Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8.

BackgroundThe Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs. The Microprocessor regulates its own levels by cleaving hairpins in the 5'UTR and coding region of the Dgcr8 mRNA, thereby destabilizing the mature transcript.Methodology/principal findingsTo determine whether the Microprocessor has a broader role in directly regulating other coding mRNA levels, we integrated results from expression profiling and ultra high-throughput deep sequencing of small RNAs. Expression analysis of mRNAs in wild-type, Dgcr8 knockout, and Dicer knockout mouse embryonic stem (ES) cells uncovered mRNAs that were specifically upregulated in the Dgcr8 null background. A number of these transcripts had evolutionarily conserved predicted hairpin targets for the Microprocessor. However, analysis of deep sequencing data of 18 to 200nt small RNAs in mouse ES, HeLa, and HepG2 indicates that exonic sequence reads that map in a pattern consistent with Microprocessor activity are unique to Dgcr8.Conclusion/significanceWe conclude that the Microprocessor's role in directly destabilizing coding mRNAs is likely specifically targeted to Dgcr8 itself, suggesting a specialized cellular mechanism for gene auto-regulation

Array languages and the challenges of modern computer architecture

There has always been a close relationship between programming language design and computer design. Electronic computers and programming languages are both 'computers' in Turing's sense. They are systems which allow the performance of bounded universal computation. Each allows any computable function to be evaluated, up to some memory limit. This equivalence has been understood since the 30s' when Turing machines (Turing 1937) were shown to be of the same computational power as the λ calculus

Efficient Construction of Probabilistic Tree Embeddings

In this paper we describe an algorithm that embeds a graph metric $(V,d_G)$ on an undirected weighted graph $G=(V,E)$ into a distribution of tree metrics $(T,D_T)$ such that for every pair $u,v\in V$, $d_G(u,v)\leq d_T(u,v)$ and ${\bf{E}}_{T}[d_T(u,v)]\leq O(\log n)\cdot d_G(u,v)$. Such embeddings have proved highly useful in designing fast approximation algorithms, as many hard problems on graphs are easy to solve on tree instances. For a graph with $n$ vertices and $m$ edges, our algorithm runs in $O(m\log n)$ time with high probability, which improves the previous upper bound of $O(m\log^3 n)$ shown by Mendel et al.\,in 2009. The key component of our algorithm is a new approximate single-source shortest-path algorithm, which implements the priority queue with a new data structure, the "bucket-tree structure". The algorithm has three properties: it only requires linear time in the number of edges in the input graph; the computed distances have a distance preserving property; and when computing the shortest-paths to the $k$-nearest vertices from the source, it only requires to visit these vertices and their edge lists. These properties are essential to guarantee the correctness and the stated time bound. Using this shortest-path algorithm, we show how to generate an intermediate structure, the approximate dominance sequences of the input graph, in $O(m \log n)$ time, and further propose a simple yet efficient algorithm to converted this sequence to a tree embedding in $O(n\log n)$ time, both with high probability. Combining the three subroutines gives the stated time bound of the algorithm. Then we show that this efficient construction can facilitate some applications. We proved that FRT trees (the generated tree embedding) are Ramsey partitions with asymptotically tight bound, so the construction of a series of distance oracles can be accelerated

Detection of potential space station control/structure interaction with CO-ST-IN

The NASA Lewis Research Center is concerned with the potential of interaction between space station controllers and the solar PV array structures. The models required to handle this problem are very large, and automated methods were developed for the transfer of data between structural dynamic and control system analysis software. These methods emphasize the need to achieve accurate coupled analysis results while using as small a model as possible. Specific tools which help the analyst in this regard include modal order techniques, the use of mode acceleration to calculate internal loads and stresses and the transfer of Craig-Bampton components to reduce problems associated with modal sufficiency. These techniques were applied to a space station model with 366 modes below 1 Hz. Attitude control, and alpha and beta joint control were simulated. The inclusion of alpha and beta joint controllers is important when examining overall space station dynamics. An initial choice of control parameters does indicate a potential for control/structure interaction during reboost. As expected this is exacerbated by increasing the rate gain and decreasing the hysteresis of the reaction control system (RCS) in order to improve rigid body performance

microRNA induced transdifferentiation

Recent months have seen rapid advances in the field of transdifferentiation, specifically in the conversion of fibroblasts to neurons. Most surprising is the observation that the ability to drive these transitions is not limited to transcription factors, but that they can be promoted by microRNAs as well. Indeed, in one case, microRNAs alone induced the transdifferentiation of fibroblasts to neuron-like cells, albeit at a low efficiency. Here, we review this rapidly advancing field, discuss possible mechanisms underlying microRNA-induced transdifferentiation and the potential for microRNAs to drive such transitions to any cell type of interest in vitro and in vivo

The Log-Interleave Bound: Towards the Unification of Sorting and the BST Model

We study the connections between sorting and the binary search tree model, with an aim towards showing that the fields are connected more deeply than is currently known. The main vehicle of our study is the log-interleave bound, a measure of the information-theoretic complexity of a permutation $\pi$. When viewed through the lens of adaptive sorting -- the study of lists which are nearly sorted according to some measure of disorder -- the log-interleave bound is comparable to the most powerful known measure of disorder. Many of these measures of disorder are themselves virtually identical to well-known upper bounds in the BST model, such as the working set bound or the dynamic finger bound, suggesting a connection between BSTs and sorting. We present three results about the log-interleave bound which solidify the aforementioned connections. The first is a proof that the log-interleave bound is always within a $\lg \lg n$ multiplicative factor of a known lower bound in the BST model, meaning that an online BST algorithm matching the log-interleave bound would perform within the same bounds as the state-of-the-art $\lg \lg n$-competitive BST. The second result is an offline algorithm in the BST model which uses $O(\text{LIB}(\pi))$ accesses to search for any permutation $\pi$. The technique used to design this algorithm also serves as a general way to show whether a sorting algorithm can be transformed into an offline BST algorithm. The final result is a mergesort algorithm which performs work within the log-interleave bound of a permutation $\pi$. This mergesort also happens to be highly parallel, adding to a line of work in parallel BST operations

Unified control/structure design and modeling research

To demonstrate the applicability of the control theory for distributed systems to large flexible space structures, research was focused on a model of a space antenna which consists of a rigid hub, flexible ribs, and a mesh reflecting surface. The space antenna model used is discussed along with the finite element approximation of the distributed model. The basic control problem is to design an optimal or near-optimal compensator to suppress the linear vibrations and rigid-body displacements of the structure. The application of an infinite dimensional Linear Quadratic Gaussian (LQG) control theory to flexible structure is discussed. Two basic approaches for robustness enhancement were investigated: loop transfer recovery and sensitivity optimization. A third approach synthesized from elements of these two basic approaches is currently under development. The control driven finite element approximation of flexible structures is discussed. Three sets of finite element basic vectors for computing functional control gains are compared. The possibility of constructing a finite element scheme to approximate the infinite dimensional Hamiltonian system directly, instead of indirectly is discussed