We show that Not-All-Equal 3-Sat remains NP-complete when restricted to instances that simultaneously satisfy the following properties: (i) The clauses are given as the disjoint union of k partitions, for any fixed $k \geq 4$, of the variable set into subsets of size 3, and (ii) each pair of distinct clauses shares at most one variable. Property (i) implies that each variable appears in exactly $k$ clauses and each clause consists of exactly 3 unnegated variables. Therewith, we improve upon our earlier result (Darmann and D\"ocker, 2020). Complementing the hardness result for at least $4$ partitions, we show that for $k\leq 3$ the corresponding decision problem is in P. In particular, for $k\in \{1,2\}$, all instances that satisfy Property (i) are nae-satisfiable. By the well-known correspondence between Not-All-Equal 3-Sat} and hypergraph coloring, we obtain the following corollary of our results: For $k\geq 4$, Bicolorability is NP-complete for linear 3-uniform $k$-regular hypergraphs even if the edges are given as a decomposition into $k$ perfect matchings; with the same restrictions, for $k \leq 3$ Bicolorability is in P, and for $k \in \{1,2\}$ all such hypergraphs are bicolorable. Finally, we deduce from a construction in the work by Pilz (Pilz, 2019) that every instance of Positive Planar Not-All-Equal Sat with at least three distinct variables per clause is nae-satisfiable. Hence, when restricted to instances with a planar incidence graph, each of the above variants of Not-All-Equal 3-Sat turns into a trivial decision problem.

Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201.

The expression of E-cadherin on Langerhans cells (LC) is required for adequate dendrite intercalation between epidermal keratinocytes. Upon disruption of epidermal homeostasis by tape stripping, E-cadherin competent LC extend dendrites reaching up to the epidermal surface, while E-cad deficient LC lack this ability.

Real-Time Innovations (RTI) has announced Connext Drive 2.0, the production-ready connectivity framework for software-defined vehicles.The system accelerates the direct integration in Autosar Classic and ROS 2 and enables developers to use datacentric connectivity with trusted system architectures.This improves entrance into development programs using existing and known platforms while eliminating the need for customer-specific programming.It also reduces overall complexity and system cost while simultaneously constructing a self-evolving system.Connext Drive 2.0 consists of components that have been safety certified by TÜV Süd.

BACKGROUND:The experimental fusion protein rFlaA:Betv1 was shown to efficiently suppress allergen-specific sensitization in mice. However, the detailed mechanism of rFlaA:Betv1-mediated immune modulation is not fully understood. In this study, we investigated the effect of rFlaA:Betv1 on naïve murine B cells.METHODS:Immune modulating capacity of rFlaA:Betv1 was screened in IL-10 reporter mice. B cells were isolated from spleens of naïve C57Bl/6, TLR5-/- , or MyD88-/- mice, stimulated with rFlaA:Betv1 and controls, and monitored for the expression of the regulatory B cell markers CD1d, CD24, CD38, and surface IgM by flow cytometry. Secreted cytokines, antibodies, and reactivity of the induced antibodies were investigated by ELISA and intracellular flow cytometry. Suppressive capacity of rFlaA:Betv1-stimulated B cells was tested in mDC:CD4+ T cell:B cell triple cultures.RESULTS:Upon in vivo application of rFlaA:Betv1 into IL-10-GFP reporter mice, CD19+ B cells were shown to produce anti-inflammatory IL-10, suggesting B cells to contribute to the immune-modulatory properties of rFlaA:Betv1. rFlaA:Betv1-induced IL-10 secretion was confirmed in human B cells isolated from buffy coats. In vitro stimulation of naïve murine B cells with rFlaA:Betv1 resulted in an mTOR- and MyD88-dependent production of IL-10 and rFlaA:Betv1 induced Bet v 1-reactive IgG production, which was not observed for IgA. rFlaA:Betv1-stimulated B cells formed a CD19+ CD24+ CD1d+ IgM+ CD38+ Breg subpopulation capable of suppressing Bet v 1-induced TH2 cytokine secretion in vitro.CONCLUSION:rFlaA:Betv1 can act as a thymus-independent B cell antigen, stimulating the mTOR- and MyD88-dependent differentiation of B cells displaying a regulatory phenotype, IL-10 secretion, antigen-binding antibody production, and a suppressive capacity in vitro.

We analyse the problem of finding an allocation of resources in a multiagent system that is as fair as possible in terms of minimising inequality between the utility levels enjoyed by the individual agents. We use the well-known Atkinson index to measure inequality and we focus on the distributed approach to multiagent resource allocation, where new allocations emerge as the result of a sequence of local deals between groups of agents who agree on an exchange of some of the items in their possession. Our results show that it is possible to design systems that provide theoretical guarantees for optimal outcomes that minimise inequality, but also that there are significant computational hurdles to be overcome in the worst case. In particular, finding an optimal allocation is computationally intractable and under the distributed approach a large number of structurally complex deals, possibly involving many agents and items, may be required before convergence to a socially optimal allocation. This remains true even in severely restricted resource allocation scenarios where all agents have the same utility function. From a methodological point of view, while much work in multiagent resource allocation relies on combinatorial arguments, here we instead use insights from basic calculus.

We analyse the problem of finding an allocation of resources in a multiagent system that is as fair as possible in terms of minimising inequality between the utility levels enjoyed by the individual agents. We use the well-known Atkinson index to measure inequality and we focus on the distributed approach to multiagent resource allocation, where new allocations emerge as the result of a sequence of local deals between groups of agents who agree on an exchange of some of the items in their possession. Our results show that it is possible to design systems that provide theoretical guarantees for optimal outcomes that minimise inequality, but also that there are significant computational hurdles to be overcome in the worst case. In particular, finding an optimal allocation is computationally intractable and under the distributed approach a large number of structurally complex deals, possibly involving many agents and items, may be required before convergence to a socially optimal allocation. This remains true even in severely restricted resource allocation scenarios where all agents have the same utility function. From a methodological point of view, while much work in multiagent resource allocation relies on combinatorial arguments, here we instead use insights from basic calculus.

BACKGROUND:Patients with chronic inflammatory diseases (e.g. psoriasis and rheumatoid arthritis) are at increased risk for the development of atherosclerosis and cardiovascular diseases (CVD). Previous studies have suggested that phosphodiesterase 4 (PDE4) inhibitors possess anti-inflammatory properties. OBJECTIVES:Here we examined the effect of the PDE4 inhibitor apremilast, a well-established anti-psoriatic drug, on pro-inflammatory responses in TNFα-activated endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-α (TNFα) in the presence or absence of apremilast. Expression levels of pro-inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT-PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP-1 monocytic cells were analysed in transwell assays. RESULTS:Apremilast suppressed TNFα-induced expression and secretion of important endothelial and monocytic pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and matrix metalloproteinase-9 (MMP9). Functionally, apremilast reduced adhesion of THP-1 cells to activated HUVECs and TEM in response to TNFα. Mechanistically, apremilast suppressed activation of nuclear factor κB (NFκB) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NFκB in activated HUVECs decreased expression of GM-CSF, VCAM-1 and E-selectin. Additionally, apremilast decreased IL-17A-induced secretion of IL-6 and CCL2. CONCLUSIONS:We demonstrate that apremilast has distinct anti-inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.

Several real-world situations can be represented in terms of agents that have preferences over activities in which they may participate. Often, the agents can take part in at most one activity (for instance, since these take place simultaneously), and there are additional constraints on the number of agents that can participate in an activity. In such a setting, we consider the task of assigning agents to activities in a reasonable way. We introduce the simplified group activity selection problem providing a general yet simple model for a broad variety of settings, and start investigating its special case where upper and lower bounds of the groups have to be taken into account. We apply different solution concepts such as envy-freeness and core stability to our setting and provide a computational complexity study for the problem of finding such solutions.

We consider the following control problem on fair allocation of indivisible goods. Given a set $I$ of items and a set of agents, each having strict linear preference over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the remaining instance; we call this problem Proportionality by Item Deletion (PID). Our main result is a polynomial-time algorithm that solves PID for three agents. By contrast, we prove that PID is computationally intractable when the number of agents is unbounded, even if the number $k$ of item deletions allowed is small, since the problem turns out to be W[3]-hard with respect to the parameter $k$. Additionally, we provide some tight lower and upper bounds on the complexity of PID when regarded as a function of $|I|$ and $k$.

This report documents the program and the outcomes of Dagstuhl Seminar 19411 “Social Agents for Teamwork and Group Interactions”. It summarises the three talks that were held during the seminar on three different perspectives: the impact of robots in human teamwork, mechanisms to support group interactions in virtual settings, and affect analysis in human-robot group settings. It also details the considerations of six working groups covering the following topics: datasets, design, team dynamics, social cognition, scenarios, and social behaviours.

The complexity of variants of 3-SAT and Not-All-Equal 3-SAT is well studied. However, in contrast, very little is known about the complexity of the problems' quantified counterparts. In the first part of this paper, we show that ∀∃ 3-SAT is Π2P-complete even if (1) each variable appears exactly twice unnegated and exactly twice negated, (2) each clause is a disjunction of exactly three distinct variables, and (3) the number of universal variables is equal to the number of existential variables. Furthermore, we show that the problem remains Π2P-complete if (1a) each universal variable appears exactly once unnegated and exactly once negated, (1b) each existential variable appears exactly twice unnegated and exactly twice negated, and (2) and (3) remain unchanged. On the other hand, the problem becomes NP-complete for certain variants in which each universal variable appears exactly once. In the second part of the paper, we establish Π2P-completeness for ∀∃ Not-All-Equal 3-SAT even if (1′) the Boolean formula is linear and monotone, (2′) each universal variable appears exactly once and each existential variable appears exactly three times, and (3′) each clause is a disjunction of exactly three distinct variables that contains at most one universal variable. On the positive side, we uncover variants of ∀∃ Not-All-Equal 3-SAT that are co-NP-complete or solvable in polynomial time.

Extracorporeal photopheresis (ECP) represents one of the most widespread and effective cell therapies for graft-versus-host disease and other T cell-mediated disorders. However, the key factors affecting the therapeutic efficacy of ECP remain unclear. We hypothesized that therapeutic effects are mediated by ECP-treated antigen-presenting dendritic cells (DC). To test this hypothesis, we used the experimental model of contact hypersensitivity (CHS). The ECP's therapeutic activity improved when the total cell dose of the ECP-treated cells was increased. We used different haptens during sensitization to demonstrate that the anti-inflammatory activity of ECP is antigen-specific. This confirmed the hypothesis that professional antigen-presenting cells are involved in the mode of action. Also, the ECP's therapeutic activity was abrogated by the depletion of CD11c+ DC, which represents fewer than 1% of all the ECP-exposed cells. Finally, we confirm the critical importance of CD11c+ DC for ECP activity by showing that only a few purified CD11c+ DC are sufficient to mediate its therapeutic effect. The finding that ECP-treated, physiological antigen-presenting DC alone mediate antigen-specific modulation of a pathological immune response may result in better-targeted interventions when treating patients.

Phylogenetics is the study of ancestral relationships between species. Its central goal is the reconstruction and analysis of phylogenetic trees and networks. Even though research in phylogenetics is motivated by biological questions and applications, it heavily relies on mathematics and computer science. Dagstuhl Seminar 19443 on Algorithms and Complexity in Phylogenetics aimed at bringing together researchers from phylogenetics and theoretical computer science to enable an exchange of expertise, facilitate interactions across both research areas, and establish new collaborations. This report documents the program and outcomes of the seminar. It contains an executive summary, abstracts of talks, short summaries of working groups, and a list of open problems that were posed during the seminar. Seminar October 27–31, 2019 – http://www.dagstuhl.de/19443 2012 ACM Subject Classification Theory of computation → Parameterized complexity and exact algorithms, Mathematics of computing → Graph algorithms, Applied computing → Molecular evolution

Allergen specific tolerance induction efficiently ameliorates subsequent allergen induced inflammatory responses. The underlying regulatory mechanisms have been attributed mainly to interleukin (IL)-10 produced by diverse hematopoietic cells, while targets of IL-10 in allergen specific tolerance induction have not yet been well defined. Here, we investigate potential cellular targets of IL-10 in allergen specific tolerance induction using mice with a cell type specific inactivation of the IL-10 receptor gene. Allergic airway inflammation was effectively prevented by tolerance induction in mice with IL-10 receptor (IL-10R) deficiency in T or B cells. Similarly, IL-10R on monocytes/macrophages and/or neutrophils was not required for tolerance induction. In contrast, tolerance induction was impaired in mice that lack IL-10R on dendritic cells: those mice developed an allergic response characterized by a pronounced neutrophilic lung infiltration, which was not ameliorated by tolerogenic treatment. In conclusion, our results show that allergen specific tolerance can be effectively induced without a direct impact of IL-10 on cells of the adaptive immune system, and highlight dendritic cells, but not macrophages nor neutrophils, as the main target of IL-10 during tolerance induction.

Phylogenetics is the study of ancestral relationships between species. Its central goal is the reconstruction and analysis of phylogenetic trees and networks. Even though research in phylogenetics is motivated by biological questions and applications, it heavily relies on mathematics and computer science. Dagstuhl Seminar 19443 on Algorithms and Complexity in Phylogenetics aimed at bringing together researchers from phylogenetics and theoretical computer science to enable an exchange of expertise, facilitate interactions across both research areas, and establish new collaborations. This report documents the program and outcomes of the seminar. It contains an executive summary, abstracts of talks, short summaries of working groups, and a list of open problems that were posed during the seminar.

The prominent Boolean formula satisfiability problem SAT is known to be [Formula: see text]-complete even for very restricted variants such as 3-SAT, Monotone 3-SAT, or Planar 3-SAT, or instances with bounded variable appearance. We settle the computational complexity status for two variants with bounded variable appearance: We show that Planar Monotone Sat — the variant of Monotone Sat in which the incidence graph is required to be planar — is [Formula: see text]-complete even if each clause consists of at most three distinct literals and each variable appears exactly three times, and that Monotone Sat is [Formula: see text]-complete even if each clause consists of three distinct literals and each variable appears exactly four times in the formula. The latter confirms a conjecture stated in scribe notes [7] of an MIT lecture by Eric Demaine. In addition, we provide hardness results with respect to bounded variable appearances for two variants of Planar Monotone Sat.

Allergic contact dermatitis and its animal model, contact hypersensitivity, are T-cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity using Eomes(Gfp/+) x Rorc(gamma t)-Cre(Tg) x Rosa26R(Yfp/+) reporter mice. Ear swelling responses, cutaneous ILC numbers, and cytokine production were determined at different time points. Functional analyses were performed in a CD90.1/.2 congenic adoptive transfer model that allowed selective antibody-mediated depletion of ILCs before hapten challenge, and in Rora(sg/flox)Il7r(Cre/+) mice, which lack ILC2. Hapten challenge induced early increases of natural killer cells in skin and ear draining lymph nodes corresponding to the peak ear swelling response. In contrast, ILC1, 2, and 3 showed a delayed increase in numbers corresponding to the contact hypersensitivity resolution phase. Hapten challenge induced increased marker cytokines in all ILC subtypes and an activated phenotype in ILC2. Depletion of all ILC resulted in a significantly enhanced ear swelling response. Similarly, ILC2-deficient mice (Rora(sg/flox)Il7r(Cre/+)) displayed increased ear swelling responses on hapten challenge, suggesting that ILC2 act as negative regulators in the type 1-dominated immune response of contact hypersensitivity.

We introduce tool auctions, a novel market mechanism for constructing a cost-efficient assembly line for producing a desired set of products from a given set of goods and tools. Such tools can be used to transform one type of good into a different one. We then study the computational complexity of tool auctions in detail, using methods from both classical and parameterized complexity theory. While solving such auctions is intractable in general, just as for the related frameworks of combinatorial and mixed auctions, we are able to identify several special cases of practical interest where designing efficient algorithms is possible.