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PubMed2026

Optimizing sparse and skew hashing: faster k-mer dictionaries.

MOTIVATION: Representing a set of k-mers-strings of length k-in small space under fast lookup queries is a fundamental requirement for several applications in Bioinformatics. A data structure based on sparse and skew hashing (SSHash) was recently proposed for this purpose (Pibiri 2022): it combines good space effectiveness with fast lookup and streaming queries. It is also order-preserving, i.e. consecutive k-mers (sharing a prefix-suffix overlap of length k-1) are assigned consecutive hash codes which helps compressing satellite data typically associated with k-mers, like abundances and color sets in colored De Bruijn graphs. RESULTS: We study the problem of accelerating queries under the sparse and skew hashing indexing paradigm, without compromising its space effectiveness. We propose a refined data structure with less complex lookups and fewer cache misses. We give a simpler and faster algorithm for streaming lookup queries. The refined architecture translates to substantial performance gains, outperforming the original version of SSHash in both index construction speed and query efficiency. Compared to indexes with similar capabilities and based on the Burrows-Wheeler transform, like SBWT and FMSI, SSHash is significantly faster to build and query. SSHash is competitive in space with the fast (and default) modality of SBWT when both k-mer strands are indexed. While larger than FMSI, it is also more than one order of magnitude faster to query. AVAILABILITY AND IMPLEMENTATION: The SSHash software is available at https://github.com/jermp/sshash, and also distributed via Bioconda. A benchmark of data structures for k-mer sets is available at https://github.com/jermp/kmer_sets_benchmark. The datasets used in this article are described and available at https://zenodo.org/records/17582116.

Algorithms↗
PubMed2002

A contingent speech technique in eye movement research on reading.

A novel eye-movement-contingent method is presented. It builds on and extends established eye-movement-contingent visual display change methods in that it uses movements of the eyes to control the presentation of acoustic information during sentence reading. In one implementation, an irrelevant spoken word is presented when the eyes cross a predetermined spatial boundary before they move on to a selected visual target word. The relationship between the spoken word and the visual target is manipulated, and the pattern of interference, caused by the presentation of the spoken word, is used to determine the nature and time course of activated representations. Results from three recently completed experiments in which the technique was used show that a word's phonological code remains active after it has been read and that the activated code has speech-like properties.

Eye Movements↗
PubMed1997

Emergence of template-and-sequence-directed (TSD) syntheses: I. A bio-geochemical model.

A biogeochemical model for the evolution of template-and-sequence-directed (TSD) syntheses of biological templates (proto-RNAs) and catalysts (peptides) is described. A fluctuating environment characterized by hydrating (cool) and dehydrating (warm) phases with cycles of consecutive organic reactions, as well as a constant supply of the polymeric building blocks is assumed. The scenario starts with the catalyzed formation of a primordial population of small random peptides, based on the relatively-ineffective mineral catalysts. The resulting peptides initiate a catalytic takeover process, during which the catalytic functions are gradually taken over by peptides. The evolution of TSD peptides is based on a combination of Lahav's (1991) co-evolution and Moller and Janssen's (1990) specific recognition sites hypotheses. During the emergence of TSD systems the fraction of TSD peptides and proto-RNA constituents rises from almost insignificance to dominance in a TSD Reactions Takeover. The TSD system is characterized by autocatalysis, positive feedback loops and a primordial genetic code. The model is the basis for a computer program (Part II of present series).

Base Sequence↗
PubMed2002

The Development of Expert Male National Collegiate Athletic Association Division I Certified Athletic Trainers.

OBJECTIVE: To identify the major influences in the development of expert male National Collegiate Athletic Association (NCAA) Division I certified athletic trainers. DESIGN AND SETTING: The participants were individually interviewed, and the data were transcribed and coded. SUBJECTS: Seven male NCAA Division I certified athletic trainers, who averaged 29 years of experience in the profession and 20 years at the Division I level. RESULTS: We found 3 higher-order categories that explained the development of the certified athletic trainers and labeled these meaningful experiences, personal attributes, and mentoring. The growth and development of the athletic trainers were influenced by a variety of meaningful experiences that began during their time as students and continued throughout their careers. These experiences involved dealing with challenging job conditions, educational conditions, and attempts to promote and improve the profession. The personal attributes category encompassed the importance of a caring and service-oriented attitude, building relationships with athletes, and maintaining strong bonds within their own families. Mentoring of these individuals occurred both inside and outside the athletic training profession. CONCLUSION: We provide a unique view of the development of athletic trainers that should be of interest to those in the field, regardless of years of experience.

Journal Article↗
PubMed1990

Intermediate energy neutron beams from the MURR.

Several reactors in the United States are potential candidates to deliver beams of intermediate energy neutrons for NCT. At this time, moderators, as compared to filters, appear to be the more effective means of tailoring the flux of these reactors. The objective is to sufficiently reduce the flux of fast neutrons while producing enough intermediate energy neutrons for treatments. At the University of Missouri Research Reactor (MURR), the code MCNP has recently been used to calculate doses in a phantom. First, "ideal" beams of 1, 35, and 1000 eV neutrons were analyzed to determine doses and advantage depths in the phantom. Second, a high quality beam that had been designed to fit in the thermal column of the MURR, was reanalyzed. MCNP calculations of the dose in phantom in this beam confirmed previous calculations and showed that this beam would be a nearly ideal one with neutrons of the desired energy and also a high neutron current. However, installation of this beam will require a significant modification of the thermal column of the MURR. Therefore, a second beam that is less difficult to build and install, but of lower neutron current, has been designed to fit in MURR port F. This beam is designed using inexpensive A1, S, and Pb. The doses calculated in the phantom placed in this beam show that it will be satisfactory for sample tests, animal tests, and possible initial patient trials. Producing this beam will require only modest modifications of the existing tube.

Facility Design and Construction↗
PubMed2000

Comparison of dosimetry recommendations for clinical proton beams.

The formalism and data in the two most recent dosimetry recommendations for clinical proton beams, ICRU Report 59 and the forthcoming IAEA Code of Practice, are compared. Chamber calibrations in terms of air kerma and absorbed dose to water are considered, including five different cylindrical ionization chamber types commonly used in proton beam dosimetry. The methodology for both types of calibration for ionization chambers is described in ICRU Report 59. The procedure based on air kerma calibrations is compared with an alternative formalism based on IAEA Codes of Practice (TRS-277, TRS-381), modified for proton beams. The new IAEA Code of Practice is exclusively based on calibrations in terms of absorbed dose to water and a direct comparison with ICRU Report 59 recommendations is made. Common to the two formalisms are the fundamental quantities Wair and w(air) and their atmospheric conditions of applicability. The difference in the recommended values of the ratio w(air)/Wair (protons to 60Co) is as large as 2.3%. The use of Wair and w(air) values for dry air (IAEA) and for ambient air (ICRU) is a contribution to the discrepancy, and the ICRU usage is questioned. For air kerma based chamber calibrations, ICRU Report 59 does not take into account the effect of different compositions of the build-up cap and chamber wall on the calibration beam quality. For the chamber types included in the study, this introduces discrepancies of up to 1.1%. Combined with differences in the recommended basic data, discrepancies in absorbed dose determination in proton beams of up to 2.1% are found. For the absorbed dose to water based formalism, differences in the formalism, notably the omission of perturbation factors for 60Co in ICRU 59, and data yield discrepancies in calculated kQ factors, and in absorbed dose determinations, between -1.5% and +2.6%, depending on the chamber type and the proton beam quality.

Air↗
PubMed2002

A new method to detect related function among proteins independent of sequence and fold homology.

A new method has been developed to detect functional relationships among proteins independent of a given sequence or fold homology. It is based on the idea that protein function is intimately related to the recognition and subsequent response to the binding of a substrate or an endogenous ligand in a well-characterized binding pocket. Thus, recognition of similar ligands, supposedly linked to similar function, requires conserved recognition features exposed in terms of common physicochemical interaction properties via the functional groups of the residues flanking a particular binding cavity. Following a technique commonly used in the comparison of small molecule ligands, generic pseudocenters coding for possible interaction properties were assigned for a large sample set of cavities extracted from the entire PDB and stored in the database Cavbase. Using a particular query cavity a series of related cavities of decreasing similarity is detected based on a clique detection algorithm. The detected similarity is ranked according to property-based surface patches shared in common by the different clique solutions. The approach either retrieves protein cavities accommodating the same (e.g. co-factors) or closely related ligands or it extracts proteins exhibiting similar function in terms of a related catalytic mechanism. Finally the new method has strong potential to suggest alternative molecular skeletons in de novo design. The retrieval of molecular building blocks accommodated in a particular sub-pocket that shares similarity with the pocket in a protein studied by drug design can inspire the discovery of novel ligands.

Algorithms↗
PubMed2005

Eros underground: Greece and Rome in gay print culture, 1953-65.

This essay surveys the building of intellectual community through print culture in the nascent gay movement in the United States and in Europe in the mid-twentieth century. Amateur historians, especially Jim Kepner and W. Dorr Legg of ONE, used Greece and Rome as models on which to base claims for gay rights. Ancient history figured in ONE's educational enterprises, including articles in the magazine ONE, the ONE Institute, and Homophile Studies. The magazine writers and their readership faced problems in the accessibility of knowledge, which the increasing circulation of the magazines corrected, to a degree. Biases surviving from the Victorian period caused the popular idea of ancient homophile culture to favor Greece over Rome, and made Greek a code word. Antiquity also played a large, though decreasing, role in formations of homoerotic fantasy during this period.

Culture↗
PubMed1998

ptGAs--genetic algorithms evolving noncoding segments by means of promoter/terminator sequences.

In this article we present work on chromosome structures for genetic algorithms (GAs) based on biological principles. Mainly, the influence of noncoding segments on GA behavior and performance is investigated. We compare representations with noncoding sequences at predefined, fixed locations with "junk" code induced by the use of promoter/terminator sequences (ptGAs) that define start and end of a coding sequence, respectively. As one of the advantages of noncoding segments a few researchers have identified the reduction of the disruptive effects of crossover, and we solidify this argument by a formal analysis of crossover disruption probabilities for noncoding segments at fixed locations. The additional use of promoter/terminator sequences not only enables evolution of parameter values, but also allows for adaptation of number, size, and location of genes (problem parameters) on an artificial chromosome. Randomly generated chromosomes of fixed length carry different numbers of promoter/terminator sequences resulting in genes of varying size and location. Evolution of these ptGA chromosomes drives the number of parameters and their values to (sub)optimal solutions. Moreover, the formation of tightly linked building blocks is enhanced by self-organization of gene locations. We also introduce a new, nondisruptive crossover operator emerging from the ptGA gene structure with adaptive crossover rate, location, and number of crossover sites. For experimental comparisons of this genetic operator to conventional crossover in GAs, as well as properties of different ptGA chromosome structures, an artificial problem from the literature is utilized. Finally, the potential of ptGA is demonstrated on an NP-complete combinatorial optimization problem.

Algorithms↗
PubMed1999

ptGAs-Genetic Algorithms Evolving Noncoding Segments by Means of Promoter/Terminator Sequences.

In this article we present work on chromosome structures for genetic algorithms (GAs) based on biological principles. Mainly, the influence of noncoding segments on GA behavior and performance is investigated. We compare representations with noncoding sequences at predefined, fixed locations with 'junk' code induced by the use of promoter/terminator sequences (ptGAs) that define start and end of a coding sequence, respectively. As one of the advantages of noncoding segments a few researchers have identified the reduction of the disruptive effects of crossover, and we solidify this argument by a formal analysis of crossover disruption probabilities for noncoding segments at fixed locations. The additional use of promoter/terminator sequences not only enables evolution of parameter values, but also allows for adaptation of number, size, and location of genes (problem parameters) on an artificial chromosome. Randomly generated chromosomes of fixed length carry different numbers of promoter/terminator sequences resulting in genes of varying size and location. Evolution of these ptGA chromosomes drives the number of parameters and their values to (sub)optimal solutions. Moreover, the formation of tightly linked building blocks is enhanced by self-organization of gene locations. We also introduce a new, nondisruptive crossover operator emerging from the ptGA gene structure with adaptive crossover rate, location, and number of crossover sites. For experimental comparisons of this genetic operator to conventional crossover in GAs, as well as properties of different ptGA chromosome structures, an artificial problem from the literature is utilized. Finally, the potential of ptGA is demonstrated on an NP-complete combinatorial optimization problem.

Journal Article↗
PubMed2007

Comparing sequences without using alignments: application to HIV/SIV subtyping.

BACKGROUND: In general, the construction of trees is based on sequence alignments. This procedure, however, leads to loss of informationwhen parts of sequence alignments (for instance ambiguous regions) are deleted before tree building. To overcome this difficulty, one of us previously introduced a new and rapid algorithm that calculates dissimilarity matrices between sequences without preliminary alignment. RESULTS: In this paper, HIV (Human Immunodeficiency Virus) and SIV (Simian Immunodeficiency Virus) sequence data are used to evaluate this method. The program produces tree topologies that are identical to those obtained by a combination of standard methods detailed in the HIV Sequence Compendium. Manual alignment editing is not necessary at any stage. Furthermore, only one user-specified parameter is needed for constructing trees. CONCLUSION: The extensive tests on HIV/SIV subtyping showed that the virus classifications produced by our method are in good agreement with our best taxonomic knowledge, even in non-coding LTR (Long Terminal Repeat) regions that are not tractable by regular alignment methods due to frequent duplications/insertions/deletions. Our method, however, is not limited to the HIV/SIV subtyping. It provides an alternative tree construction without a time-consuming aligning procedure.

Animals↗
PubMed1996

WHONET: removing obstacles to the full use of information about antimicrobial resistance.

A rich store of detailed information about antimicrobial resistance is at each medical center in paper files inaccessible to analysis or in electronic files too diverse to support a common analytical software. WHONET puts that information on a personal computer at each center in a file code and format that is the same at all centers, so that one software can then fully analyze the files at any center or those merged from many centers. The software monitors the complex matrix of interrelationships between all the measurements of resistance to antimicrobials of tested isolates of each species and of control strains. Differences at a center over time or between centers reflect differences in test performance or in the prevalence of specific resistant strains, which may be tracked. The software helps workers who are knowledgeable about resistance, infection control and clinical use of antimicrobials at any center to control test quality and integrate the management of resistance there. Their ongoing monitoring and experience locally also builds the quality and interpretation of the files merged from many centers.

Drug Resistance, Microbial↗
PubMed2006

Engineering stem cells into organs: topobiological transformations demonstrated by beak, feather, and other ectodermal organ morphogenesis.

To accomplish regenerative medicine, several critical issues in stem cell biology have to be solved, including the identification of sources, the expanding population, building them into organs, and assimilating them to the host. Although many stem cells can now differentiate along certain lineages, knowledge on how to use them to build organs lags behind. Here we focus on topobiological events that bridge this gap, for example, the regulation of number, size, axes, shape, arrangement, and architecture during organogenesis. Rather than reviewing detail molecular pathways known to disrupt organogenesis when perturbed, we highlight conceptual questions at the topobiological level and ask how cellular and molecular mechanisms can work to explain these phenomena. The avian integument is used as the Rosetta stone because the molecular activities are linked to organ forms that are visually apparent and have functional consequences during evolution with fossil records and extant diversity. For example, we show that feather pattern formation is the equilibrium of stochastic interactions among multiple activators and inhibitors. Although morphogens and receptors are coded by the genome, the result is based on the summed physical-chemical properties on the whole cell's surface and is self-organizing. For another example, we show that developing chicken and duck beaks contain differently configured localized growth zones (LoGZs) and can modulate chicken beaks to phenocopy diverse avian beaks in nature by altering the position, number, size, and duration of LoGZs. Different organs have their unique topology and we also discuss shaping mechanisms of liver and different ways of branching morphogenesis. Multi-primordium organs (e.g., feathers, hairs, and teeth) have additional topographic specificities across the body surface, an appendage field, or within an appendage. Promises and problems in reconstitute feather/hair follicles and other organs are discussed. Finally, simple modification at the topobiological level may lead to novel morphology for natural selection at the evolution level.

Animals↗
PubMed2004

Programming of a flexible computer simulation to visualize pharmacokinetic-pharmacodynamic models.

Teaching pharmacokinetic-pharmacodynamic (PK/PD) models can be made more effective using computer simulations. We propose the programming of educational PK or PK/PD computer simulations as an alternative to the use of pre-built simulation software. This approach has the advantage of adaptability to non-standard or complicated PK or PK/PD models. Simplicity of the programming procedure was achieved by selecting the LabVIEW programming environment. An intuitive user interface to visualize the time courses of drug concentrations or effects can be obtained with pre-built elements. The environment uses a wiring analogy that resembles electrical circuit diagrams rather than abstract programming code. The goal of high interactivity of the simulation was attained by allowing the program to run in continuously repeating loops. This makes the program behave flexibly to the user input. The programming is described with the aid of a 2-compartment PK simulation. Examples of more sophisticated simulation programs are also given where the PK/PD simulation shows drug input, concentrations in plasma, and at effect site and the effects themselves as a function of time. A multi-compartmental model of morphine, including metabolite kinetics and effects is also included. The programs are available for download from the World Wide Web at http:// www. klinik.uni-frankfurt.de/zpharm/klin/ PKPDsimulation/content.html. For pharmacokineticists who only program occasionally, there is the possibility of building the computer simulation, together with the flexible interactive simulation algorithm for clinical pharmacological teaching in the field of PK/PD models.

Algorithms↗
PubMed2001

Informatics in managed care: HIM adds value to data.

The third installment of the Journal of AHIMA's special series on managed care focuses on informatics--methods that add value to data, turning it into useful information. How do informatics and managed care fit together and what is HIM's role in this picture? The HIM professional's knowledge is critical to the health team responsible for the interpretation and use of statically valid information. For example, HIM professionals are well positioned in their understanding of the construct and application of coding classification systems (ICD-9-CM, CPT, etc.), and groupers (DRGs, APCs, ETGs, etc.). Their unique training positions them to understand the associated rules, principles, guidelines, and nuances associated with correct coding and grouping. And when codes or groupers change, HIM professionals work closely with the health team to ensure parity, validity and reliability of the appropriate data or data sets. Managed care organizations use value-added data, as you will see in this article, to evaluate contract pricing, develop contracts, evaluate existing services or detail benefit plans, process and in some instances pay claims, and report results to a number of interested parties. The previous article in this series ("Can You Manage Managed Care?" July/August 2001) focused on effective management of data, including data acquisition. This article takes us to the next level, where informatics creates value-added information, and discusses some important uses of this information within managed care. These articles build on two of the functional areas that form the HIM process within managed care organizations. Author Scott Stratton studied under the creators of DRGs and was involved in the development of their nursing home counterpart, RUGs. He also has worked with the creators of ETGs. As a result, he can present the perspective and context within which these systems were created and intended. and how they form the foundation for informatics as a functional area within managed care.

Diagnosis-Related Groups↗
PubMed2005

Revealing molecular targets for enterovirus type 71 detection by profile hidden Markov models.

The enterovirus infection in 1998 claimed 78 deaths in Taiwan, with an average of 40 fatalities each year after. Traditional serum-based diagnostic methods often fail to detect enteroviruses due to antigenic changes. As a result, many isolates remain untyped and are absent from the enterovirus surveillance and epidemiological investigations. We present a profile hidden Markov model (HMM) method for molecular typing of enterovirus 71 (EV71). Based on the enteroviral sequences retrieved from GenBank, we build a nucleotide-based and an amino acid-based profile HMM for each EV71 gene using the package HMMER. HMMER bit score-based Z-scores for EV71 and non-EV71 sequences are calculated for each of these profile HMMs. In a genome-wide analysis, we find that the distribution of the EV71 Z-scores and that of the non-EV71 Z-scores have disjoint support for nucleotide-based VP1 profile HMM if the sequence is longer than 150 bases; a VP1-based molecular typing method for EV71 is thus proposed. We also report VP4 an alternative molecular target for detecting EV71, while the two UTRs and all the genes coding the internal proteins cannot be used for such purpose. To demonstrate the performance of the nucleotide-based EV71 VP1 profile HMM, 330 enterovirus VP1 nucleotide sequences newly reported to GenBank are typed with this method. All the EV71 sequences are detected with no error.

Amino Acid Sequence↗
PubMed2003

Coarse-grained sequences for protein folding and design.

We present the results of sequence design on our off-lattice minimalist model in which no specification of native-state tertiary contacts is needed. We start with a sequence that adopts a target topology and build on it through sequence mutation to produce new sequences that comprise distinct members within a target fold class. In this work, we use the alpha/beta ubiquitin fold class and design two new sequences that, when characterized through folding simulations, reproduce the differences in folding mechanism seen experimentally for proteins L and G. The primary implication of this work is that patterning of hydrophobic and hydrophilic residues is the physical origin for the success of relative contact-order descriptions of folding, and that these physics-based potentials provide a predictive connection between free energy landscapes and amino acid sequence (the original protein folding problem). We present results of the sequence mapping from a 20- to the three-letter code for determining a sequence that folds into the WW domain topology to illustrate future extensions to protein design.

Amino Acid Sequence↗
PubMed2006

Understanding African Americans' views of the trustworthiness of physicians.

BACKGROUND: Many scholars have written about the historical underpinnings and likely consequences of African Americans distrust in health care, yet little research has been done to understand if and how this distrust affects African Americans' current views of the trustworthiness of physicians. OBJECTIVE: To better understand what trust and distrust in physicians means to African Americans. DESIGN: Focus-group study, using an open-ended discussion guide. SETTING: Large public hospital and community organization in Chicago, IL. PATIENTS: Convenience sample of African-American adult men and women. MEASUREMENTS: Each focus group was systematically coded using grounded theory analysis. The research team then identified themes that commonly arose across the 9 focus groups. RESULTS: Participants indicated that trust is determined by the interpersonal and technical competence of physicians. Contributing factors to distrust in physicians include a lack of interpersonal and technical competence, perceived quest for profit and expectations of racism and experimentation during routine provision of health care. Trust appears to facilitate care-seeking behavior and promotes patient honesty and adherence. Distrust inhibits care-seeking, can result in a change in physician and may lead to nonadherence. CONCLUSIONS: Unique factors contribute to trust and distrust in physicians among African-American patients. These factors should be considered in clinical practice to facilitate trust building and improve health care provided to African Americans.

Adult↗