Testing Conditional Independence of Discrete Distributions

We study the problem of testing \emph{conditional independence} for discrete distributions. Specifically, given samples from a discrete random variable $(X, Y, Z)$ on domain $[\ell_1]\times[\ell_2] \times [n]$, we want to distinguish, with probability at least $2/3$, between the case that $X$ and $Y$ are conditionally independent given $Z$ from the case that $(X, Y, Z)$ is $\epsilon$-far, in $\ell_1$-distance, from every distribution that has this property. Conditional independence is a concept of central importance in probability and statistics with a range of applications in various scientific domains. As such, the statistical task of testing conditional independence has been extensively studied in various forms within the statistics and econometrics communities for nearly a century. Perhaps surprisingly, this problem has not been previously considered in the framework of distribution property testing and in particular no tester with sublinear sample complexity is known, even for the important special case that the domains of $X$ and $Y$ are binary. The main algorithmic result of this work is the first conditional independence tester with {\em sublinear} sample complexity for discrete distributions over $[\ell_1]\times[\ell_2] \times [n]$. To complement our upper bounds, we prove information-theoretic lower bounds establishing that the sample complexity of our algorithm is optimal, up to constant factors, for a number of settings. Specifically, for the prototypical setting when $\ell_1, \ell_2 = O(1)$, we show that the sample complexity of testing conditional independence (upper bound and matching lower bound) is \[ \Theta\left({\max\left(n^{1/2}/\epsilon^2,\min\left(n^{7/8}/\epsilon,n^{6/7}/\epsilon^{8/7}\right)\right)}\right)\,. \

Learning circuits with few negations

Monotone Boolean functions, and the monotone Boolean circuits that compute them, have been intensively studied in complexity theory. In this paper we study the structure of Boolean functions in terms of the minimum number of negations in any circuit computing them, a complexity measure that interpolates between monotone functions and the class of all functions. We study this generalization of monotonicity from the vantage point of learning theory, giving near-matching upper and lower bounds on the uniform-distribution learnability of circuits in terms of the number of negations they contain. Our upper bounds are based on a new structural characterization of negation-limited circuits that extends a classical result of A. A. Markov. Our lower bounds, which employ Fourier-analytic tools from hardness amplification, give new results even for circuits with no negations (i.e. monotone functions)

Musical coordination in a large group without plans nor leaders

A widespread belief is that large groups engaged in joint actions that require a high level of flexibility are unable to coordinate without the introduction of additional resources such as shared plans or hierarchical organizations. Here, we put this belief to a test, by empirically investigating coordination within a large group of 16 musicians performing collective free improvisation—a genre in which improvisers aim at creating music that is as complex and unprecedented as possible without relying on shared plans or on an external conductor. We show that musicians freely improvising within a large ensemble can achieve significant levels of coordination, both at the level of their musical actions (i.e., their individual decisions to play or to stop playing) and at the level of their directional intentions (i.e., their intentions to change or to support the music produced by the group). Taken together, these results invite us to reconsider the range and scope of actions achievable by large groups, and to explore alternative organizational models that emphasize decentralized and unscripted forms of collective behavior

Testing probability distributions underlying aggregated data

In this paper, we analyze and study a hybrid model for testing and learning probability distributions. Here, in addition to samples, the testing algorithm is provided with one of two different types of oracles to the unknown distribution $D$ over $[n]$. More precisely, we define both the dual and cumulative dual access models, in which the algorithm $A$ can both sample from $D$ and respectively, for any $i\in[n]$, - query the probability mass $D(i)$ (query access); or - get the total mass of $\{1,\dots,i\}$, i.e. $\sum_{j=1}^i D(j)$ (cumulative access) These two models, by generalizing the previously studied sampling and query oracle models, allow us to bypass the strong lower bounds established for a number of problems in these settings, while capturing several interesting aspects of these problems -- and providing new insight on the limitations of the models. Finally, we show that while the testing algorithms can be in most cases strictly more efficient, some tasks remain hard even with this additional power

Demographic profiles and environmental drivers of variation relate to individual breeding state in a long-lived trans-oceanic migratory seabird, the Manx shearwater

Understanding the points in a species breeding cycle when they are most vulnerable to environmental fluctuations is key to understanding interannual demography and guiding effective conservation and management. Seabirds represent one of the most threatened groups of birds in the world, and climate change and severe weather is a prominent and increasing threat to this group. We used a multi-state capture-recapture model to examine how the demographic rates of a long-lived trans-oceanic migrant seabird, the Manx shearwater Puffinus puffinus, are influenced by environmental conditions experienced at different stages of the annual breeding cycle and whether these relationships vary with an individual's breeding state in the previous year (i.e., successful breeder, failed breeder and non-breeder). Our results imply that populations of Manx shearwaters are comprised of individuals with different demographic profiles, whereby more successful reproduction is associated with higher rates of survival and breeding propensity. However, we found that all birds experienced the same negative relationship between rates of survival and wind force during the breeding season, indicating a cost of reproduction (or central place constraint for non-breeders) during years with severe weather conditions. We also found that environmental effects differentially influence the breeding propensity of individuals in different breeding states. This suggests individual spatio-temporal variation in habitat use during the annual cycle, such that climate change could alter the frequency that individuals with different demographic profiles breed thereby driving a complex and less predictable population response. More broadly, our study highlights the importance of considering individual-level factors when examining population demography and predicting how species may respond to climate change

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

Demographic profiles and environmental drivers of variation relate to individual breeding state in a long-lived trans-oceanic migratory seabird, the Manx shearwater.

Understanding the points in a species breeding cycle when they are most vulnerable to environmental fluctuations is key to understanding interannual demography and guiding effective conservation and management. Seabirds represent one of the most threatened groups of birds in the world, and climate change and severe weather is a prominent and increasing threat to this group. We used a multi-state capture-recapture model to examine how the demographic rates of a long-lived trans-oceanic migrant seabird, the Manx shearwater Puffinus puffinus, are influenced by environmental conditions experienced at different stages of the annual breeding cycle and whether these relationships vary with an individual's breeding state in the previous year (i.e., successful breeder, failed breeder and non-breeder). Our results imply that populations of Manx shearwaters are comprised of individuals with different demographic profiles, whereby more successful reproduction is associated with higher rates of survival and breeding propensity. However, we found that all birds experienced the same negative relationship between rates of survival and wind force during the breeding season, indicating a cost of reproduction (or central place constraint for non-breeders) during years with severe weather conditions. We also found that environmental effects differentially influence the breeding propensity of individuals in different breeding states. This suggests individual spatio-temporal variation in habitat use during the annual cycle, such that climate change could alter the frequency that individuals with different demographic profiles breed thereby driving a complex and less predictable population response. More broadly, our study highlights the importance of considering individual-level factors when examining population demography and predicting how species may respond to climate change

SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in C. elegans

Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans

SLC11A1 (NRAMP1) Polymorphisms and Tuberculosis Susceptibility: Updated Systematic Review and Meta-Analysis

Background: Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations. Methods: We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using metaanalysis. Results: In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17– 1.54), 1.25 (95 % CI, 1.04–1.50), 1.23 (95 % CI, 1.04–1.44), 1.31 (95%CI, 1.08–1.59) for 39 UTR, D543N, INT4, and 59 (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base. Conclusions: The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis