Lambda-prophage induction modeled as a cooperative failure mode of lytic repression

We analyze a system-level model for lytic repression of lambda-phage in E. coli using reliability theory, showing that the repressor circuit comprises 4 redundant components whose failure mode is prophage induction. Our model reflects the specific biochemical mechanisms involved in regulation, including long-range cooperative binding, and its detailed predictions for prophage induction in E. coli under ultra-violet radiation are in good agreement with experimental data.Comment: added referenc

3D Geometric Analysis of Tubular Objects based on Surface Normal Accumulation

This paper proposes a simple and efficient method for the reconstruction and extraction of geometric parameters from 3D tubular objects. Our method constructs an image that accumulates surface normal information, then peaks within this image are located by tracking. Finally, the positions of these are optimized to lie precisely on the tubular shape centerline. This method is very versatile, and is able to process various input data types like full or partial mesh acquired from 3D laser scans, 3D height map or discrete volumetric images. The proposed algorithm is simple to implement, contains few parameters and can be computed in linear time with respect to the number of surface faces. Since the extracted tube centerline is accurate, we are able to decompose the tube into rectilinear parts and torus-like parts. This is done with a new linear time 3D torus detection algorithm, which follows the same principle of a previous work on 2D arc circle recognition. Detailed experiments show the versatility, accuracy and robustness of our new method.Comment: in 18th International Conference on Image Analysis and Processing, Sep 2015, Genova, Italy. 201

On the Complexity of Searching in Trees: Average-case Minimization

We focus on the average-case analysis: A function w : V -> Z+ is given which defines the likelihood for a node to be the one marked, and we want the strategy that minimizes the expected number of queries. Prior to this paper, very little was known about this natural question and the complexity of the problem had remained so far an open question. We close this question and prove that the above tree search problem is NP-complete even for the class of trees with diameter at most 4. This results in a complete characterization of the complexity of the problem with respect to the diameter size. In fact, for diameter not larger than 3 the problem can be shown to be polynomially solvable using a dynamic programming approach. In addition we prove that the problem is NP-complete even for the class of trees of maximum degree at most 16. To the best of our knowledge, the only known result in this direction is that the tree search problem is solvable in O(|V| log|V|) time for trees with degree at most 2 (paths). We match the above complexity results with a tight algorithmic analysis. We first show that a natural greedy algorithm attains a 2-approximation. Furthermore, for the bounded degree instances, we show that any optimal strategy (i.e., one that minimizes the expected number of queries) performs at most O(\Delta(T) (log |V| + log w(T))) queries in the worst case, where w(T) is the sum of the likelihoods of the nodes of T and \Delta(T) is the maximum degree of T. We combine this result with a non-trivial exponential time algorithm to provide an FPTAS for trees with bounded degree

Scheduling Algorithms for Procrastinators

This paper presents scheduling algorithms for procrastinators, where the speed that a procrastinator executes a job increases as the due date approaches. We give optimal off-line scheduling policies for linearly increasing speed functions. We then explain the computational/numerical issues involved in implementing this policy. We next explore the online setting, showing that there exist adversaries that force any online scheduling policy to miss due dates. This impossibility result motivates the problem of minimizing the maximum interval stretch of any job; the interval stretch of a job is the job's flow time divided by the job's due date minus release time. We show that several common scheduling strategies, including the "hit-the-highest-nail" strategy beloved by procrastinators, have arbitrarily large maximum interval stretch. Then we give the "thrashing" scheduling policy and show that it is a \Theta(1) approximation algorithm for the maximum interval stretch.Comment: 12 pages, 3 figure

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

Small and mighty: adaptation of superphylum Patescibacteria to groundwater environment drives their genome simplicity.

BackgroundThe newly defined superphylum Patescibacteria such as Parcubacteria (OD1) and Microgenomates (OP11) has been found to be prevalent in groundwater, sediment, lake, and other aquifer environments. Recently increasing attention has been paid to this diverse superphylum including > 20 candidate phyla (a large part of the candidate phylum radiation, CPR) because it refreshed our view of the tree of life. However, adaptive traits contributing to its prevalence are still not well known.ResultsHere, we investigated the genomic features and metabolic pathways of Patescibacteria in groundwater through genome-resolved metagenomics analysis of > 600 Gbp sequence data. We observed that, while the members of Patescibacteria have reduced genomes (~ 1 Mbp) exclusively, functions essential to growth and reproduction such as genetic information processing were retained. Surprisingly, they have sharply reduced redundant and nonessential functions, including specific metabolic activities and stress response systems. The Patescibacteria have ultra-small cells and simplified membrane structures, including flagellar assembly, transporters, and two-component systems. Despite the lack of CRISPR viral defense, the bacteria may evade predation through deletion of common membrane phage receptors and other alternative strategies, which may explain the low representation of prophage proteins in their genomes and lack of CRISPR. By establishing the linkages between bacterial features and the groundwater environmental conditions, our results provide important insights into the functions and evolution of this CPR group.ConclusionsWe found that Patescibacteria has streamlined many functions while acquiring advantages such as avoiding phage invasion, to adapt to the groundwater environment. The unique features of small genome size, ultra-small cell size, and lacking CRISPR of this large lineage are bringing new understandings on life of Bacteria. Our results provide important insights into the mechanisms for adaptation of the superphylum in the groundwater environments, and demonstrate a case where less is more, and small is mighty

Design of an Agile Unmanned Combat Vehicle - A Product of the DARPA UGCV Program

The unmanned ground combat vehicle (UGCV) design evolved by the SAIC team on the DARPA UGCV Program is summarized in this paper. This UGCV design provides exceptional performance against all of the program metrics and incorporates key attributes essential for high performance robotic combat vehicles. This performance includes protection against 7.62 mm threats, C130 and CH47 transportability, and the ability to accept several relevant weapons payloads, as well as advanced sensors and perception algorithms evolving from the PerceptOR program. The UGCV design incorporates a combination of technologies and design features, carefully selected through detailed trade studies, which provide optimum performance against mobility, payload, and endurance goals without sacrificing transportability, survivability, or life cycle cost. The design was optimized to maximize performance against all Category I metrics. In each case, the performance of this design was validated with detailed simulations, indicating that the vehicle exceeded the Category I metrics. Mobility metrics were analyzed using high fidelity VisualNastran vehicle models, which incorporate the suspension control algorithms and controller cycles times. DADS/Easy 5 3-D models and ADAMS simulations were also used to validate vehicle dynamics and control algorithms during obstacle negotiation