Competing interactions in two dimensional Coulomb systems: Surface charge heterogeneities in co-assembled cationic-anionic incompatible mixtures

A binary mixture of oppositely charged components confined to a plane such as cationic and anionic lipid bilayers may exhibit local segregation. The relative strength of the net short range interactions, which favors macroscopic segregation, and the long range electrostatic interactions, which favors mixing, determines the length scale of the finite size or microphase segregation. The free energy of the system can be examined analytically in two separate regimes, when considering small density fluctuations at high temperatures, and when considering the periodic ordering of the system at low temperatures (F. J. Solis and M. Olvera de la Cruz, J. Chem. Phys. 122, 054905 (2000)). A simple Molecular Dynamics simulation of oppositely charged monomers, interacting with a short range Lennard Jones potential and confined to a two dimensional plane, is examined at different strengths of short and long range interactions. The system exhibits well-defined domains that can be characterized by their periodic length-scale as well as the orientational ordering of their interfaces. By adding salt, the ordering of the domains disappears and the mixture macroscopically phase segregates in agreement with analytical predictions.Comment: 8 pages, 5 figures, accepted for publication in J. Chem. Phys, Figure 1 include

Spontaneous chirality via long-range electrostatic forces

We consider a model for periodic patterns of charges constrained over a cylindrical surface. In particular we focus on patterns of chiral helices, achiral rings or vertical lamellae, with the constraint of global electroneutrality. We study the dependence of the patterns' size and pitch angle on the radius of the cylinder and salt concentration. We obtain a phase diagram by using numerical and analytic techniques. For pure Coulomb interactions, we find a ring phase for small radii and a chiral helical phase for large radii. At a critical salt concentration, the characteristic domain size diverges, resulting in macroscopic phase segregation of the components and restoring chiral symmetry. We discuss possible consequences and generalizations of our model.Comment: Revtex, 4 pages, 4 figure

Charged Particles on Surfaces: Coexistence of Dilute Phases and Periodic Structures on Membranes

We consider a mixture of one neutral and two oppositely charged types of molecules confined to a surface. Using analytical techniques and molecular dynamics simulations, we construct the phase diagram of the system and exhibit the coexistence between a patterned solid phase and a charge-dilute phase. The patterns in the solid phase arise from competition between short-range immiscibility and long-range electrostatic attractions between the charged species. The coexistence between phases leads to observations of stable patterned domains immersed in a neutral matrix background.Comment: 5 pages, 3 figure

Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation

Dysregulation of the cell cycle is a hallmark of cancer that leads to aberrant cellular proliferation. CDK4/6 are cyclin-dependent kinases activated in response to proliferative signaling, which induce RB hyper-phosphorylation and hence activation of E2F transcription factors, thus promoting cell cycle progression through the S phase. Pharmacologic inhibition of CDK4/6 by palbociclib, ribociclib, or abemaciclib has been showing promising activity in multiple cancers with the best results achieved in combination with other agents. Indeed, CDK4/6 inhibitors are currently approved in combination with endocrine therapy for the treatment of estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer. Moreover, a number of clinical trials are currently underway to test the efficacy of combining CDK4/6 inhibitors with different drugs not only in breast but also in other types of cancer. Beyond the inhibition of cell proliferation, CDK4/6 inhibitors have recently revealed new effects on cancer cells and on tumor microenvironment. In particular, it has been reported that these agents induce a senescent-like phenotype, impact on cell metabolism and exert both immunomodulatory and immunogenic effects. Here we describe recent data on the anti-tumor effects of CDK4/6 inhibitors as single agents or in combined therapies, focusing in particular on their metabolic and immunomodulatory activities

Formation and nucleolytic processing of Cas9-induced DNA breaks in human cells quantified by droplet digital PCR

Cas9 endonuclease from S. pyogenes is widely used to induce controlled double strand breaks (DSB) at desired genomic loci for gene editing. Here, we describe a droplet digital PCR (ddPCR) method to precisely quantify the kinetic of formation and 5\u2032-end nucleolytic processing of Cas9-induced DSB in different human cells lines. Notably, DSB processing is a finely regulated process, which dictates the choice between non-homologous end joining (NHEJ) and homology directed repair (HDR). This step of DSB repair is also a relevant point to be taken into consideration to improve Cas9-mediated technology. Indeed, by this protocol, we show that processing of Cas9-induced DSB is impaired by CTIP or BRCA1 depletion, while it is accelerated after down-regulation of DNAPKcs and 53BP1, two DSB repair key factors. In conclusion, the method we describe here can be used to study DSB repair mechanisms, with direct utility for molecularly optimising the knock-out/in outcomes in genome manipulation

Thesaurus: un database per il patrimonio culturale sommerso

Thesaurus Project aims at promoting the knowledge of the underwater cultural heritage, ancient and modern, through the application of several typologies of tools: underwater autonomous vehicles, which will be able to explore the sea bottom in teams communicating with each other; a database, which will be useful to store and manage all the information referring to archaeological or historical objects, shipwrecks and sites. This paper aims to explain the logic structure of the database indicating the particular needs of the research, the different typologies of items which have to be managed (archaeological and historical objects; ancient, medieval or modern shipwrecks; underwater sites; written or figurative sources, etc.), the relation with other similar databases and projects. The main task of this part of Thesaurus is to plan and organize an IT system, which will allow archaeologists to describe information in detail, in order to make an efficient managing and retrieving data system available

Assessment of the influence of electric arc furnace slag as a non-conventional filler for Nitrile Butadiene Rubber

Reinforcement of polymers by the addition of particles filler is a complex phenomenon that depends mainly on the hydrodynamic effect and a complex interplay between polymer, filler, and interfacial region. Mineral fillers are usually adopted as low-cost extenders due to their lower cost. In this study, the influence of a waste material such as electric arc furnace steel slag is assessed as filler for Nitrile-Butadiene Rubber following experimental procedures and analytical calculations adopted for traditional fillers. It was found that the slag content affects the static and the dynamic properties by increasing the material's capability to storage and dissipate energy. In addition to an important contribution of the hydrodynamic effect, the presence of an increasing immobilized rubber fraction around the slag particles (quantified by a differential scanning calorimetry analysis) plays a central role. The slag stiffens the NBR composite; the increase of static tensile and dynamic shear storage moduli was found to be consistent with the Halpin-Tsai and Guth-Gold prevision models respectively. Moreover, the non-linear dynamic behavior was found to be well-fitted by the Kraus equation models. The reinforcing ability of the slag particles as filler was confirmed by the negative slope of the Kraus plot on swelling data

The Response Regulator YycF Inhibits Expression of the Fatty Acid Biosynthesis Repressor FabT in Streptococcus pneumoniae

The YycFG (also known as WalRK, VicRK, MicAB, or TCS02) two-component system (TCS) is highly conserved among Gram-positive bacteria with a low G+C content. In Streptococcus pneumoniae the YycF response regulator has been reported to be essential due to its control of pcsB gene expression. Previously we showed that overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes involved in cell wall metabolism and fatty acid biosynthesis, giving rise to anomalous cell division and increased chain length of membrane fatty acids. Here, we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a TIGR4 mutant depleted of YycG, and analyzed their effects on expression of proteins involved in fatty acid biosynthesis during activation of the TCS. We demonstrate that transcription of the fab genes and levels of their products were only altered in the YycF overexpressing strain, indicating that the unphosphorylated form of YycF is involved in the regulation of fatty acid biosynthesis. In addition, DNA-binding assays and in vitro transcription experiments with purified YycF and the promoter region of the FabTH-acp operon support a direct inhibition of transcription of the FabT repressor by YycF, thus confirming the role of the unphosphorylated form in transcriptional regulation.This work was supported by the Spanish Ministry of Industry and Laboratorios SALVAT within the European project Eureka Σ! 3554-DEADBUGS by the Spanish Ministry of Economics and Competitiveness grants AGL2012-40084C03-01 and AGL2015-65010-C3-1-R, and by the European Union grant FP7-PEOPLE-ITN-2008-238490. The work at the CIB was performed under the auspices of the Consejo Superior de Investigaciones Científicas.S

One pot-like regiospecific access to 1-aryl-1H-pyrazol-3(2H)-one derivatives and evaluation of the anticancer activity

A set of variously substituted 1-arylpyrazol-3-one derivatives, including the di-ortho-aryl substituted ones, was synthesized as new potential anticancer compounds. To fulfill this aim, herein a regiospecific synthesis was proposed utilizing a new revisited one pot procedure, starting from commercial anilines and easily accessible 2,5-dimethyl-furan-3-one. In the course of the sequential ordered steps, in some cases, a nitro group displacement by chlorine took place to a minor extent. The in vitro screening against the full panel of ~60 human cancer cell lines (NCI) showed a moderate, but promising selective antiproliferative activity against the UO31 renal tumor cell line, only in compounds with the introduction on the phenyl moiety of a -CF3 or two Cl groups

Attractive Interactions Between Rod-like Polyelectrolytes: Polarization, Crystallization, and Packing

We study the attractive interactions between rod-like charged polymers in solution that appear in the presence of multi-valence counterions. The counterions condensed to the rods exhibit both a strong transversal polarization and a longitudinal crystalline arrangement. At short distances between the rods, the fraction of condensed counterions increases, and the majority of these occupy the region between the rods, where they minimize their repulsive interactions by arranging themselves into packing structures. The attractive interaction is strongest for multivalent counterions. Our model takes into account the hard-core volume of the condensed counterions and their angular distribution around the rods. The hard core constraint strongly suppresses longitudinal charge fluctuations.Comment: 4 figures, uses revtex, psfig and epsf. The new version contains a different introduction, and the bibliography has been expande