Deriving structural information from non-coding ribonucleic acids by mass spectrometry

The purpose of this study is to describe the development of application of mass spectrometry for the structural analyses of non-coding ribonucleic acids during past decade. Mass spectrometric methods are compared of traditional gel electrophoretic methods, the characteristics of performance of mass spectrometric, analyses are studied and the future trends of mass spectrometry of ribonucleic acids are discussed. Non-coding ribonucleic acids are short polymeric biomolecules which are not translated to proteins, but which may affect the gene expression in all organisms. Regulatory ribonucleic acids act through transient interactions with key molecules in signal transduction pathways. Interactions are mediated through specific secondary and tertiary structures. Posttranscriptional modifications in the structures of molecules may introduce new properties to the organism, such as adaptation to environmental changes or development of resistance to antibiotics. In the scope of this study, the structural studies include i) determination of the sequence of nucleobases in the polymer chain, ii) characterisation and localisation of posttranscriptional modifications in nucleobases and in the backbone structure, iii) identification of ribonucleic acid-binding molecules and iv) probing of higher order structures in the ribonucleic acid molecule. Bacteria, archaea, viruses and HeLa cancer cells have been used as target organisms. Synthesised ribonucleic acids consisting of structural regions of interest have been frequently used. Electrospray ionisation (ESI) and matrix-assisted laser desorption ionisation (MALDI) have been used for ionisation of ribonucleic analytes. Ammonium acetate and 2-propanol are common solvents for ESI. Trihydroxyacetophenone is the optimal MALDI matrix for ionisation of ribonucleic acids and peptides. Ammonium salts are used in ESI buffers and MALDI matrices as additives to remove cation adducts. Reverse phase high performance liquid chromatography has been used for desalting and fractionation of analytes either off-line of on-line, coupled with ESI source. Triethylamine and triethylammonium bicarbonate are used as ion pair reagents almost exclusively. Fourier transform ion cyclotron resonance analyser using ESI coupled with liquid chromatography is the platform of choice for all forms of structural analyses. Time-of-flight (TOF) analyser using MALDI may offer sensitive, easy-to-use and economical solution for simple sequencing of longer oligonucleotides and analyses of analyte mixtures without prior fractionation. Special analysis software is used for computer-aided interpretation of mass spectra. With mass spectrometry, sequences of 20-30 nucleotides of length may be determined unambiguously. Sequencing may be applied to quality control of short synthetic oligomers for analytical purposes. Sequencing in conjunction with other structural studies enables accurate localisation and characterisation of posttranscriptional modifications and identification of nucleobases and amino acids at the sites of interaction. High throughput screening methods for RNA-binding ligands have been developed. Probing of the higher order structures has provided supportive data for computer-generated three dimensional models of viral pseudoknots. In conclusion. mass spectrometric methods are well suited for structural analyses of small species of ribonucleic acids, such as short non-coding ribonucleic acids in the molecular size region of 20-30 nucleotides. Structural information not attainable with other methods of analyses, such as nuclear magnetic resonance and X-ray crystallography, may be obtained with the use of mass spectrometry. Sequencing may be applied to quality control of short synthetic oligomers for analytical purposes. Ligand screening may be used in the search of possible new therapeutic agents. Demanding assay design and challenging interpretation of data requires multidisclipinary knowledge. The implement of mass spectrometry to structural studies of ribonucleic acids is probably most efficiently conducted in specialist groups consisting of researchers from various fields of science.

Strategic Information Acquisition: Applications to Herding and Auctions

The information that the economic agents have and regard relevant to their decision making is often assumed to be exogenous in economics. It is assumed that the agents either poses or can observe the payoff relevant information without having to exert any effort to acquire it. In this thesis we relax the assumption of ex-ante fixed information structure and study what happens to the equilibrium behavior when the agents must also decide what information to acquire and when to acquire it. This thesis addresses this question in the two essays on herding and two essays on auction theory. In the first two essays, that are joint work with Klaus Kultti, we study herding models where it is costly to acquire information on the actions that the preceding agents have taken. In our model the agents have to decide both the action that they take and additionally the information that they want to acquire by observing their predecessors. We characterize the equilibrium behavior when the decision to observe preceding agents' actions is endogenous and show how the equilibrium outcome may differ from the standard model, where all preceding agents actions are assumed to be observable. In the latter part of this thesis we study two dynamic auctions: the English and the Dutch auction. We consider a situation where bidder(s) are uninformed about their valuations for the object that is put up for sale and they may acquire this information for a small cost at any point during the auction. We study the case of independent private valuations. In the third essay of the thesis we characterize the equilibrium behavior in an English auction when there are informed and uninformed bidders. We show that the informed bidder may jump bid and signal to the uninformed that he has a high valuation, thus deterring the uninformed from acquiring information and staying in the auction. The uninformed optimally acquires information once the price has passed a particular threshold and the informed has not signalled that his valuation is high. In addition, we provide an example of an information structure where the informed bidder initially waits and then makes multiple jumps. In the fourth essay of this thesis we study the Dutch auction. We consider two cases where all bidders are all initially uninformed. In the first case the information acquisition cost is the same across all bidders and in the second also the cost of information acquisition is independently distributed and private information to the bidders. We characterize a mixed strategy equilibrium in the first and a pure strategy equilibrium in the second case. In addition we provide a conjecture of an equilibrium in an asymmetric situation where there is one informed and one uninformed bidder. We compare the revenues that the first price auction and the Dutch auction generate and we find that under some circumstances the Dutch auction outperforms the first price sealed bid auction. The usual first price sealed bid auction and the Dutch auction are strategically equivalent. However, this equivalence breaks down in case information is acquired during the auction.

Molecular structure-activity relationship study of some non-steroidal antiinflammatory agents using electrostatic potential mapping

A series of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acids (DOAA) which are known to be anti-inflammatory agents were studied. The geometries of some of the molecules obtained from X-ray crystallography were used in the calculations as such while the geometries of their derivatives were obtained by local, partial geometry optimization around the Sites of substitution employing the AMI method, keeping the remaining parts of the geometries the same as those in the parent molecules. Molecular electrostatic potential (MEP) mapping was performed for the molecules using optimized hybridization displacement charges (HDC) combined with Lowdin charges, as this charge distribution has been shown earlier to yield near ab initio quality results. A good correlation has been found between the MEP values near the oxygen atoms of the hydroxyl groups of the carboxy groups of the molecules and their anti-inflammatory activities. The result is broadly in agreement with the model proposed earlier by other authors regarding the structure-activity relationship for other similar molecules.

Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies

Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (tp) a modified nucleobase, and nicotinamide (nie) or vitamin B3, and characterized by spectroscopy and X-ray crystallography. In vitro cytotoxicity studies of the complexes on various human cancer cell lines such as Colo295, H226, HOP62, K562, MCF7 and T24 show that Cu(PPh3)(2)(tp)Cl] and Cu(PPh3)(2)(tp)ClO4 (2) have in vitro cytotoxicity comparable to cisplatin. Complex Cu(nic)(3)PPh3]ClO4 (3) is non-toxic and increases the life span by about 55 % in spontaneous breast tumor model. DNA binding and cleavage studies show that complex (3) binds to calf thymus DNA with an apparent binding constant of 5.9 x 10(5)M and completely cleaves super-coiled DNA at a concentration of 400 mu M, whereas complexes (1) and (2) do not bind DNA and do not show any cleavage even at 1200 mu M. Thus, complex (3) may exhibit cytotoxicity Via DNA cleavage whereas the mechanism of cytotoxicity of (1) and (2) probably involves a different pathway.

A sharable instructable agent for information filtering

In this paper we present an information filtering agent called sharable instructable information filtering agent (SIIFA). It adopted the approach of sharable instructable agents. SIIFA provides comprehensible and flexible interaction to represent and filter the documents. The representation scheme in SIIFA is personalized. It, either fully or partly, can be shared among the users of the stream while not revealing their interests and can be easily edited. SIIFA is evaluated on the comp.ai.neural-nets Usent newsgroup documents and compared with the vector space method.

Forming Networks of Strategic Agents with Desired Topologies

Many networks such as social networks and organizational networks in global companies consist of self-interested agents. The topology of these networks often plays a crucial role in important tasks such as information diffusion and information extraction. Consequently, growing a stable network having a certain topology is of interest. Motivated by this, we study the following important problem: given a certain desired network topology, under what conditions would best response (link addition/deletion) strategies played by self-interested agents lead to formation of a stable network having that topology. We study this interesting reverse engineering problem by proposing a natural model of recursive network formation and a utility model that captures many key features. Based on this model, we analyze relevant network topologies and derive a set of sufficient conditions under which these topologies emerge as pairwise stable networks, wherein no node wants to delete any of its links and no two nodes would want to create a link between them.

Sufficient conditions for formation of a network topology by self-interested agents

Networks such as organizational network of a global company play an important role in a variety of knowledge management and information diffusion tasks. The nodes in these networks correspond to individuals who are self-interested. The topology of these networks often plays a crucial role in deciding the ease and speed with which certain tasks can be accomplished using these networks. Consequently, growing a stable network having a certain topology is of interest. Motivated by this, we study the following important problem: given a certain desired network topology, under what conditions would best response (link addition/deletion) strategies played by self-interested agents lead to formation of a pairwise stable network with only that topology. We study this interesting reverse engineering problem by proposing a natural model of recursive network formation. In this model, nodes enter the network sequentially and the utility of a node captures principal determinants of network formation, namely (1) benefits from immediate neighbors, (2) costs of maintaining links with immediate neighbors, (3) benefits from indirect neighbors, (4) bridging benefits, and (5) network entry fee. Based on this model, we analyze relevant network topologies such as star graph, complete graph, bipartite Turan graph, and multiple stars with interconnected centers, and derive a set of sufficient conditions under which these topologies emerge as pairwise stable networks. We also study the social welfare properties of the above topologies.

A Multi-phase Approach for Improving Information Diffusion in Social Networks

For maximizing influence spread in a social network, given a certain budget on the number of seed nodes, we investigate the effects of selecting and activating the seed nodes in multiple phases. In particular, we formulate an appropriate objective function for two-phase influence maximization under the independent cascade model, investigate its properties, and propose algorithms for determining the seed nodes in the two phases. We also study the problem of determining an optimal budget-split and delay between the two phases.

Evolution of Cooperation in the Snowdrift Game with Incomplete Information and Heterogeneous Population

Differently from previous studies of tag-based cooperation, we assume that individuals fail to recognize their own tag. Due to such incomplete information, the action taken against the opponent cannot be based on similarity, although it is still motivated by the tag displayed by the opponent. We present stability conditions for the case when individuals play unconditional cooperation, unconditional defection or conditional cooperation. We then consider the removal of one or two strategies. Results show that conditional cooperators are the most resilient agents against extinction and that the removal of unconditional cooperators may lead to the extinction of unconditional defectors.

Uncertain Information Structures and Backward Induction

In everyday economic interactions, it is not clear whether sequential choices are visible or not to other participants: agents might be deluded about opponents'capacity to acquire,interpret or keep track of data, or might simply unexpectedly forget what they previously observed (but not chose). Following this idea, this paper drops the assumption that the information structure of extensive-form games is commonly known; that is, it introduces uncertainty into players' capacity to observe each others' past choices. Using this approach, our main result provides the following epistemic characterisation: if players (i) are rational,(ii) have strong belief in both opponents' rationality and opponents' capacity to observe others' choices, and (iii) have common belief in both opponents' future rationality and op-ponents' future capacity to observe others' choices, then the backward induction outcome obtains. Consequently, we do not require perfect information, and players observing each others' choices is often irrelevant from a strategic point of view. The analysis extends {from generic games with perfect information to games with not necessarily perfect information{the work by Battigalli and Siniscalchi (2002) and Perea (2014), who provide different sufficient epistemic conditions for the backward induction outcome.

Effect of information transmission on cooperative behavior

Considering the fact, in the real world, that information is transmitted with a time delay, we study an evolutionary spatial prisoner's dilemma game where agents update strategies according to certain information that they have learned. In our study, the game dynamics are classified by the modes of information learning as well as game interaction, and four different combinations, i.e. the mean-field case, case I, case II and local case, are studied comparatively. It is found that the time delay in case II smoothes the phase transition from the absorbing states of C (or D) to their mixing state, and promotes cooperation for most parameter values. Our work provides insights into the temporal behavior of information and the memory of the system, and may be helpful in understanding the cooperative behavior induced by the time delay in social and biological systems.

Novel information sharing syntax for data sharing between police and community partners, using role-based security.

The exchange of information between the police and community partners forms a central aspect of effective community service provision. In the context of policing, a robust and timely communications mechanism is required between police agencies and community partner domains, including: Primary healthcare (such as a Family Physician or a General Practitioner); Secondary healthcare (such as hospitals); Social Services; Education; and Fire and Rescue services. Investigations into high-profile cases such as the Victoria Climbié murder in 2000, the murders of Holly Wells and Jessica Chapman in 2002, and, more recently, the death of baby Peter Connelly through child abuse in 2007, highlight the requirement for a robust information-sharing framework. This paper presents a novel syntax that supports information-sharing requests, within strict data-sharing policy definitions. Such requests may form the basis for any information-sharing agreement that can exist between the police and their community partners. It defines a role-based architecture, with partner domains, with a syntax for the effective and efficient information sharing, using SPoC (Single Point-of-Contact) agents to control in-formation exchange. The application of policy definitions using rules within these SPoCs is inspired by network firewall rules and thus define information exchange permissions. These rules can be imple-mented by software filtering agents that act as information gateways between partner domains. Roles are exposed from each domain to give the rights to exchange information as defined within the policy definition. This work involves collaboration with the Scottish Police, as part of the Scottish Institute for Policing Research (SIPR), and aims to improve the safety of individuals by reducing risks to the community using enhanced information-sharing mechanisms.

The Influence of Epistemology on the Design of Artificial Agents

Lee, M. H., Lacey, N. J. (2003). The Influence of Epistemology on the Design of Artificial Agents. Minds and Machines, 13 (3), 367-395

A decentralized model of information pricing in networks

We propose a recursive method of pricing an information good in a network of holders and demanders of this good. The prices are determined via a unique equilibrium outcome in a sequence of bilateral bargaining games that are played by connected agents. If the information is an homogenous, non-depreciating good without network effects we derive explicit formulae which elucidate the role of the link pattern among the players. Particularly, we find out that the equilibrium price is intimately related to the existence of cycles in the network: It is zero if a cycle covers the trading pair and it is proportional to the direct and indirect utility that the good generates otherwise.