Relevance of novel inflammatory markers in stroke-induced immunosuppression

BACKGROUND: Acute ischemic stroke (AIS) has a biphasic effect on the peripheral immune system. The initial inflammatory response is followed by systemic immunosuppression, referred to as stroke-induced immunosuppression (SIIS), leading to severe complications in stroke patients. We aimed to identify an inflammatory marker that best represents this biphasic immunological response after AIS. METHODS: We investigated the alteration of CRP, WBC, neutrophil count, suPAR levels, CD4+ CD25high Tregs, CD64+ and CD177+ neutrophils and monocytes in 12 acute ischemic stroke patients free of infection within 6 hours and one week after the insult. As controls, 14 age-matched healthy individuals were included. RESULTS: CRP, WBC and neutrophil count values were comparable in stroke patients within 6 hours and controls, however, they were elevated in stroke one week after the insult. suPAR levels were higher in both stroke groups compared to controls. The prevalence of CD64+ neutrophils was higher in stroke patients within 6 hours than in controls and it decreased in stroke one week after the insult below the level in controls (5.95 [5.41-8.75] % vs. 32.38 [9.21-43.93] % vs. 4.06 [1.73-6.77] %, p < 0.05). CONCLUSIONS: Our pilot study identified that the prevalence of CD64+ neutrophils may reflect a biphasic alteration of the immune response following AIS. Since its level decreases below baseline after one week of the CNS insult in stroke patients without infection, it might serve as a reliable candidate to identify the developing inflammatory response due to infection after stroke in the future

Problems and results in partially ordered sets, graphs and geometry

The thesis consist of three independent parts. In the first part, we investigate the height sequence of an element of a partially ordered set. Let $x$ be an element of the partially ordered set $P$. Then $h_i(x)$ is the number of linear extensions of $P$ in which $x$ is in the $i$th lowest position. The sequence ${h_i(x)}$ is called the height sequence of $x$ in $P$. Stanley proved in 1981 that the height sequence is log-concave, but no combinatorial proof has been found, and Stanley's proof does not reveal anything about the deeper structure of the height sequence. In this part of the thesis, we provide a combinatorial proof of a special case of Stanley's theorem. The proof of the inequality uses the Ahlswede--Daykin Four Functions Theorem. In the second part, we study two classes of segment orders introduced by Shahrokhi. Both classes are natural generalizations of interval containment orders and interval orders. We prove several properties of the classes, and inspired by the observation, that the classes seem to be very similar, we attempt to find out if they actually contain the same partially ordered sets. We prove that the question is equivalent to a stretchability question involving certain sets of pseudoline arrangements. We also prove several facts about continuous universal functions that would transfer segment orders of the first kind into segments orders of the second kind. In the third part, we consider the lattice whose elements are the subsets of ${1,2,ldots,n}$. Trotter and Felsner asked whether this subset lattice always contains a monotone Hamiltonian path. We make progress toward answering this question by constructing a path for all $n$ that satisfies the monotone properties and covers every set of size at most $3$. This portion of thesis represents joint work with David M.~Howard.Ph.D.Committee Chair: Trotter, William T.; Committee Member: Duke, Richard A.; Committee Member: Randall, Dana; Committee Member: Thomas, Robin; Committee Member: Yu, Xingxin

Fine-grained complexity of coloring unit disks and balls

International audienceOn planar graphs, many classic algorithmic problems enjoy a certain ``square rootphenomenon'' and can be solved significantly fasterthan what is known to be possible on general graphs: for example,\textsc{Independent Set}, \textsc{3-Coloring}, \textsc{Hamiltonian Cycle}, \textsc{Dominating Set} can be solved in time$2^{O(\sqrt{n})}$ on an $n$-vertex planar graph, while no $2^{o(n)}$algorithms exist for general graphs, assuming the Exponential TimeHypothesis (ETH). The square root in the exponent seems to be bestpossible for planar graphs: assuming the ETH, the running time for theseproblems cannot be improved to $2^{o(\sqrt{n})}$. In some cases, asimilar speedup can be obtained for 2-dimensional geometric problems,for example, there are $2^{O(\sqrt{n}\log n)}$ time algorithms for\textsc{Independent Set} on unit disk graphs or for \textsc{TSP} on2-dimensional point sets.In this paper, we explore whether such a speedup is possible for geometric coloring problems. On the one hand, geometric objects can behave similarly to planar graphs: \textsc{3-Coloring} can be solved in time $2^{O(\sqrt{n})}$ on the intersection graph of $n$ disks in the plane and, assuming the ETH, there is no such algorithm with running time $2^{o(\sqrt{n})}$. On the other hand, if the number $\ell$ of colors is part of the input, then no such speedup is possible: Coloring the intersection graph of $n$ unit disks with $\ell$ colors cannot be solved in time $2^{o(n)}$, assuming the ETH. More precisely, we exhibit a smooth increase of complexity as the number $\ell$ of colors increases: If we restrict the number of colors to $\ell=\Theta(n^{\alpha})$ for some $0\le \alpha\le 1$, then the problem of coloring the intersection graph of $n$ disks with $\ell$ colors\begin{itemize}\item can be solved in time $\exp \left( O(n^{\frac{1+\alpha}{2}}\log n) \right)=\exp \left( O(\sqrt{n\ell}\log n) \right)$, and%using a combination of fairly standard techniques, and\item cannot be solved in time $\exp \left ( o(n^{\frac{1+\alpha}{2}})\right )=\exp \left( o(\sqrt{n\ell}) \right)$, even on unit disks, unless the ETH fails.\end{itemize}More generally, we consider the problem of coloring $d$-dimensional balls in the Euclidean space and obtain analogous results showing that the problem \begin{itemize}\item can be solved in time $\exp \left( O(n^{\frac{d-1+\alpha}{d}}\log n) \right)$ $=\exp \left( O(n^{1-1/d}\ell^{1/d}\log n) \right)$, and\item cannot be solved in time $\exp \left(O(n^{\frac{d-1+\alpha}{d}-\epsilon})\right)= \exp \left(O(n^{1-1/d-\epsilon}\ell^{1/d})\right)$ for any $\epsilon>0$, even for unit balls, unless the ETH fails.\end{itemize}Finally, we prove that fatness is crucial to obtain subexponential algorithms for coloring. We show that existence of an algorithm coloring an intersection graph of segments using a constant number of colors in time $2^{o(n)}$ already refutes the ETH

Isolation of allithiamine from Hungarian red sweet pepper seed (Capsicum annuum L.)

A natural fat-soluble thiamine derivative, namely N-[(4-amino-2-methylpyrimidin-5-yl)methyl]-N-[(2E)-5-hydroxy-3-(prop-2-en-1-yldisulfanyl)pent-2-en-2-yl]formamide (allithiamine) has been identified only in garlic (Allium sativum) until now. Hungarian red sweet pepper (Capsicum annuum) was found as a new source of allithiamine. Extraction procedure and analytical method were developed for the isolation of allithiamine and a chemical synthesis of the compound was also developed. First solid-liquid extraction was performed with 96 % ethanol to isolate allithiamine from pepper seeds. Thereafter, solid phase extraction was applied from ethanolic extract using C18 cartridge to concentrate and purify samples for further analysis. The structure of the synthesized and the isolated compounds was verified by reverse phase HPLC, HPLC-MS, MALD-TOF MS and NMR. Furthermore, effect of allithiamine was investigated on streptozotocin-induced diabetic mice with neuropathy. The results show that neuropathic pain sensation is improved by allithiamine treatment similarly to benfothiamine

Impact of ergothioneine, hercynine, and histidine on oxidative degradation of hyaluronan and wound Healing

A high-molecular weight hyaluronan is oxidatively degraded by Cu(II) ions and ascorbate—the so called Weissberger biogenic oxidative system—which is one of the most potent generators of reactive oxygen species, namely •OH radicals. Ergothioneine, hercynine, or histidine were loaded into chitosan/hyaluronan composite membranes to examine their effect on skin wound healing in ischemic rabbits. We also explored the ability of ergothioneine, hercynine, or histidine to inhibit hyaluronan degradation. Rotational viscometry showed that ergothioneine decreased the degree of hyaluronan radical degradation in a dose-dependent manner. While histidine was shown to be potent in scavenging •OH radicals, however, hercynine was ineffective. In vivo results showed that the addition of each investigated agent to chitosan/hyaluronan membranes contributed to a more potent treatment of ischemic skin wounds in rabbits compared to untreated animals and animals treated only with chitosan/hyaluronan membranes

‘Proactive’ use of cue-context congruence for building reinforcement learning’s reward function

Background: Reinforcement learning is a fundamental form of learning that may be formalized using the Bellman equation. Accordingly an agent determines the state value as the sum of immediate reward and of the discounted value of future states. Thus the value of state is determined by agent related attributes (action set, policy, discount factor) and the agent’s knowledge of the environment embodied by the reward function and hidden environmental factors given by the transition probability. The central objective of reinforcement learning is to solve these two functions outside the agent’s control either using, or not using a model.Results: In the present paper, using the proactive model of reinforcement learning we offer insight on how the brain creates simplified representations of the environment, and how these representations are organized to support the identification of relevant stimuli and action. Furthermore, we identify neurobiological correlates of our model by suggesting that the reward and policy functions, attributes of the Bellman equitation, are built by the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. Conclusions: Based on this we propose that the OFC assesses cue-context congruence to activate the most context frame. Furthermore given the bidirectional neuroanatomical link between the OFC and model-free structures, we suggest that model-based input is incorporated into the reward prediction error (RPE) signal, and conversely RPE signal may be used to update the reward-related information of context frames and the policy underlying action selection in the OFC and ACC, respectively. Furthermore clinical implications for cognitive behavioral interventions are discussed

Toward a High Spatial Resolution Aerial Monitoring Network for Nature Conservation—How Can Remote Sensing Help Protect Natural Areas?

Aerial surveys have always significantly contributed to the accurate mapping of certain geographical phenomena. Remote sensing opened up new perspectives in nature monitoring with state-of-the-art technical solutions using modern onboard recording equipment. We developed the technical background and the methodology that supports detailed and cost-effective monitoring of a network of natural areas, thereby detecting temporal changes in the spatial pattern of land cover, species, biodiversity, and other natural features. In this article, we share our experiences of the technical background, geometric accuracy and results of comparisons with selected Copernicus Land Monitoring products and an Ecosystem Map based on the testing of our methodology at 25 sites in Hungary. We combined a high-spatial-resolution aerial remote sensing service with field studies to support an efficient nature conservation monitoring network at 25 permanent sites. By analyzing annually (or more frequently) orthophotos taken with a range of 0.5–5 cm spatial resolution and 3D surface models of aerial surveys, it is possible to map the upper canopy of vegetation species. Furthermore, it allows us to accurately follow the changes in the dynamics at the forest edge and upper canopy, or the changes in species’ dominance in meadows. Additionally, spatial data obtained from aerial surveys and field studies can expand the knowledge base of the High-Resolution Aerial Monitoring Network (HRAMN) and support conservation and restoration management. A well-conducted high-resolution survey can reveal the impacts of land interventions and habitat regeneration. By building the HRAMN network, nature conservation could have an up-to-date database that could prompt legal processes, establish protection designation procedures and make environmental habitat management more cost-effective. Landscape protection could also utilize the services of HRAMN in planning and risk reduction interventions through more reliable inputs to environmental models