On The I/O Complexity of Dynamic Distinct Counting

In dynamic distinct counting, we want to maintain a multi-set S of integers under insertions to answer efficiently the query: how many distinct elements are there in S? In external memory, the problem admits two standard solutions. The first one maintains $S$ in a hash structure, so that the distinct count can be incrementally updated after each insertion using O(1) expected I/Os. A query is answered for free. The second one stores S in a linked list, and thus supports an insertion in O(1/B) amortized I/Os. A query can be answered in O(N/B log_{M/B} (N/B)) I/Os by sorting, where N=|S|, B is the block size, and M is the memory size. In this paper, we show that the above two naive solutions are already optimal within a polylog factor. Specifically, for any Las Vegas structure using N^{O(1)} blocks, if its expected amortized insertion cost is o(1/log B}), then it must incur Omega(N/(B log B)) expected I/Os answering a query in the worst case, under the (realistic) condition that N is a polynomial of B. This means that the problem is repugnant to update buffering: the query cost jumps from 0 dramatically to almost linearity as soon as the insertion cost drops slightly below Omega(1)

Glycinergic feedback enhances synaptic gain in the distal retina

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of the Physiological Society for personal use, not for redistribution. The definitive version was published in Journal of Physiology 592 (2014): 1479-1492, doi:10.1113/jphysiol.2013.265785.Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole-cell recordings, intracellular recordings, and specific antibody labeling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors, and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the post-synaptic glycine currents from axon-detached bipolar cells while stimulating pre-synaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors, and suppresses the uptake of glutamate by the EAAT2 transporter on photoreceptors. The net effect is a significant increase in the synaptic gain between photoreceptors and their second-order neurons.This study was supported by grants from the National Science Foundation (NSF, IOS-1021646, WS) and the National Eye Institute (NEI, EY 14161, WS)

Endogenous small-noncoding RNAs and their roles in chilling response and stress acclimation in Cassava

BACKGROUND: Small noncoding RNA (sncRNA), including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs) are key gene regulators in eukaryotes, playing critical roles in plant development and stress tolerance. Trans-acting siRNAs (ta-siRNAs), which are secondary siRNAs triggered by miRNAs, and siRNAs from natural antisense transcripts (nat-siRNAs) are two well-studied classes of endo-siRNAs. RESULTS: In order to understand sncRNAs’ roles in plant chilling response and stress acclimation, we performed a comprehensive study of miRNAs and endo-siRNAs in Cassava (Manihot esculenta), a major source of food for the world populations in tropical regions. Combining Next-Generation sequencing and computational and experimental analyses, we profiled and characterized sncRNA species and mRNA genes from the plants that experienced severe and moderate chilling stresses, that underwent further severe chilling stress after chilling acclimation at moderate stress, and that grew under the normal condition. We also included castor bean (Ricinus communis) in our study to understand conservation of sncRNAs. In addition to known miRNAs, we identified 32 (22 and 10) novel miRNAs as well as 47 (26 and 21) putative secondary siRNA-yielding and 8 (7 and 1) nat-siRNA-yielding candidate loci in Cassava and castor bean, respectively. Among the expressed sncRNAs, 114 miRNAs, 12 ta-siRNAs and 2 nat-siRNAs showed significant expression changes under chilling stresses. CONCLUSION: Systematic and computational analysis of microRNAome and experimental validation collectively showed that miRNAs, ta-siRNAs, and possibly nat-siRNAs play important roles in chilling response and chilling acclimation in Cassava by regulating stress-related pathways, e.g. Auxin signal transduction. The conservation of these sncRNA might shed lights on the role of sncRNA-mediated pathways affected by chilling stress and stress acclimation in Euphorbiaceous plants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-634) contains supplementary material, which is available to authorized users

Genome-wide comparison of DNA hydroxymethylation in mouse embryonic stem cells and neural progenitor cells by a new comparative hMeDIP-seq method

The genome-wide distribution patterns of the ‘6th base’ 5-hydroxymethylcytosine (5hmC) in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, it has been challenging to directly compare different data sets and samples using data generated by this method. Here, we report a new comparative hMeDIP-seq method, which involves barcoding different input DNA samples at the start and then performing hMeDIP-seq for multiple samples in one hMeDIP reaction. This approach extends the barcode technology from simply multiplexing the DNA deep sequencing outcome and provides significant advantages for quantitative control of all experimental steps, from unbiased hMeDIP to deep sequencing data analysis. Using this improved method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESC-derived neural progenitor cells (NPCs). We identified differentially hydroxymethylated regions (DHMRs) between ESCs and NPCs and uncovered an intricate relationship between the alteration of DNA hydroxymethylation and changes in gene expression during neural lineage commitment of ESCs. Presumably, the DHMRs between ESCs and NPCs uncovered by this approach may provide new insight into the function of 5hmC in gene regulation and neural differentiation. Thus, this newly developed comparative hMeDIP-seq method provides a cost-effective and user-friendly strategy for direct genome-wide comparison of DNA hydroxymethylation across multiple samples, lending significant biological, physiological and clinical implications