Short proofs of the Kneser-Lovász coloring principle

We prove that propositional translations of the Kneser–Lovász theorem have polynomial size extended Frege proofs and quasi-polynomial size Frege proofs for all fixed values of k. We present a new counting-based combinatorial proof of the K neser–Lovász theorem based on the Hilton–Milner theorem; this avoids the topological arguments of prior proofs for all but finitely many base cases. We introduce new “truncated Tucker lemma” principles, which are miniaturizations of the octahedral Tucker lemma. The truncated Tucker lemma implies the Kneser–Lovász theorem. We show that the k=1 case of the truncated Tucker lemma has polynomial size extended Frege proofs.Peer ReviewedPostprint (author's final draft

Mimicking Cellular Signaling Pathways within Synthetic Multicompartment Vesicles with Triggered Enzyme Activity and Induced Ion Channel Recruitmen

Subcellular compartmentalization of cells, a defining characteristic of eukaryotes, is fundamental for the fine tuning of internal processes and the responding to external stimuli. Reproducing and controlling such compartmentalized hierarchical organization, responsiveness, and communication is important toward understanding biological systems and applying them to smart materials. Herein, a cellular signal transduction strategy (triggered release from subcompartments) is leveraged to develop responsive, purely artificial, polymeric multicompartment assemblies. Incorporation of responsive nanoparticles-loaded with enzymatic substrate or ion channels-as subcompartments inside micrometer-sized polymeric vesicles (polymersomes) allowed to conduct bioinspired signaling cascades. Response of these subcompartments to an externally added stimulus is achieved and studied by using confocal laser scanning microscopy (CLSM) coupled with in situ fluorescence correlation spectroscopy (FCS). Signal triggered activity of an enzymatic reaction is demonstrated in multicompartments through recombination of compartmentalized substrate and enzyme. In parallel, a two-step signaling cascade is achieved by triggering the recruitment of ion channels from inner subcompartments to the vesicles' membrane, inducing ion permeability, mimicking endosome-mediated insertion of internally stored channels. This design shows remarkable versatility, robustness, and controllability, demonstrating that multicompartment polymer-based assemblies offer an ideal scaffold for the development of complex cell-inspired responsive systems for applications in biosensing, catalysis, and medicine

Multicompartment Polymer Vesicles with Artificial Organelles for Signal-Triggered Cascade Reactions Including Cytoskeleton Formation

Abstract Organelles, i.e., internal subcompartments of cells, are fundamental to spatially separate cellular processes, while controlled intercompartment communication is essential for signal transduction. Furthermore, dynamic remodeling of the cytoskeleton provides the mechanical basis for cell shape transformations and mobility. In a quest to develop cell-like smart synthetic materials, exhibiting functional flexibility, a self-assembled vesicular multicompartment system, comprised of a polymeric membrane (giant unilamellar vesicle, GUV) enveloping polymeric artificial organelles (vesicles, nanoparticles), is herein presented. Such multicompartment assemblies respond to an external stimulus that is transduced through a precise sequence. Stimuli-triggered communication between two types of internal artificial organelles induces and localizes an enzymatic reaction and allows ion-channel mediated release from storage vacuoles. Moreover, cytoskeleton formation in the GUVs` lumen can be triggered by addition of ionophores and ions. An additional level of control is achieved by signal-triggered ionophore translocation from organelles to the outer membrane, triggering cytoskeleton formation. This system is further used to study the diffusion of various cytoskeletal drugs across the synthetic outer membrane, demonstrating potential applicability, e.g., anticancer drug screening. Such multicompartment assemblies represent a robust system harboring many different functionalities and are a considerable leap in the application of cell logics to reactive and smart synthetic materials

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation

Algorithm Synthesis by Lazy Thinking: Using Problem Schemes

Recently, as part of a general formal (i.e. logic based) methodology for mathematical knowledge management we also introduced a method for the automated synthesis of correct algorithms, which we called the lazy thinking method. For a given concrete problem specification (in predicate logic), the method tries out various algorithm schemes and derives specifications for the subalgorithms in the algorithm scheme

Arabidopsis loss-of-function mutant in the lysine pathway points out complex regulation mechanisms

AbstractIn plants, the amino acids lysine, threonine, methionine and isoleucine have L-aspartate-β-semialdehyde (ASA) as a common precursor in their biosynthesis pathways. How this ASA precursor is dispersed among the different pathways remains vague knowledge. The proportional balances of free and/or protein-bound lysine, threonine, isoleucine and methionine are a function of protein synthesis, secondary metabolism and plant physiology. Some control points determining the flux through the distinct pathways are known, but an adequate explanation of how the competing pathways share ASA in a fine-tuned amino acid biosynthesis network is yet not available. In this article we discuss the influence of lysine biosynthesis on the adjacent pathways of threonine and methionine. We report the finding of an Arabidopsis thaliana dihydrodipicolinate synthase T-DNA insertion mutant displaying lower lysine synthesis, and, as a result of this, a strongly enhanced synthesis of threonine. Consequences of these cross-pathway regulations are discussed

Identification of genes involved in Cd tolerance in Arabidopsis halleri

info:eu-repo/semantics/publishe

Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options–from surgery to immunotherapy trials–it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution

Benchmark Networks for grid integration impact studies of large PV plants

The increased amount of Photovoltaic (PV) power installed into the power system every year places this renewable way of producing electricity on the third position in the renewable sources hierarchy after hydro and wind solutions. Having significant levels of renewable power penetration into the system led to stability concerns of the entire system affecting its reliability and availability. In consequence system operators such as the European Network of Transmission System Operators for Electricity (ENTSO-E) had an immediate response imposing strict operating regulations in order to keep the system stable and harmonize the operation of the renewable plants with the entire system. For this purpose valid grid benchmarks such as IEEE 12 bus system for High Voltage (HV) and Cigré benchmark cell model for Medium Voltage (MV) have to be developed, tested together and prove that in the future power system with large PV penetration levels on every level, the system continues to be reliable and redundant.</p