The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases.

The proteasome produces MHC class I-restricted antigenic peptides carrying N-terminal extensions, which are trimmed by other peptidases in the cytosol or within the endoplasmic reticulum. In this study, we show that the N-terminal editing of an antigenic peptide with a predicted low TAP affinity can occur in the cytosol. Using proteomics, we identified two cytosolic peptidases, tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, that trimmed the N-terminal extensions of the precursors produced by the proteasome, and led to a transient enrichment of the final antigenic peptide. These peptidases acted either sequentially or redundantly, depending on the extension remaining at the N terminus of the peptides released from the proteasome. Inhibition of these peptidases abolished the CTL-mediated recognition of Ag-expressing cells. Although we observed some proteolytic activity in fractions enriched in endoplasmic reticulum, it could not compensate for the loss of tripeptidyl peptidase II/puromycin-sensitive aminopeptidase activities.

Evaluation in vitro de la réactivité des particules fines et ultrafines : rapport scientifique final

Une des percées les plus importantes dans la recherche sur les nanoparticules (ambiantes et manufacturées) a été la reconnaissance de leur potentiel à générer un stress oxydatif au niveau cellulaire. Dans cette optique, la mesure du potentiel oxydant intrinsèque des particules pourrait présenter une première étape dans l'évaluation des dangers. Ce projet méthodologique avait pour but de caractériser le potentiel oxydant de différentes nanoparticules « modèles » (ambiantes et manufacturées) au moyen de trois tests acellulaires (Test DTT, Test DCFH, Test oxymétrique) et d'utiliser ces résultats pour proposer une méthode de « référence ». D'autre part, nous avons appliqué la méthode sélectionnée à deux cas (exposition d'ouvriers à des particules de combustion et évaluation du danger de différentes nanoparticules manufacturées) afin de déterminer quels sont les paramètres qui influencent la mesure. Les résultats obtenus indiquent que la préparation des suspensions joue un rôle dans la mesure de ce potentiel oxydant. La réactivité dépend de la concentration du surfactant et de la durée de sonication. D'autre part, l'ordre de réactivité est dépendant de la métrique utilisée (masse ou surface) pour exprimer les résultats. Parmi les trois tests considérés, le test DTT pourrait être le plus utile pour effectuer une évaluation initiale du danger potentiel de nanoparticules ambiantes ou manufacturées. Ce test pourrait être intégré dans une stratégie d'évaluation de la toxicité des nanoparticules. Le test DTT correspond bien un test intégratif. Pour des situations de travail dans lesquelles les particules de combustion sont majoritaires, les paramètres physico-chimiques qui corrèlent de manière significative avec la réactivité DTT sont la surface des particules, les concentrations de carbone organique, la somme des concentrations de quatre quinones et les concentrations de fer et cuivre. Un nombre plus faible de corrélations est observé dans des ateliers mécaniques, suggérant que d'autres composés non mesurés interviennent également dans cette réactivité. Concernant les nanoparticules carbonées manufacturées, les fonctions chimiques de surface corrélées avec la réactivité DTT sont des fonctions acides et des fonctions inconnues pouvant dismuter. D'autre part, la solubilité et la possibilité de former des complexes avec le DTT sur la surface des NP manufacturées influencent le résultat de réactivité.

Final Report: Legislative Property Tax Study Committee, January 2009

The Committee was authorized to meet three days during the 2007 Legislative Interim and two days during the 2008 Legislative Interim. The Committee met on September 12, 2007; November 7, 2007; December 5, 2007; November 14, 2008; and January 7, 2009, at the State Capitol, Des Moines, Iowa. In 2008, the Committee retained consultants from the Institute for Public Policy at George Washington University to study property taxation and other forms of revenue generation used by local governments in Iowa and other states.

Final Report Energy Efficiency Plans and Programs Study Committee, February 2009

The Legislative Council created the Energy Efficiency Plans and Programs Study Committee for the 2008 Legislative Interim pursuant to the passage of S.F. 2386 during the 2008 Legislative Session, which provided, in Section 8: The Legislative Council is requested to establish an interim study committee to examine the existence and effectiveness of energy efficiency plans and programs implemented by gas and electric public utilities, with an emphasis on results achieved by current plans and programs from the demand, or customer, perspective, and to make recommendations for additional requirements applicable to energy efficiency plans and programs that would improve such results. In conducting the study and developing recommendations, the Committee shall consider testimony from the Iowa Utilities Board, rate and nonrate-regulated gas and electric utilities, the Consumer Advocate, state agencies involved with energy efficiency program administration, environmental groups and associations, and consumers.

100 Years of Concrete Pavements in Iowa Final Report, March 2009

Portland cement concrete (PCC) pavements have given excellent service history for Iowa. The first concrete pavement was placed in Le Mars in 1904 and was in service until 1968. The Eddyville Cemetery Road placed in 1909 is still in service today. Many other pavements placed during the 1920s and 1930s are still in service today. The objective of this report is to document various changes in specifications, pavement design and equipment for PCC paving from the early 1900s to present. This includes changes that were made to the specification book and supplemental specifications. Where possible, information is given as a basis for the change in specifications.

FirstSearch: servei en línia per a l'usuari final

Descripció del servei en línia FirstSearch d'OCLC. Es detallen les bases de dades que ofereix, l'accés, tarificació, el llenguatge d'interrogació emprat i es presenta el mòdul d'obtenció de documents que pot gestionar cada un dels usuaris finals i amb el qual es poden aconseguir un gran nombre dels documents que contenen les bases de dades consultades.

Fingerprint Card and Final Disposition Report Procedures, January 10, 2008

This is a manual produced by the Iowa Department of Public Safety on how to process a fingerprint card for an arrested person.

Governor's Committee on Government Spending Reform : final report, 1996.

Final Report of the Governor's Committee on Government Spending, 1996. The Governor reconvened the Fisher Commission to see what could be done to maintain the fiscal discipline that had been evident since the State spending reforms were put in place, 1992.

Memòria final Catalunya i França: cors amics

Aquest projecte s'emmarca dins l'estudi i aplicació de la creativitat i la cultura mitjançant la difusió musical als àmbits de la divulgació i a l'articulació de programes de concert per part de possibles entitats que poguessin estar interessades en aprofundir i difondre al públic en general, els repertoris, autors i estils de la música coral que han estat a cavall d'ambdós territoris: Catalunya i França, al llarg de la història.

Council Bluffs Interstate System (I-29, I-80 and I-480) Final Environment Impact Statement, July, 2005

The Iowa Department of Transportation (Iowa DOT), Nebraska Department of Roads (NDOR), and the Federal Highway Administration (FHWA) are proposing improvements to the interstate system in the Omaha/Council Bluffs metropolitan area, extending across the Missouri River on Interstate 80 (I-80) to east of the Interstate 480 (I-480) interchange in Omaha, Nebraska (see Figure 1-1). The study considers long-term, broad-based transportation improvements along Interstate I-29 (I-29), I-80, and I-480, including approximately 18 mainline miles of interstate and 14 interchanges (3 system1, 11 service), that would add capacity and correct functional issues along the mainline and interchanges and upgrade the I-80 Missouri River Crossing. These improvements, once implemented, would bring the segments of I-80 and I-29 up to current engineering standards and modernize the roadway to accommodate future traffic needs.

Cetuximab In Combination With Docetaxel In Patients (Pts) With Metastatic Castration Resistant (Mcrpc) And Docetaxel-Refractory Prostate Cancer: Final Analysis Of The Multicenter Phase Ii Trial Sakk 08/07

There is no registered treatment (ttr) for pts with mCRPC who have progressive disease during or shortly after docetaxel (doc). EGFR overexpression increases in prostate cancer during the course of the disease. We investigated efficacy and safety of the combination of the monoclonal EGFR antibody cetuximab (cet) and doc in pts with mCRPC who are doc-refractory. Methods: Pts with mCRPC progressing during or < 90 days after at least 12 weeks of doc were included. Ttr consisted of the same doc regimen as prior to progression (35mg/m2 d1,8,15 q4w or 75mg/m2 q3w) in combination with cet (400mg/m2 d1, then 250mg/m2 weekly). Primary endpoint was progression free survival (PFS) at 12 weeks defined as absence of PSA progression or progression of metastases (mets). Secondary endpoints included toxicity, PFS at 24 weeks, PSA response, response of measureable disease and overall survival. 35 pts were needed in a Simon's two stage optimal design with a power of 90% and a significance level of 5% in order to test PFS rate at 12 weeks of £10% vs ?30%. Results: 35 evaluable pts were enrolled at 15 Swiss centers between 7/08 and 9/09. Median follow up was 14.8 months. Confirmed PFS at 12 weeks was 34% (95%CI 19-52%), PFS at 24 weeks was 20% and overall survival was 12.0 months (95%CI 7.1 -15.6). 20% (7/35) had a confirmed decline in PSA ? 50% and 31% (11/35) had a confirmed PSA decline ? 30%. Of pts with measurable disease (n=24) PR, SD and PD at week 12 was 4%, 54% and 25%, respectively (17% not evaluable). 3/9 (33%) pts with PDduring last doc ttr before inclusion reached the primary endpoint compared to 7/18 (39%) with PR or SD to last doc. 54% of evaluable pts experienced grade 3 and 6% grade 4 toxicity. Discussion: The result of the primary endpoint was promising in this first trial to test cet in combination with doc in pts with docetaxel-refractory mCRPC. Because this goal was achieved in such a highly pretreated pts population it appears that inhibition of the EGFR pathway may play a more important and persistent role in the treatment of prostate cancer than perceived so far. Further research is therefore warranted. Disclosure: R. Cathomas: - Membership on advisory board for sanofi aventis (suisse) and Merck. S. Gillessen: - Membership in advisory board for Sanofi Aventis. All other authors have declared no conflicts of interest.

Evaluation du projet EVITA: rapport final

Le projet EVITA (EValuation Indication, Traitement ambulatoire, Accompagnement) s'inscrit dans le Plan cantonal d'action Alcool (2007-2012), lui-même en conformité avec le Plan national Alcool (2007-2011). Ce projet est un mandat du Service de la santé publique qui a pour objectif la mise en oeuvre et l'évaluation d'un dispositif cantonal d'indication et de suivi (DCIS) constituant une porte d'entrée unique. Le DCIS est constitué d'un partenariat entre la Fondation vaudoise contre l'alcoolisme (FVA) et le Centre de traitement en alcoologie (CTA) du CHUV. C'est l'Unité d'évaluation de programmes de prévention (UEPP) de l'Institut universitaire de médecine sociale et préventive (IUMSP) qui a été chargée par le CTA, mandant, de l'évaluation du projet EVITA et qui en a rédigé le protocole. [Introduction, p. 5]