displaying in full view portraits, hand moulds and original manuscripts on and by great figures of French culture, arts and politics. The essay discusses how the image of the hand, omnipresent in the filmmaker's work and collections, bridges his passion for the theatre, collecting and film. The hand is central to Guitry's gestures of display, his presentational aesthetics. It is also the key signifier for traces of French identity and artistic genius.
'Fais de cela un monument'
Authors: Kimyongür Angela
Published: September 2005

This article focuses on Louis Aragon's representation of the experience of the Second World War in his prose writing, and more particularly on the roles of memory and commemoration in this representation. Alongside his Resistance poetry, Aragon composed clandestine texts which were conceived as written memorials to fellow communists killed during the war, memorials which stress communist heroism and patriotism. His novel Les Communistes, published between 1949 and 1951, was also intended to bear witness to the experience of French communists during the war, but it also demonstrates the difficulties of remembrance. It looks back on the Second World War as a source of painful memories which the author sometimes struggles to voice. Particular attention is paid to Aragon's re-creation of the Dunkirk episode, a narrative refined through several versions.
An Abstract Framework for Elliptic Inverse Problems: Part 1. An Output Least-Squares Approach
Authors: Gockenbach Mark S. , Khan Akhtar A.
Published: September 2005

The solution of an elliptic boundary value problem is an infinitely differentiable function of the coefficient in the partial differential equation. When the (coefficient-dependent) energy norm is used, the result is a smooth, convex output least-squares functional. Using total variation regularization, it is possible to estimate discontinuous coefficients from interior measurements. The minimization problem is guaranteed to have a solution, which can be obtained in the limit from finite-dimensional discretizations of the problem. These properties hold in an abstract framework that encompasses several interesting problems: the standard (scalar) elliptic BVP in divergence form, the system of isotropic elasticity, and others.
Probing stereoselective inhibition of the acyl binding site of cholesterol esterase with four diastereomers of 2'-N-α-methylbenzylcarbamyl-1, 1'-bi-2-naphthol
Authors: Chiou Shyh-Ying , Lai Cheng-Yue , Lin Long-Yau , Lin Gialih
Published: September 2005

Background

Recently there has been increased interest in pancreatic cholesterol esterase due to correlation between enzymatic activity in vivo and absorption of dietary cholesterol. Cholesterol esterase plays a role in digestive lipid absorption in the upper intestinal tract, though its role in cholesterol absorption in particular is controversial. Serine lipases, acetylcholinesterase, butyrylcholinesterase, and cholesterol esterase belong to a large family of proteins called the α/β-hydrolase fold, and they share the same catalytic machinery as serine proteases in that they have an active site serine residue which, with a histidine and an aspartic or glutamic acid, forms a catalytic triad. The aim of this work is to study the stereoselectivity of the acyl chain binding site of the enzyme for four diastereomers of an inhibitor.

Results

Four diastereomers of 2'-N-α-methylbenzylcarbamyl-1, 1'-bi-2-naphthol (1) are synthesized from the condensation of R-(+)- or S-(-)-1, 1'-bi-2-naphthanol with R-(+)- or S-(-)-α-methylbenzyl isocyanate in the presence of a catalytic amount of pyridine in CH2Cl2. The [α]25
D values for (1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1 are +40, +21, -21, and -41°, respectively. All four diastereomers of inhibitors are characterized as pseudo substrate inhibitors of pancreatic cholesterol esterase. Values of the inhibition constant (K

i
), the carbamylation constant (k
2), and the bimolecular rate constant (k

i
) for these four diastereomeric inhibitors are investigated. The inhibitory potencies for these four diastereomers are in the descending order of (1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1. The k
2 values for these four diastereomers are about the same. The enzyme stereoselectivity for the 1, 1'-bi-2-naphthyl moiety of the inhibitors (R > S, ca. 10 times) is the same as that for 2'-N-butylcarbamyl-1, 1'-bi-2-naphthol (2). The enzyme stereoselectivity for the α-methylbenzylcarbamyl moiety of the inhibitors is also R > S (2–3 times) due to the constraints in the acyl binding site.

Conclusion

We are the first to report that the acyl chain binding site of cholesterol esterase shows stereoselectivity for the four diastereomers of 1.
EXPANDER – an integrative program suite for microarray data analysis
Authors: Shamir Ron , Maron-Katz Adi , Tanay Amos , Linhart Chaim , Steinfeld Israel , Sharan Roded , Shiloh Yosef , Elkon Ran
Published: September 2005

Background

Gene expression microarrays are a prominent experimental tool in functional genomics which has opened the opportunity for gaining global, systems-level understanding of transcriptional networks. Experiments that apply this technology typically generate overwhelming volumes of data, unprecedented in biological research. Therefore the task of mining meaningful biological knowledge out of the raw data is a major challenge in bioinformatics. Of special need are integrative packages that provide biologist users with advanced but yet easy to use, set of algorithms, together covering the whole range of steps in microarray data analysis.

Results

Here we present the EXPANDER 2.0 (EXPression ANalyzer and DisplayER) software package. EXPANDER 2.0 is an integrative package for the analysis of gene expression data, designed as a 'one-stop shop' tool that implements various data analysis algorithms ranging from the initial steps of normalization and filtering, through clustering and biclustering, to high-level functional enrichment analysis that points to biological processes that are active in the examined conditions, and to promoter cis-regulatory elements analysis that elucidates transcription factors that control the observed transcriptional response. EXPANDER is available with pre-compiled functional Gene Ontology (GO) and promoter sequence-derived data files for yeast, worm, fly, rat, mouse and human, supporting high-level analysis applied to data obtained from these six organisms.

Conclusion

EXPANDER integrated capabilities and its built-in support of multiple organisms make it a very powerful tool for analysis of microarray data. The package is freely available for academic users at http://www.cs.tau.ac.il/~rshamir/expander
Comparative analysis of a BAC contig of porcine chromosome 13q31-q32 and human chromosome 3q21-q22
Authors: Van Poucke Mario , Bourry David , Piumi François , Mattheeuws Marc , Van Zeveren Alex , Chardon Patrick , Peelman Luc J
Published: September 2005

Background

The gene(s) encoding the ETEC F4ab/ac receptors, involved in neonatal diarrhoea in pigs (a disease not yet described in humans), is located close to the TF locus on Sscr13. In order to reveal and characterize possible candidate genes encoding these receptors, a porcine physical map of the TF region is indispensable.

Results

A contig of 33 BAC clones, covering approximately 1.35 Mb surrounding the TF locus on Sscr13q31-q32, was built by chromosome walking. A total of 22,552 bp from the BAC contig were sequenced and compared with database sequences to identify genes, ESTs and repeat sequences, and to anchor the contig to the syntenic region of the human genome sequence (Hsap3q21-q22). The contig was further annotated based on this human/porcine comparative map, and was also anchored to the Sanger porcine framework map and the integrated map of Sscr13 by RH mapping.

Conclusion

The annotated contig, containing 10 genes and 2 ESTs, showed a complete conservation of linkage (gene order and orientation) with the human genome sequence, based on 46 anchor points. This underlines the importance of the human/porcine comparative map for the identification of porcine genes associated with genetic defects and economically important traits, and for assembly of the porcine genome sequence.
Construction and validation of a Bovine Innate Immune Microarray
Authors: Donaldson Laurelea , Vuocolo Tony , Gray Christian , Strandberg Ylva , Reverter Antonio , McWilliam Sean , Wang YongHong , Byrne Keren , Tellam Ross
Published: September 2005

Background

Microarray transcript profiling has the potential to illuminate the molecular processes that are involved in the responses of cattle to disease challenges. This knowledge may allow the development of strategies that exploit these genes to enhance resistance to disease in an individual or animal population.

Results

The Bovine Innate Immune Microarray developed in this study consists of 1480 characterised genes identified by literature searches, 31 positive and negative control elements and 5376 cDNAs derived from subtracted and normalised libraries. The cDNA libraries were produced from 'challenged' bovine epithelial and leukocyte cells. The microarray was found to have a limit of detection of 1 pg/μg of total RNA and a mean slide-to-slide correlation co-efficient of 0.88. The profiles of differentially expressed genes from Concanavalin A (ConA) stimulated bovine peripheral blood lymphocytes were determined. Three distinct profiles highlighted 19 genes that were rapidly up-regulated within 30 minutes and returned to basal levels by 24 h; 76 genes that were up-regulated between 2–8 hours and sustained high levels of expression until 24 h and 10 genes that were down-regulated. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray analysis. The results indicate that there is a dynamic process involving gene activation and regulatory mechanisms re-establishing homeostasis in the ConA activated lymphocytes. The Bovine Innate Immune Microarray was also used to determine the cross-species hybridisation capabilities of an ovine PBL sample.

Conclusion

The Bovine Innate Immune Microarray has been developed which contains a set of well-characterised genes and anonymous cDNAs from a number of different bovine cell types. The microarray can be used to determine the gene expression profiles underlying innate immune responses in cattle and sheep.
Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis
Authors: Zimmermann-Nielsen Erik , Grønbæk Henning , Dahlerup Jens Frederik , Baatrup Gunnar , Thorlacius-Ussing Ole
Published: September 2005

Background

Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment.

Methods

Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used

Results

Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05).

Conclusion

Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation.
Children in reviews: Methodological issues in child-relevant evidence syntheses
Authors: Cramer Kristie , Wiebe Natasha , Moyer Virginia , Hartling Lisa , Williams Katrina , Swingler George , Klassen Terry P
Published: September 2005

Background

The delivery of optimal medical care to children is dependent on the availability of child relevant research. Our objectives were to: i) systematically review and describe how children are handled in reviews of drug interventions published in the Cochrane Database of Systematic Reviews (CDSR); and ii) determine when effect sizes for the same drug interventions differ between children and adults.

Methods

We systematically identified all of the reviews relevant to child health in the CDSR 2002, Issue 4. Reviews were included if they investigated the efficacy or effectiveness of a drug intervention for a condition that occurs in both children and adults. Information was extracted on review characteristics including study methods, results, and conclusions.

Results

From 1496 systematic reviews, 408 (27%) were identified as relevant to both adult and child health; 52% (213) of these included data from children. No significant differences were found in effect sizes between adults and children for any of the drug interventions or conditions investigated. However, all of the comparisons lacked the power to detect a clinically significant difference and wide confidence intervals suggest important differences cannot be excluded. A large amount of data was unavailable due to inadequate reporting at the trial and systematic review level.

Conclusion

Overall, the findings of this study indicate there is a paucity of child-relevant and specific evidence generated from evidence syntheses of drug interventions. The results indicate a need for a higher standard of reporting for participant populations in studies of drug interventions.
Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control
Authors: Boulos Maged N Kamel
Published: September 2005

This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at http://www.healthcybermap.org/GoogleMapsAPI/ – Google Maps API (Application Programming Interface) version, http://www.healthcybermap.org/GoogleEarthKML/ – Google Earth KML (Keyhole Markup Language) version, and http://www.healthcybermap.org/MSNVirtualEarth/ – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future.
Contrasting effects of peroxisome-proliferator-activated receptor (PPAR)γ agonists on membrane-associated prostaglandin E2 synthase-1 in IL-1β-stimulated rat chondrocytes: evidence for PPARγ-independent inhibition by 15-deoxy-Δ12,14prostaglandin J2
Authors: Bianchi Arnaud , Moulin David , Sebillaud Sylvie , Koufany Meriem , Galteau Marie-Madeleine , Netter Patrick , Terlain Bernard , Jouzeau Jean-Yves
Published: September 2005

Microsomal prostaglandin E synthase (mPGES)-1 is a newly identified inducible enzyme of the arachidonic acid cascade with a key function in prostaglandin (PG)E2 synthesis. We investigated the kinetics of inducible cyclo-oxygenase (COX)-2 and mPGES-1 expression with respect to the production of 6-keto-PGF1α and PGE2 in rat chondrocytes stimulated with 10 ng/ml IL-1β, and compared their modulation by peroxisome-proliferator-activated receptor (PPAR)γ agonists. Real-time PCR analysis showed that IL-1β induced COX-2 expression maximally (37-fold) at 12 hours and mPGES-1 expression maximally (68-fold) at 24 hours. Levels of 6-keto-PGF1α and PGE2 peaked 24 hours after stimulation with IL-1β; the induction of PGE2 was greater (11-fold versus 70-fold, respectively). The cyclopentenone 15-deoxy-Δ12,14prostaglandin J2 (15d-PGJ2) decreased prostaglandin synthesis in a dose-dependent manner (0.1 to 10 μM), with more potency on PGE2 level than on 6-keto-PGF1α level (-90% versus -66% at 10 μM). A high dose of 15d-PGJ2 partly decreased COX-2 expression but decreased mPGES-1 expression almost completely at both the mRNA and protein levels. Rosiglitazone was poorly effective on these parameters even at 10 μM. Inhibitory effects of 10 μM 15d-PGJ2 were neither reduced by PPARγ blockade with GW-9662 nor enhanced by PPARγ overexpression, supporting a PPARγ-independent mechanism. EMSA and TransAM® analyses demonstrated that mutated IκBα almost completely suppressed the stimulating effect of IL-1β on mPGES-1 expression and PGE2 production, whereas 15d-PGJ2 inhibited NF-κB transactivation. These data demonstrate the following in IL-1-stimulated rat chondrocytes: first, mPGES-1 is rate limiting for PGE2 synthesis; second, activation of the prostaglandin cascade requires NF-κB activation; third, 15d-PGJ2 strongly inhibits the synthesis of prostaglandins, in contrast with rosiglitazone; fourth, inhibition by 15d-PGJ2 occurs independently of PPARγ through inhibition of the NF-κB pathway; fifth, mPGES-1 is the main target of 15d-PGJ2.
Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study
Authors: Shatalova Ekaterina G , Walther Susan E , Favorova Olga O , Rebbeck Timothy R , Blanchard Rebecca L
Published: September 2005

Introduction

Estrogens are important in breast cancer development. SULT1A1 and UGT1A1 catalyze estrogen metabolism and are polymorphic. The SULT1A1*2 protein exhibits low activity, and a TA repeat within the UGT1A1 promoter alters the level of expression of the protein. We hypothesized that the SULT1A1*2 allozyme has decreased capacity to sulfate estrogens, that the SULT1A1*2 allele conferred increased capacity of cells to proliferate in response to estrogens, and that individuals with the variant SULT1A1 and UGT1A1 genotypes exhibited different breast tumor characteristics.

Methods

The capacity for SULT1A1*2 to sulfate 17β-estradiol and the capacity for cells expressing SULT1A1*1 or SULT1A1*2 to proliferate in response to 17β-estradiol was evaluated. A case-series study was performed in a total of 210 women with incident breast cancer, including 177 Caucasians, 25 African-Americans and eight women of other ethnic background. The SULT1A1 and UGT1A1 genotypes were determined and a logistic regression model was used to analyze genotype–phenotype associations.

Results

We determined that the SULT1A1*1/*1 high-activity genotype was associated with tumor size ≤2 cm (odds ratio = 2.63, 95% confidence interval = 1.25–5.56, P = 0.02). Individuals with low-activity UGT1A1 genotypes (UGT1A1*28/*28 or UGT1A1*28/*34) were more likely to have an age at diagnosis ≥60 years (odds ratio = 3.70, 95% confidence interval = 1.33–10.00, P = 0.01). Individuals with both SULT1A1 and UGT1A1 high-activity genotypes had low tumor grade (odds ratio = 2.56, 95% confidence interval = 1.04–6.25, P = 0.05). Upon stratification by estrogen receptor status, significant associations were observed predominantly in estrogen receptor-negative tumors.

Conclusion

The data suggest that genetic variation in SULT1A1 and UGT1A1 may influence breast cancer characteristics and might be important for breast cancer prognosis.