In this paper, the kinetic study of the reaction between substituted 1,4-benzoquinones (RBQs) and Na2SO3 (S(IV)) is presented in aqueous solutions at different pH values and reagent concentrations. The stoichiometry of the reaction is 1:2 RBQs:S(IV) and one equivalent of chloride ion was also detected as a product when using mono- (2-CBQ) or dichloro-benzoquinones (2,5-DCBQ; 2,6-DCBQ) as reactants. This shows that reductive dehalogenation occurs instead of simple reduction to the corresponding substituted 1,4-hydroquinones (RBQHs) and quinone bisulfites are formed, analogously to the addition of bisulfite ion to carbonyl compounds. Various sulfonated quinones have been identified as products by electrospray mass spectrometry. Kinetic traces at different wavelengths were obtained by the stopped-flow technique with spectrophotometric detection, a kinetic fitting program (ZiTa) was used to fit a multi-step model to the data. A detailed mathematical evaluation of the reaction scheme was carried out under non-pseudo-first order conditions showing that our model can be fitted with a double exponential function even when none of the reagents are in large excess.

The hEag1 (Kv10.1) K+ channel is normally found in the brain, but it is ectopically expressed in tumor cells, including osteosarcoma. Based on the pivotal role of ion channels in osteogenesis, we tested whether pharmacological modulation of hEag1 may affect osteogenic differentiation of osteosarcoma cell lines. Using molecular biology (RT-PCR), electrophysiology (patch-clamp) and pharmacology (astemizole sensitivity, IC50 = 0.135 μM) we demonstrated that SaOS-2 osteosarcoma cells also express hEag1 channels. SaOS-2 cells also express to KCa1.1 K+ channels as shown by mRNA expression and paxilline sensitivity of the current. The inhibition of hEag1 (2 μM astemizole) or KCa1.1 (1 mM TEA) alone did not induce Ca2+ deposition in SaOS-2 cultures, however, these inhibitors, at identical concentrations, increased Ca2+ deposition evoked by the classical or pathological (inorganic phosphate, Pi) induction pathway without causing cytotoxicity, as reported by three completer assays (LDH release, MTT assay and SRB protein assay). We observed a similar effect of astemizole on Ca2+ deposition in MG-63 osteosarcoma cultures as well. We propose that the increase in the osteogenic stimuli-induced mineral matrix formation of osteosarcoma cell lines by inhibiting hEag1 may be a useful tool to drive terminal differentiation of osteosarcoma.

We address an old (1977) conjecture of a subset of the authors (a variant of Ryser’s conjecture): in every r-coloring of the edges of a biclique [A,B] (complete bipartite graph), A ∪ B can be covered by the vertices of at most 2r − 2 monochromatic connected components. We reduce this conjecture to design-like conjectures, where the monochromatic components of the color classes are bicliques [X,Y ] with nonempty blocks X and Y . It can be also assumed that each color class covers A∪B (spanning), moreover, no X-blocks or Y -blocks properly contain each other (antichain property). We prove this reduced conjecture for r ≤ 5. We show that the width (the number of bicliques) in every color class of any spanning r-coloring is at most 2r−1 (and this is best possible). On the other hand there exist spanning r-colorings such that the width of every color class is Ω(r3/2). We discuss the dual form of the conjecture which relates to transversals of intersecting and cross-intersecting r-partite hypergraphs.

The immunological synapse (IS) is a specialized contact area formed between a T cell and an antigen presenting cell (APC). Besides molecules directly involved in antigen recognition such as the TCR/CD3 complex, ion channels important in the membrane potential and intracellular free Ca2+ concentration control of T cells are also recruited into the IS. These are the voltage-gated Kv1.3 and Ca2+-activated KCa3.1 K+ channels and the calcium release-activated Ca2+ channel (CRAC). However, the consequence of this recruitment on membrane potential and Ca2+ level control is not known. Here we demonstrate that the membrane potential (MP) of murine T cells conjugated with APCs in an IS shows characteristic oscillations. We found that depolarization of the membrane by current injection or by increased extracellular K+ concentration produced membrane potential oscillations (MPO) significantly more frequently in conjugated T cells than in lone T cells. Furthermore, oscillation of the free intracellular Ca2+ concentration could also be observed more frequently in cells forming an IS than in lone cells. We suggest that in the IS the special arrangement of channels and the constrained space between the interacting cells creates a favorable environment for these oscillations, which may enhance the signaling process leading to T cell activation.

The paper focuses on the teaching practice of technical teacher training students. In parallel to the new teacher training system mentor training has been introduced in Hungary. The details of the changes are surveyed and the mentoring tasks outlined.

We investigate a communication setup where a source output is sent through a free noisy channel first and an additional codeword is sent through a noiseless but expensive channel later. With the help of the second message the decoder should be able to decide with zero-error whether its decoding of the first message was error-free. This scenario leads to the definition of a digraph parameter that generalizes Witsenhausen's zero-error rate for directed graphs. We investigate this new parameter for some specific directed graphs and explore its relations to other digraph parameters like Sperner capacity and dichromatic number.When the original problem is modified to require zero-error decoding of the complete message then we arrive back to the Witsenhausen rate of an appropriately defined undirected graph.

Margatoxin (MgTx), an alpha-KTx scorpion toxin, is considered a selective inhibitor of the Kv1.3K + channel. This peptide is widely used in ion channel research; however, a comprehensive study of its selectivity with electrophysiological methods has not been published yet. The lack of selectivity might lead to undesired side effects upon therapeutic application or may lead to incorrect conclusion regarding the role of a particular ion channel in a physiological or pathophysiological response either in vitro or in vivo.Using the patch-clamp technique we characterized the selectivity profile of MgTx using L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing Kv1.3 channels and transiently transfected tsA201 cells expressing hKv1.1, hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, rKv2.1, Shaker-IR, hERG, hKCa1.1, hKCa3.1 and hNav1.5 channels. MgTx is indeed a high affinity inhibitor of Kv1.3 (Kd = 11.7 pM) but is not selective, it inhibits the Kv1.2 channel with similar affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM).Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3 inhibitor, and thus, experiments aiming at elucidating the significance of Kv13 in in vitro or in vivo physiological responses have to be carefully evaluated. (C) 2014 Elsevier Ltd. All rights reserved.

Brown, Nowakowski and Rall defined the ultimate categorical independence ratio of a graph G as A(G)=limk→∞i(G×k), where i(G)=α(G)|V(G)| denotes the independence ratio of a graph G, and G×k is the kth categorical power of G. Let a(G)=max{|U||U|+|NG(U)|:U is an independent set of G}, where NG(U) is the neighborhood of U in G. In this paper we answer a question of Alon and Lubetzky, namely we prove that A(G)=a(G) if a(G)⩽12, and A(G)=1 otherwise. We also discuss some other open problems related to A(G) which are immediately settled by this result.

For $r\geq 2$, $\alpha \geq r-1$ and $k\geq 1$, let $c(r,\alpha ,k)$ be the smallest integer $c$ such that the vertex set of any non-trivial $r$-uniform $k$-edge-colored hypergraph ${\cal H}$ with $\alpha ({\cal H})=\alpha$ can be covered by $c$ monochromatic connected components. Here $\alpha({\cal{H}})$ is the maximum cardinality of a subset $A$ of vertices in $\cal{H}$ such that $A$ does not contain any edges. An old conjecture of Ryser is equivalent to $c(2,\alpha,k)=\alpha (r-1)$ and a recent result of Z. Király states that $c(r,r-1,k)=\lceil \frac{k}{r}\rceil$ for any $r\ge 3$.Here we make the first step to treat non-complete hypergraphs, showing that $c(r,r,r)=2$ for $r\ge 2$ and $c(r,r,r+1)=3$ for $r\ge 3$.

Ion channel inhibitor peptide toxins have become lead compounds for potential therapeutic use in the last decade. In the case of Kv1.3, the voltage-gated K+ channel responsible for membrane potential control in lymphocytes, high affinity and selectivity toxins have been used to demonstrate therapeutic application of peptide inhibitors in vitro as well as in vivo. Margatoxin (MgTx) is often considered as a high affinity and selective inhibitor of the Kv1.3 channel. MgTx consists of 39 amino acids stabilized by 3 disulfide bridges isolated from the venom of the scorpion Centruroides margaritatus. This peptide is widely used in the area of ion channel research, often to verify Kv1.3 expression in the plasma membrane. However, a comprehensive study of its selectivity with electrophysiological methods has not been published yet. We conducted electrophysiological measurements with the patch-clamp technique in voltage clamp mode to test the selectivity of MgTx. Measurements were carried out on L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing Kv1.3 channels and transiently transfected tsA201 cells with the following ion channels: hKv1.1, hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, hKv2.1, Shaker-IR, hERG, hKCa1.1, hKCa3.1 and hNav1.5. Margatoxin is indeed a high affinity inhibitor of the Kv1.3 channel (Kd = 11.7 pM) but is not selective, since it inhibited Kv1.2 channel with similarly high affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM and 1.7 nM for human and murine Kv1.1 respectively). Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3 inhibitor, and thus, experiments aiming at elucidating the significance of Kv1.3 in in vitro or in vivo physiological responses using MgTx need to be carefully evaluated.

Abstract: During the last few decades many short-chain peptides have been isolated from the venom of different scorpion species. These toxins inhibit a variety of K+ channels by binding to and plugging the pore of the channels from the extracellular side thereby inhibiting ionic fluxes through the plasma membrane. The high affinity and selectivity of some toxins promote these peptides to become lead compounds for potential therapeutic use. Voltage-gated K+ channels can be classified into several families based on their gating properties and sequence homology. Members of a given family may have high sequence similarity, such as Kv1.1, Kv1.2 and Kv1.3 channels, therefore selective inhibitors of one specific channel are quite rare. The lack of selectivity of such peptides and the inhibition of more types of channels might lead to undesired side effects upon therapeutic application or may lead to incorrect conclusion regarding the role of a particular ion channel in a physiological or pathophysiological response either in vitro or in vivo. Margatoxin (MgTx) is often considered as a high affinity and selective inhibitor of the Kv1.3 channel. MgTx consists of 39 amino acids stabilized by 3 disulfide bridges isolated from the venom of the scorpion Centruroides margaritatus. This peptide is widely used in ion channel research, however, a comprehensive study of its selectivity with electrophysiological methods has not been published yet. Using the patch-clamp technique we conducted a comprehensive assessment of the selectivity of MgTx. Measurements were carried out on L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing Kv1.3 channels and transiently transfected tsA201 cells with the following ion channels: hKv1.1, hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, rKv2.1, Shaker-IR, hERG, hKCa1.1, hKCa3.1 and hNav1.5. Margatoxin is indeed high affinity inhibitor of Kv1.3 channel (Kd = 11.7 pM) but is not selective, since it inhibits the Kv1.2 channel with even higher affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM). Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3 inhibitor, and thus, experiments aiming at elucidating the significance of Kv1.3 in in vitro or in vivo physiological responses have to be carefully evaluated.

P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA)). The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX) in KB-V1 (Pgp+) cells in vitro almost to the level of KB-3-1 (Pgp-) cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID) mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET) based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs), it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC).

The study outlines the significant periods of technical teacher training in Hungary embedded in the harmonization process of the European diversity.

Assume that D is a digraph without cyclic triangles and its vertices are partitioned into classes A_1,...,A_t of independent vertices. A set $U=\cup_{i\in S} A_i$ is called a dominating set of size |S| if for any vertex $v\in \cup_{i\notin S} A_i$ there is a w in U such that (w,v) is in E(D). Let beta(D) be the cardinality of the largest independent set of D whose vertices are from different partite classes of D. Our main result says that there exists a h=h(beta(D)) such that D has a dominating set of size at most h. This result is applied to settle a problem related to generalized Gallai colorings, edge colorings of graphs without 3-colored triangles.

Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood–brain barrier.

We show that two results on covering of edge colored graphs by monochromatic connected parts can be extended to partitioning. We prove that for any $2$-edge-colored non-trivial $r$-uniform hypergraph $H$, the vertex set can be partitioned into at most $\alpha (H)-r+2$ monochromatic connected parts, where $\alpha (H)$ is the maximum number of vertices that does not contain any edge. In particular, any $2$-edge-colored graph $G$ can be partitioned into $\alpha(G)$ monochromatic connected parts, where $\alpha (G)$ denotes the independence number of $G$. This extends König's theorem, a special case of Ryser's conjecture. Our second result is about Gallai-colorings, i.e. edge-colorings of graphs without $3$-edge-colored triangles. We show that for any Gallai-coloring of a graph $G$, the vertex set of $G$ can be partitioned into monochromatic connected parts, where the number of parts depends only on $\alpha(G)$. This extends its cover-version proved earlier by Simonyi and two of the authors.

Brown, Nowakowski and Rall defined the ultimate categorical independence ratio of a graph G as A(G)=\lim_{k\to \infty} i(G^{\times k}), where i(G)=\frac{\alpha (G)}{|V(G)|} denotes the independence ratio of a graph G, and G^{\times k} is the k-th categorical power of G. Let a(G)=\max{\frac{|U|}{|U|+|N_G(U)|}: U is an independent set of G}}, where N_G(U) is the neighborhood of U in G. In this paper we answer a question of Alon and Lubetzky, namely we prove that if a(G)\le 1/2 then A(G)=a(G), and if a(G)>1/2 then A(G)=1. We also discuss some other open problems related to A(G) which are immediately settled by this result.

P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[F-18]fluoro-2-deoxy-D-glucose ((18)FDG) and [Tc-99m]hexakis-2-methoxybutyl isonitrile (Tc-99m-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells.Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2 mu M) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and Tc-99m-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50 mu M paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123. DNR and Tc-99m-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA + UIC2 or Pad l + UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, Tc-99m-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, Tc-99m-MIBI and (18)FDG. (C) 2010 Elsevier B.V. All rights reserved.

Körner and Malvenuto asked whether one can find $\binom{n}{\lfloor n/2\rfloor}$ linear orderings (i.e., permutations) of the first $n$ natural numbers such that any pair of them places two consecutive integers somewhere in the same position. This led to the notion of graph-different permutations. We extend this concept to directed graphs, focusing on orientations of the semi-infinite path whose edges connect consecutive natural numbers. Our main result shows that the maximum number of permutations satisfying all the pairwise conditions associated with all of the various orientations of this path is exponentially smaller, for any single orientation, than the maximum number of those permutations which satisfy the corresponding pairwise relationship. This is in sharp contrast to a result of Gargano, Körner, and Vaccaro concerning the analogous notion of Sperner capacity of families of finite graphs. We improve the exponential lower bound for the original problem and list a number of open questions.