The loop group and the cobar construction

"Vegeu el resum a l'inici del document del fitxer adjunt."

Validation and long-term evaluation of a modified on-line chiral analytical method for therapeutic drug monitoring of (R,S)-methadone in clinical samples.

Matrix effects, which represent an important issue in liquid chromatography coupled to mass spectrometry or tandem mass spectrometry detection, should be closely assessed during method development. In the case of quantitative analysis, the use of stable isotope-labelled internal standard with physico-chemical properties and ionization behaviour similar to the analyte is recommended. In this paper, an example of the choice of a co-eluting deuterated internal standard to compensate for short-term and long-term matrix effect in the case of chiral (R,S)-methadone plasma quantification is reported. The method was fully validated over a concentration range of 5-800 ng/mL for each methadone enantiomer with satisfactory relative bias (-1.0 to 1.0%), repeatability (0.9-4.9%) and intermediate precision (1.4-12.0%). From the results obtained during validation, a control chart process during 52 series of routine analysis was established using both intermediate precision standard deviation and FDA acceptance criteria. The results of routine quality control samples were generally included in the +/-15% variability around the target value and mainly in the two standard deviation interval illustrating the long-term stability of the method. The intermediate precision variability estimated in method validation was found to be coherent with the routine use of the method. During this period, 257 trough concentration and 54 peak concentration plasma samples of patients undergoing (R,S)-methadone treatment were successfully analysed for routine therapeutic drug monitoring.

Does Internationalization Alter the R&D-Productivity Relationship?

R&D investment is an important driver of productivity gains. However, firms differ in their ability to appropiate the returns to their R&D efforts. This paper analyses to what extent firm's internationalization influences the endogenous relation between R&D and productivity. In particular, we assess the contribution of R&D to productivity for a panel of UK firms that differ in their degree of internationalization. We find that, on average, multinationals obtain higher gains from their investment in R&D. However, the influence of internationalization on the contribution of R&D to productivity varies along the distribution of the returns to R&D. Keywords: R&D, Multinationals, Productivity. JEL Codes: C14, D24, F23.

A doubling measure on R(d) can charge a rectifiable curve

"Vegeu el resum a l'inici del document del fitxer adjunt"

Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.

Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.

Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients.

ABSTRACT: BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg.h/L, range for the 7 patients: 40-118 mg.h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg.h/L, range: 44-118 mg.h/L). CONCLUSIONS: Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.

Determinación cualitativa de los componentes del cemento portland CEM I 52,5-R endurecido

Se pretende contribuir al esclarecimiento de la causa o causas de la importante disminución de la resistencia de las pastas de cemento portland sometidas a altas temperaturas. Para ello el primer paso y el que desarrolla este trabajo final de carrera es la determinación de los diferentes componentes de las pastas de cemento portland y más concretamente las fases en las que se encuentran los C-S-H a diferentes edades ya que son los responsables de las principales resistencias mecánicas de los materiales realizados con cemento portland, como los morteros y los hormigones.

A high-throughput test to detect C.E.R.A. doping in blood.

C.E.R.A., a continuous erythropoietin receptor activator, is a new third-generation erythropoiesis-stimulating agent (ESA) that has recently been linked with abuse in endurance sports. In order to combat this new form of doping, we examined an enzyme-linked immunosorbent assay (ELISA) designed to detect the presence of C.E.R.A. in serum samples. The performance of the assay was evaluated using a pilot excretion study that involved six subjects receiving C.E.R.A. Validation data demonstrated an excellent reproducibility and ensured the applicability of the assay for anti-doping purposes. To maximize the chances of detecting the drug in serum samples, we propose the use of this specific ELISA test as a high-throughput screening method, combined with a classic isoelectric focusing test as a confirmatory assay. This strategy should make C.E.R.A. abuse relatively easy to detect, thereby preventing the future use of this drug as a doping agent.

Kabīr et la répétition du nom de Rāma, réalisation spirituelle et mémoire de Dieu

L'intention de l'A. est d'analyser la répétition du Nom de Rāma chez Kabīr. Cette technique prend un sens particulier chez ce poète, étroitement lié au souvenir constant de Dieu, à une vision imprégnée à la fois de spéculations métaphysiques et d'une profonde dévotion amoureuse. L'A. tente d'évaluer l'impact des différents courants qui ont forgé la pensée de Kabir et de démontrer leur importance dans l'oeuvre du poète. Par cet effort, il espère contribuer à éclairer l'atmosphère religieuse de l'époque et de situer une des pratiques très importantes de mantra dans le contexte de la bhakti médiévale

Rhipidocotyle gibsoni n. sp. from a Brazilian Freshwater Fish and Rhipidocotyle froesi n.sp. for r. baculum (linton, 1905) of Eckmann (1932) (Bucephalidae; Digenea)

Rhipidocotyle gibsoni n.sp. is described from Acestrorhynchus lacustris from Paraná River, brazil. It is most closely related to r. froesi n. sp. and to R. eckmanni in the shape of the cephalic hood, differing in the extent of the uterus, in the position of the vitelline follicles and in that the host is a freshwater fish. Rhipidocotyle froesi n. sp. is proposed for the marine specimens described by Eckmann (1932) as R. baculum (Linton, 1905).

Mīrā's Yoga

(Résumé de l'ouvrage) This book contains most of the papers presented at the seventh International conference on Early Literature in New Indo-Aryan Languages, held at Venice in 1997. They are grouped in part by geographical area, in part by subject matter, in a crossing of boundaries that sharpens the exchange between the two.

Effect of Niclosamide (Bayluscide WP 70 (R)), Anacardium occidentale hexane extract and Euphorbia splendens latex on behavior of Biomphalaria glabrata (Say, 1818), under laboratory conditions

The repellent effect of the molluscicides Niclosamide (Bayluscide WP 70 (R)), Anacardium occidentale and the latex of Euphorbia splendens on Biomphalaria glabrata was observed through the investigation of the occurrence of escape behavior among molluscs that were exposed to dosages lower than the LD 50. The total number of individuals out of water among the surviving snails in the control group provided a "Natural Escape Index". The comparison between this total and the total number of surviving snails in each group exposed to the different dosages of the molluscicides after 24 hr provided the "Molluscicide Escape Index" and the detection of a "Repellency Range" to these snails. The escape indexes for Niclosamide, A. occidentale and E. splendens were 10, 6.22 and 6.44 respectively. Repellency occurred at the following concentration ranges: 0.01, 0.02 and 0.03 ppm Bayluscide, 0.1, 0.2 and 0.3 ppm A. occidentale and 0.05, 0.10, 0.15 and 0.20 ppm E. splendens. The Natural Escape Index obtained in the control group was zero.

Genetic variability and differentiation between populations of Rhodnius prolixus and R. pallescens, vectors of Chagas' Disease in Colombia

Enzyme polymorphism in Rhodnius prolixus and R. pallescens (Hemiptera, Reduviidae), principal vectors of Chagas' disease in Colombia, was analyzed using starch gel electrophoresis. Three geographic locations were sampled in order to determine gene flow between populations and to characterize intra- and interspecific differences. Of 25 enzymes assayed 10 were successfully resolved and then used to score the genetic variation. The enzymes PEPD, GPI, PGM and ICD were useful to differentiate these species and PGD, PGM and MDH distinguished between sylvatic and domiciliary populations of R. prolixus. Both polymorphism and heterozygosity indicated greater genetic variability in sylvatic habitats (H = 0.021) compared to domiciliary habitats (H = 0.006) in both species. Gene flow between sylvatic and domiciliary populations in R. prolixus was found to be minimal. This fact and the genetic distance between them suggest a process of genetic isolation in the domiciliary population.