Bi-η\eta and bi-λ\lambda deformations of Z4\mathbb{Z}_4 permutation supercosets

Integrable string sigma models on AdS$_3$ backgrounds with 16 supersymmetries have the distinguishing feature that their superisometry group is a direct product. As a result the deformation theory of these models is particularly rich since the two supergroups in the product can be deformed independently. We construct bi-$\eta$ and bi-$\lambda$ deformations of two classes of $\mathbb{Z}_4$ permutation supercoset sigma models, which describe sectors of the Green-Schwarz and pure-spinor string worldsheet theories on type II AdS$_3$ backgrounds with pure R-R flux. We discuss an important limit of these models when one supergroup is undeformed. The associated deformed supergravity background should preserve 8 supersymmetries and is expected to have better properties than the full bi-deformation. As a step towards investigating the quantum properties of these models, we study the two-loop RG flow of the bosonic truncation of the bi-$\lambda$ deformation.Comment: 35 pages, published versio

Sigma models with local couplings: a new integrability-RG flow connection

We consider several classes of σ-models (on groups and symmetric spaces, η-models, ⋋-models) with local couplings that may depend on the 2d coordinates, e.g. on time τ . We observe that (i) starting with a classically integrable 2d σ-model, (ii) formally promoting its couplings hα to functions hα(τ ) of 2d time, and (iii) demanding that the resulting time-dependent model also admits a Lax connection implies that hα(τ ) must solve the 1-loop RG equations of the original theory with τ interpreted as RG time. This provides a novel example of an ‘integrability-RG flow’ connection. The existence of a Lax connection suggests that these time-dependent σ-models may themselves be understood as integrable. We investigate this question by studying the possibility of constructing non-local and local conserved charges. Such σ-models with D-dimensional target space and time-dependent couplings subject to the RG flow naturally appear in string theory upon fixing the light-cone gauge in a (D + 2)-dimensional conformal σ-model with a metric admitting a covariantly constant null Killing vector and a dilaton linear in the null coordinate

SN2010jp (PTF10aaxi): A Jet-Driven Type II Supernova

We present photometry and spectroscopy of the peculiar TypeII supernova (SN) 2010jp, also named PTF10aaxi. The light curve exhibits a linear decline with a relatively low peak absolute magnitude of only -15.9, and a low radioactive decay luminosity at late times that suggests a nickel mass below 0.003 $M_{\odot}$. Spectra of SN2010jp display an unprecedented triple-peaked H$\alpha$ line profile, showing: (1) a narrow (800 km/s) central component that suggests shock interaction with dense CSM; (2) high-velocity blue and red emission features centered at -12600 and +15400 km/s; and (3) broad wings extending from -22000 to +25000 km/s. These features persist during 100 days after explosion. We propose that this line profile indicates a bipolar jet-driven explosion, with the central component produced by normal SN ejecta and CSM interaction at mid latitudes, while the high-velocity bumps and broad line wings arise in a nonrelativistic bipolar jet. Two variations of the jet interpretation seem plausible: (1) A fast jet mixes 56Ni to high velocities in polar zones of the H-rich envelope, or (2) the reverse shock in the jet produces blue and red bumps in Balmer lines when a jet interacts with dense CSM. Jet-driven SNeII are predicted for collapsars resulting from a wide range of initial masses above 25 $M_{\odot}$ at sub-solar metallicity. This seems consistent with the SN host environment, which is either an extremely low-luminosity dwarf galaxy or very remote parts of an interacting pair of star-forming galaxies. It also seems consistent with the low 56Ni mass that may accompany black hole formation. We speculate that the jet survives to produce observable signatures because the star's H envelope was mostly stripped away by previous eruptive mass loss.Comment: 11 pages, 9 figures, submitted to MNRA

Truly reconciled? A dyadic analysis of post-conflict social reintegration in Northern Uganda

In the aftermath of civil war or violent internal conflict, one of the key peacebuilding challenges is the reconciliation of former enemies who are members of the same small-scale societies. A failure of social reintegration may contribute to what is known as a conflict trap. To detect lingering hostile attitudes among a community’s various factions is crucial, but the approaches adopted in previous studies tend to focus on the impact of conflict on one or other aggregated indicator of social cohesion rather than on how violence-affected individuals regard and act towards their fellow community members. Here we demonstrate the value of concentrating on this latter dyadic component of social interactions and we use behavioural experiments and a social tie survey to assess, in an appropriately disaggregated manner, social cohesion in a post-conflict setting in northern Uganda. Whereas in self-reported surveys, ex-combatants appear to be well-connected, active members of their communities, the experiments unveil the continued reluctance of other community members to share or cooperate with them; fewer resources are committed to ex-combatants than to others, which is statistically significant. The dyadic nature of our analysis allows us to detect which groups are more prone to discriminate against ex-combatants, which may help facilitate targeted interventions

RAMPART : a model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting

AstraZeneca LP have provided an educational grant for the trial and free of charge durvalumab and tremelimumab. A small grant is also provided by Kidney Cancer UK. MRC CTU at UCL provides funding for staff working on the trial.The development of therapeutics in oncology is a highly active research area for the pharmaceutical and biotechnology industries, but also has a strong academic base. Many new agents have been developed in recent years, most with specific biological targets. This has mandated the need to look at different ways to streamline the evaluation of new agents. One solution has been the development of adaptive trial designs that allow the evaluation of multiple agents, concentrating on the most promising agents while screening out those which are unlikely to benefit patients. Another way forward has been the growth of partnerships between academia and industry with the shared goal of designing and conducting high quality clinical trials which answer important clinical questions as efficiently as possible. The RAMPART trial (NCT03288532) brings together both of these processes in an attempt to improve outcomes for patients with locally advanced renal cell carcinoma (RCC), where no globally acceptable adjuvant strategy after nephrectomy currently exist. RAMPART is led by the MRC CTU at University College London (UCL), in collaboration with other international academic groups and industry. We aim to facilitate the use of data from RAMPART, (dependent on outcomes), for a future regulatory submission that will extend the license of the agents being investigated. We share our experience in order to lay the foundations for an effective trial design and conduct framework and to guide others who may be considering similar collaborations.Publisher PDFPeer reviewe

RAMPART : a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

AstraZeneca LP have provided an educational grant for the trial and free of charge durvalumab and tremelimumab. A small grant is also provided by Kidney Cancer UK. MRC CTU at UCL also provides funding for staff working on the trial. The TransRAMPART sample collection is being funded by a Prospective Sample Collection award from Cancer Research UK.Background 20–60% of patients with initially locally advanced Renal Cell Carcinoma (RCC) develop metastatic disease despite optimal surgical excision. Adjuvant strategies have been tested in RCC including cytokines, radiotherapy, hormones and oral tyrosine-kinase inhibitors (TKIs), with limited success. The predominant global standard-of-care after nephrectomy remains active monitoring. Immune checkpoint inhibitors (ICIs) are effective in the treatment of metastatic RCC; RAMPART will investigate these agents in the adjuvant setting. Methods/design RAMPART is an international, UK-led trial investigating the addition of ICIs after nephrectomy in patients with resected locally advanced RCC. RAMPART is a multi-arm multi-stage (MAMS) platform trial, upon which additional research questions may be addressed over time. The target population is patients with histologically proven resected locally advanced RCC (clear cell and non-clear cell histological subtypes), with no residual macroscopic disease, who are at high or intermediate risk of relapse (Leibovich score 3–11). Patients with fully resected synchronous ipsilateral adrenal metastases are included. Participants are randomly assigned (3,2:2) to Arm A - active monitoring (no placebo) for one year, Arm B - durvalumab (PD-L1 inhibitor) 4-weekly for one year; or Arm C - combination therapy with durvalumab 4-weekly for one year plus two doses of tremelimumab (CTLA-4 inhibitor) at day 1 of the first two 4-weekly cycles. The co-primary outcomes are disease-free-survival (DFS) and overall survival (OS). Secondary outcomes include safety, metastasis-free survival, RCC specific survival, quality of life, and patient and clinician preferences. Tumour tissue, plasma and urine are collected for molecular analysis (TransRAMPART).Publisher PDFPeer reviewe

MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model

Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine—lesioned Parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD

Bi-η and bi-λ deformations of ℤ4 permutation supercosets

Integrable string sigma models on AdS3 backgrounds with 16 supersymmetries have the distinguishing feature that their superisometry group is a direct product. As a result the deformation theory of these models is particularly rich since the two supergroups in the product can be deformed independently. We construct bi-η and bi-λ deformations of two classes of ℤ4 permutation supercoset sigma models, which describe sectors of the Green-Schwarz and pure-spinor string worldsheet theories on type II AdS3 backgrounds with pure R-R flux. We discuss an important limit of these models when one supergroup is undeformed. The associated deformed supergravity background should preserve 8 supersymmetries and is expected to have better properties than the full bi-deformation. As a step towards investigating the quantum properties of these models, we study the two-loop RG flow of the bosonic truncation of the bi-λ deformation