Modelling bargaining behaviors within biotech clusters - Towards the "power of the weak" emergence?

If spatial and industrial economics theorical models, such as industrial districts, clusters, or learning regions propose a large analysis of differentiated coordination mecanisms, it however not really takes into account behavior of dispute dynamics, such as conflict of bargaining and power, which can explain both diversity and ambivalence of local coordinations. So, our purpose in this contribution is to bring to light that bargaining and power conflicts are at stake in coordinations structuration within territories. We base this contribution on Artificial Life simulations involving public and private local actors who bargain to share a local resource using more or less sophisticated strategies. On a methodologic point of view, our thought is based on an empirical established fact. Analysis of a biotechnology cluster in Toulouse-France (Leroux I., 2002, 2004) indeed contributes to bring to light that coordinations involving pharmaceutical industry, local communities and local research laboratories are based on direct or indirect evolving domination and concession bargaining games. If industrial firms play "the power of the weak" game, making concession of their decision power to public research laboratories, they endeavour systematically to exerce an influence or a discrimination power, by using hided and indirect means that forward by local communities.Starting from this established fact, we propose Artificial Life simulations of local bargaining games, inspired from the T. Ellingsen (1997) bargaining evolutionnary game. This is a Nash demand game under ultimatum. It leads to the interaction of obstinate agents whose demands are independent of those of the adversaries, and sophisticated agents who adapt their demand to that hoped for of their adversaries rather than gain nothing. As a result, our simulations show that bargainings between these local actors lead to an agreement which is not a perfect share, or an "universal" rule, but a compromise frequently hiding complex mecanisms of domination and concession. The main contribution of these simulations, which are based on genetic algorithms, is to put in a prominent position the variations of behavioral rules. We show how bargaining is an evolving processus based on domination and concession behaviors (influence, coercion,…) bringing to light the T. Schelling (1960) "power of the weak". This result brings to the fore the question of flexibility and phasing dynamics of power behaviors in local coordination bargainings. This model can contributes to open new researches focused on power and conflict strategies within local coordinations.

Modelling bargaining behaviors within biotech clusters - Towards the "power of the weak" emergence?

If spatial and industrial economics theorical models, such as industrial districts, clusters, or learning regions propose a large analysis of differentiated coordination mecanisms, it however not really takes into account behavior of dispute dynamics, such as conflict of bargaining and power, which can explain both diversity and ambivalence of local coordinations. So, our purpose in this contribution is to bring to light that bargaining and power conflicts are at stake in coordinations structuration within territories. We base this contribution on Artificial Life simulations involving public and private local actors who bargain to share a local resource using more or less sophisticated strategies. On a methodologic point of view, our thought is based on an empirical established fact. Analysis of a biotechnology cluster in Toulouse-France (Leroux I., 2002, 2004) indeed contributes to bring to light that coordinations involving pharmaceutical industry, local communities and local research laboratories are based on direct or indirect evolving domination and concession bargaining games. If industrial firms play "the power of the weak" game, making concession of their decision power to public research laboratories, they endeavour systematically to exerce an influence or a discrimination power, by using hided and indirect means that forward by local communities.Starting from this established fact, we propose Artificial Life simulations of local bargaining games, inspired from the T. Ellingsen (1997) bargaining evolutionnary game. This is a Nash demand game under ultimatum. It leads to the interaction of obstinate agents whose demands are independent of those of the adversaries, and sophisticated agents who adapt their demand to that hoped for of their adversaries rather than gain nothing. As a result, our simulations show that bargainings between these local actors lead to an agreement which is not a perfect share, or an "universal" rule, but a compromise frequently hiding complex mecanisms of domination and concession. The main contribution of these simulations, which are based on genetic algorithms, is to put in a prominent position the variations of behavioral rules. We show how bargaining is an evolving processus based on domination and concession behaviors (influence, coercion,…) bringing to light the T. Schelling (1960) "power of the weak". This result brings to the fore the question of flexibility and phasing dynamics of power behaviors in local coordination bargainings. This model can contributes to open new researches focused on power and conflict strategies within local coordinations

Evaluation des risques sanitaires liés à l'injection de biogaz épure dans un réseau de gaz naturel

National audienceCe document reprend l'avis de l'Agence Française de Sécurité Sanitaire de l'Environnement et du Travail (Afsset) émis à la suite de l'expertise collective menée pour l'évaluation de risques sanitaires liés à l'injection de biogaz dans le réseau de gaz naturel. L'intégralité de cette expertise est publiée et disponible sur le site internet de l'Agence, seuls les grands axes sont présentés dans ce document. Suite aux recommandations émises par l'Afsset, des travaux ont été initiés afin de recueillir et analyser des données de composition sur le biogaz issus de boues de STEP. L'INERIS est en charge de ce projet. Par la suite, les données seront utilisées afin d'évaluer les risques accidentels (consécutifs à la valorisation du biogaz, au transport par canalisation et à la valorisation énergétique, industrielle et domestique) ; ainsi que les risques sanitaires pour les utilisateurs (consécutifs à l'injection dans le réseau de gaz naturel)

Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon-ribavirin combination therapy after 4 weeks of treatment

Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 mu g pegylated interferon (PEG-IFN)-alpha-2a (weekly) and ribavirin 1000-1200mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (= 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-alpha-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-alpha-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml. Eur J Gastroenterol Hepatol 22:1443-1448 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge

End-stage liver disease caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct-acting antiviral therapies have reduced efficacy in patients with end-stage liver disease and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct but overlapping epitope in the viral E2 glycoprotein to protect humanized mice from a patient-derived HCV challenge. Their neutralizing activity was assessed using the HCVpp and HCVcc systems expressing multiple patient-derived envelopes and a human-liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient-derived HCV genotype 1b isolate, while three out of four AP33-treated mice were completely protected. In contrast, only one out of four 3/11-treated mice remained HCV RNA negative throughout the observation period, while the other three had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro. Conclusion: Although mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Since mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and re-infected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition our data is valuable for the design of a prophylactic vaccine

Development and characterization of a human monoclonal antibody for prevention of HCV recurrence in liver transplant patients

More than 170 million people worldwide are chronically infected with hepatitis C virus (HCV) and are at risk of developing liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver transplantation is the only option for patients with HCV-induced end-stage liver diseases. Nevertheless, infection of the newly grafted liver occurs immediately and universally after transplantation. Despite the recent progress in HCV therapy, a prophylactic vaccine is still not available. The role of neutralizing monoclonal antibodies (mAbs) in protection from different viral infections including HCV, HIV and Ebola has been reported. In the last few years, several mAbs with neutralizing activity have been described but only few mAbs have been evaluated in vivo. In the present study, we describe the development of a mAb, designated 2A5, isolated from HCV genotype 1b chronic patient. ELISA results indicated high affinity of mAb 2A5 towards HCV envelope glycoprotein (E1E2). The binding activity was completely lost against denatured E1E2 protein indicating that it targets a conformational epitope within the envelope region. Epitope mapping using alanine mutants of E1E2 proteins defined critical binding residues within the regions 419-447 and 612-617. Results of pseudoparticles (HCVpp) and cell culture produced virus (HCVcc) neutralization showed broad neutralizing activity of mAb 2A5 against all HCV genotypes. The efficacy study of mAb 2A5 in immune-deficient mice of which the liver is repopulated with human hepatocytes (humanized mice) showed complete protection from HCV challenge for genotypes 1a and 4a, while partial protection was achieved for genotypes 1b and 6a. Sequence analysis of E1E2 protein from non-protected mice did not revealed resistance mutations at interaction residues of mAb 2A5. In conclusion, mAb 2A5 shows potent anti-HCV neutralizing activity both in vitro and in vivo and could hence provide an effective strategy to prevent HCV recurrence in chronically infected HCV liver transplant patients. In addition, the broad neutralizing activity of this mAb presents a valuable epitope for the design of HCV vaccine with cross-protection activity

Validation of an enzyme-linked immunosorbent assay for the quantification of human IgG directed against the repeat region of the circumsporozoite protein of the parasite Plasmodium falciparum.

BACKGROUND: Several pre-erythrocytic malaria vaccines based on the circumsporozoite protein (CSP) antigen of Plasmodium falciparum are in clinical development. Vaccine immunogenicity is commonly evaluated by the determination of anti-CSP antibody levels using IgG-based assays, but no standard assay is available to allow comparison of the different vaccines. METHODS: The validation of an anti-CSP repeat region enzyme-linked immunosorbent assay (ELISA) is described. This assay is based on the binding of serum antibodies to R32LR, a recombinant protein composed of the repeat region of P. falciparum CSP. In addition to the original recombinant R32LR, an easy to purify recombinant His-tagged R32LR protein has been constructed to be used as solid phase antigen in the assay. Also, hybridoma cell lines have been generated producing human anti-R32LR monoclonal antibodies to be used as a potential inexhaustible source of anti-CSP repeats standard, instead of a reference serum. RESULTS: The anti-CSP repeats ELISA was shown to be robust, specific and linear within the analytical range, and adequately fulfilled all validation criteria as defined in the ICH guidelines. Furthermore, the coefficient of variation for repeatability and intermediate precision did not exceed 23%. Non-interference was demonstrated for R32LR-binding sera, and the assay was shown to be stable over time. CONCLUSIONS: This ELISA, specific for antibodies directed against the CSP repeat region, can be used as a standard assay for the determination of humoral immunogenicity in the development of any CSP-based P. falciparum malaria vaccine

Risk assessment of biogas in kitchens

International audienceThe health risk associated with human exposure to pollutants while using biogas for cooking was assessed following the methodology described by the US - National Research Council. Information of hazardous compounds and compositions of several biogas types were extracted from scientific literature. Compositions were dependent on the biogas origin (production process). First, a quantitative approach was conducted to identify substances with a high health risk based on their Human Toxicity Values. Then, a subsequent qualitative analysis was performed to complete the health risk assessment based on other toxicology data, effectiveness of purification processes, variability of the waste materials used for biogas generation and, when possible, a comparison with natural gas. The main conclusion of the study was that the injection in the grid of upgraded biogas originating from household and organic waste landfills, did not present an increase of health risks when compared to the domestic use of natural gas