Large N 2D Yang-Mills Theory and Topological String Theory

We describe a topological string theory which reproduces many aspects of the 1/N expansion of SU(N) Yang-Mills theory in two spacetime dimensions in the zero coupling (A=0) limit. The string theory is a modified version of topological gravity coupled to a topological sigma model with spacetime as target. The derivation of the string theory relies on a new interpretation of Gross and Taylor's ``\Omega^{-1} points.'' We describe how inclusion of the area, coupling of chiral sectors, and Wilson loop expectation values can be incorporated in the topological string approach.Comment: 95 pages, 15 Postscript figures, uses harvmac (Please use the "large" print option.) Extensive revisions of the sections on topological field theory. Added a compact synopsis of topological field theory. Minor typos corrected. References adde

Parameterized Complexity Results for General Factors in Bipartite Graphs with an Application to Constraint Programming

The NP-hard general factor problem asks, given a graph and for each vertex a list of integers, whether the graph has a spanning subgraph where each vertex has a degree that belongs to its assigned list. The problem remains NP-hard even if the given graph is bipartite with partition U+V, and each vertex in U is assigned the list {1}; this subproblem appears in the context of constraint programming as the consistency problem for the extended global cardinality constraint. We show that this subproblem is fixed-parameter tractable when parameterized by the size of the second partite set V. More generally, we show that the general factor problem for bipartite graphs, parameterized by |V|, is fixed-parameter tractable as long as all vertices in U are assigned lists of length 1, but becomes W[1]-hard if vertices in U are assigned lists of length at most 2. We establish fixed-parameter tractability by reducing the problem instance to a bounded number of acyclic instances, each of which can be solved in polynomial time by dynamic programming.Comment: Full version of a paper that appeared in preliminary form in the proceedings of IPEC'1

Stimuli-Responsive Polyguanidino-Oxanorbornene Membrane Transporters as Multicomponent Sensors in Complex Matrices

We introduce guanidinium-containing synthetic polymers based on polyguanidino-oxanorbornenes (PGONs) as anion transporters in lipid bilayers that can be activated and inactivated by chemical stimulation. According to fluorogenic anion export experiments with vesicles, PGON transporters are most active in neutral bilayers near their phase transition, with EC50's in the nanomolar range. Six times higher effective transporter concentrations were measured with aminonaphthalene-1,3,6-trisulfonate than with 5(6)-carboxyfluorescein, demonstrating the importance of anion binding for transport and excluding nonspecific efflux. Negative surface potentials efficiently annihilate transport activity, while inside-negative membrane potentials slightly increase it. These trends demonstrate the functional importance of counterions to hinder the binding of hydrophilic counterions and to minimize the global positive charge of the transporter-counterion complexes. Strong, nonlinear increases in activity with polymer length reveal a significant polymer effect. Overall, the characteristics of PGONs do not match those of similar systems (for example, polyarginine) and hint toward an interesting mode of action, clearly different from nonspecific leakage caused by detergents. The activity of PGONs increases in the presence of amphiphilic anions such as pyrenebutyrate (EC50 = 70 microM), while several other amphiphilic anions tested were inactive. PGONs are efficiently inactivated by numerous hydrophilic anions including ATP (IC 50 = 150 microM), ADP (IC50 = 460 microM), heparin (IC50 = 1.0 microM), phytate (IC50 = 0.4 microM), and CB hydrazide (IC50 = 26 microM). The compatibility of this broad responsiveness with multicomponent sensing in complex matrices is discussed and illustrated with lactate sensing in sour milk. The PGON lactate sensor operates together with lactate oxidase as a specific signal generator and CB hydrazide as an amplifier for covalent capture of the pyruvate product as CB hydrazone (IC50 = 1.5 microM)

Feeling-of-knowing experiences breed curiosity

A central tenet in theoretical work on metacognition is that retrieval experiences during memory search can exert control over behaviour. States of curiosity, which reflect motivational tendencies to seek out information, may play a critical role in this control function. We conducted two experiments to address this idea, focusing on links between feeling-of knowing (FOK) experiences, memory-search duration, and subsequent information-seeking behaviour. We administered an episodic FOK paradigm that probed memory for previously studied face-name pairs, and subsequently provided an opportunity to select limited pairs for restudy. This set-up allowed us to test whether current search duration and subsequent restudy choices are biased towards items with high FOK ratings. Results revealed a positive relationship between FOK ratings and the response times of these judgements. We observed a similar positive relationship between FOK ratings and subsequent item selection for restudy. Moreover, experimental manipulations of FOK ratings based on familiarity of the face cues also had parallel effects. Our findings suggest that metacognitive experiences during unsuccessful retrieval from episodic memory can induce states of curiosity that shape behaviour beyond the immediate retrieval context. Curiosity may act as a bond to ensure that memory gaps identified through unsuccessful retrieval adaptively guide future learning

Step size of the rotary proton motor in single FoF1-ATP synthase from a thermoalkaliphilic bacterium by DCO-ALEX FRET

Thermophilic enzymes can operate at higher temperatures but show reduced activities at room temperature. They are in general more stable during preparation and, accordingly, are considered to be more rigid in structure. Crystallization is often easier compared to proteins from bacteria growing at ambient temperatures, especially for membrane proteins. The ATP-producing enzyme FoF1-ATP synthase from thermoalkaliphilic Caldalkalibacillus thermarum strain TA2.A1 is driven by a Fo motor consisting of a ring of 13 c-subunits. We applied a single-molecule F\"orster resonance energy transfer (FRET) approach using duty cycle-optimized alternating laser excitation (DCO-ALEX) to monitor the expected 13-stepped rotary Fo motor at work. New FRET transition histograms were developed to identify the smaller step sizes compared to the 10-stepped Fo motor of the Escherichia coli enzyme. Dwell time analysis revealed the temperature and the LDAO dependence of the Fo motor activity on the single molecule level. Back-and-forth stepping of the Fo motor occurs fast indicating a high flexibility in the membrane part of this thermophilic enzyme.Comment: 14 pages, 7 figure

Designing the Metaverse

The Metaverse, a term coined in science fiction, is now being discussed seriously as a new form of infrastructure. The Metaverse is intended to make possible thematically interconnected immersive experiences. In this paper, we conceptualize the Metaverse as a meta design space. Within this space, designers create various interconnected design spaces. We highlight how the key dimensions of human experience (time, space, actors, and artifacts) each introduce tensions for making decisions in those design spaces, and we highlight the transitions between design spaces. This conceptual language opens up this novel and emergent phenomenon both to those wishing to design new disruptive technolo-gies and those seeking to improve existing platform strategies. We conclude by highlighting how the Metaverse will not only comprise immersive virtual experiences but also transitions between physical and virtual experiences

Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR

<p>Abstract</p> <p>Background</p> <p>Ranaviruses (family <it>Iridoviridae</it>) are important pathogens of lower vertebrates. However, little is known about how they circumvent the immune response of their hosts. Many ranaviruses contain a predicted protein, designated vIF2α, which shows homology with the eukaryotic translation initiation factor 2α. In analogy to distantly related proteins found in poxviruses vIF2α might act as an inhibitor of the antiviral protein kinase PKR.</p> <p>Results</p> <p>We have characterized the function of vIF2α from <it>Rana catesbeiana </it>virus Z (RCV-Z). Multiple sequence alignments and secondary structure prediction revealed homology of vIF2α with eIF2α throughout the S1-, helical- and C-terminal domains. Genetic and biochemical analyses showed that vIF2α blocked the toxic effects of human and zebrafish PKR in a heterologous yeast system. Rather than complementing eIF2α function, vIF2α acted in a manner comparable to the vaccinia virus (VACV) K3L protein (K3), a pseudosubstrate inhibitor of PKR. Both vIF2α and K3 inhibited human PKR-mediated eIF2α phosphorylation, but not PKR autophosphorylation on Thr446. In contrast the E3L protein (E3), another poxvirus inhibitor of PKR, inhibited both Thr446 and eIF2α Ser51 phosphorylation. Interestingly, phosphorylation of eIF2α by zebrafish PKR was inhibited by vIF2α and E3, but not by K3. Effective inhibition of PKR activity coincided with increased PKR expression levels, indicative of relieved autoinhibition of PKR expression. Experiments with vIF2α deletion constructs, showed that both the N-terminal and helical domains were sufficient for inhibition of PKR, whereas the C-terminal domain was dispensable.</p> <p>Conclusions</p> <p>Our results show that RCV-Z vIF2α is a functional inhibitor of human and zebrafish PKR, and probably functions in similar fashion as VACV K3. This constitutes an important step in understanding the interaction of ranaviruses and the host innate immune system.</p

Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α‑Fluorination of Ketenes: Synthetic and Mechanistic Studies

The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C_6F_5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C_6F_5ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N-acylpyridinium salt, have been examined