The German Internationale Bauausstellung (IBA) and Urban Regeneration: Lessons from the IBA Emscher Park

URBAN. REGENERATION. Lessons. from. the. IBA. Emscher. Park. Philip Pinch and Neil Adams Summary The German approach of using international building exhibitions (Internationale Bauausstellung) to provide an impetus for innovation ..

Editorial: crime patterns in time and space: the dynamics of crime opportunities in urban areas

The routine activity approach and associated crime pattern theory emphasise how crime emerges from spatio-temporal routines. In order to understand this crime should be studied in both space and time. However, the bulk of research into crime patterns and related activities has investigated the spatial distributions of crime, neglecting the temporal dimension. Specifically, disaggregation of crime by place and by time, for example hour of day, day of week, month of year, season, or school day versus none school day, is extremely relevant to theory. Modern data make such spatio-temporal disaggregation increasingly feasible, as exemplified in this special issue. First, much larger data files allow disaggregation of crime data into temporal and spatial slices. Second, new forms of data are generated by modern technologies, allowing innovative and new forms of analyses. Crime pattern analyses and routine activity inquiries are now able to explore avenues not previously available. The unique collection of nine papers in this thematic issue specifically examine spatio-temporal patterns of crime to; demonstrate the value of this approach for advancing knowledge in the field; consider how this informs our theoretical understanding of the manifestations of crime in time and space; to consider the prevention implications of this; and to raise awareness of the need for further spatio-temporal research into crime event

Multiple exon skipping strategies to by-pass dystrophin mutations.

Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic mutations, a third strategy, not applicable to whole exon deletions, may be possible. The removal of only one frame-shifting exon flanking the mutation-carrying exon may restore the reading frame and allow synthesis of a functional dystrophin isoform, providing that no premature termination codons are encountered. For these mutations, the removal of only one exon offers a simpler, cheaper and more feasible alternative approach to the dual exon skipping that would otherwise be considered. We present strategies to by-pass intra-exonic dystrophin mutations that clearly demonstrate the importance of tailoring exon skipping strategies to specific patient mutations

Indicators for Spatial Planning and Territorial Cohesion: Stakeholder-Driven Selection Approach for Improving Usability at Regional and Local Levels

© 2015 Regional Studies Association.González A., Daly G., Pinch P., Adams N., Valtenbergs V., Burns M. C. and Johannesson H. Indicators for spatial planning and territorial cohesion: stakeholder-driven selection approach for improving usability at regional and local levels, Regional Studies. Reformed European Union Cohesion Policy aims at delivering a coherent investment policy to achieve the Europe 2020 Strategy goals and to reduce regional disparities. Spatial indicators measure progress towards agreed policy goals and support place-based approaches to policy implementation. Despite the range of indicators available, development of a standardized approach in support of Cohesion Policy has received little empirical attention. A set of key spatial indicators has been identified in a stakeholder-driven process. The methodological approach applied is presented and resulting indicators critically appraised with regards to their applicability and potential for assisting improved integration between Cohesion Policy and spatial planning

Long-term glycine propionyl-l-carnitine supplemention and paradoxical effects on repeated anaerobic sprint performance

<p>Abstract</p> <p>Background</p> <p>It has been demonstrated that acute GPLC supplementation produces enhanced anaerobic work capacity with reduced lactate production in resistance trained males. However, it is not known what effects chronic GPLC supplementation has on anaerobic performances or lactate clearance.</p> <p>Purpose</p> <p>The purpose of this study was to examine the long-term effects of different dosages of GPLC supplementation on repeated high intensity stationary cycle sprint performance.</p> <p>Methods</p> <p>Forty-five resistance trained men participated in a double-blind, controlled research study. All subjects completed two testing sessions, seven days apart, 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL), in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Following completion of the second test session, the 45 subjects were randomly assigned to receive 1.5 g, 3.0 g, or 4.5 g GPLC per day for a 28 day period. Subjects completed a third test session following the four weeks of GPLC supplementation using the same testing protocol. Values of peak power (PP), mean power (MP) and percent decrement of power (DEC) were determined per bout and standardized relative to body mass. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts.</p> <p>Results</p> <p>There were no significant effects of condition or significant interaction effects detected for PP and MP. However, results indicated that sprint bouts three, four and five produced 2 - 5% lower values of PP and 3 - 7% lower values of MP with GPLC at 3.0 or 4.5 g per day as compared to baseline values. Conversely, 1.5 g GPLC produced 3 - 6% higher values of PP and 2 -5% higher values of MP compared with PL baseline values. Values of DEC were significantly greater (15-20%) greater across the five sprint bouts with 3.0 g or 4.5 g GPLC, but the 1.5 g GPLC supplementation produced DEC values -5%, -3%, +4%, +5%, and +2% different from the baseline PL values. The 1.5 g group displayed a statistically significant 24% reduction in net lactate accumulation per unit power output (p < 0.05).</p> <p>Conclusions</p> <p>The effects of GPLC supplementation on anaerobic work capacity and lactate accumulation appear to be dosage dependent. Four weeks of GPLC supplementation at 3.0 and 4.5 g/day resulted in reduced mean values of power output with greater rates of DEC compared with baseline while 1.5 g/day produced higher mean values of MP and PP with modest increases of DEC. Supplementation of 1.5 g/day also produced a significantly lower rate of lactate accumulation per unit power output compared with 3.0 and 4.5 g/day. In conclusion, GPLC appears to be a useful dietary supplement to enhance anaerobic work capacity and potentially sport performance, but apparently the dosage must be determined specific to the intensity and duration of exercise.</p

Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

<p>Abstract</p> <p>Background</p> <p>Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds.</p> <p>Methods</p> <p>Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25.</p> <p>Results</p> <p>It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer.</p> <p>Conclusion</p> <p>This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.</p

The Werner Syndrome Helicase/Exonuclease Processes Mobile D-Loops through Branch Migration and Degradation

RecQ DNA helicases are critical for preserving genome integrity. Of the five RecQ family members identified in humans, only the Werner syndrome protein (WRN) possesses exonuclease activity. Loss of WRN causes the progeroid disorder Werner syndrome which is marked by cancer predisposition. Cellular evidence indicates that WRN disrupts potentially deleterious intermediates in homologous recombination (HR) that arise in genomic and telomeric regions during DNA replication and repair. Precisely how the WRN biochemical activities process these structures is unknown, especially since the DNA unwinding activity is poorly processive. We generated biologically relevant mobile D-loops which mimic the initial DNA strand invasion step in HR to investigate whether WRN biochemical activities can disrupt this joint molecule. We show that WRN helicase alone can promote branch migration through an 84 base pair duplex region to completely displace the invading strand from the D-loop. However, substrate processing is altered in the presence of the WRN exonuclease activity which degrades the invading strand both prior to and after release from the D-loop. Furthermore, telomeric D-loops are more refractory to disruption by WRN, which has implications for tighter regulation of D-loop processing at telomeres. Finally, we show that WRN can recognize and initiate branch migration from both the 5′ and 3′ ends of the invading strand in the D-loops. These findings led us to propose a novel model for WRN D-loop disruption. Our biochemical results offer an explanation for the cellular studies that indicate both WRN activities function in processing HR intermediates

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs