bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Structure‐Activity Relationships of 3H‐Quinazolin‐4‐ones and 3H‐Pyrido[2,3‐d]pyrimidin‐4‐ones as CXCR3 receptor antagonists
Authors: Storelli Stefania , Verzijl Dennis , Al‐Badie Jawad , Elders Niels , Bosch Leontien , Timmerman Henk , Smit Martine J. , De Esch Iwan J. P. , Leurs Rob 
Published: June 2007

AbstractCXC chemokine receptor‐3 (CXCR3) is a G‐protein coupled receptor (GPCR) predominantly expressed on activated T lymphocytes that promote Th1 responses. Previously, we described the 3H‐quinazolin‐4‐one containing VUF 5834 (decanoic acid {1‐[3‐(4‐cyano‐phenyl)‐4‐oxo‐3,4‐dihydro‐quinazolin‐2‐yl]‐ethyl}‐(2‐dimethylamino‐ethyl)‐amide) as a small‐molecule CXCR3 antagonist with submicromolar affinity and as a lead structure for the development of CXCR3 antagonists. More recently, the related 3H‐pyrido[2,3‐d]pyrimidin‐4‐one compounds AMG 487 and NBI‐74330 have been reported as nanomolar CXCR3 antagonists and these ligands are currently under clinical investigation. The aim of this study is to link the structure‐activity relationship (SAR) of the previously published class of 3H‐quinazolin‐4‐one containing CXCR3 ligands with these novel clinical candidates. From the modification of the lead structure VUF 5834 emerged the importance of the (4‐fluoro‐3‐(trifluoromethyl)phenyl)acetyl and the 3‐methylen‐pyridine as substituents to improve the affinity at the human CXCR3 receptor, whereas other features are less important. The described molecules serve as tool to investigate the role of the CXCR3 receptor in various inflammatory conditions.
Reinsurance control in a model with liabilities of the fractional Brownian motion type
Authors: Frangos N. E. , Vrontos S. D. , Yannacopoulos A. N. 
Published: June 2007

AbstractWe propose a model for reinsurance control for an insurance firm in the case where the liabilities are driven by fractional Brownian motion, a stochastic process exhibiting long‐range dependence. The problem is transformed to a nonlinear programming problem, the solution of which provides the optimal reinsurance policy. The effect of various parameters of the model, such as the safety loading of the reinsurer and the insurer, the Hurst parameter, etc. on the optimal reinsurance program is studied in some detail. Copyright © 2007 John Wiley & Sons, Ltd.
Will knowledge of human genome variation result in changing cancer paradigms?
Authors: Gottlieb Bruce , Beitel Lenore K. , Trifiro Mark 
Published: June 2007

AbstractOur incomplete understanding of carcinogenesis may be a significant reason why some cancer mortality rates are still increasing. This lack of understanding is likely due to a research approach that relies heavily on genetic comparison between cancerous and non‐cancerous tissues and cells, which has led to the identification of genes of cancer proliferation rather than differentiation. Recent observations showing that a tremendous degree of natural human genetic variation occurs are likely to lead to a shift in the basic paradigms of cancer genetics, in that there is a need to consider both the nature of the genes involved, and the idea that not every genetic variation identified in these genes may be associated with carcinogenesis. Based on studies using LCM and micro‐genetic analyses, we propose that significant cancer initiating events may take place during the very early stages of development of cancer‐susceptible tissues and that using such techniques might greatly help us in our understanding of carcinogenesis. BioEssays 29:678–685, 2007. © 2007 Wiley Periodicals, Inc.
Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis (NASH)
Authors: Sazci Ali , Ergul Emel , Aygun Cem , Akpinar Gurler , Senturk Omer , Hulagu Sadettin 
Published: June 2007

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms result in hyperhomocysteinemia. To examine whether the C677T and A1298C polymorphisms of the MTHFR gene were associated with NASH, we analysed the allele and genotype distribution of the MTHFR C677T and A1298C polymorphisms in 57 well‐diagnosed NASH patients, 324 healthy controls in a case‐control study of Turkish subjects of Caucasian origin. The diagnosis of the NASH patients was based on liver biopsy. The method used in the analysis of genotypes was PCR‐RFLP. The MTHFR A1298C polymorphism was significantly associated with NASH (χ2 = 8.439;p = 0.015) in the total NASH patients compared with healthy controls. The MTHFR 1298C allele (odds ratio (OR) = 2.480; 95%CI = 1.286–4.782;χ2 = 7.703; df = 1;p = 0.006) was significantly associated with NASH in the total NASH patients. The MTHFR C677C/A1298C compound genotype (OR = 2.218; 95%CI = 1.003–4.906;χ2 = 3.998; df = 1;p = 0.046) in men patients was also significantly associated with NASH. Likewise the MTHFR C1298C genotype was significantly associated with NASH in women patients with NASH (OR = 2.979; 95%CI = 1.027–8.641;χ2 = 4.343; df = 1;p = 0.037). In conclusion, the MTHFR 1298C allele in all NASH patients, C1298C genotype, C677C/C1298C compound genotype in women NASH patients and C677C/A1298C compound genotype in men NASH patients were genetic risk factors for NASH. Copyright © 2007 John Wiley & Sons, Ltd.
Selective Detection of Sugar Phosphates by Capillary Electrophoresis/Mass Spectrometry and Its Application to an Engineered E. coli Host
Authors: Hui Joseph P. M. , Yang Jie , Thorson Jon S. , Soo Evelyn C. 
Published: June 2007

AbstractA highly selective method employing capillary electrophoresis and electrospray mass spectrometry (CE‐ESMS) with precursor ion scanning for fragment ions characteristic of phosphate‐linked sugars was developed for the determination of “unnatural” sugar phosphates generated in vivo, as part of a natural product glycorandomization study. Cell lysates from an engineered E. coli host were probed for “natural” and “unnatural” sugar phosphates resulting from in vivo galactokinase (GalK) bioconversions, and tandem mass spectrometry experiments were performed to confirm the identities of the sugar phosphates. Among the 22 cell lysates that were studied, 13 were found to contain the expected natural and “unnatural” sugar phosphates. This was in agreement with the GalK in vitro conversion yields, in which an in vitro yield of ≤15 % coincided with a lack of observable in vivo bioconversion. In addition, the CE‐ESMS and precursor ion scanning method was capable of separating sugar phosphate regioisomers such as hexose‐6‐phosphate and hexose‐1‐phosphate.
Rheolytic percutaneous thrombectomy for acute pulmonary embolism in a pediatric patient
Authors: Sur James P. , Garg Ravi K. , Jolly Neeraj 
Published: June 2007

AbstractAcute massive pulmonary embolism can have significant hemodynamic effects in both adults and children. We describe the case of a 10‐year‐old boy who developed cardiogenic shock after suffering a massive pulmonary embolism. A significant thrombus burden was removed using a catheter‐based strategy of rheolytic thrombectomy, leading to stabilization of the patient. © 2007 Wiley‐Liss, Inc.
Reduced vascular complications and length of stay with transradial rescue angioplasty for acute myocardial infarction
Authors: Cruden Nicholas L.M. , Teh Chun H. , Starkey Ian R. , Newby David E. 
Published: June 2007

AbstractObjectives:The aim of this study was to compare clinical outcomes for transradial and transfemoral percutaneous coronary intervention in patients with ST‐segment elevation myocardial infarction undergoing rescue angioplasty.Background:Transfemoral percutaneous coronary intervention in patients with acute myocardial infarction treated with systemic thrombolysis is associated with a significant risk of vascular complications. A transradial approach may reduce vascular complications, improve mobilization and facilitate earlier discharge.Methods:In a retrospective analysis, clinical outcomes for 287 consecutive patients undergoing rescue angioplasty for acute myocardial infarction were determined. Data were recorded using a standardized proforma and analyzed using SPSS.Results:Procedural success was similar for the transradial and transfemoral routes (98% vs. 93%; P = 0.3). There was a reduction in vascular complications (0 (0%) vs. 32 (13%); P < 0.01) and post‐procedural length of stay (7.0 ± 7.9 vs. 7.9 ± 5.6 days; P < 0.005) in the radial group when compared with the femoral group. There were no differences in procedural or in‐hospital mortality, procedure duration, or radiation dose between the two groups.Conclusion:Rescue angioplasty performed via the radial artery is safe, effective, and associated with a reduction in vascular complications and length of hospital stay when compared with the femoral approach. These findings suggest that where facilities and experience allow rescue angioplasty in patients with acute myocardial infarction should be performed via the radial artery. © 2007 Wiley‐Liss, Inc.
Closure of unroofed coronary sinus with a covered stent in a symptomatic infant
Authors: Torres Alejandro , Gersony Welton M. , Hellenbrand William 
Published: June 2007

AbstractA covered stent was used for percutaneous closure of an unroofed coronary sinus in an infant with congestive heart failure secondary to increased pulmonary flow. Prior to the stent deployment, the location of the entrance of the coronary vein into the coronary sinus was demonstrated with a selective left coronary artery angiogram to facilitate placement of the stent. The procedure was well tolerated without complications. The infant's symptoms improved significantly after the procedure. © 2007 Wiley‐Liss, Inc.
Atmosphärische Aerosole: Quellen, Vorkommen, Zusammensetzung
Authors: Schnelle‐Kreis Jürgen , Sklorz Martin , Herrmann Hartmut , Zimmermann Ralf 
Published: June 2007

AbstractDie Zusammensetzung des Aerosols und seine physikalischen und chemischen Eigenschaften beeinflussen seine Wirkungen auf die Chemie der Atmosphäre, das Klima der Erde und die menschliche Gesundheit. Die in der Atmosphäre vorliegenden Partikel werden entweder durch anthropogene und natürliche Quellen direkt in die Atmosphäre emittiert (Primärpartikel), oder aus anorganischen Spurengasen oder gasförmigen organischen Substanzen gebildet (Sekundärpartikel). Sobald Partikel in der Luft sind, können sich ihre Größe, Zusammensetzung und Konzentration aufgrund vielfältiger Prozesse verändern. Die wichtigsten Prozesse sind Koagulation, Gas‐Partikel‐Verteilung, Partikel‐Phasen Chemie (z.B. Oxidation, Polymerisation) und Deposition. Neben einigen anorganischen Spurenkomponenten bestehen troposphärische Partikel im Allgemeinen aus Sulfat, Nitrat, Ammonium, Metallen, Wasser sowie elementarem Kohlenstoff (EC) und organischem Kohlenstoff (OC). Obwohl in jüngster Zeit wesentliche Fortschritte in der Charakterisierung von Aerosolen gemacht wurden, sind die Kenntnisse über die Eigenschaften und die Zusammensetzung der Aerosolpartikel noch relativ gering. Dies gilt insbesondere für die Zusammensetzung der organischen Fraktion der Partikel die einen starken Einfluss auf die physikochemischen, klima‐ und gesundheitsrelevanten Eigenschaften der Partikel hat.
Chemie von Aerosolen
Authors: Hoffmann Thorsten , Zetzsch Cornelius , Rossi Michel J. 
Published: June 2007

AbstractAtmosphärische Aerosolpartikel sind keine chemisch inerten Teilchen, deren Bildungsmechanismen, Verweildauer oder Funktion in der Atmosphäre lediglich von mechanischen oder physikalischen Prozessen abhängen. Sowohl bei der Bildung von Aerosolpartikeln als auch im Verlauf ihres Verbleibs in der Atmosphäre spielen chemische Reaktionen eine wesentliche Rolle. Chemische Reaktionen laufen an der Oberfläche und im Inneren von Aerosolpartikeln ab und können sowohl die atmosphärische Gasphasenchemie beeinflussen, z.B. indem sie sowohl als Reaktionsmedium für ansonsten langsam verlaufende Gasphasenreaktionen dienen, als auch die Eigenschaften der Partikel, beispielsweise ihre Funktion als Kondensationskerne bei der Wolkenbildung.
Feinstäube und menschliche Gesundheit
Authors: Bruckmann Peter , Eikmann Thomas 
Published: June 2007

AbstractFeinstäube (PM10) in der Umwelt sind heutzutage – wegen ihrer negativen gesundheitlichen Einwirkungen auf Atemwege und das Herzkreislaufsystem – als das wichtigste lufthygienische Problem anzusehen. Die zurzeit gültigen Grenzwerte müssen überall, insbesondere auch an Brennpunkten mit hoher Luftbelastung (z.B. an stark befahrenen Straßen) eingehalten werden. In der geplanten Revision der Luftqualitätsrichtlinien der EU sollen in einer Neubewertung der Gesundheitsrisiken neue Grenzwerte (für PM2.5) zusätzlich zu den bestehenden Grenzwerten für PM10 festgelegt werden. Dabei müssen auch die neuen Erkenntnisse zum Wirkmechanismus der Feinstäube sowie beobachtete Effekte bei der Durchführung von Luftreinhaltemaßnahmen Berücksichtigung finden.
Luftchemie und Klima
Authors: Feichter Johann , Schurath Ulrich , Zellner Reinhard 
Published: June 2007

AbstractIn der Öffentlichkeit wird Luftverschmutzung als ein lokales Problem betrachtet, das sich auf Ballungszentren und Industriegebiete beschränkt. Der vom Menschen verursachte Einfluss auf das Klima wurde hingegen als globales Problem erkannt. Tatsächlich sind aber die Ursachen für Luftverschmutzung und Klimabeeinflussung dieselben, nämlich zunehmende Freisetzungen von Spurenstoffen wie Kohlendioxid, Methan, Kohlenmonoxid, Kohlenwasserstoffe, Schwefeldioxid und Stickoxide aus Verkehr, Hausbrand, Industrie und Landwirtschaft. Umwelt‐ und Klimaschutz erfordern also dieselben Maßnahmen, Reduktion der vom Menschen verursachten Spurenstofffreisetzungen. Klima und Umwelt sind darüber hinaus auch miteinander verknüpft, insofern als Wetter und Klima sowohl Emissionen aus biogenen Quellen wie marine Biosphäre oder Vegetation als auch den Transport in der Atmosphäre und das Auswaschen von Spurenstoffen durch Niederschlag beeinflussen und damit die atmosphärischen Konzentrationen von Spurenstoffen. Das Klima ändert sich und wird sich weiterhin ändern und damit auch die Luftqualität. Strategien zu Klima‐ und Umweltschutz erfordern in Zukunft bessere Zusammenarbeit zwischen den verschiedenen Wissenschaftsdiziplinen.
Atmosphärische Spurenstoffe und ihre Sondierung
Authors: Burrows John , Fischer Herbert , Künzi Klaus F. , Pfeilsticker Klaus , Platt Ulrich , Richter Andreas , Riese Martin , Stiller Gabriele , Wagner Thomas 
Published: June 2007

AbstractIn der Zeit des globalen Wandels stellt die Untersuchung der Erdatmosphäre eine große Herausforderung dar. Zum einen werden für belastbare Wettervorhersagen ständig meteorologische Parameter benötigt. Zum anderen ist der durch natürliche und menschliche Ursachen beschleunigte Wandel der Atmosphäre so besorgniserregend, dass die möglichen Folgen dieses Wandels für die heutige und zukünftige Zivilisation besser vorhergesagt werden sollten. Hierfür sind umfangreiche und genaue Untersuchungen der atmosphärischen Zusammensetzung, der Strahlung in der Atmosphäre, des Energiebudgets und der Dynamik notwendig. Solche Untersuchungen werden u.a. mit in‐situ‐Methoden praktisch in allen Regionen der Atmosphäre durchgeführt, wobei raffinierte Messinstrumente auf unterschiedlichen Fluggeräten (Zeppeline, Flugzeuge, Ballone, und Raketen) eingesetzt werden. Die Fernerkundung atmosphärischer Spurenstoffe und Parameter ist praktisch nur durch die Analyse elektromagnetischer Strahlung möglich. Identifiziert werden die Moleküle aufgrund ihrer charakteristischen Spektren; die Konzentration der Spurenstoffe ergibt sich aus der Stärke der thermischen Emission oder der Abschwächung eines externen Signals. Vor etwas mehr als 45 Jahren wurde das erste Bild der Erde vom Weltraum aus aufgenommen. Seither sind Satellitenbilder zum vertrauten Bestandteil unserer Alltagswelt und zum unerlässlichen Hilfsmittel der Meteorologie geworden. Neben der bildgebenden Fernerkundung wurden seither aber auch spektroskopische Satelliteninstrumente entwickelt und eingesetzt. Solche Instrumente arbeiten in verschiedenen Spektralbereichen und erlauben heute die Messung einer Vielzahl von atmosphärischen Spurenstoffen auf globaler Skala.
MHC‐peptide‐specific antibodies reveal inefficient presentation of an HLA‐A*0201‐restricted, Melan‐A‐derived peptide after active intracellular processing
Authors: Held Gerhard , Wadle Andreas , Dauth Nina , Stewart‐Jones Guillaume , Sturm Christine , Thiel Markus , Zwick Carsten , Dieckmann Detlef , Schuler Gerold , Hoogenboom Hennie R. , Lévy Frédéric , Cerundolo Vincenzo , Pfreundschuh Michael , Renner Christoph 
Published: June 2007

AbstractMHC‐peptide‐specific Fab antibodies binding to HLA‐A*0201 complexes presenting the wild‐type EAAGIGILTV (EAA) or analogue Melan‐A 10‐mer ELAGIGILTV (ELA) peptide were generated to study efficacy of peptide processing and presentation. None of the selected Fab antibodies detected the naturally processed EAA/HLA‐A*0201 complex on melanoma tumor cells, confirming the known low peptide number on the cell surface. To study the effect of peptide presentation and processing in more detail, genes coding for the A27L‐mutated Melan‐A protein or the processed ELA peptide were introduced into HLA‐A*0201+ B cells by infection with the respective recombinant vaccinia virus construct producing equimolar amounts of GFP‐ubiquitin directly linked to the fragment of interest. Correlating GFP expression to actual numbers of peptide presented, 110–260 ELA peptides had to be synthesized to be presented by a single MHC class I antigen‐peptide complex. This number increased 10‐ to 20‐fold when ELA peptide presentation from the A27L‐mutated full length Melan‐A protein was studied, since 1600–5200 GFP molecules needed to be synthesized for the detection of one ELA peptide. Our results indicate that peptide processing rather than presentation is the rate‐limiting step in our experimental setting and is much more ineffective for Melan‐A than has been previously shown for other MHC class I‐restricted epitopes.
Impact of cellular lifespan on the T cell receptor repertoire
Authors: Hamrouni Abdelbasset , Olsson Anna , Wiegers G. Jan , Villunger Andreas 
Published: June 2007

AbstractPro‐survival members of the Bcl‐2 family are potent inhibitors of cell death and determine the lifespan of immature thymocytes by counteracting the intrinsically active apoptotic program in these cells. BH3‐only proteins are potent antagonists of Bcl‐2‐like molecules and regulate death and survival of lymphocytes during their development and homeostasis. The intrinsic lifespan of CD4+8+ double‐positive thymocytes was reported to actively shape the diversity of the immune repertoire, since mice overexpressing Bcl‐xL were reported to show a bias towards the usage of distal 3′ Jα elements 1. To gain support for this concept, we analyzed TCRα rearrangements in T lymphocytes that show an extended lifespan due to either loss of the BH3‐only protein Bim or overexpression of Bcl‐2. A minor but reproducible skewing towards the usage of the more distal 3′ Jα elements was observed in developing thymocytes and mature T cells from bim–/– and vav‐bcl‐2 transgenic mice, indicating that prolonged survival of double‐positive thymocytes does have a significant impact on the selected TCRα repertoire. However, the changes that we observed were less pronounced than those found in lck‐bcl‐xL transgenic mice, pointing towards qualitative differences between Bcl‐2‐ and Bcl‐xL‐mediated cell death inhibition during T cell development.
Modulation of Vα19 NKT cell immune responses by α‐mannosyl ceramide derivatives consisting of a series of modified sphingosines
Authors: Shimamura Michio , Huang Yi‐Ying , Okamoto Naoki , Suzuki Nahoko , Yasuoka Jouji , Morita Kenji , Nishiyama Akira , Amano Yuusuke , Mishina Tadashi 
Published: June 2007

AbstractWe have demonstrated that analogues of α‐mannosyl ceramide (α‐ManCer) consisting of a series of immunosuppressive 2‐aminoalcohol derivatives in place of sphingosine promote a greater immune response from mouse invariant Vα19‐Jα26 (AV19‐AJ33) TCR‐bearing NKT (Vα19 NKT) cells than α‐ManCer itself. To further characterize the immune responses of Vα19 NKT cells to the α‐ManCer analogues, cytokine production by the cells was examined in detail. We found that certain α‐ManCer derivatives individually induced either Th1‐ or Th2‐dominant cytokine production in culture. The Th1‐ or Th2‐biased immune responses of Vα19 NKT cells were dependent on MHC class I‐like MR1, since they were induced by coculture with the MR1 transfectants previously loaded with the glycolipids and were inhibited in the presence of anti‐MR1 antiserum. Presumably, the recognition of the α‐mannosyl residue of the α‐ManCer analogues by the invariant TCR is individually modulated, depending on the altered interaction with the groove of the antigen‐presenting MR1. Priming of the Vα19 invariant TCR‐transgenic mice in vivo with these glycolipid derivatives resulted in the induction of the Th1‐ or Th2‐biased immune responses. Thus, these α‐ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Vα19 NKT cells.
CD28:B7 interaction is necessary for the protective effect of T cell vaccination in EAE
Authors: Yang Yuhong , Ratts Robert B. , Hussain Rehana Z. , Northrop Sara C. , Ben Li‐Hong , Lovett‐Racke Amy , Racke Michael K. 
Published: June 2007

AbstractThe mechanisms of T cell vaccination (TCV) are still unclear, especially the molecular interactions for recognition of autoreactive T cells by the immune system. Here we investigated the role of CD28:B7 interaction in TCV‐induced protection in the murine EAE model. We demonstrate that there is increased expression of both B7–1 and B7–2 on autoreactive Th1 cells compared to Th2 cells. Blockade of B7 on the vaccinating autoreactive T cell surface or blockade of CD28 in recipient mice reduced the protective effect of TCV. Furthermore, we showed that TCV significantly inhibited Ag‐specific CD4 and CD8 T cell proliferation and decreased Ag‐specific IFN‐γ production by CD4 T cells in mice undergoing TCV, and blocking of B7 on the surface of vaccinating T cells reduced this inhibition on Ag‐specific CD4 and CD8 T cell proliferation, more significantly on Ag‐specific CD4 T cell proliferation. These data indicated that B7 expression on autoreactive T cells is necessary for the recognition of autoreactive T cells by the immune system and subsequent protection from EAE in mice undergoing TCV.
IL‐2Rβ links IL‐2R signaling with Foxp3 expression
Authors: Soper David M. , Kasprowicz Deborah J. , Ziegler Steven F. 
Published: June 2007

AbstractImmunological tolerance to self antigens is a tightly regulated process. Recent work has demonstrated that the forkhead family member Foxp3 is a critical element in the differentiation and function of mouse CD4+CD25+ regulatory T cells (Treg). Recent work has suggested an important role for IL‐2 in the development and maintenance of Treg. To directly assess the effect of IL‐2 signaling on Treg development and function, we analyzed mice that were genetically deficient in components of the IL‐2 receptor (IL‐2R). Mice lacking CD25 (IL‐2Rα) displayed a slight decrease in Treg within the thymus, while peripheral numbers are unchanged. In contrast, we found that mice deficient in CD122 (IL‐2Rβ) had a profound reduction in both thymic and peripheral Treg, coinciding with more rapid development of a fatal lymphoproliferative disease. Expression of a Foxp3 transgene restored Treg and protected against the onset of autoimmunity. Thus, a signal mediated by IL‐2Rβ is essential for the development and homeostasis of Foxp3+ Treg in vivo.