Horizontal Agreements and R&D Complementarities: Merger versus RJV

We study the decision of two rms within an oligopoly concerning whether to enter into a horizontal agreement to exploit complementarities between their R&D activities and, if so, whether to merge or form a research joint venture (RJV). In contrast to horizontal merger, there is a probability that an RJV contract will fail to enforce R&D sharing. We nd that a horizontal agreement always arises. The insiders' merger/RJV choice involves a trade-o : While merger o ers certainty that R&D complementarities will be exploited, it leads to a pro t-reducing reaction by outsiders on the product market, where competition is Cournot. Greater brand similarity and contract enforceability (\quality") both favour RJV, while greater R&D complementarity favours merger. Interestingly, the insiders may choose to merge even when RJV contracts are always enforceable, and they may opt to form an RJV even when the likelihood of enforceability is negligible.

An Empirical Examination of the R&D Boundaries of the Firm - A Problem-Solving Perspective

We consider, both theoretically and empirically, how different organization modes are aligned to govern the efficient solving of technological problems. The data set is a sample from the Chinese consumer electronics industry. Following mainly the problem solving perspective (PSP) within the knowledge based view (KBV), we develop and test several PSP and KBV hypotheses, in conjunction with competing transaction cost economics (TCE) alternatives, in an examination of the determinants of the R&D organization mode. The results show that a firm’s existing knowledge base is the single most important explanatory variable. Problem complexity and decomposability are also found to be important, consistent with the theoretical predictions of the PSP, but it is suggested that these two dimensions need to be treated as separate variables. TCE hypotheses also receive some support, but the estimation results seem more supportive of the PSP and the KBV than the TCE.

Genome-wide linkage in a highly consanguineous pedigree reveals two novel loci on chromosome 7 for non-syndromic familial Premature Ovarian Failure.

BACKGROUND: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.¦METHODOLOGY/PRINCIPAL FINDINGS: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.¦CONCLUSIONS/SIGNIFICANCE: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function.

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"

Frequent MAGE mutations in human melanoma.

Abstract: Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. Methodology/Principal Findings: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. Significance: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.

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.

Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND: The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS: CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS: Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS: The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Global transcriptome sequencing identifies chlamydospore specific markers in Candida albicans and Candida dubliniensis.

Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.

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.

Adult abundance, biting behavior and parity of Anopheles aquasalis, Curry 1932 in two malarious areas of Sucre State, Venezuela

The principal vector of malaria in eastern Venezuela, Anopheles aquasalis, is exophagic and exophilic. Control using indoor insecticide house sprays has failed to lower the number of malaria cases. Therefore, studies were initiated in two villages of the eastern coastal state of Sucre to better understand this vector's biology and develop a more integrated control program. An. aquasalis was found to have a crepuscular biting behavior with a major peak at dusk and a minor peak at dawn. Mosquitos were collected more outdoors than indoors. Forty-seven percent of the biting took place before people went to bed (22:30 hr) and 69% of the mosquitos biting during this time period bite outdoors. Outdoor biting could be the reason why indoor spraying alone did not lower malaria cases. Seasonal abundance was greater in the rainy season compared to the dry season. Seasonal parous rates were high (78.3%-100%) and similar indoors and outdoors and between dry and wet season in Santa F e. In Guayana, the seasonal parity was lower (34.6%-42.2%) than Santa F e with indoor parity slightly higher than outdoors. Malaria cases were higher in Santa F e, but adult mosquito density was much lower than in Guayana. This difference could have been due to higher parity in Santa F e compared to Guayana. The greater distance to the nearest breeding site and presence of alternative hosts in Guayana can not be discounted as factors which contributed to the difference in malaria transmission between locations. We concluded that knowledge on seasonal occurrence, biting activity, resting behavior and breeding site location can be used to design a new control strategy for this vector.

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

Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic postconditioning in vivo.

Myocardial ischemic postconditioning (PosC) describes an acquired resistance to lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R applied immediately after the ischemic insult. Cardioprotection is conveyed by parallel signaling pathways converging to prevent mitochondria permeability transition. Recent observations indicated that PostC is associated with free radicals generation, including nitric oxide (NO(.)) and superoxide (O2 (.-)), and that cardioprotection is abrogated by antioxidants. Since NO. And O2 (. -) react to form peroxynitrite, we hypothesized that postC might trigger the formation of peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds ischemia/30 seconds reperfusion) was applied at the end of index ischemia. In a subgroup of rats, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (FeTPPS) was given intravenously (10 mg/kg(-1)) 5 minutes before PostC. Myocardial nitrotyrosine was determined as an index of peroxynitrite formation. Infarct size (colorimetric technique and plasma creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip pressure transducer), were determined. A significant generation of 3-nitrotyrosine was detected just after the PostC manoeuvre. PostC resulted in a marked reduction of infarct size, CK release and LV systolic dysfunction. Treatment with FeTPPS before PostC abrogated the beneficial effects of PostC on myocardial infarct size and LV function. Thus, peroxynitrite formed in the myocardium during PostC induces cardioprotective mechanisms improving both structural and functional integrity of the left ventricle exposed to ischemia and reperfusion in vivo.