Start-ups, firm growth and the consolidation of the French biotech industry

Based on an original dataset, we analyze empirically the determinants of firm growth in the French biotech industry during two periods, 1996-1999 and 1999-2002. We have two main results. First, Gibrat's law is violated. The growth of annual turnover is influenced by teh initial size of the firm. The effect is non-linear, negative for small firms. Second, location has a significant impact on growth. We use different sets of dummies to characterize location and different measures of firm growth. As a whole, our results point at Marseilles (and its region) and Nanterre (but not Paris and Evry) as favorable places for the growth of firms between 1999 and 2002. For the 1996-1999, the favorable places are Strasbourg (and Alsace) and Rh“ne-Alpes (Lyon/Grenoble). Our analysis thus suggests that the changes in the (notably legal) environment of French biotech firms that took place in 1999 had a drastic effect of the comparative advantages of locations for biotech firms.BIOTECHNOLOGY; INDUSTRIAL CLUSTERING; FIRM GROWTH; FRANCE

Ségrégation intergranulaire des éléments de la famille du soufre dans le fer pur

Les mécanismes de ségrégation intergranulaire des éléments soufre, sélénium et tellure ont été étudiés en utilisant d'une part nos propres mesures de ségrégation obtenues par rétrodiffusion élastique d'ions accélérés dans le cas des éléments sélénium et tellure, d'autre part quelques résultats de la littérature obtenus par spectroscopie Auger dans le cas des ségrégations de soufre. L'ensemble des résultats montre que la ségrégation intergranulaire des trois métalloïdes obéit aux mêmes lois. Il s'agit essentiellement d'une ségrégation d'équilibre, réversible et activée thermiquement qui n'est pas modifiée par la présence de carbone ségrégé aux joints de grains. Une équation générale est proposée. Elle permet de décrire nos résultats ainsi que certains résultats de la littérature

Diversification and hybridization in firm knowledge bases in nanotechnologies

The paper investigates the linkages between the characteristics of technologies and the structure of a firms' knowledge base. Nanotechnologies have been defined as converging technologies that operate at the nanoscale, and which require integration to fulfill their economic promises. Based on a worldwide database of nanofirms, the paper analyses the degree of convergence and the convergence mechanisms within firms. It argues that the degree of convergence in a firm's nano-knowledge base is relatively independent from the size of the firm's nano-knowledge base. However, while firms with small nano-knowledge bases tend to exploit convergence in each of their patents/publications, firms with large nano-knowledge bases tend to separate their nano-R&D activities in the different established fields and achieve diversity through the juxtaposition of the output of these independent activitie

Are Laparoscopic Staplers Effective for Ligation of Large Intraabdominal Arteries?

AbstractObjectives. To evaluate ligation of aortoiliac arteries with laparoscopic staplers in order to develop specifically designed staplers.Methods. Cadaveric study. Seven human cadaver aortas were stapled using EndoGIA60® staplers. Efficiency was evaluated macroscopically and on a hydrodynamic bench.Clinical study. Twelve patients had ligation of 14 large abdominal arteries (aorta: nine, iliac artery: four, hepatic artery: one) using a laparoscopic stapler. Stapling efficiency was judged on peroperative clinical and postoperative CT scan criteria.Results. Cadaveric study. Stapling was performed perfectly on four moderately calcified aortas, without leakage with a pulsatile pressure of >250 mmHg. For three aortas with severe calcification, stapling was not efficient and major leakage occurred.Clinical study. Stapling appeared clinically efficient on all arteries but one aorta: this severely calcified aorta was ligated conventionally. The staplers are not easy to use due to their shape and their lack of articulation. After a mean follow-up of 31.3 months, all the other stapled arteries were effectively ligated.Conclusion. The commercially available staplers can be used securely on moderately calcified arteries but stapling of severely calcified arteries should be avoided. These devices should be redesigned to facilitate their use in vascular surgery

Continuous macroscopic limit of a discrete stochastic model for interaction of living cells

In the development of multiscale biological models it is crucial to establish a connection between discrete microscopic or mesoscopic stochastic models and macroscopic continuous descriptions based on cellular density. In this paper a continuous limit of a two-dimensional Cellular Potts Model (CPM) with excluded volume is derived, describing cells moving in a medium and reacting to each other through both direct contact and long range chemotaxis. The continuous macroscopic model is obtained as a Fokker-Planck equation describing evolution of the cell probability density function. All coefficients of the general macroscopic model are derived from parameters of the CPM and a very good agreement is demonstrated between CPM Monte Carlo simulations and numerical solution of the macroscopic model. It is also shown that in the absence of contact cell-cell interactions, the obtained model reduces to the classical macroscopic Keller-Segel model. General multiscale approach is demonstrated by simulating spongy bone formation from loosely packed mesenchyme via the intramembranous route suggesting that self-organizing physical mechanisms can account for this developmental process.Comment: 4 pages, 3 figure

Phase Transition in Liquid Drop Fragmentation

A liquid droplet is fragmented by a sudden pressurized-gas blow, and the resulting droplets, adhered to the window of a flatbed scanner, are counted and sized by computerized means. The use of a scanner plus image recognition software enables us to automatically count and size up to tens of thousands of tiny droplets with a smallest detectable volume of approximately 0.02 nl. Upon varying the gas pressure, a critical value is found where the size-distribution becomes a pure power-law, a fact that is indicative of a phase transition. Away from this transition, the resulting size distributions are well described by Fisher's model at coexistence. It is found that the sign of the surface correction term changes sign, and the apparent power-law exponent tau has a steep minimum, at criticality, as previously reported in Nuclear Multifragmentation studies [1,2]. We argue that the observed transition is not percolative, and introduce the concept of dominance in order to characterize it. The dominance probability is found to go to zero sharply at the transition. Simple arguments suggest that the correlation length exponent is nu=1/2. The sizes of the largest and average fragments, on the other hand, do not go to zero but behave in a way that appears to be consistent with recent predictions of Ashurst and Holian [3,4].Comment: 10 pages, 11 figures. LaTeX (revtex4) with psfig/epsfi

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

High-Temperature-Induced Defects in Tomato (Solanum lycopersicum) Anther and Pollen Development Are Associated with Reduced Expression of B-Class Floral Patterning Genes

Citation: Muller, F., Xu, J. M., Kristensen, L., Wolters-Arts, M., de Groot, P. F. M., Jansma, S. Y., . . . Rieu, I. (2016). High-Temperature-Induced Defects in Tomato (Solanum lycopersicum) Anther and Pollen Development Are Associated with Reduced Expression of B-Class Floral Patterning Genes. Plos One, 11(12), 14. doi:10.1371/journal.pone.0167614Sexual reproduction is a critical process in the life-cycle of plants and very sensitive to environmental perturbations. To better understand the effect of high temperature on plant reproduction, we cultivated tomato (Solanum lycopersicum) plants in continuous mild heat. Under this condition we observed a simultaneous reduction in pollen viability and appearance of anthers with pistil-like structures, while in a more thermotolerant genotype, both traits were improved. Ectopic expression of two pistil-specific genes, TRANSMITTING TISSUE SPECIFIC and TOMATO AGAMOUS LIKE11, in the anthers confirmed that the anthers had gained partial pistil identity. Concomitantly, expression of the B-class genes TOMATO APETALA3, TOMATO MADS BOX GENE6 (TM6) and LePISTILLATA was reduced in anthers under continuous mild heat. Plants in which TM6 was partially silenced reacted hypersensitively to temperature elevation with regard to the frequency of pistilloid anthers, pollen viability and pollen quantity. Taken together, these results suggest that high-temperature induced down-regulation of tomato B-class genes contributes to anther deformations and reduced male fertility. Improving our understanding of how temperature perturbs the molecular mechanisms of anther and pollen development will be important in the view of maintaining agricultural output under current climate changes

First Report of Root and Collar Rot Caused by Fusarium tricinctum and Fusarium avenaceum on Carrot in France

In 2017, carrot (Daucus carota L.) seed production represented around 22% of the area devoted to the production of vegetable fine seeds. Since 2015, symptoms of root and collar rot have been observed in carrot seed parcels located in the Central Region, one of the most important production zone in France. Diseased plants became dried prematurely, compromising seed development. Depending on the year and the climatic conditions, the disease in a same field can be considered as epidemic (rate losses between 30 to 100% of plants in 2016) or can impact plants more sporadically (less than 10% in 2017 and 2018). Sixteen diseased carrot samples (Nantaise type) were collected from five fields of seed production in the Central Region: two fields in 2016 and 2017, one field in 2018. Seven fungal isolates, obtained from lesions, were grown on Potato Dextrose Agar (PDA) medium and incubated for one week at 20°C in darkness. From the colony top, fluffy mycelium pigmented in pink, red, purple or orange was observed, with a red color at the reverse. To induce sporulation, isolates were grown on Synthetischer Nährstoffarmer Agar (SNA) medium during three weeks at 24°C in near-UV radiations under a 12h-photoperiod. Four isolates (FT001, FT003, FT007, FT017) developed orange sporodochia with lunar or crescent-shaped macroconidia (40.3 ± 0.8 × 5.9 ± 0.1 µm; n=90) and lime or pear-shaped microconidia (10.7 ± 0.2 × 7.7 ± 0.2 µm; n=60), as described in Fusarium tricinctum (Leslie and Summerell 2006). Three isolates (FA001, FA002, FA006) developed orange sporodochia with sickle-shaped macroconidia (50.5 ± 1.1 × 5.0 ± 0.1 µm; n= 60), but no microconidia, as observed in Fusarium avenaceum (Leslie and Summerell 2006). To confirm the identification, DNA was extracted from the mycelium of the seven isolates and molecular markers (ATP citrate lyase, ACL1; RNA polymerase II, RPB2) were used for PCR amplification (Gräfenhan et al. 2011; O’Donnell et al. 2013). The ACL1 sequences from the seven field isolates (GenBank Accession numbers MK183788-MK183791; MK181528-MK181530) were 99-100% identical with the ACL1 sequence of a reference F. tricinctum isolate (query coverages 99-100%; E-values of 0.0) and a reference F. avenaceum isolate (query coverages 98-99%; E-values of 0.0) [respectively DAOM 235630 isolate, GenBank Acc. No. JX397813 and BBA64135 isolate, GenBank Acc. No. JX397768, Niessen et al. 2012]. Using RPB2, sequences from field isolates (GenBank Acc. No. MK183109-MK183115) were 98.5-99.9% identical with the RPB2 sequence of a reference F. tricinctum isolate (query coverages 96-100%; E-values of 0.0) and a reference F. avenaceum isolate (query coverages 95-100%; E-values of 0.0) [respectively MRC 1895 isolate, GenBank Acc. No. MH582113 and MRC 1413 isolate, GenBank Acc. No. MH582082, O’Donnell et al. 2018]. To confirm pathogenicity, FT001 and FA002 were inoculated on collars of 10-weeks old carrot plants in the greenhouse. Forty plants per isolate and 40 control plants were used. Ten microliters of a conidial suspension (105 conidia.mL-1) - or sterile water for the controls - were deposited at the collar, previously wounded using a scalpel blade. Necrotic lesions developed at 20 dpi (FT001) and at 30 dpi (FA002). Fusarium tricinctum and F. avenaceum were re-isolated from the lesions and identified by sequencing using ACL1 and RPB2 markers. No isolation of Fusarium was obtained from the controls. To our knowledge, this is the first report of F. tricinctum and F. avenaceum in carrot in France

Clinical Studies into the Causes of Idiopathic Macular Telangiectasia Type 2: Sleep Apnoea and Macular Telangiectasia: The SAMTel Project

Purpose: To assess the prevalence of Obstructive Sleep Apnoea (OSA) in a population with Macular Telangiectasia Type 2 (MacTel) and how OSA impacts on MacTel progression. Methods: In this case-control study participants completed a questionnaire which incorporated the Berlin Questionnaire (BQ) and questions regarding anthropometric data and medical history. A subset was sequentially selected to undertake overnight sleep analysis using the ResMed ApneaLink™. Using data acquired from the Busselton Population and Medical Research Foundation participants were case-matched based on age, sex and body mass index (BMI) along with, where possible, the presence of hypertension and diabetes. Results: There were 57 (30 ApneaLink) MacTel and 183 controls, respectively. There was no difference in self-reported sleep disordered breathing outcomes between the cohorts using the BQ (p=0.95). Analysis of key indices from ApneaLink recordings found that those with an Apnoea – Hypopnoea Index (AHI) and Oxygen Desaturation Index (ODI) > 5 episodes per hour had a more advanced stage of MacTel (AHI p = 0.05, ODI p = 0.03). 2 year MacTel disease progression rates were unremarkable. Conclusion: Patients with MacTel have a high prevalence of OSA which appears to result in a more advanced form of the disease