Evolution of Protein Molecules

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.

http://science.sciencemag.org/content/sci/332/6034/1196.full.pdf

Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades

A number of different approaches have been described to identify proteins from tandem mass spectrometry (MS/MS) data. The most common approaches rely on the available databases to match experimental MS/MS data. These methods suffer from several drawbacks and cannot be used for the identification of proteins from unknown genomes. In this communication, we describe a new de novo sequencing software package, PEAKS, to extract amino acid sequence information without the use of databases. PEAKS uses a new model and a new algorithm to efficiently compute the best peptide sequences whose fragment ions can best interpret the peaks in the MS/MS spectrum. The output of the software gives amino acid sequences with confidence scores for the entire sequences, as well as an additional novel positional scoring scheme for portions of the sequences. The performance of PEAKS is compared with Lutefisk, a well-known de novo sequencing software, using quadrupole-time-of-flight (Q-TOF) data obtained for several tryptic peptides from standard proteins.

/pdf/peaks-powerful-software-for-peptide-de-novo-sequencing-by-1htzy7q8mi.pdf

PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry

The impressive capabilities of the mammalian brain—ranging from perception, pattern recognition and memory formation to decision making and motor activity control—have inspired their re-creation in a wide range of artificial intelligence systems for applications such as face recognition, anomaly detection, medical diagnosis and robotic vehicle control Yet before neuron-based brains evolved, complex biomolecular circuits provided individual cells with the ‘intelligent’ behaviour required for survival However, the study of how molecules can ‘think’ has not produced an equal variety of computational models and applications of artificial chemical systems Although biomolecular systems have been hypothesized to carry out neural-network-like computations in vivo and the synthesis of artificial chemical analogues has been proposed theoretically, experimental work has so far fallen short of fully implementing even a single neuron Here, building on the richness of DNA computing and strand displacement circuitry, we show how molecular systems can exhibit autonomous brain-like behaviours Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, we systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks Our approach even allows us to implement a Hopfield associative memory with four fully connected artificial neurons that, after training in silico, remembers four single-stranded DNA patterns and recalls the most similar one when presented with an incomplete pattern Our results suggest that DNA strand displacement cascades could be used to endow autonomous chemical systems with the capability of recognizing patterns of molecular events, making decisions and responding to the environment

/pdf/neural-network-computation-with-dna-strand-displacement-2m7egtgffn.pdf

Neural network computation with DNA strand displacement cascades

In this paper, we study the two-vertex connectivity augmentation problem in an undirected graph whose vertices are partitioned into k sets. Our objective is to add the smallest number of edges to the graph such that the resulting graph is 2-vertex connected under the constraint that each new edge is between two different sets in the partition. We propose an algorithm to solve the above augmentation problem that runs in linear time in the size of the input graph.

Two-Vertex Connectivity Augmentations for Graphs with a Partition Constraint (Extended Abstract)

Mortgage is one of the most popular instruments in the financial markets. In this study, we consider three actions, i.e., to default, to prepay, and to maintain the mortgage, that a borrower may have in mortgage horizon. We provide an effective pricing formula, which not only considers the effect that default might affect the mortgage value, but also accurately computes the impact due to prepayment risk. Our model defines the prepayment value of the mortgage as the amount of outstanding principal, in contrast to defining prepayment value as a constant proportion of maintaining value of the mortgage. We present a new closed-form pricing formula of risky mortgage and also derive its yield to maturity, duration and convexity to provide a framework for risk management.

/pdf/outstanding-principal-as-prepayment-value-a-closed-form-1ugje7v3nb.pdf

Outstanding Principal as Prepayment Value: A Closed-Form Formula for Mortgage Pricing *

We present an algorithm for computing a maximum agreement subtree of two unrooted evolutionary trees. It takes O(n^{1.5} log n) time for trees with unbounded degrees, matching the best known time complexity for the rooted case. Our algorithm allows the input trees to be mixed trees, i.e., trees that may contain directed and undirected edges at the same time. Our algorithm adopts a recursive strategy exploiting a technique called label compression. The backbone of this technique is an algorithm that computes the maximum weight matchings over many subgraphs of a bipartite graph as fast as it takes to compute a single matching.

Cavity Matchings, Label Compressions, and Unrooted Evolutionary Trees

In this paper, we study the problem of designing proxies (or portfolios) for various stock market indices based on historical data. We use four different methods for computing market indices, all of which are formulas used in actual stock market analysis. For each index, we consider three criteria for designing the proxy: the proxy must either track the market index, outperform the market index, or perform within a margin of error of the index while maintaining a low volatility. In eleven of the twelve cases (all combinations of four indices with three criteria except the problem of sacrificing return for less volatility using the price-relative index) we show that the problem is NP-hard, and hence most likely intractable.

Ming-Yang Kao

Papers

Two-Vertex Connectivity Augmentations for Graphs with a Partition Constraint (Extended Abstract)

Outstanding Principal as Prepayment Value: A Closed-Form Formula for Mortgage Pricing *

Cavity Matchings, Label Compressions, and Unrooted Evolutionary Trees

Designing Proxies for Stock Market Indices is Computationally Hard

Efficient submesh permutations in wormhole-routed meshes