Shape formation by programmable particles

Shape formation (or pattern formation) is a basic distributed problem for systems of computational mobile entities. Intensively studied for systems of autonomous mobile robots, it has recently been investigated in the realm of programmable matter, where entities are assumed to be small and with severely limited capabilities. Namely, it has been studied in the geometric Amoebot model, where the anonymous entities, called particles, operate on a hexagonal tessellation of the plane and have limited computational power (they have constant memory), strictly local interaction and communication capabilities (only with particles in neighboring nodes of the grid), and limited motorial capabilities (from a grid node to an empty neighboring node); their activation is controlled by an adversarial scheduler. Recent investigations have shown how, starting from a well-structured configuration in which the particles form a (not necessarily complete) triangle, the particles can form a large class of shapes. This result has been established under several assumptions: agreement on the clockwise direction (i.e., chirality), a sequential activation schedule, and randomization (i.e., particles can flip coins to elect a leader). In this paper we provide a characterization of which shapes can be formed deterministically starting from any simply connected initial configuration of n particles. The characterization is constructive: we provide a universal shape formation algorithm that, for each feasible pair of shapes (S0, SF), allows the particles to form the final shape SF (given in input) starting from the initial shape S0, unknown to the particles. The final configuration will be an appropriate scaled-up copy of SF depending on n. If randomization is allowed, then any input shape can be formed from any initial (simply connected) shape by our algorithm, provided that there are enough particles. Our algorithm works without chirality, proving that chirality is computationally irrelevant for shape formation. Furthermore, it works under a strong adversarial scheduler, not necessarily sequential. We also consider the complexity of shape formation both in terms of the number of rounds and the total number of moves performed by the particles executing a universal shape formation algorithm. We prove that our solution has a complexity of O(n2) rounds and moves: this number of moves is also asymptotically worst-case optimal

Mutual visibility by luminous robots without collisions

We consider the Mutual Visibility problem for anonymous dimensionless robots with obstructed visibility moving in a plane: starting from distinct locations, the robots must reach, without colliding, a configuration where no three of them are collinear. We study this problem in the luminous robots model, in which each robot has a visible light that can assume colors from a fixed set. Among other results, we prove that Mutual Visibility can be solved in SSynch with 2 colors and in ASynch with 3 colors. If an adversary can interrupt and stop a robot moving to its computed destination, Mutual Visibility is still solvable in SSynch with 3 colors and, if the robots agree on the direction of one axis, also in ASynch. As a byproduct, we provide the first obstructed-visibility solutions to two classical problems for oblivious robots: collision-less convergence to a point (also known as near-gathering) and circle formation

Population protocols with faulty interactions: The impact of a leader

We consider the problem of simulating traditional popula-tion protocols under weaker models of communication, which include one-way interactions (as opposed to two-way interactions) and omission faults (i.e., failure by an agent to read its partner’s state during an inter-action), which in turn may be detectable or undetectable. We focus on the impact of a leader, and we give a complete characterization of the models in which the presence of a unique leader in the system allows the construction of simulators: when simulations are possible, we give explicit protocols; when they are not, we give proofs of impossibility. Specifically, if each agent has only a finite amount of memory, the simulation is pos-sible only if there are no omission faults. If agents have an unbounded amount of memory, the simulation is possible as long as omissions are detectable. If an upper bound on the number of omissions involving the leader is known, the simulation is always possible, except in the one-way model in which one side is unable to detect the interaction

Oblivious permutations on the plane

We consider a distributed system of n identical mobile robots operating in the two dimensional Euclidian plane. As in the previous studies, we consider the robots to be anonymous, oblivious, dis-oriented, and without any communication capabilities, operating based on the Look-Compute-Move model where the next location of a robot depends only on its view of the current configuration. Even in this seemingly weak model, most formation problems which require constructing specific configurations, can be solved quite easily when the robots are fully synchronized with each other. In this paper we introduce and study a new class of problems which, unlike the studied formation problems, cannot always be solved even in the fully synchronous model with atomic and rigid moves. This class of problems requires the robots to permute their locations in the plane. In particular, we are interested in implementing two special types of permutations - permutations without any fixed points and permutations of order n. The former (called Move-All) requires each robot to visit at least two of the initial locations, while the latter (called Visit-All) requires every robot to visit each of the initial locations in a periodic manner. We provide a characterization of the solvability of these problems, showing the main challenges in solving this class of problems for mobile robots. We also provide algorithms for the feasible cases, in particular distinguishing between one-step algorithms (where each configuration must be a permutation of the original configuration) an

Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis

In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = -0.435, P = 0.023).These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity

Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis

Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients

Increased Numbers of IL-7 Receptor Molecules on CD4+CD25−CD107a+ T-Cells in Patients with Autoimmune Diseases Affecting the Central Nervous System

BACKGROUND: High content immune profiling in peripheral blood may reflect immune aberrations associated with inflammation in multiple sclerosis (MS) and other autoimmune diseases affecting the central nervous system. METHODS AND FINDINGS: Peripheral blood mononuclear cells from 46 patients with multiple sclerosis (MS), 9 patients diagnosed with relapsing remitting MS (RRMS), 13 with secondary progressive multiple sclerosis (SPMS), 9 with other neurological diseases (OND) and well as 15 healthy donors (HD) were analyzed by 12 color flow cytometry (TCRalphabeta, TCRgammadelta, CD4, CD8alpha, CD8beta, CD45RA, CCR7, CD27, CD28, CD107a, CD127, CD14) in a cross-sectional study to identify variables significantly different between controls (HD) and patients (OND, RRMS, SPMS). We analyzed 187 individual immune cell subsets (percentages) and the density of the IL-7 receptor alpha chain (CD127) on 59 individual immune phenotypes using a monoclonal anti-IL-7R antibody (clone R34.34) coupled to a single APC molecule in combination with an APC-bead array. A non-parametric analysis of variance (Kruskal-Wallis test) was conducted in order to test for differences among the groups in each of the variables. To correct for the multiplicity problem, the FDR correction was applied on the p-values. We identified 19 variables for immune cell subsets (percentages) which allowed to segregate healthy individuals and individuals with CNS disorders. We did not observe differences in the relative percentage of IL-7R-positive immune cells in PBMCs. In contrast, we identified significant differences in IL-7 density, measured on a single cell level, in 2/59 variables: increased numbers of CD127 molecules on TCRalphabeta+CD4+CD25 (intermed) T-cells and on TCRalphabeta+CD4+CD25-CD107a+ T-cells (mean: 28376 Il-7R binding sites on cells from HD, 48515 in patients with RRMS, 38195 in patients with SPMS and 33692 IL-7 receptor binding sites on cells from patients with OND). CONCLUSION: These data show that immunophenotyping represents a powerful tool to differentiate healthy individuals from individuals suffering from neurological diseases and that the number of IL-7 receptor molecules on differentiated TCRalphabeta+CD4+CD25-CD107a+ T-cells, but not the percentage of IL-7R-positive cells, segregates healthy individuals from patients with neurological disorders

Erythropoietin: A potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE

Background: Beneficial effects of short-term erythropoietin (EPO) theraphy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis(EAE)-the animal model of multiple sclerosis. We have found that EPO treatment substantially reduces the acute clinical paralysis seen EAE mice and this improvements is accompanied by a large reduction in the mononuclear cell infiltration and downregulation of glial MHC class II expression within the inflamed CNS. Other reports have recently indicated that peripherally generated anti-inflammatory CD4 +Foxp3 3 regulatory T cells (Tregs) and the IL17-producing CD4+ T helper cell (Th17) subpopulations play key antagonistic roles in EAE pathogenesis. However, no information regardind the effects of EPO theraphy on the behavior of the general mononuclear-lymphocyte population, Tregs or Th17 cells in EAE has emerged. Methods and Findings: We first determined in vivo that EPO theraphy markedly suppressed MOG specific T cell proliferation and sharply reduced the number of reactive dendritic cells (CD11c positive) in EAE lumph modes during both inductive and later symptomatic phases of MOG 35-55 induced EAE. We then determined the effect in vivo of EPO on numbers of peripheral Treg cells and Th17 cells. We found that EPO treatment modulated immune balance in both the periphery and the inflamed spinal cord by promoting a large expansion in Treg cells, inhibiting Th17 polarization and abrogating proliferation of the antigen presenting dendritic cell population. Finally we utilized tissue culture assays to show that exposure to EPO in vitro similarly downregulated MOG-specific T cell proliferation and also greatly suppressed T cell production of pro-inflammatory cytokines. Conclusions: Taken together, our findings reveal an important new locus whereby EPO induces substantial long-term tissue protection in the host through signalling to several critical subsets of immune cells that reside in the peripheral lymphatic system.published_or_final_versio

Loureirin B, an essential component of Sanguis Draxonis, inhibits Kv1.3 channel and suppresses cytokine release from Jurkat T cells

Sanguis draxonis (SD), also known as “Dragon’s Blood”, is a traditional herb medicine that has been used to treat a variety of complications with unknown mechanisms. Recent studies show that SD displays immunosuppressive activities and improves symptoms of type I diabetes in animal models. However, the mechanisms underlying SD’s immunosuppressive actions are not completely understood. The voltage-gated Kv1.3 channel plays a critical role in the pathogenesis of autoimmune diseases by regulating the functions of both T cells and B cells. Here we investigated the effect of SD and one of its active components loureirin B (LrB) on Kv1.3. Both SD and LrB inhibited Kv1.3-mediated currents, produced a membrane depolarization, and reduced Ca(2+) influx in Jurkat T cells. In addition, application of LrB inhibited phytohemagglutinin (PHA)-induced IL-2 release from activated Jurkat T cells. Furthermore, point mutations in the selective filter region significantly reduced the inhibitory effect of LrB on Kv1.3. The results of these experiments provide evidence that LrB is a channel blocker of Kv1.3 by interacting with amino acid residues in its selective filter region. Direct inhibition of Kv1.3 in T cells by SD and LrB might be the cellular and molecular basis of SD-mediated immunosuppression