Soft effective interactions between weakly charged polyelectrolyte chains

We apply extensive Molecular Dynamics simulations and analytical considerations in order to study the conformations and the effective interactions between weakly charged, flexible polyelectrolyte chains in salt-free conditions. We focus on charging fractions lying below 20%, for which case there is no Manning condensation of counterions and the latter can be thus partitioned in two states: those that are trapped within the region of the flexible chain and the ones that are free in the solution. We examine the partition of counterions in these two states, the chain sizes and the monomer distributions for various chain lengths, finding that the monomer density follows a Gaussian shape. We calculate the effective interaction between the centers of mass of two interacting chains, under the assumption that the chains can be modeled as two overlapping Gaussian charge profiles. The analytical calculations are compared with measurements from Molecular Dynamics simulations. Good quantitative agreement is found for charging fractions below 10%, where the chains assume coil-like configurations, whereas deviations develop for charge fraction of 20%, in which case a conformational transition of the chain towards a rodlike configuration starts to take place.Comment: 38 pages, 12 figures, 2 tables. Revised version of the manuscript. Selected for publication in the V\irtual Journal of Biological Physics Research, issue of 1 september, 200

Strategies for distributing goals in a team of cooperative agents

This paper addresses the problem of distributing goals to individual agents inside a team of cooperative agents. It shows that several parameters determine the goals of particular agents. The first parameter is the set of goals allocated to the team; the second parameter is the description of the real actual world; the third parameter is the description of the agents' ability and commitments. The last parameter is the strategy the team agrees on: for each precise goal, the team may define several strategies which are orders between agents representing, for instance, their relative competence or their relative cost. This paper also shows how to combine strategies. The method used here assumes an order of priority between strategie

Fluid-fluid demixing transitions in colloid--polyelectrolyte star mixtures

We derive effective interaction potentials between hard, spherical colloidal particles and star-branched polyelectrolytes of various functionalities and smaller size than the colloids. The effective interactions are based on a Derjaguin-like approximation, which is based on previously derived potentials acting between polyelectrolyte stars and planar walls. On the basis of these interactions we subsequently calculate the demixing binodals of the binary colloid--polyelectrolyte star mixture, employing standard tools from liquid-state theory. We find that the mixture is indeed unstable at moderately high overall concentrations. The system becomes more unstable with respect to demixing as the star functionality and the size ratio grow.Comment: 24 pages, 9 figures, submitted to Journal of Physics: Condensed Matte

Directional approach to spatial structure of solutions to the Navier-Stokes equations in the plane

We investigate a steady flow of incompressible fluid in the plane. The motion is governed by the Navier-Stokes equations with prescribed velocity $u_\infty$ at infinity. The main result shows the existence of unique solutions for arbitrary force, provided sufficient largeness of $u_\infty$. Furthermore a spacial structure of the solution is obtained in comparison with the Oseen flow. A key element of our new approach is based on a setting which treats the directino of the flow as \emph{time} direction. The analysis is done in framework of the Fourier transform taken in one (perpendicular) direction and a special choice of function spaces which take into account the inhomogeneous character of the symbol of the Oseen system. From that point of view our technique can be used as an effective tool in examining spatial asymptotics of solutions to other systems modeled by elliptic equations

Decrement Operators in Belief Change

While research on iterated revision is predominant in the field of iterated belief change, the class of iterated contraction operators received more attention in recent years. In this article, we examine a non-prioritized generalisation of iterated contraction. In particular, the class of weak decrement operators is introduced, which are operators that by multiple steps achieve the same as a contraction. Inspired by Darwiche and Pearl's work on iterated revision the subclass of decrement operators is defined. For both, decrement and weak decrement operators, postulates are presented and for each of them a representation theorem in the framework of total preorders is given. Furthermore, we present two sub-types of decrement operators

The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity

The pancreas is a complex organ that consists of separate endocrine and exocrine cell compartments. Although great strides have been made in identifying regulatory factors responsible for endocrine pancreas formation, the molecular regulatory circuits that control exocrine pancreas properties are just beginning to be elucidated. In an effort to identify genes involved in exocrine pancreas function, we have examined Mist1, a basic helix-loop-helix transcription factor expressed in pancreatic acinar cells. Mist1-null (Mist1KO) mice exhibit extensive disorganization of exocrine tissue and intracellular enzyme activation. The exocrine disorganization is accompanied by increases in p8, RegI/PSP, and PAP1/RegIII gene expression, mimicking the molecular changes observed in pancreatic injury. By 12 m, Mist1KO mice develop lesions that contain cells coexpressing acinar and duct cell markers. Analysis of the factors involved in cholecystokinin (CCK) signaling reveal inappropriate levels of the CCK receptor A and the inositol-1,4,5-trisphosphate receptor 3, suggesting that a functional defect exists in the regulated exocytosis pathway of Mist1KO mice. Based on these observations, we propose that Mist1KO mice represent a new genetic model for chronic pancreas injury and that the Mist1 protein serves as a key regulator of acinar cell function, stability, and identity

PolicyKit: Building Governance in Online Communities

The software behind online community platforms encodes a governance model that represents a strikingly narrow set of governance possibilities focused on moderators and administrators. When online communities desire other forms of government, such as ones that take many members' opinions into account or that distribute power in non-trivial ways, communities must resort to laborious manual effort. In this paper, we present PolicyKit, a software infrastructure that empowers online community members to concisely author a wide range of governance procedures and automatically carry out those procedures on their home platforms. We draw on political science theory to encode community governance into policies, or short imperative functions that specify a procedure for determining whether a user-initiated action can execute. Actions that can be governed by policies encompass everyday activities such as posting or moderating a message, but actions can also encompass changes to the policies themselves, enabling the evolution of governance over time. We demonstrate the expressivity of PolicyKit through implementations of governance models such as a random jury deliberation, a multi-stage caucus, a reputation system, and a promotion procedure inspired by Wikipedia's Request for Adminship (RfA) process.Comment: to be published in ACM UIST 202

Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing