Alexander S. Kulikov

SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing

The lions share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

A new approach to proving upper bounds for MAX-2-SAT

In this paper we present a new approach to proving upper bounds for the maximum 2-satisfiability problem (MAX-2-SAT). We present a new 2K/5.5-time algorithm for MAX-2-SAT, where K is the number of clauses in an input formula. We also obtain a 2N/6 bound, where N is the number of variables in an input formula, for a particular case of MAX-2-SAT, where each variable appears in at most three 2-clauses. This immediately implies a 2N/6 bound, where N is the number of vertices in an input graph, for the independent set problem on 3-regular graphs. The key point of our improvement is a combined complexity measure for estimating the running time of an algorithm. By using a new complexity measure we are able to provide a much simpler proof of new upper bounds for MAX-2-SAT than proofs of previously known bounds.

Vasorelaxant and antiplatelet activity of 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide: role of soluble guanylate cyclase, nitric oxide and thiols

Certain heterocyclic N‐oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity of the furoxan derivative condensed with pyridazine di‐N‐oxide 4,7‐dimethyl‐1,2,5‐oxadiazolo[3,4‐d]pyridazine 1,5,6‐trioxide (FPTO) and the corresponding furazan (FPDO) was studied. FPTO reacted with thiols generating nitrite (NO), S‐nitrosoglutathione and hydroxylamine (nitroxyl) and converted oxyHb to metHb. FPDO did not generate detectable amounts of NO‐like species but reacted with thiols and oxyHb. FPTO and FPDO haem‐dependently stimulated the activity of soluble guanylate cyclase (sGC) and this stimulation was inhibited by 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and by 0.1 mM dithiothreitol. FPTO relaxed noradrenaline‐precontracted aortic rings and its concentration‐response curve was biphasic (pIC50=9.03±0.13 and 5.85±0.06). FPDO was significantly less potent vasodilator (pIC50=5.19±0.14). The vasorelaxant activity of FPTO and FPDO was inhibited by ODQ. oxyHb significantly inhibited only FPTO‐dependent relaxation. FPTO and FPDO were equipotent inhibitors of ADP‐induced platelet aggregation (IC50=0.63±0.15 and 0.49±0.05 μM, respectively). The antiplatelet activity of FPTO (but not FPDO) was partially suppressed by oxyHb. The antiaggregatory effects of FPTO and FPDO were only partially blocked by sGC inhibitors. FPTO and FPDO (10–20 μM) significantly increased cyclic GMP levels in aortic rings and platelets and this increase was blocked by ODQ. Thus, FPTO can generate NO and, like FPDO, reacts with thiols and haem. The vasorelaxant activity of FPTO and FPDO is sGC‐dependent and a predominant role is played by NO at FPTO concentrations below 1 μM. On the contrary, inhibition of platelet aggregation is only partially related to sGC activation.

Experimental hypothyroidism increases immobility in rats in the forced swim paradigm

Effects of severe and mild hypothyroidism on the immobile response to inescapable stress were examined in male Wistar rats using the forced swim paradigm. Rats were exposed to two sessions of inescapable swim stress: pretest (for 15 min) followed by test (for 5 min) 24 h later. Surgically thyroidectomized rats showed a significant increase (by 90%) in immobility during test compared to sham rats. Chronic administration of high (200 micrograms/kg per day) but not low (15 micrograms/kg per day) dose of T4 prevented the increase in immobility in thyroidectomized rats. Normal rats submitted to iodine-free diet for 2 weeks in order to produce a mild hypothyroidism showed a significant increase (by 60%) in immobility time during test compared to control rats. The results indicate that hypothyroid rats are more vulnerable to inescapable stress than normothyroid rats.

Synthesis of hetarylsulfanyl- and hetaryloxyfuroxans by nucleophilic substitution of nitro group in nitrofuroxans with heterocyclic thiol and hydroxy derivatives*

We report a general method for the synthesis of previously unknown heterocyclic systems containing furoxan and heterocyclic fragments linked by S- and О-bridges, based on nucleophilic substitution of nitro group in 4-nitrofuroxans with HetS and HetO groups introduced by reactions with hetarylthiols and hydroxy heterocycles in 1,8-diazabicyclo[5.4.0]undec-7-ene/МеCN system at room temperature. We showed that hetarylthiols reacted with 4-nitrofuroxans containing aliphatic, benzyl, and aromatic substituents at the ring С-3 atom, allowing to obtain a library of previously unknown hetarylsulfanylfuroxans, while the reaction with hydroxy heterocycles was successful only in the case of 4-nitro-3-phenylfuroxan, the rest of the nitrofuroxans showing low reactivity, and substitution products could be obtained only in certain cases. 4-Nitrofuroxans with electron-withdrawing substituents (NO2, CONH2) acted as oxidants, forming 1,2-di(hetaryl)disulfides.

An elementary proof of a 3n - o(n) lower bound on the circuit complexity of affine dispersers

A Boolean function f: F2n → F2 is called an affine disperser of dimension d, if f is not constant on any affine subspace of F2n of dimension at least d. Recently Ben-Sasson and Kopparty gave an explicit construction of an affine disperser for sublinear d. The main motivation for studying such functions comes from extracting randomness from structured sources of imperfect randomness. In this paper, we show another application: we give a very simple proof of a 3n-o(n) lower bound on the circuit complexity (over the full binary basis) of affine dispersers for sublinear dimension. The same lower bound 3n-o(n) (but for a completely different function) was given by Blum in 1984 and is still the best known. The main technique is to substitute variables by linear functions. This way the function is restricted to an affine subspace of F2n. An affine disperser for sublinear dimension then guarantees that one can make n - o(n) such substitutions before the function degenerates. It remains to show that each such substitution eliminates at least 3 gates from a circuit.

Note: On covering graphs by complete bipartite subgraphs

We prove that, if a graph with e edges contains m vertex-disjoint edges, then m^2/e complete bipartite subgraphs are necessary to cover all its edges. Similar lower bounds are also proved for fractional covers. For sparse graphs, this improves the well-known fooling set lower bound in communication complexity. We also formulate several open problems about covering problems for graphs whose solution would have important consequences in the complexity theory of boolean functions.

Synthesis of furoxan derivatives based on 4-aminofuroxan-3-carboxylic acid azide

A convenient preparative method was developed for the synthesis of 4-amino-3-furoxancarboxylic acid azide, which is a universal synthon for the preparation of functional furoxan derivatives. This method was used for preparing new azo-, azoxy-, azido-, cyano-, nitro-, carbonylamino-, and hydroxylamino-substituted furoxan derivatives, which have earlier been difficultly accessible.

Finding Efficient Circuits Using SAT-Solvers

In this paper we report preliminary results of experiments with finding efficient circuits (over binary bases) using SAT-solvers. We present upper bounds for functions with constant number of inputs as well as general upper bounds that were found automatically. We focus mainly on MOD-functions. Besides theoretical interest, these functions are also interesting from a practical point of view as they are the core of the residue number system. In particular, we present a circuit of size 3n + c over the full binary basis computing

Automated Proofs of Upper Bounds on the Running Time of Splitting Algorithms

{\rm MOD}_3^n