Lenwood S. Heath

H++: a server for estimating pKas and adding missing hydrogens to macromolecules.

The structure and function of macromolecules depend critically on the ionization (protonation) states of their acidic and basic groups. A number of existing practical methods predict protonation equilibrium pK constants of macromolecules based upon their atomic resolution Protein Data Bank (PDB) structures; the calculations are often performed within the framework of the continuum electrostatics model. Unfortunately, these methodologies are complex, involve multiple steps and require considerable investment of effort. Our web server provides access to a tool that automates this process, allowing both experts and novices to quickly obtain estimates of pKs as well as other related characteristics of biomolecules such as isoelectric points, titration curves and energies of protonation microstates. Protons are added to the input structure according to the calculated ionization states of its titratable groups at the user-specified pH; the output is in the PQR (PDB + charges + radii) format. In addition, corresponding coordinate and topology files are generated in the format supported by the molecular modeling package AMBER. The server is intended for a broad community of biochemists, molecular modelers, structural biologists and drug designers; it can also be used as an educational tool in biochemistry courses.

Visualizing search results: some alternatives to query-document similarity

A digital library of computer science literature, Envision provides powerful information visualization by displaying search results as a matrix of icons, with layout semantics under user control. Envision’s Graphic View interacts with an Item Summary Window giving users access to bibliographic information, and XMosaic provides access to complete bibliographic information, abstracts, and full content. While many visualization interfaces for information retrieval systems depict ranked query-document similarity, Envision graphically presents a variety of document characteristics and supports an extensive range of user tasks. Formative usability evaluation results show great user satisfaction with Envision’s style of presentation and the document characteristics visualized.

Users, user interfaces, and objects: Envision, a digital library

Project Envision aims to build a “user-centered database from the computer science literature,” initially using the publications of the Association for Computing Machinery (ACM). Accordingly, we have interviewed potential users, as well as experts in library, information, and computer science—to understand their needs, to become aware of their perception of existing information systems, and to collect their recommendations. Design and formative usability evaluation of our interface have been based on those interviews, leading to innovative query formulation and search results screens that work well according to our usability testing. Our development of the Envision database, system software, and protocol for client-server communication builds upon work to identify and represent “objects” that will facilitate reuse and high-level communication of information from author to reader (user). All these efforts are leading not only to a usable prototype digital library but also to a set of nine principles for digital libraries, which we have tried to follow, covering issues of representation, architecture, and interfacing.

Photosynthetic Acclimation Is Reflected in Specific Patterns of Gene Expression in Drought-Stressed Loblolly Pine

Because the product of a single gene can influence many aspects of plant growth and development, it is necessary to understand how gene products act in concert and upon each other to effect adaptive changes to stressful conditions. We conducted experiments to improve our understanding of the responses of loblolly pine (Pinus taeda) to drought stress. Water was withheld from rooted plantlets of to a measured water potential of -1 MPa for mild stress and -1.5 MPa for severe stress. Net photosynthesis was measured for each level of stress. RNA was isolated from needles and used in hybridizations against a microarray consisting of 2,173 cDNA clones from five pine expressed sequence tag libraries. Gene expression was estimated using a two-stage mixed linear model. Subsequently, data mining via inductive logic programming identified rules (relationships) among gene expression, treatments, and functional categories. Changes in RNA transcript profiles of loblolly pine due to drought stress were correlated with physiological data reflecting photosynthetic acclimation to mild stress or photosynthetic failure during severe stress. Analysis of transcript profiles indicated that there are distinct patterns of expression related to the two levels of stress. Genes encoding heat shock proteins, late embryogenic-abundant proteins, enzymes from the aromatic acid and flavonoid biosynthetic pathways, and from carbon metabolism showed distinctive responses associated with acclimation. Five genes shown to have different transcript levels in response to either mild or severe stress were chosen for further analysis using real-time polymerase chain reaction. The real-time polymerase chain reaction results were in good agreement with those obtained on microarrays.

Practical minimal perfect hash functions for large databases

We describe the first practical algorithms for finding minimal perfect hash functions that have been used to access very large databases (i.e., having over 1 million keys). This method extends earlier work wherein an 0(n-cubed) algorithm was devised, building upon prior work by Sager that described an 0(n-to the fourth) algorithm. Our first linear expected time algorithm makes use of three key insights: applying randomness whereever possible, ordering our search for hash functions based on the degree of the vertices in a graph that represents word dependencies, and viewing hash value assignment in terms of adding circular patterns of related words to a partially filled disk. Our second algorithm builds functions that are slightly more complex, but does not build a word dependency graph and so approaches the theoretical lower bound on function specification size. While ultimately applicable to a wide variety of data and file access needs, these algorithms have already proven useful in aiding our work in improving the performance of CD-ROM systems and our construction of a Large External Network Database (LEND) for semantic networks and hypertext/hypermedia collections. Virginia Disc One includes a demonstration of a minimal perfect hash function running on a PC to access a 130,198 word list on that CD-ROM. Several other microcomputer, minicomputer, and parallel processor versions and applications of our algorithm have also been developed. Tests including those wiht a French word list of 420,878 entries and a library catalog key set with over 3.8 million keys have shown that our methods work with very large databases.

Laying out graphs using queues

The problem of laying out the edges of a graph using queues is studied. In a k-queue layout, vertices of the graph are placed in some linear order and each edge is assigned to exactly one of the k queues so that the edges assigned to each queue obey a first-in/first-out discipline. This layout problem abstracts a design problem of fault-tolerant processor arrays, a problem of sorting with parallel queues, and a problem of scheduling parallel processors. A number of basic results about queue layouts of graphs are established, and these results are contrasted with their analogues for stack layouts of graphs (the book-embedding problem). The 1-queue graphs (they are almost leveled-planar graphs) are characterized. It is proved that the problem of recognizing 1-queue graphs is NP-complete. Queue layouts for some specific classes of graphs are given. Relationships between the queuenumber of a graph and its bandwidth and separator size are presented. An apparent tradeoff between the queuewidth and the number of...

Stack and Queue Layouts of Directed Acyclic Graphs: Part I

Stack layouts and queue layouts of undirected graphs have been used to model problems in fault-tolerant computing and in parallel process scheduling. However, problems in parallel process scheduling are more accurately modeled by stack and queue layouts of directed acyclic graphs (dags). A stack layout of a dag is similar to a stack layout of an undirected graph, with the additional requirement that the nodes of the dag be in some topological order. A queue layout is defined in an analogous manner. The stacknumber ( queuenumber) of a dag is the smallest number of stacks (queues) required for its stack layout (queue layout). In this paper, bounds are established on the stacknumber and queuenumber of two classes of dags: tree dags and unicyclic dags. In particular, any tree dag can be laid out in 1 stack and in at most 2 queues; and any unicyclic dag can be laid out in at most 2 stacks and in at most 2 queues. Forbidden subgraph characterizations of 1-queue tree dags and 1-queue cycle dags are also presented. Part II of this paper presents algorithmic results---in particular, linear time algorithms for recognizing 1-stack dags and 1-queue dags and proof of NP-completeness for the problem of recognizing a 4-queue dag and the problem of recognizing a 9-stack dag.

The PMU Placement Problem

The PMU placement problem is an optimization problem abstracted from an approach to supervising an electrical power system. The power system is modeled as a graph, and adequate supervision of the system requires that the voltage at each node and the current through each edge be observable. A phasor measurement unit (PMU) is a monitor that can be placed at a node to directly observe the voltage at that node, as well as the current and its phase through all incident edges. The PMU placement problem is to place PMUs at a minimum number of nodes so that the entire electric power system is observed. A new simpler definition of graph observability and several complexity results for the PMU placement problem are presented. The PMU placement problem is shown to be NP-complete even for planar bipartite graphs. Several fundamental properties of PMU placements are proven, including the property that a minimum PMU placement requires no more than 1/3 of the nodes in a connected graph of at least 3 nodes.

Comparing queues and stacks as mechanisms for laying out graphs

The relative powers of queues and stacks are compared as mechanisms for laying out the edges of a graph. In a k-queue layout, vertices of the graph are placed in some linear order (also called a linear arrangement), and each edge is assigned to exactly one of the k queues, so that the edges assigned to each queue obey a first-in/first-out (FIFO) discipline. As the vertices are scanned left to right, an edge is enqueued on its assigned queue when its left endpoint is encountered and is dequeued from its queue when its right endpoint is encountered. In a k-stack layout, vertices of the graph are placed in some linear order, and each edge is assigned to exactly one of the k stacks so that the edges assigned to each stack obey a last-in/first-out discipline. As the vertices are scanned left to right, an edge is pushed on its assigned stack when its left endpoint is encountered and is popped from its stack when its right endpoint is encountered. The paper has three main results. First, a tradeoff between queue...

Order-preserving minimal perfect hash functions and information retrieval

Rapid access to information is essential for a wide variety of retrieval systems and applications. Hashing has long been used when the fastest possible direct search is desired, but is generally not appropriate when sequential or range searches are also required. This paper describes a hashing method, developed for collections that are relatively static, that supports both direct and sequential access. Indeed, the algorithm described gives hash functions that are optimal in terms of time and hash table space utilization, and that preserve any a priori ordering desired. Furthermore, the resulting order preserving minimal perfect hash functions (OPMPHFs) can be found using space and time that is on average linear in the number of keys involved.