Competition-regulation interface in telecommunications: what's left of the essential facility doctrine

1noThe essential facility doctrine lies at the core of telecoms regulation since its very first steps in the United States and in the European Union. Later, the doctrine spread around the world and currently stands as a key pillar of the liberalization efforts underway in several countries. However, the concept of essential facility is a very dynamic one in the telecoms field, which makes it hard for regulators and regulated stakeholders to strike the right balance between incentives to invest in new infrastructure and securing access-based competition in the short run. Experiment such as the ''stepping stones'' approach in the US and the ''investment ladder'' approach in the EU have led to very mixed results, in the US, the FCC eventually abandoned this approach to stimulate investment in new high-speed infrastructure through ''access holidays''. The decline of the essential facilities doctrine in the US was not echoed by any relaxation of regulatory obligations in the EU, Canada and other countries, to the contrary, the US now seems likely to reconsider the essential facilities doctrine, at least in the application of antitrust law. Whether this will lead to a revival of the doctrine in the US and around the world, especially for next generation access networks, remains to be seen. The paper argues that interpreting the concept of essential facilities too broadly is likely to lead to insufficient incentives to invest in the future, it is thus advisable to get back to a narrow interpretation of this doctrine, in order to strike the right balance between the incentives to engage in infrastructure-based competition and the goal of boosting service-based competition in the short-term. Several debates that are currently raging around the world-including the debate over NGA deployment and the net neutrality querelle-are likely to be affected by the essential facilities doctrine in the years to come.openopenRENDA, A.Renda, Andre

Reduced mutation rate and increased transformability of transposon-free Acinetobacter baylyi ADP1-ISx

ABSTRACT The genomes of most bacteria contain mobile DNA elements that can contribute to undesirable genetic instability in engineered cells. In particular, transposable insertion sequence (IS) elements can rapidly inactivate genes that are important for a designed function. We deleted all six copies of IS 1236 from the genome of the naturally transformable bacterium Acinetobacter baylyi ADP1. The natural competence of ADP1 made it possible to rapidly repair deleterious point mutations that arose during strain construction. In the resulting ADP1-ISx strain, the rates of mutations inactivating a reporter gene were reduced by 7- to 21-fold. This reduction was higher than expected from the incidence of new IS 1236 insertions found during a 300-day mutation accumulation experiment with wild-type ADP1 that was used to estimate spontaneous mutation rates in the strain. The extra improvement appears to be due in part to eliminating large deletions caused by IS 1236 activity, as the point mutation rate was unchanged in ADP1-ISx. Deletion of an error-prone polymerase ( dinP ) and a DNA damage response regulator ( umuD Ab [the umuD gene of A. baylyi ]) from the ADP1-ISx genome did not further reduce mutation rates. Surprisingly, ADP1-ISx exhibited increased transformability. This improvement may be due to less autolysis and aggregation of the engineered cells than of the wild type. Thus, deleting IS elements from the ADP1 genome led to a greater than expected increase in evolutionary reliability and unexpectedly enhanced other key strain properties, as has been observed for other clean-genome bacterial strains. ADP1-ISx is an improved chassis for metabolic engineering and other applications. IMPORTANCE Acinetobacter baylyi ADP1 has been proposed as a next-generation bacterial host for synthetic biology and genome engineering due to its ability to efficiently take up DNA from its environment during normal growth. We deleted transposable elements that are capable of copying themselves, inserting into other genes, and thereby inactivating them from the ADP1 genome. The resulting “clean-genome” ADP1-ISx strain exhibited larger reductions in the rates of inactivating mutations than expected from spontaneous mutation rates measured via whole-genome sequencing of lineages evolved under relaxed selection. Surprisingly, we also found that IS element activity reduces transformability and is a major cause of cell aggregation and death in wild-type ADP1 grown under normal laboratory conditions. More generally, our results demonstrate that domesticating a bacterial genome by removing mobile DNA elements that have accumulated during evolution in the wild can have unanticipated benefits. </jats:p

Aligning Policies for Low-Carbon Systemic Innovation in Europe

This report considers potential policy options to promote ‘systemic innovation’ that foster decarbonisation, with a specific focus on the EU. By using the term ‘systemic’, we point to a variety of domains in which innovation can occur – not only technological, but also organisational innovation, (brought about by disruptive new business models); institutional (by revising both legal and economic incentives); and societal (requiring a change in consumption and behaviour), and emphasise how entire systems (e.g., energy, mobility, shelter) can be transformed through socio-economic change

The Stellar Halo Metallicity - Luminosity Relationship for Spiral Galaxies

The stellar halos of spiral galaxies bear important chemo-dynamical signatures of galaxy formation. We present here the analysis of 89 semi-cosmological spiral galaxy simulations, spanning ~ 4 magnitudes in total galactic luminosity. These simulations sample a wide variety of merging histories and show significant dispersion in halo metallicity at a given total luminosity - more than a factor of ten in metallicity. Our preliminary analysis suggests that galaxies with a more extended merging history possess halos which have younger and more metal rich stellar populations than the stellar halos associated with galaxies with a more abbreviated assembly. A correlation between halo metallicity and its surface brightness has also been found, reflecting the correlation between halo metallicity and its stellar mass. Our simulations are compared with recent Hubble Space Telescope observations of resolved stellar halos in nearby spirals.Comment: 5 pages, 4 figures. MNRAS Letters, in pres

Chromosome Segregation Is Biased by Kinetochore Size

Chromosome missegregation during mitosis or meiosis is a hallmark of cancer and the main cause of prenatal death in humans. The gain or loss of specific chromosomes is thought to be random, with cell viability being essentially determined by selection. Several established pathways including centrosome amplification, sister-chromatid cohesion defects, or a compromised spindle assembly checkpoint can lead to chromosome missegregation. However, how specific intrinsic features of the kinetochore—the critical chromosomal interface with spindle microtubules—impact chromosome segregation remains poorly understood. Here we used the unique cytological attributes of female Indian muntjac, the mammal with the lowest known chromosome number (2n = 6), to characterize and track individual chromosomes with distinct kinetochore size throughout mitosis. We show that centromere and kinetochore functional layers scale proportionally with centromere size. Measurement of intra-kinetochore distances, serial-section electron microscopy, and RNAi against key kinetochore proteins confirmed a standard structural and functional organization of the Indian muntjac kinetochores and revealed that microtubule binding capacity scales with kinetochore size. Surprisingly, we found that chromosome segregation in this species is not random. Chromosomes with larger kinetochores bi-oriented more efficiently and showed a 2-fold bias to congress to the equator in a motor-independent manner. Despite robust correction mechanisms during unperturbed mitosis, chromosomes with larger kinetochores were also strongly biased to establish erroneous merotelic attachments and missegregate during anaphase. This bias was impervious to the experimental attenuation of polar ejection forces on chromosome arms by RNAi against the chromokinesin Kif4a. Thus, kinetochore size is an important determinant of chromosome segregation fidelity

Ab initio detection of fuzzy amino acid tandem repeats in protein sequences

Background Tandem repetitions within protein amino acid sequences often correspond to regular secondary structures and form multi-repeat 3D assemblies of varied size and function. Developing internal repetitions is one of the evolutionary mechanisms that proteins employ to adapt their structure and function under evolutionary pressure. While there is keen interest in understanding such phenomena, detection of repeating structures based only on sequence analysis is considered an arduous task, since structure and function is often preserved even under considerable sequence divergence (fuzzy tandem repeats). Results In this paper we present PTRStalker, a new algorithm for ab-initio detection of fuzzy tandem repeats in protein amino acid sequences. In the reported results we show that by feeding PTRStalker with amino acid sequences from the UniProtKB/Swiss-Prot database we detect novel tandemly repeated structures not captured by other state-of-the-art tools. Experiments with membrane proteins indicate that PTRStalker can detect global symmetries in the primary structure which are then reflected in the tertiary structure. Conclusions PTRStalker is able to detect fuzzy tandem repeating structures in protein sequences, with performance beyond the current state-of-the art. Such a tool may be a valuable support to investigating protein structural properties when tertiary X-ray data is not available

Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype

Nonsense-mediated mRNA decay (NMD) is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The nine most common genotypes, each with an incidence rate of 1.5% or over, and together accounting for 80% of genotype frequencies, underwent statistical analysis. Genotype prevalence was calculated within the overall group. Results are expressed as proportions with 95% confidence intervals; P≤0.05 was considered statistically significant. A binomial distribution was assumed for each group; z-tests were used to compare genotype frequencies observed in the patient group with frequencies in the affected fetus group. In the absence of selecting factors, prevalence of these two genotypes was compared between a cohort of 568 β-thalassemia patients (PTS) and 577 affected fetuses (FOET) detected during the same period. IVS1,nt110/cd39 was significantly more prevalent in FOET than PTS (P<0.0001), while there was no significant difference in prevalence of cd39/cd39 in FOET compared with PTS (P=0.524). These results suggest a cd39 genotype NMD mechanism may be associated with improved clinical outcomes in thalassemia major

Ex post evaluation of the MAP 2001-2005 initiative and suggestions for the CIP 2007-2013

In the EU25, some 23 million SMEs represent 99% of all enterprises, provide 75 million jobs and make a 55% contribution towards the creation of wealth: in addition, one third of employees and over two thirds of private-sector employees in Europe work in SMEs. Given their outstanding strategic importance, the European Commission has launched several policies to promote the development of SMEs, their access to finance and investment in R&D and innovation. A prominent role among EU programmes targeting SMEs is played by the Multi-Annual Programme for Enterprise and Entrepreneurship 2001-2005 (MAP), funded by Community budget and co-financing instruments. The MAP has been extended until the end of 2006 to create a bridge with the forthcoming Competitiveness and Innovation Framework Programme (CIP), a very ambitious project that will run from 2007 to 2013. Against this background, the Budgetary Committee of the European Parliament commissioned CEPS to evaluate the output of the MAP over the period 2000-2005 in terms of relevance, effectiveness, efficiency and utility, by highlighting the value for money of the programmes and related actions, and emphasising whether the funds dedicated to their implementation have produced the expected quantitative and qualitative effects. In this report, CEPS was also asked to provide some orientations for future-generation programmes, namely the CIP. The authors focus in particular on the actions undertaken between 2001 and 2006, as they provide more relevant and consistent information on the output of the MAP initiative and, in turn, better orientation for the forthcoming CIP

Seven exercises planned to stimulate the flow of ideas in creative composition

Thesis (Ed.M.)--Boston Universit