Existence of a tricritical point for the Blume-Capel model on Zd\mathbb{Z}^d

We prove the existence of a tricritical point for the Blume-Capel model on $\mathbb{Z}^d$ for every $d\geq 2$. The proof in $d\geq 3$ relies on a novel combinatorial mapping to an Ising model on a larger graph, the techniques of Aizenman, Duminil-Copin, and Sidoravicious (Comm. Math. Phys, 2015), and the celebrated infrared bound. In $d=2$, the proof relies on a quantitative analysis of crossing probabilities of the dilute random cluster representation of the Blume-Capel. In particular, we develop a quadrichotomy result in the spirit of Duminil-Copin and Tassion (Moscow Math. J., 2020), which allows us to obtain a fine picture of the phase diagram in $d=2$, including asymptotic behaviour of correlations in all regions. Finally, we show that the techniques used to establish subcritical sharpness for the dilute random cluster model extend to any $d\geq 2$.Comment: 55 pages. 4 figures. v2 includes fixes of typos and clarification

Multiscale coupling and the maximum of P(ϕ)2\mathcal{P}(\phi)_2 models on the torus

We establish a coupling between the $\mathcal{P}(\phi)_2$ measure and the Gaussian free field on the two-dimensional unit torus at all spatial scales, quantified by probabilistic regularity estimates on the difference field. Our result includes the well-studied $\phi^4_2$ measure. The proof uses an exact correspondence between the Polchinski renormalisation group approach, which is used to define the coupling, and the Bou\'e-Dupuis stochastic control representation for $\mathcal{P}(\phi)_2$. More precisely, we show that the difference field is obtained from a specific minimiser of the variational problem. This allows to transfer regularity estimates for the small-scales of minimisers, obtained using discrete harmonic analysis tools, to the difference field. As an application of the coupling, we prove that the maximum of the $\mathcal{P}(\phi)_2$ field on the discretised torus with mesh-size $\epsilon > 0$ converges in distribution to a randomly shifted Gumbel distribution as $\epsilon \rightarrow 0$.Comment: 45 page

Quasi-invariant Gaussian measures for the nonlinear wave equation in three dimensions

We prove quasi-invariance of Gaussian measures supported on Sobolev spaces under the dynamics of the three-dimensional defocusing cubic nonlinear wave equation. As in the previous work on the two-dimensional case, we employ a simultaneous renormalization on the energy functional and its time derivative. Two new ingredients in the three-dimensional case are (i) the construction of the weighted Gaussian measures, based on a variational formula for the partition function inspired by Barashkov and Gubinelli (2018), and (ii) an improved argument in controlling the growth of the truncated weighted Gaussian measures, where we combine a deterministic growth bound of solutions with stochastic estimates on random distributions.Comment: 35 pages. We now prove the full quasi-invariance resul

Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands

Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure–activity relationships of the series are not obviously related to the quadruplex binding

A naphthalene diimide G-quadruplex ligand inhibits cell growth and down-regulates BCL-2 expression in an imatinib-resistant gastrointestinal cancer cell line

Gastro-intestinal tumours (GISTs) are driven by aberrant expression of the c-KIT oncoprotein. They can be effectively treated by the kinase inhibitor imatinib, which locks the c-KIT kinase domain into an inactive conformation. However resistance to imatinib, driven by active-site mutations, is a recurrent clinical challenge, which has been only partly met by the subsequent development of second and third-generation c-KIT inhibitors. It is reported here that a tetra-substituted naphthalene diimide derivative, which is a micromolar inhibitor of cell growth in a wild-type patient-derived GIST cell line, has a sub-micromolar activity in two distinct patient-derived imatinib-resistant cell lines. The compound has been previously shown to down-regulate expression of the c-KIT protein in a wild-type GIST cell line. It does not affect c-KIT protein expression in a resistant cell line to the same extent, whereas it profoundly down-regulates the expression of the anti-apoptopic protein BCL-2. It is proposed that the mechanism of action involves targeting quadruplex nucleic acid structures, and in particular those in the BCL-2 gene and its RNA transcript. The BCL-2 protein is up-regulated in the GIST-resistant cell line, and is strongly down-regulated after treatment. The compound strongly stabilises a range of G-quadruplexes including a DNA one from the BCL-2 promoter and an RNA quadruplex from its 5′-UTR region. A reporter assay construct incorporating the 5′-UTR quadruplex sequence demonstrates down-regulation of BCL-2 expression

Learning To Be Affected: Social suffering and total pain at life’s borders.

The practice of Live Sociology in situations of pain and suffering is the author’s focus. An outline of the challenges of understanding pain is followed by a discussion of Bourdieu’s ‘social suffering’ (1999) and the palliative care philosophy of ‘total pain’. Using examples from qualitative research on disadvantaged dying migrants in the UK, attention is given to the methods that are improvised by dying people and care practitioners in attempts to bridge intersubjective divides, where the causes and routes of pain can be ontologically and temporally indeterminate and/or withdrawn. The paper contends that these latter phenomena are the incitement for the inventive bridging and performative work of care and Live Sociological methods, both of which are concerned with opposing suffering. Drawing from the ontology of total pain, I highlight the importance of (i) an engagement with a range of materials out of which attempts at intersubjective bridging can be produced, and which exceed the social, the material, and the temporally linear; and (ii) an empirical sensibility that is hospitable to the inaccessible and non-relational

Lung involvement at presentation predicts disease activity and permanent organ damage at 6, 12 and 24 months follow - up in ANCA - associated vasculitis.

BACKGROUND: Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. RESULTS: 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p \u3c 0.0001, rs = 0.5871). No differences between BVAS and VDI scores were seen for both groups, however in the lung-involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p = 0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p = 0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p = 0.027, p = 0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p \u3c 0.001). CONCLUSION: AAV subjects with lung involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy

Acute ischaemic stroke in Listeria monocytogenes meningoencephalitis.

Listeria monocytogenes is the third most frequent cause of bacterial meningitis and has a predilection for elderly patients and the immunosuppressed. A small number of patients with Listeria monocytogenes meningoencephalitis have previously been reported to experience stroke-like symptoms that were attributed to microabscess formation and the mass effect of collections of infection in the brain. These infections led to temporary neurological deficits that resolved with antimicrobial treatment, rather than to true strokes with permanent neurological deficits. This report discusses the case of an 80- year-old male, who was immunosuppressed with mesalazine for the treatment of Crohn's disease, and who went on to develop Listeria monocytogenes meningoencephalitis. 1 week into his admission, for antibiotic therapy, the patient began to experience new onset right upper limb weakness, nystagmus and past pointing. These symptoms were initially thought to be a complication of the infection. However, subsequent diffusion-weighted MRI revealed that the patient had more likely suffered an acute ischaemic event and a contrast-enhanced MRI performed later could not detect any abscess or large infective focus in a region that could explain the symptoms. This case report highlights the fact that ischaemic and infective pathologists may coexist in immunosuppressed Listeria patients and that clinical signs and symptoms should guide the use of appropriate imaging modalities such as MRI to clarify differentials so that ischaemia is not mistaken for the more common stroke mimic caused by infection in these patients