Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding

Genome-wide binding preferences of the key components of eukaryotic pre-initiation complex (PIC) have been recently measured with high resolution in Saccharomyces cerevisiae by Rhee and Pugh (Nature (2012) 483:295-301). Yet the rules determining the PIC binding specificity remain poorly understood. In this study we show that nonconsensus protein-DNA binding significantly influences PIC binding preferences. We estimate that such nonconsensus binding contribute statistically at least 2-3 kcal/mol (on average) of additional attractive free energy per protein, per core promoter region. The predicted attractive effect is particularly strong at repeated poly(dA:dT) and poly(dC:dG) tracts. Overall, the computed free energy landscape of nonconsensus protein-DNA binding shows strong correlation with the measured genome-wide PIC occupancy. Remarkably, statistical PIC binding preferences to both TFIID-dominated and SAGA-dominated genes correlate with the nonconsensus free energy landscape, yet these two groups of genes are distinguishable based on the average free energy profiles. We suggest that the predicted nonconsensus binding mechanism provides a genome-wide background for specific promoter elements, such as transcription factor binding sites, TATA-like elements, and specific binding of the PIC components to nucleosomes. We also show that nonconsensus binding influences transcriptional frequency genome-wide

The Computational Power of Beeps

In this paper, we study the quantity of computational resources (state machine states and/or probabilistic transition precision) needed to solve specific problems in a single hop network where nodes communicate using only beeps. We begin by focusing on randomized leader election. We prove a lower bound on the states required to solve this problem with a given error bound, probability precision, and (when relevant) network size lower bound. We then show the bound tight with a matching upper bound. Noting that our optimal upper bound is slow, we describe two faster algorithms that trade some state optimality to gain efficiency. We then turn our attention to more general classes of problems by proving that once you have enough states to solve leader election with a given error bound, you have (within constant factors) enough states to simulate correctly, with this same error bound, a logspace TM with a constant number of unary input tapes: allowing you to solve a large and expressive set of problems. These results identify a key simplicity threshold beyond which useful distributed computation is possible in the beeping model.Comment: Extended abstract to appear in the Proceedings of the International Symposium on Distributed Computing (DISC 2015

Classical Bound for Mach-Zehnder Super-Resolution

The employment of path entangled multiphoton states enables measurement of phase with enhanced precision. It is common practice to demonstrate the unique properties of such quantum states by measuring super-resolving oscillations in the coincidence rate of a Mach-Zehnder interferometer. Similar oscillations, however, have also been demonstrated in various configurations using classical light only; making it unclear what, if any, are the classical limits of this phenomenon. Here we derive a classical bound for the visibility of super-resolving oscillations in a Mach-Zehnder. This provides an easy to apply, fundamental test of non-classicality. We apply this test to experimental multiphoton coincidence measurements obtained using photon number resolving detectors. Mach-Zehnder super-resolution is found to be a highly distinctive quantum effect.Comment: 4 pages, 4 figure, Comments welcom

NXNSAttack: Recursive DNS Inefficiencies and Vulnerabilities

This paper exposes a new vulnerability and introduces a corresponding attack, the NoneXistent Name Server Attack (NXNSAttack), that disrupts and may paralyze the DNS system, making it difficult or impossible for Internet users to access websites, web e-mail, online video chats, or any other online resource. The NXNSAttack generates a storm of packets between DNS resolvers and DNS authoritative name servers. The storm is produced by the response of resolvers to unrestricted referral response messages of authoritative name servers. The attack is significantly more destructive than NXDomain attacks (e.g., the Mirai attack): i) It reaches an amplification factor of more than 1620x on the number of packets exchanged by the recursive resolver. ii) In addition to the negative cache, the attack also saturates the 'NS' section of the resolver caches. To mitigate the attack impact, we propose an enhancement to the recursive resolver algorithm, MaxFetch(k), that prevents unnecessary proactive fetches. We implemented the MaxFetch(1) mitigation enhancement on a BIND resolver and tested it on real-world DNS query datasets. Our results show that MaxFetch(1) degrades neither the recursive resolver throughput nor its latency. Following the discovery of the attack, a responsible disclosure procedure was carried out, and several DNS vendors and public providers have issued a CVE and patched their systems

Fast Consensus under Eventually Stabilizing Message Adversaries

This paper is devoted to deterministic consensus in synchronous dynamic networks with unidirectional links, which are under the control of an omniscient message adversary. Motivated by unpredictable node/system initialization times and long-lasting periods of massive transient faults, we consider message adversaries that guarantee periods of less erratic message loss only eventually: We present a tight bound of $2D+1$ for the termination time of consensus under a message adversary that eventually guarantees a single vertex-stable root component with dynamic network diameter $D$, as well as a simple algorithm that matches this bound. It effectively halves the termination time $4D+1$ achieved by an existing consensus algorithm, which also works under our message adversary. We also introduce a generalized, considerably stronger variant of our message adversary, and show that our new algorithm, unlike the existing one, still works correctly under it.Comment: 13 pages, 5 figures, updated reference