The impact of local taxes on plants location decision

Determinants of plant locations are known to be multiple. Locations of partners and competitors are crucial, as well as the territory's local characteristics. Some local characteristics can be natural. Others, like local taxes, reflect local agents' decisions. To what extent are local taxes taken into consideration during the plant location process? We build a Poisson model to explain the number of firm creations observed in a given municipality in a given year. Correlations and first results tend to show that there exists some unobserved attractivity factors correlated with the level of local taxes. To deal with endogeneity, we present an approach close to the Regression Discontinuity Design. Finally, we find that, everything else being equal, higher local taxes actually deter firms from investing in a given zone.local attractivity, local taxes, plant location decisions, regression discontinuity design, Poisson regression, spatial economics

The impact of French Zones Franches Urbaines on employment and business creation

In 2004, 41 Zones Franches Urbaines (ZFU) have replaced less generous Zones de Redynamisation Urbaine (ZRU). ZFUs are particularly generous Enterprise Zones schemes in which establishments are exempted from all taxes and social contributions for 5 years. A first wave of ZFUs was zoned in 1997, followed by a second one in 2004 and a third one in 2006. In spite of the cost of such policies (the net cost of the second-wave ZFUs was around 125 million euros in 2005), the impact has never been assessed by econometricians. In this study, we aim to evaluate the net effect of the ZFU policy on both employment and business creations, using the transformation of less generous ZRUs into ZFUs in 2004. We use micro data on establishments and jobs at an infra-municipal scale. Differences-in-differences as well as standard propensity score matching are used to try to take selection bias into account. We finally identify a significantly positive effect on both business creations and employment. Yet, these effects are weak especially when compared to the magnitude of the costs.local employment, local policies, enterprise zones, evaluation

What kernel methods bring to the analysis of spatial concentration of migrants in France: 1968-1999

Most studies about the geographical location of a phenomenon or a population first aggregate data according to administrative boundaries which are generally not related to the issue. When the population under study is rare, and when the sample is not exhaustive, these aggregation choices often lead the results. In this study, we use non-parametric kernel techniques to estimate ratios of population densities. Using this kind of method is not technically costly and allows one to obtain the optimal trade-off between variance and bias. We apply this technique to the distribution of immigrants over the French territory, using data form population censures between 1968 to 1999. Another contribution of this work is to propose a concentration index based on the density ratios obtained in the first step.spatial concentration, geographical location, segregation indices, non-parametric estimation, immigration

PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation

Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne’s muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine™ 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms

Space Division Multiplexing in Optical Fibres

Optical communications technology has made enormous and steady progress for several decades, providing the key resource in our increasingly information-driven society and economy. Much of this progress has been in finding innovative ways to increase the data carrying capacity of a single optical fibre. In this search, researchers have explored (and close to maximally exploited) every available degree of freedom, and even commercial systems now utilize multiplexing in time, wavelength, polarization, and phase to speed more information through the fibre infrastructure. Conspicuously, one potentially enormous source of improvement has however been left untapped in these systems: fibres can easily support hundreds of spatial modes, but today's commercial systems (single-mode or multi-mode) make no attempt to use these as parallel channels for independent signals.Comment: to appear in Nature Photonic

Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo

While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential

The Native Copper- and Zinc- Binding Protein Metallothionein Blocks Copper-Mediated Aβ Aggregation and Toxicity in Rat Cortical Neurons

Background: A major pathological hallmark of AD is the deposition of insoluble extracellular b-amyloid (Ab) plaques. There are compelling data suggesting that Ab aggregation is catalysed by reaction with the metals zinc and copper. Methodology/Principal Findings: We now report that the major human-expressed metallothionein (MT) subtype, MT-2A, is capable of preventing the in vitro copper-mediated aggregation of Ab1–40 and Ab1–42. This action of MT-2A appears to involve a metal-swap between Zn 7MT-2A and Cu(II)-Ab, since neither Cu 10MT-2A or carboxymethylated MT-2A blocked Cu(II)-Ab aggregation. Furthermore, Zn7MT-2A blocked Cu(II)-Ab induced changes in ionic homeostasis and subsequent neurotoxicity of cultured cortical neurons. Conclusions/Significance: These results indicate that MTs of the type represented by MT-2A are capable of protecting against Ab aggregation and toxicity. Given the recent interest in metal-chelation therapies for AD that remove metal from Ab leaving a metal-free Ab that can readily bind metals again, we believe that MT-2A might represent a different therapeuti

Place-based tax exemptions and displacement effects: An evaluation of the Zones Franches Urbaines program

We propose to evaluate the impact of the French Zones Franches Urbaines on economic activity. This public-funded place-based program, comparable to US enterprise zones, exempts new and existing firms from taxes for a period of at least 5 years. For the purpose of this evaluation, we merged several administrative datasets at the firm level. This allows us to exhaustively observe business creations and stocks, as well as employment and financial outcomes for each firm at a precise geographical level. We focus on the second wave of the program, during which treated territories were selected among a pool of deprived territories according to a known set of covariates. The way treatment was assigned makes the conditional independence assumption credible in our case. Overall, we find significant effects on business creation and on employment while the effect on firms that were located in the treated areas before the program is not significant, regardless of the outcome. Finally, we provide evidence of significant negative spillovers of the program on neighboring areas.enterprise zone, local employment, place-based policies, propensity score matching, externalities