bluuebunny/crossref_metadata_2025 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

CXC 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

We 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

Our 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

Nonalcoholic 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

A 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

Acute 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

Objectives:

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

A 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

Die 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

Atmosphärische 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

Feinstäube (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

In 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

In 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

MHC‐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

Pro‐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

We 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

The 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

Immunological 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.
Antigen‐specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis
Authors: Purtha Whitney E. , Myers Nancy , Mitaksov Vesselin , Sitati Elizabeth , Connolly Janet , Fremont Daved H. , Hansen Ted H. , Diamond Michael S.
Published: June 2007

Infection with West Nile virus (WNV) causes fatal encephalitis in immunocompromised animals. Previous studies in mice have established that T cell protection is required for clearance of WNV infection from tissues and preventing viral persistence. The current study assessed whether specific WNV peptide epitopes could elicit a cytotoxic T lymphocyte (CTL) response capable of protecting against virus infection. Hidden Markov model analysis was used to identify WNV‐encoded peptides that bound the MHC class I proteins Kb or Db. Of the 35 peptides predicted to bind MHC class I molecules, one immunodominant CTL recognition peptide was identified in each of the envelope and non‐structural protein 4B genes. Addition of these but not control peptides to CD8+ T cells from WNV‐infected mice induced IFN‐γ production. CTL clones that were generated ex vivo lysed peptide‐pulsed or WNV‐infected target cells in an antigen‐specific manner. Finally, adoptive transfer of a mixture of envelope‐ and non‐structural protein 4B‐specific CTL to recipient mice protected against lethal WNV challenge. Based on this, we conclude that CTL responses against immundominant WNV epitopes confer protective immunity and thus should be targets for inclusion in new vaccines.
Voltammetry of Electroinactive Species Using Quinone/Hydroquinone Redox: A Known Redox System Viewed in a New Perspective
Authors: Rafiee Mohammad , Nematollahi Davood
Published: June 2007

Electrochemical behavior of p‐benzoquinone (Q), hydroquinone (H2Q) and quinhydrone complex (QH) have been investigated in aqueous unbuffered solutions. The results revealed that in unbuffered solution the half wave potential of hydroquinone has a significant difference with quinone's half wave potential. It shown that, added acid in an unbuffered solution of Q, give rise to a new reduction peak at a more positive potential than original reduction peak of Q. The half‐peak potential of this new peak is dependent on acidity of added acid (pKa) and its height is proportional to the acid concentration. Also, added base in an unbuffered solution of H2Q, give rise to a new oxidation peak at a more negative potential than original oxidation peak of H2Q. The half‐peak potential of this new peak is dependent on basicity of added base (pKb) and its height is proportional to the base concentration. This paper shows new perspectives for a known system in aqueous unbuffered solutions, by means of voltammetric responses that can be exploited for the electrochemical investigation of non electroactive species such as HPO$\rm{ _4^{2 - } }$, HCO$\rm{ _3^ - }$ or CH3COOH.
Differences in depression symptoms in patients with Alzheimer's and Parkinson's diseases: evidence from the 15‐item Geriatric Depression Scale (GDS‐15)
Authors: Weintraub Daniel , Xie Sharon , Karlawish Jason , Siderowf Andrew
Published: June 2007

Objective

Depression occurs frequently in patients with both Alzheimer's disease (AD) and Parkinson's disease (PD), but there has been little comparison of depression symptoms in the two populations.

Method

The 15‐item Geriatric Depression Scale (GDS‐15) was administered as a depression screening instrument to 232 AD patients and 266 PD specialty care patients with at most mild dementia. Logistic regression models were used to determine disease‐specific associations with individual GDS‐15 items, and factor analysis was used to assess GDS‐15 factor structure in the two populations.

Results

Controlling for total GDS‐15 score and other covariates, AD patients reported more dissatisfaction with life (p = 0.03) and memory problems (p < 0.001), while PD patients reported more fearfulness (p = 0.01), helplessness (p < 0.01), a preference to stay at home (p = 0.02), and diminished energy (p < 0.01). Three factors were generated in PD (explaining 55% of the total variance) and five in AD (explaining 59% of the total variance), and the two main factors generated in both populations related primarily to unhappiness and negative thoughts.

Conclusions

The factor structure of the GDS‐15 is similar in AD and PD patients with at most mild stage dementia, but between‐group differences on 6 of the GDS‐15 items suggests the non‐specificity of certain items in the two populations. Copyright © 2007 John Wiley & Sons, Ltd.
Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration
Authors: Rozzini Luca , Chilovi Barbara Vicini , Conti Marta , Bertoletti Erik , Delrio Ilenia , Trabucchi Marco , Padovani Alessandro
Published: June 2007

Background

Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD.

Aim

To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI).

Methods and Materials

One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow‐up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow‐up, were defined as Stable.

Results

Demented MCI (N = 40; 33.6%) were older (mean age 73.5 ± 8.5 vs. 69.2 ± 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS‐Cog (mean score 10.7 ± 3.9 vs 6.7 ± 3.4; p = .000) and by MMSE (mean score 26.1 ± 1.9 vs. 27.3 ± 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 ± 0.4 vs 0.1 ±  0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 ± 0.8 vs. 0.1 ± 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS‐Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD.

Conclusions

In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow‐up. Copyright © 2007 John Wiley & Sons, Ltd.
Venlafaxine versus nortriptyline in the treatment of elderly depressed inpatients: a randomised, double‐blind, controlled trial
Authors: Kok Rob M. , Nolen Willem A. , Heeren Thea J.
Published: June 2007

Background

The majority of the trials in the elderly are outpatient trials which excluded psychotic patients and patients with common comorbid physical disorders. Consequently information is lacking about the more complex cases of elderly depressed patients, as found in inpatient wards.

Objective

To evaluate the effectiveness of two antidepressants, venlafaxine and nortriptyline, in a clinically representative sample of elderly depressed inpatients.

Method

A 12‐week, double blind, randomised, controlled trial in 81 elderly inpatients from one centre. All patients fulfilled DSM‐IV criteria for major depression and were assessed using the Montgomery Åsberg Depression Rating Scale, the Hamilton Depression Rating Scale, the Geriatric Depression Scale, the Clinical Global Improvement and the Symptom, sign, and Side‐effect Checklist.

Results

Overall, remission was achieved by 26 (32.1%) of the patients. There was no statistically significant difference in the number of patients achieving remission on the MADRS between venlafaxine (11 out of 40 patients) and nortriptyline (15 out of 41 patients; p = 0.381) or in any of the secondary outcome variables. The number and severity of side‐effects was not statistically different between both treatment groups and most side effects were mild or moderate in intensity.

Conclusions

In elderly inpatients with severe depression, venlafaxine and nortriptyline appeared to be equally effective and equally well tolerated. Copyright © 2007 John Wiley & Sons, Ltd.
Cerebro‐ and cardiovascular conditions in adults with schizophrenia treated with antipsychotic medications
Authors: Jerrell Jeanette M. , McIntyre Roger S.
Published: June 2007

Objective

To report on the relative risk of cerebro‐ and cardiovascular disorders associated with antipsychotic treatment among adults with schizophrenia.

Method

Medical and pharmacy claims data from the South Carolina Medicaid program were extracted to compare the prevalence rates for four coded cerebrovascular (cerebrovascular disease; cerebrovascular accident; cerebrovascular hemorrhage; and peripheral vascular disease) and four cardiovascular (myocardial infarction; ischemic heart disease; arrhythmias; and cardiomyopathy) conditions. The analysis employed a retrospective cohort design with a 3 years time period as the interval of interest. Schizophrenic adults (18–54) (n = 2251) prescribed one of six atypical or two conventional antipsychotic medications were identified and comprised the analysis set.

Results

Incidence rates for cerebrovascular disorders ranged from 0.5 to 3.6%. No significant association between antipsychotic usage and cerebrovascular disorders was noted largely due to the low base rate. Incidence rates for overall cardiovascular conditions ranged from 6 to 20%. The odds of developing cardiomyopathy were significantly lower for aripiprazole (OR = −3.45; p = 0.02), while the odds of developing hypertension were significantly lower for males (OR = −1.37; p = 0.009) but significantly higher for patients prescribed ziprasidone (OR = 1.91; p = 0.01) relative to conventional antipsychotics.

Conclusion

No significant association between antipsychotic usage and cerebro‐ or cardiovascular disorders was noted. Copyright © 2007 John Wiley & Sons, Ltd.
Operational performance of current synthetic aperture radar sensors in mapping soil surface characteristics in agricultural environments: application to hydrological and erosion modelling
Authors: Baghdadi Nicolas , Cerdan Olivier , Zribi Mehrez , Auzet Véronique , Darboux Frédéric , El Hajj Mahmoud , Kheir Rania Bou
Published: June 2007

Synthetic aperture radar (SAR) sensors are often used to characterize the surface of bare soils in agricultural environments. They enable the soil moisture and roughness to be estimated with constraints linked to the configurations of the sensors (polarization, incidence angle and radar wavelength). These key soil characteristics are necessary for different applications, such as hydrology and risk prediction.

This article reviews the potential of currently operational SAR sensors and those planned for the near future to characterize soil surface as a function of users' needs. It details what it is possible to achieve in terms of mapping soil moisture and roughness by specifying optimal radar configurations and the precision associated with the estimation of soil surface characteristics.

The summary carried out for the present article shows that mapping soil moisture is optimal with SAR sensors at low incidence angles (<35 ). This configuration, which enables an estimated moisture accuracy greater than 6% is possible several times a month taking into account all the current and future sensors. Concerning soil roughness, it is best mapped using three classes (smooth, moderately rough, and rough). Such mapping requires high‐incidence data, which is possible with certain current sensors (RADARSAT‐1 and ASAR both in band C). When L‐band sensors (ALOS) become available, this mapping accuracy should improve because the sensitivity of the radar signal to Soil Surface Characteristics (SSC) increases with wavelength. Finally, the polarimetric mode of certain imminent sensors (ALOS, RADARSAT‐2, TerraSAR‐X, etc.), and the possibility of acquiring data at very high spatial resolution (metre scale), offer great potential in terms of improving the quality of SSC mapping. Copyright © 2007 John Wiley & Sons, Ltd.
On the estimation of antecedent wetness conditions in rainfall–runoff modelling
Authors: Brocca L. , Melone F. , Moramarco T.
Published: June 2007

The analysis of the physical processes involved in a conceptual model of soil water content balance is addressed with the objective of its application as a component of rainfall–runoff modelling. The model uses routinely measured meteorological variables (rainfall and air temperature) and incorporates a limited number of significant parameters. Its performance in estimating the soil moisture temporal pattern was tested through local measurements of volumetric water content carried out continuously on an experimental plot located in central Italy. The analysis was carried out for different periods in order to test both the representation of infiltration at the short time‐scale and drainage and evapotranspiration processes at the long time‐scale. A robust conceptual model was identified that incorporated the Green–Ampt approach for infiltration and a gravity‐driven approximation for drainage. A sensitivity analysis was performed for the selected model to assess the model robustness and to identify the more significant parameters involved in the principal processes that control the soil moisture temporal pattern.

The usefulness of the selected model was tested for the estimation of the initial wetness conditions for rainfall–runoff modelling at the catchment scale. Specifically, the runoff characteristics (runoff depth and peak discharge) were found to be dependent on the pre‐event surface soil moisture. Both observed values and those estimated by the model gave good results. On the contrary, with the antecedent wetness conditions furnished by two versions of the antecedent precipitation index (API), large errors were obtained. Copyright © 2007 John Wiley & Sons, Ltd.
Mapping multi‐year ground water salinity patterns in irrigation areas using time‐series analysis of ground water salinity maps
Authors: Gundogdu Kemal Sulhi , Akkaya Aslan S.Tulin
Published: June 2007

In irrigation areas, ground water salinity (GWS) levels may vary depending on the amount and quality of irrigation water applied and on the activity of the drainage system. GWS plays a vital role in irrigation systems by influencing whether the environment is suitable for plant growth. Hence, it is necessary to monitor changes in GWS both temporally and spatially. Maps are generally used to visualize this information. However, evaluation of temporal and spatial variations of GWS can be difficult because of the necessity of assessing many maps together to understand both temporal and spatial changes.

In this study, a data assessment method that can be used for multi‐year ground water salinity evaluations is presented. The method looks at the spatial and temporal relationships between the main salinity classes present in the study area, their typical locations (i.e. areas where the salinity classes are most frequently located), and the alternate salinity classes in those locations in any of the years of the time series. As a case study, the method was applied to multi‐year (1990–2000) GWS observations in the Mustafakemalpasa irrigation project (19 370 ha) in the Marmara region of north‐western Turkey. Copyright © 2007 John Wiley & Sons, Ltd.
Fuzzy model identification based on cluster estimation for reservoir inflow forecasting
Authors: Nayak P. C. , Sudheer K. P.
Published: June 2007

Fuzzy theory appears to be extremely effective at handling dynamic, non‐linear and noisy data, especially when the underlying physical relationships are not fully understood. Since hydrologists are still uncertain about many of the aspects of the physical processes in the watershed, fuzzy theory has proved to be a very attractive tool enabling them to investigate such problems. The effectiveness of the fuzzy model lies in the identification of the antecedent membership function (MF), which is generally addressed through a fuzzy clustering approach. Most of the applications of fuzzy computing in hydrology seem to have selected the clustering algorithm quite arbitrarily. However, it is apparent that, as the antecedent parameters are based solely on the identified clusters, the method used for clustering should certainly have an impact on the overall performance of the model. This paper presents the results of a study conducted to investigate the impact of choice of clustering algorithm on the overall performance of a fuzzy‐based hydrologic model. The research is illustrated through a case study of developing a Takagi–Sugeno fuzzy model for reservoir inflow forecasting in the Narmada basin, India. The model was developed using two popular clustering techniques, namely Gustafson–Kessel (GK) and subtractive clustering (SC), and was extensively evaluated for performance based on various statistical indices. The results show that the model performance is comparable at a 1 h lead forecast. However, it is observed that the GK approach results in a better performance than the SC approach in computing forecasts at higher lead times. The analysis suggest that the GK method clusters the input space based on the actual pattern, since it uses a membership‐grade weighted‐distance measure as the measure of closeness, whereas the SC method classifies the input space more logically according to the magnitude of flow available in the data set. Copyright © 2007 John Wiley & Sons, Ltd.
Opportunities for manipulating catchment water balance by changing vegetation type on a topographic sequence: a simulation study
Authors: Wang Enli , Cresswell Hamish , Paydar Zahra , Gallant John
Published: June 2007

This simulation study explores opportunities to reduce catchment deep drainage through better matching land use with soil and topography, including the ‘harvesting’ (evapotranspiration) of excess water running on to lower land units. A farming system simulator was coupled with a catchment hydrological framework to enable analysis of climate variability and 11 different land‐use options as they impact the catchment water balance. These land‐use options were arranged in different configurations down a sequence of three hydrologically interconnected slope units (uphill, mid‐slope and valley floor land units) in a subcatchment of Simmons Creek, southern New South Wales, Australia. With annual crops, the valley floor land units were predicted to receive 187 mm year−1 of run‐on water in addition to annual rainfall in 1 in 10 years, and in excess of 94 mm year−1 in 1 in 4 years. In this valley floor position, predicted drainage averaged approximately 110 mm year−1 under annual crops and pastures, whereas permanent tree cover or perennial lucerne was predicted to reduce drainage by up to 99%. The planting of trees or lucerne on the valley floor units could ‘harvest’ run‐on water, reducing drainage for the whole subcatchment with proportionately small reduction in land areas cropped. Upslope land units, even though often having shallower soil, will not necessarily be the most effective locations to plant perennial vegetation for the purposes of recharge reduction. Water harvesting opportunities are site specific, dependent on the amounts and frequency of flows of water to lower landscape units, the amounts and frequency of deep drainage on the different land units, the relative areas of the different land units, and interactions with land use in the different slope positions. Copyright © 2007 John Wiley & Sons, Ltd.
Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF‐1 receptor tyrosine kinases, blocks the growth of HER2‐overexpressing human breast cancer cells
Authors: Zavodovskaya Marianna , Campbell Michael J. , Maddux Betty A. , Shiry Laura , Allan Geoffrey , Hodges Leslie , Kushner Peter , Kerner John A. , Youngren Jack F. , Goldfine Ira D.
Published: June 2007

We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF‐1 receptor (IGF‐1R) and the HER2 receptor in breast cancer cells. Herein, we studied the effects of NDGA on the growth of estrogen receptor (ER) positive MCF‐7 cells engineered to overexpress HER2 (MCF‐7/HER2‐18). These cells are an in vitro model of HER2‐driven, ER positive, tamoxifen resistant breast cancer. NDGA was equally effective at inhibiting the growth of both parental MCF‐7 and MCF‐7/HER2‐18 cells. Half maximal effects for both cell lines were in the 10–15 µM range. The growth inhibitory effects of NDGA were associated with an S phase arrest in the cell cycle and the induction of apoptosis. NDGA inhibited both IGF‐1R and HER2 kinase activities in these breast cancer cells. In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF‐1R inhibitor, was more effective in MCF‐7/HER2‐18 cells than in the parental MCF‐7 cells and IGF binding protein‐3 (IGFBP‐3) was more effective against MCF‐7 cells compared to MCF‐7/HER2‐18. MCF‐7/HER2‐18 cells are known to be resistant to the effects of the estrogen receptor inhibitor, tamoxifen. Interestingly, NDGA not only inhibited the growth of MCF‐7/HER2‐18 on its own, but it also demonstrated additive growth inhibitory effects when combined with tamoxifen. These studies suggest that NDGA may have therapeutic benefits in HER2‐positive, tamoxifen resistant, breast cancers in humans. J. Cell. Biochem. 103: 624–635, 2008. © 2007 Wiley‐Liss, Inc.
The fate of cranial neural crest cells in the Australian lungfish, Neoceratodus forsteri
Authors: Ericsson Rolf , Joss Jean , Olsson Lennart
Published: June 2007

The cranial neural crest has been shown to give rise to a diversity of cells and tissues, including cartilage, bone and connective tissue, in a variety of tetrapods and in the zebrafish. It has been claimed, however, that in the Australian lungfish these tissues are not derived from the cranial neural crest, and even that no migrating cranial neural crest cells exist in this species. We have earlier documented that cranial neural crest cells do migrate, although they emerge late, in the Australian lungfish. Here, we have used the lipophilic fluorescent dye, DiI, to label premigratory cranial neural crest cells and follow their fate until stage 43, when several cranial skeletal elements have started to differentiate. The timing and extent of their migration was investigated, and formation of mandibular, hyoid and branchial streams documented. Cranial neural crest was shown to contribute cells to several parts of the head skeleton, including the trabecula cranii and derivatives of the mandibular arch (e.g., Meckel's cartilage, quadrate), the hyoid arch (e.g., the ceratohyal) and the branchial arches (ceratobranchials I–IV), as well as to the connective tissue surrounding the myofibers in cranial muscles. We conclude that cranial neural crest migration and fate in the Australian lungfish follow the stereotyped pattern documented in other vertebrates. J. Exp. Zool. (Mol. Dev. Evol.) 310B:345–354, 2008. © 2007 Wiley‐Liss, Inc.
Mixing genres and matching people: a study in innovation and team composition in Hollywood
Authors: Perretti Fabrizio , Negro Giacomo
Published: June 2007

The study of innovation in cultural industries has addressed primarily the role played by organizational and environmental determinants. Research on teams has shown that innovation also depends on team composition and related team‐level processes. In this study we develop two hypotheses arguing that the introduction of newcomers, and new combinations of both newcomers and old‐timers in teams show positive relationships with innovation. We test our theory in the U.S. feature film industry and consider genre innovation as our measure of innovation. We use data on 6446 motion pictures produced by the Hollywood Majors in the period 1929–1958 for our empirical analysis. Copyright © 2007 John Wiley & Sons, Ltd.