Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues

Understanding the information needs of users of public information about higher education

Report to HEFCE by Oakleigh Consulting and Staffordshire University. "This study's aims were to carry out research into understanding the needs of intended users (primarily prospective students but with some focus on their advisors and employers) of public information on higher education (HE). The work focussed on England, but also took into account Wales, Scotland and Northern Ireland where relevant." - Page 1

Towards gg→HHgg\to HH at next-to-next-to-leading order: light-fermionic three-loop corrections

We consider light-fermion three-loop corrections to $gg\to HH$ using forward scattering kinematics in the limit of a vanishing Higgs boson mass, which covers a large part of the physical phase space. We compute the form factors and discuss the technical challenges. The approach outlined in this letter can be used to obtain the full virtual corrections to $gg\to HH$ at next-to-next-to-leading order.Comment: 12 page

The archaeology of South Sudan from c. 3000 BC to AD 1500

This paper reviews the current state of archaeological research within the boundaries of the modern country of South Sudan, with a particular focus on the period between c. 3000 BC and AD 1500. While various historical factors and more recent political unrest have long stymied concerted archaeological efforts in the region, such surveys as have been undertaken are summarised and synthesised here, most notably the four expeditions funded by the British Institute in Eastern Africa between 1977 and 1981. Though scant, the data recovered during these and other research projects point to great diversity within the archaeological record of South Sudan, highlighting the region’s importance for addressing such large-scale issues as the transition between (or indeed the co-occurrence of) Later Stone Age and Early Iron Age lifeways, including the spread of pastoralism, arable agriculture and iron-working technology from northern to eastern Africa. The region likewise appears to have been central to the occurrence of large-scale population movements during both the Early and Later Iron Ages. However, we also emphasise the relevance of the archaeology of this period for better understanding more localised trajectories of socio-cultural change, particularly for adding time-depth to historical narratives of relevance to contemporary South Sudanese communities. / Cet article passe en revue l’état actuel des recherches archéologiques à l’intérieur des frontières de l’État actuel du Sud-Soudan, mettant un accent particulier sur la période entre 3000 av. J.-C. et 1500 après J.-C. Divers facteurs historiques, aussi bien que des troubles politiques plus récents, ont longtemps entravé les efforts archéologiques concertés dans la région. Les enquêtes qui ont néanmoins pu être réalisées sont résumées et synthétisées ici, en particulier les quatre expéditions financées par le British Institute in Eastern Africa entre 1977 et 1981. Bien que minces, les données recueillies au cours de ces projets de recherche et d’autres font ressortir une grande diversité dans les données archéologiques du Sud-Soudan, soulignant l’importance de cette région pour traiter de questions aussi vastes que la transition entre (ou la contemporanéité) des moyens de subsistance de l’âge de pierre final et de l’âge du fer ancien, y compris l’extension du pastoralisme, de l’agriculture arable et de la technologie du travail du fer du nord vers l’est de l’Afrique. La région semble aussi avoir joué un rôle central dans des mouvements de population à grande échelle pendant l’âge du fer aussi bien ancien que plus récent. Cependant, nous soulignons également l’importance de l'archéologie de cette période pour une meilleure compréhension des trajectoires plus locales de changement socioculturel, et en particulier le potentiel qui s’offre de pouvoir ajouter de la profondeur aux récits historiques pertinents pour les communautés actuelles du Sud-Soudan

Next-to-leading order electroweak corrections to gg → HH and gg → gH in the large-mt limit

We compute two-loop electroweak corrections to Higgs boson pair and Higgs plus jet production, taking into account all sectors of the Standard Model. All diagrams with virtual top quarks are computed in an expansion for large top quark mass up to order $1/m^8_t$ or more. We present analytic results for the form factors and discuss the convergence properties. For the process $gg → gH$ we also consider QCD corrections in the large-$m_t$ limit

Next-to-leading order electroweak corrections to gg→HHgg \to HH and gg→gHgg \to gH in the large-mtm_t limit

We compute two-loop electroweak corrections to Higgs boson pair and Higgs plus jet production, taking into account all sectors of the Standard Model. All diagrams with virtual top quarks are computed in an expansion for large top quark mass up to order $1/m_t^8$ or more. We present analytic results for the form factors and discuss the convergence properties. For the process $gg\to gH$ we also consider QCD corrections in the large-$m_t$ limit

Analytic approximations of 2→22\to 2 processes with massive internal particles

We consider two-loop corrections to $2\to 2$ scattering processes with massive particles in the final state and massive particles in the loop. We discuss the combination of analytic expansions in the high-energy limit and for small Mandelstam variable~$t$. For the example of double Higgs boson production we show that the whole phase space can be covered and time-consuming numerical integrations can be avoided.Comment: 25 page

Local Realism of Macroscopic Correlations

We show that for macroscopic measurements which cannot reveal full information about microscopic states of the system, the monogamy of Bell inequality violations present in quantum mechanics implies that practically all correlations between macroscopic measurements can be described by local realistic models. Our results hold for sharp measurement and arbitrary closed quantum systems.Comment: 9 pages incl. one Appendix, 2 figure

Use of very high resolution climate model data for hydrological modelling: baseline performance and future flood changes

Increasingly, data from Regional Climate Models (RCMs) are used to drive hydrological models, to investigate the potential water-related impacts of climate change, particularly for flood and droughts. Generally, some form of further downscaling of RCM data has been required, but recently the first decadal-length runs of very high resolution RCMs (with convection-permitting scales) have been performed. Here, a set of such runs for southern Britain has been used to drive a gridded hydrological model. Results using a 1.5km RCM nested in a 12km RCM driven by European-reanalysis boundary conditions show that the 1.5km RCM generally performs worse than the 12km RCM for simulating river flows in 32 example catchments. The clear spatial patterns of bias are consistent with bias patterns shown in the RCM precipitation data. Results using 1.5km and 12km RCM runs for the current climate and a potential future climate (driven by GCM boundary conditions) show clear differences in projected changes in flood peaks. The 1.5km RCM tends towards larger increases than the 12km RCM, particularly in spring and winter. If robust, this could have important consequences for adaptation planning under climate change, but further research is required, particularly given the greater biases in the baseline flow simulations driven by 1.5km RCM data, and the use of only a single short future climate projection