Non-Abelian symmetries and disorder: a broad non-ergodic regime and anomalous thermalization

Symmetries play a central role in single-particle localization. Recent research focused on many-body localized (MBL) systems, characterized by new kind of integrability, and by the area-law entanglement of eigenstates. We investigate the effect of a non-Abelian $SU(2)$ symmetry on the dynamical properties of a disordered Heisenberg chain. While $SU(2)$ symmetry is inconsistent with the conventional MBL, a new non-ergodic regime is possible. In this regime, the eigenstates exhibit faster than area-law, but still a strongly sub-thermal scaling of entanglement entropy. Using exact diagonalization, we establish that this non-ergodic regime is indeed realized in the strongly disordered Heisenberg chains. We use real-space renormalization group (RSRG) to construct approximate excited eigenstates, and show their accuracy for systems of size up to $L=26$. As disorder strength is decreased, a crossover to the thermalizing phase occurs. To establish the ultimate fate of the non-ergodic regime in the thermodynamic limit, we develop a novel approach for describing many-body processes that are usually neglected by RSRG, accessing systems of size $L>2000$. We characterize the resonances that arise due to such processes, finding that they involve an ever growing number of spins as the system size is increased. The probability of finding resonances grows with the system size. Even at strong disorder, we can identify a large lengthscale beyond which resonances proliferate. Presumably, this eventually would drive the system to a thermalizing phase. However, the extremely long thermalization time scales indicate that a broad non-ergodic regime will be observable experimentally. Our study demonstrates that symmetries control dynamical properties of disordered, many-body systems. The approach introduced here provides a versatile tool for describing a broad range of disordered many-body systems.Comment: 25 pages, 21 figure

Direct measurement of DNA-mediated adhesion between lipid bilayers

Multivalent interactions between deformable mesoscopic units are ubiquitous in biology, where membrane macromolecules mediate the interactions between neighbouring living cells and between cells and solid substrates. Lately, analogous artificial materials have been synthesised by functionalising the outer surface of compliant Brownian units, for example emulsion droplets and lipid vesicles, with selective linkers, in particular short DNA sequences. This development extended the range of applicability of DNA as a selective glue, originally applied to solid nano and colloidal particles. On very deformable lipid vesicles, the coupling between statistical effects of multivalent interactions and mechanical deformation of the membranes gives rise to complex emergent behaviours, as we recently contributed to demonstrate [Parolini et al., Nature Communications, 2015, 6, 5948]. Several aspects of the complex phenomenology observed in these systems still lack a quantitative experimental characterisation and fundamental understanding. Here we focus on the DNA-mediated multivalent interactions of a single liposome adhering to a flat supported bilayer. This simplified geometry enables the estimate of the membrane tension induced by the DNA-mediated adhesive forces acting on the liposome. Our experimental investigation is completed by morphological measurements and the characterisation of the DNA-melting transition, probed by in-situ F\"{o}rster Resonant Energy Transfer spectroscopy. Experimental results are compared with the predictions of an analytical theory that couples the deformation of the vesicle to a full description of the statistical mechanics of mobile linkers. With at most one fitting parameter, our theory is capable of semi-quantitatively matching experimental data, confirming the quality of the underlying assumptions.Comment: 16 pages, 7 figure

Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein

Background: In left ventricular assist device (LVAD) recipients, plasma levels of interleukin (IL)-6 are associated with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, reflecting postoperative risk. However, it is not clear how the cardiac. Conclusions: Cardiac IL-6 levels do not contribute to improve risk profile of LVAD recipients in relation to clinical inpatient post-implantation. Instead, plasma IL-6 and serum CRP concentrations are more effective in predicting the severity of the clinical course in the early phase of LVAD therapy. level of IL-6, detectable on the tissue samples at the time of implantation, can contribute to predict the post-operative outcome

Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients

BACKGROUND: Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients. METHOD: Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay. RESULTS: Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels. CONCLUSIONS: The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile

CALCIUM HANDLING IN MYOGENIC PROGENITORS AND SKELETAL MYOBLASTS: THE ROLE OF CD20

The calcium ion plays an essential role in the physiology of all living cells. Accordingly, multiple mechanisms contribute to the precise control of its intracellular concentration ([Ca2+]i). Particularly in skeletal muscle, the efficient regulation of cytosolic Ca2+ is crucial for tissue functionality and impairment of Ca2+ homeostasis has been shown to contribute to the etiology of muscular disorders such as Duchenne muscular dystrophy (DMD). Although the impairment of Ca2+ homeostasis affecting dystrophic muscular cells has been extensively reported, the pathways involved in calcium-release and the role of store-operated Ca2+ channels in dystrophic myogenic progenitors were not investigated before. Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation of CD133+ cells displaying myogenic properties. Interestingly, expression of the B-cell marker CD20 was observed in blood-derived CD133+ stem cells. Among the scarce available data about the biological role of the membrane protein CD20, there are some evidences of its involvement in the regulation of intracellular calcium concentration ([Ca2+]i). Here, we show that a CD20-related pathway leading to an increase of cytosolic calcium is differently activated in normal and dystrophic blood-derived CD133+ stem cells, supporting the assumption of a CD20-related calcium impairment affecting dystrophic cells. Although CD20 can modulate cytosolic calcium through a specific signaling pathway, other studies demonstrated its association with lipid raft domains of the plasma membrane, where it probably functions directly as a store-operated Ca2+ channel. Recent works indicated that store-operated Ca2+ entry (SOCE) plays a central role in skeletal muscle physiology and development, but there remain a number of unresolved issues relating to SOCE modulation in this tissue. That being so, and considering that blood and muscle share common mesodermic origins, we were prompted to investigate whether CD20 contributes to calcium handling in committed muscular cells. Expression of CD20 was observed in skeletal muscle, displaying a membrane localization in myoblasts and adult muscle fibers. Additionally, we showed that inhibition of CD20 resulted in specific impairment of SOCE in C2C12 myoblasts. Together, reported findings contributed to identify deregulated pathways affecting dystrophic stem cells and potentially involved in DMD pathology. Moreover, our results suggested that functional CD20 is required for SOCE to consistently occur in C2C12 myoblasts, providing a novel insight to improve the understanding of store-operated Ca2+ entry regulation in skeletal muscle

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Distributed Rendering for Video Games via Object Streaming

Propelled by the growing availability of broadband connection in recent years, the gaming industry is now devoting a considerable amount of resources and investments in online and cloud gaming. In legacy online gaming, the gaming experience is usually provided with the support of remote servers, and online players rely on their local PCs or consoles, which hold a local copy of all the content (assets) and must follow some minimum requirements in hardware and software specifications. Whereas, on cloud gaming, intensive computational tasks are almost completely offloaded to dedicated servers: video frames are rendered on the remote machine, encoded and sent to the players as a video stream. This approach soften the need for updated and powerful devices, but it suffers from all the limitations and problems inherent to multimedia real-time streaming. In this paper we explore an hybrid approach between a (video) streaming-based cloud gaming and the traditional approach where all assets are local to the player. We propose a solution where the rendering pipeline is split between server and client. In this distributed architecture, the server manages most of the game scene description, runs the game simulation, performs the first segment of the graphics pipeline’s application stage, and finally sends a stream of pre-processed graphical objects to the client, which performs the final rendering steps. The proposed approach reduces the computational burden on the server, which is not required to perform rendering, improving scalability when compared with cloud gaming solutions based on video streaming