A percolation transition in Yang-Mills matter at finite number of colours

We examine baryonic matter at quark chemical potential of the order of the confinement scale, \mu_q\sim \lqcd. In this regime, quarks are supposed to be confined but baryons are close to the ``tightly packed limit'' where they nearly overlap in configuration space. We show that this system will exhibit a percolation phase transition {\em when varied in the number of colours} $N_c$: at high $N_c$, large distance correlations at quark level are possible even if the quarks are essentially confined. At low $N_c$, this does not happen. We discuss the relevance of this for dense nuclear matter, and argue that our results suggest a new ``phase transition'', varying $N_c$ at constant $\mu_q$.Comment: Accepted for publication, Physical Review Letters. Title changed from original, "Quarkyonic percolation at finite number of colors", at the request of the edito

Integrable structures in LGTs near the deconfinement transition

In this contribution we review some recent results about the emergence of 2D integrable systems in 3D Lattice Gauge Theories near the deconfinement transition. We focus on some concrete examples involving the flux tube thickness, the ratio of k-string tensions and Polyakov loops correlators in various models.Comment: 8 pages, Poster contribution to the XXVII International Symposium on Lattice Field Theory, July 26-31, 2009, Peking University, Beijing, Chin

Critical domain walls in the Ashkin-Teller model

We study the fractal properties of interfaces in the 2d Ashkin-Teller model. The fractal dimension of the symmetric interfaces is calculated along the critical line of the model in the interval between the Ising and the four-states Potts models. Using Schramm's formula for crossing probabilities we show that such interfaces can not be related to the simple SLE$_\kappa$, except for the Ising point. The same calculation on non-symmetric interfaces is performed at the four-states Potts model: the fractal dimension is compatible with the result coming from Schramm's formula, and we expect a simple SLE$_\kappa$ in this case.Comment: Final version published in JSTAT. 13 pages, 5 figures. Substantial changes in the data production, analysis and in the conclusions. Added a section about the crossing probability. Typeset with 'iopart

Zika virus induces FOXG1 nuclear displacement and downregulation in human neural progenitors

Congenital alterations in the levels of the transcription factor Forkhead box g1 (FOXG1) coding gene trigger "FOXG1 syndrome," a spectrum that recapitulates birth defects found in the "congenital Zika syndrome," such as microcephaly and other neurodevelopmental conditions. Here, we report that Zika virus (ZIKV) infection alters FOXG1 nuclear localization and causes its downregulation, thus impairing expression of genes involved in cell replication and apoptosis in several cell models, including human neural progenitor cells. Growth factors, such as EGF and FGF2, and Thr271 residue located in FOXG1 AKT domain, take part in the nuclear displacement and apoptosis protection, respectively. Finally, by progressive deletion of FOXG1 sequence, we identify the C-terminus and the residues 428-481 as critical domains. Collectively, our data suggest a causal mechanism by which ZIKV affects FOXG1, its target genes, cell cycle progression, and survival of human neural progenitors, thus contributing to microcephaly

Onset Transition to Cold Nuclear Matter from Lattice QCD with Heavy Quarks

Lattice QCD at finite density suffers from a severe sign problem, which has so far prohibited simulations of the cold and dense regime. Here we study the onset of nuclear matter employing a three-dimensional effective theory derived by combined strong coupling and hopping expansions, which is valid for heavy but dynamical quarks and has a mild sign problem only. Its numerical evaluations agree between a standard Metropolis and complex Langevin algorithm, where the latter is free of the sign problem. Our continuum extrapolated data clearly show a first order phase transition building up at $\mu_B \approx m_B$ as the temperature approaches zero. An excellent description of the data is achieved by an analytic solution in the strong coupling limit.Comment: Four pages, three figures; uses REVTeX-4. Version accepted by PRL. Title changed upon request by the Editor

The hERG1 potassium channel behaves as prognostic factor in gastric dysplasia endoscopic samples

Purpose: Gastric cancer (GC) is still a relevant health issue worldwide. The identification of prognostic factors for progression of gastric dysplasia (GD), the main pre-cancerous lesion of the intestinal-type GC, is hence mandatory.Patients and methods: A cohort of 83 GD endoscopic samples belonging to Italian subjects was collected. hERG1 expression was evaluated by immunohistochemistry and scored 0-3, depending on the percentage of stained cells. Expression data were analysed in conjunction with clinico-pathological and survival data.Results: hERG1 turned out to be expressed in 67.47% (56 out of 83) of the GD samples. hERG1 expression was higher in high-grade GD compared to low-grade GD (29 out of 39, 74.36% vs 27 out of 44, 61.36%), although the statistical significance was not reached (P=0.246). No association emerged between hERG1 expression and clinical features of the patients (age, gender, localization, H. pylori infection, gastritis and intestinal metaplasia). In a subset of cases for which sequential samples of gastric lesions (from GD to Early Gastric Cancer and Advanced Gastric Cancer) were available, hERG1 expression was maintained in all the steps of gastric carcinogenesis from GD onwards. A general trend to increased expression in advanced lesions was observed. hERG1 score had a statistically significant impact on both Progression-Free Survival (P=0.018) and Overall Survival (P=0.031). In particular, patients displaying a high hERG1 score have a shorter survival.Conclusion: hERG1 is aberrantly expressed in human GD samples and has an impact on both PFS and OS, hence representing a novel prognostic marker for progression of GD towards GC of the intestinal histotype. Once properly validated, hERG1 detection could be included in the clinical practice, during endoscopic surveillance protocols, for the management of GD at higher risk of progression, as already proposed for Barrett's oesophagus

po 317 a novel bispecific antibody to harness the herg1 β1 macromolecular complex for cancer therapy

Introduction Among hindrances in cancer treatment, the lack of appropriate markers to be exploited for targeted therapy, and the need of new potential drugs are two big challenges.hERG1 potassium channels area novel class of oncological targets and one of the most intriguing aspects of their involvement in tumour establishment and progression is the interaction with adhesion molecules, such as integrins. It has been recently demonstrated that macromolecular complexes formed between hERG1 and β1 integrins selectively occurs in many types of cancer (Becchetti A et al., 2017). In this scenario, hERG1 could be exploited as a therapeutic target providing non cardiotoxic strategies aimed at blocking hERG1. Material and methods A scDb, a bifunctional single-chain diabody, directed against hERG1/β1 complex, was developed via SOE-PCR methodology. Such antibody was tested on HCT116 cells in lateral motility and western blotting experiments. Moreover immunohistochemistry (IHC) was performed on metastatic colorectal cancer (mCRC) paraffin embedded samples using the scDb, an anti-hERG1 and an anti-b1 integrin. Results and discussions Performing IHC on sequential sections of mCRC confirmed the specificity of the scDb for both hERG1 and b1 integrin. In vitro data provide evidences that the administering of the bispecific antibody has an impact on lateral motility. Moreover, signalling pathways are also affected by the antibody treatment, as AKT phosphorylation and HIF1α levels are decreased when the molecule is administered.Such findings might suggest a possible effect of the bispecific antibody on the VEGF-A signalling pathway, which are consistent with our previous hypothesis (Becchetti A et al., 2017) of a possible cross-talk leading to a deep impact on VEGF expression and, thus, on neoangiogenesis. Conclusion scDb-hERG1/β1 could be used as a potential new treatment for cancer patients and as an early molecular diagnostic marker. In fact, the selective expression of hERG1/β1 complex in cancer cells and its role in angiogenesis and cancer progression suggests that a molecule selectively targeting the complex will be an invaluable tool for cancer treatment

Centre symmetric 3d effective actions for thermal SU(N) Yang-Mills from strong coupling series

We derive three-dimensional, Z(N)-symmetric effective actions in terms of Polyakov loops by means of strong coupling expansions, starting from thermal SU(N) Yang-Mills theory in four dimensions on the lattice. An earlier action in the literature, corresponding to the (spatial) strong coupling limit, is thus extended by several higher orders, as well as by additional interaction terms. We provide analytic mappings between the couplings of the effective theory and the parameters $N_\tau,\beta$ of the original thermal lattice theory, which can be systematically improved. We then investigate the deconfinement transition for the cases SU(2) and SU(3) by means of Monte Carlo simulations of the effective theory. Our effective models correctly reproduce second order 3d Ising and first order phase transitions, respectively. Furthermore, we calculate the critical couplings $\beta_c(N_\tau)$ and find agreement with results from simulations of the 4d theory at the few percent level for $N_\tau=4-16$.Comment: 27 pages, 21 figures; final version published in JHEP; attached the corresponding Erratum (ref. JHEP 1107:014,2011, DOI 10.1007/JHEP07(2011)014) for ease of consultatio

Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells.

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence

Evaluation of intracellular signalling pathways in response to insulin-like growth factor I in apoptotic-resistant activated human hepatic stellate cells

BACKGROUND: Human hepatic stellate cells have been shown to be resistant to apoptotic stimuli. This is likely dependent on the activation of anti-apoptotic pathways upon transition of these cells to myofibroblast-like cells. In particular, previous studies have demonstrated an increased expression of the anti-apoptotic protein Bcl-2 and a decreased expression of the pro-apoptotic protein Bax during the transition of the hepatic stellate cell phenotype from quiescent to myofibroblast-like cells. However, the role and expression of other key anti-apoptotic and survival pathways elicited by polypeptide growth factors involved in the chronic wound healing process remain to be elucidated. In particular, insulin growth factor-I promotes chemotactic and mitogenic effects in activated human hepatic stellate cells and these effects are mediated by the activation of PI 3-K. The role of insulin growth factor-I as a survival factor in human hepatic stellate cells needs to be substantiated. The aim of this study was to evaluate the involvement of other key anti-apoptotic pathways such as PI-3K/Akt/p-Bad in response to insulin growth factor-I. RESULTS: Insulin growth factor-I induced activation of Akt followed by Bad phosphorylation after 15 minutes of incubation. These effects were PI-3k dependent since selective inhibitors of this molecule, wortmannin and LY294002, inhibited both Akt and Bad phosphorylation. The effect of insulin growth factor-I on the activation of two downstream targets of Akt activation, that is, GSK3 and FHKR, both implicated in the promotion of cell survival was also investigated. Both targets became phosphorylated after 15 minutes of incubation, and these effects were also PI-3K-dependent. Despite the activation of this survival pathway insulin growth factor-I did not have a remarkable biological effect, probably because other insulin growth factor-I-independent survival pathways were already maximally activated in the process of hepatic stellate cell activation. However, after incubation of the cells with a strong apoptotic stimuli such as Fas ligand+cycloheximide, a small percentage of hepatic stellate cells underwent programmed cell death that was partially rescued by insulin growth factor-I. CONCLUSION: In addition to Bcl-2, several other anti-apoptotic pathways are responsible for human hepatic stellate cell resistance to apoptosis. These features are relevant for the progression and limited reversibility of liver fibrosis in humans