The Equivalence of Sampling and Searching

In a sampling problem, we are given an input x, and asked to sample approximately from a probability distribution D_x. In a search problem, we are given an input x, and asked to find a member of a nonempty set A_x with high probability. (An example is finding a Nash equilibrium.) In this paper, we use tools from Kolmogorov complexity and algorithmic information theory to show that sampling and search problems are essentially equivalent. More precisely, for any sampling problem S, there exists a search problem R_S such that, if C is any "reasonable" complexity class, then R_S is in the search version of C if and only if S is in the sampling version. As one application, we show that SampP=SampBQP if and only if FBPP=FBQP: in other words, classical computers can efficiently sample the output distribution of every quantum circuit, if and only if they can efficiently solve every search problem that quantum computers can solve. A second application is that, assuming a plausible conjecture, there exists a search problem R that can be solved using a simple linear-optics experiment, but that cannot be solved efficiently by a classical computer unless the polynomial hierarchy collapses. That application will be described in a forthcoming paper with Alex Arkhipov on the computational complexity of linear optics.Comment: 16 page

Computer-aided verification in mechanism design

In mechanism design, the gold standard solution concepts are dominant strategy incentive compatibility and Bayesian incentive compatibility. These solution concepts relieve the (possibly unsophisticated) bidders from the need to engage in complicated strategizing. While incentive properties are simple to state, their proofs are specific to the mechanism and can be quite complex. This raises two concerns. From a practical perspective, checking a complex proof can be a tedious process, often requiring experts knowledgeable in mechanism design. Furthermore, from a modeling perspective, if unsophisticated agents are unconvinced of incentive properties, they may strategize in unpredictable ways. To address both concerns, we explore techniques from computer-aided verification to construct formal proofs of incentive properties. Because formal proofs can be automatically checked, agents do not need to manually check the properties, or even understand the proof. To demonstrate, we present the verification of a sophisticated mechanism: the generic reduction from Bayesian incentive compatible mechanism design to algorithm design given by Hartline, Kleinberg, and Malekian. This mechanism presents new challenges for formal verification, including essential use of randomness from both the execution of the mechanism and from the prior type distributions. As an immediate consequence, our work also formalizes Bayesian incentive compatibility for the entire family of mechanisms derived via this reduction. Finally, as an intermediate step in our formalization, we provide the first formal verification of incentive compatibility for the celebrated Vickrey-Clarke-Groves mechanism

The significance of GATA3 expression in breast cancer: a 10-year follow-up study.

GATA3 is a transcription factor closely associated with estrogen receptor alpha in breast carcinoma, with a potential prognostic utility. This study investigated the immunohistochemical expression of GATA3 in estrogen receptor alpha-positive and estrogen receptor alpha-negative breast carcinomas. One hundred sixty-six cases of invasive breast carcinomas with 10-year follow-up information were analyzed. Positive GATA3 and estrogen receptor alpha cases were defined as greater than 20% of cells staining. Time to cancer recurrence and time to death were analyzed with survival methods. Of 166 patients, 40 were estrogen receptor alpha negative and 121 estrogen receptor alpha positive. Thirty-eight (23%) recurrences and 51 (31%) deaths were observed. In final multivariable analyses, GATA3-positive tumors had about two thirds the recurrence risk of GATA3-negative tumors (hazard ratio = 0.65, P = .395) and comparable mortality risk (hazard ratio = 0.86, P = .730). In prespecified subgroup analyses, the protective effect of GATA3 expression was most pronounced among estrogen receptor alpha-positive patients who received tamoxifen (hazard ratio = 0.57 for recurrence and 0.68 for death). We found no statistically significant differences in recurrence or survival rates between GATA3-positive and GATA3-negative tumors. However, there was a suggestion of a modest-to-strong protective effect of GATA3 expression among estrogen receptor alpha-positive patients receiving hormone therapy

The Complexity of Nash Equilibria in Simple Stochastic Multiplayer Games

We analyse the computational complexity of finding Nash equilibria in simple stochastic multiplayer games. We show that restricting the search space to equilibria whose payoffs fall into a certain interval may lead to undecidability. In particular, we prove that the following problem is undecidable: Given a game G, does there exist a pure-strategy Nash equilibrium of G where player 0 wins with probability 1. Moreover, this problem remains undecidable if it is restricted to strategies with (unbounded) finite memory. However, if mixed strategies are allowed, decidability remains an open problem. One way to obtain a provably decidable variant of the problem is restricting the strategies to be positional or stationary. For the complexity of these two problems, we obtain a common lower bound of NP and upper bounds of NP and PSPACE respectively.Comment: 23 pages; revised versio

The impact of temperature changes on summer time ozone and its precursors in the Eastern Mediterranean

Changes in temperature due to variability in meteorology and climate change are expected to significantly impact atmospheric composition. The Mediterranean is a climate sensitive region and includes megacities like Istanbul and large urban agglomerations such as Athens. The effect of temperature changes on gaseous air pollutant levels and the atmospheric processes that are controlling them in the Eastern Mediterranean are here investigated. The WRF/CMAQ mesoscale modeling system is used, coupled with the MEGAN model for the processing of biogenic volatile organic compound emissions. A set of temperature perturbations (spanning from 1 to 5 K) is applied on a base case simulation corresponding to July 2004. The results indicate that the Eastern Mediterranean basin acts as a reservoir of pollutants and their precursor emissions from large urban agglomerations. During summer, chemistry is a major sink at these urban areas near the surface, and a minor contributor at downwind areas. On average, the atmospheric processes are more effective within the first 1000 m above ground. Temperature increases lead to increases in biogenic emissions by 9±3% K<sup>−1</sup>. Ozone mixing ratios increase almost linearly with the increases in ambient temperatures by 1±0.1 ppb O<sub>3</sub> K<sup>−1</sup> for all studied urban and receptor stations except for Istanbul, where a 0.4±0.1 ppb O<sub>3</sub> K<sup>−1</sup> increase is calculated, which is about half of the domain-averaged increase of 0.9±0.1 ppb O<sub>3</sub> K<sup>−1</sup>. The computed changes in atmospheric processes are also linearly related with temperature changes

Circular Networks from Distorted Metrics

Trees have long been used as a graphical representation of species relationships. However complex evolutionary events, such as genetic reassortments or hybrid speciations which occur commonly in viruses, bacteria and plants, do not fit into this elementary framework. Alternatively, various network representations have been developed. Circular networks are a natural generalization of leaf-labeled trees interpreted as split systems, that is, collections of bipartitions over leaf labels corresponding to current species. Although such networks do not explicitly model specific evolutionary events of interest, their straightforward visualization and fast reconstruction have made them a popular exploratory tool to detect network-like evolution in genetic datasets. Standard reconstruction methods for circular networks, such as Neighbor-Net, rely on an associated metric on the species set. Such a metric is first estimated from DNA sequences, which leads to a key difficulty: distantly related sequences produce statistically unreliable estimates. This is problematic for Neighbor-Net as it is based on the popular tree reconstruction method Neighbor-Joining, whose sensitivity to distance estimation errors is well established theoretically. In the tree case, more robust reconstruction methods have been developed using the notion of a distorted metric, which captures the dependence of the error in the distance through a radius of accuracy. Here we design the first circular network reconstruction method based on distorted metrics. Our method is computationally efficient. Moreover, the analysis of its radius of accuracy highlights the important role played by the maximum incompatibility, a measure of the extent to which the network differs from a tree.Comment: Submitte

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Alignment-Free Phylogenetic Reconstruction

14th Annual International Conference, RECOMB 2010, Lisbon, Portugal, April 25-28, 2010. ProceedingsWe introduce the first polynomial-time phylogenetic reconstruction algorithm under a model of sequence evolution allowing insertions and deletions (or indels). Given appropriate assumptions, our algorithm requires sequence lengths growing polynomially in the number of leaf taxa. Our techniques are distance-based and largely bypass the problem of multiple alignment