CiteULike: Author Bowers

Anton, a special-purpose machine for molecular dynamics simulation

David Shaw — 2008-07-01T12:30:10-00:00

Commun. ACM, Vol. 51, No. 7. (July 2008), pp. 91-97.

Synteny and Collinearity in Plant Genomes

Haibao Tang — 2008-04-25T01:20:19-00:00

Science, Vol. 320, No. 5875. (25 April 2008), pp. 486-488.

Correlated gene arrangements among taxa provide a valuable framework for inference of shared ancestry of genes and for the utilization of findings from model organisms to study less-well-understood systems. In angiosperms, comparisons of gene arrangements are complicated by recurring polyploidy and extensive genome rearrangement. New genome sequences and improved analytical approaches are clarifying angiosperm evolution and revealing patterns of differential gene loss after genome duplication and differential gene retention associated with evolution of some morphological complexity. Because of variability in DNA substitution rates among taxa and genes, deviation from collinearity might be a more reliable phylogenetic character. 10.1126/science.1153917

The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)

Ray Ming — 2008-04-23T19:37:29-00:00

Nature, Vol. 452, No. 7190. (24 April 2008), pp. 991-996.

Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA.

BT Chen — 2008-08-01T13:43:31-00:00

Neuron, Vol. 59, No. 2. (31 July 2008), pp. 288-297.

Persistent drug-seeking behavior is hypothesized to co-opt the brain's natural reward-motivational system. Although ventral tegmental area (VTA) dopamine (DA) neurons represent a crucial component of this system, the synaptic adaptations underlying natural rewards and drug-related motivation have not been fully elucidated. Here, we show that self-administration of cocaine, but not passive cocaine infusions, produced a persistent potentiation of VTA excitatory synapses, which was still present after 3 months abstinence. Further, enhanced synaptic function in VTA was evident even after 3 weeks of extinction training. Food or sucrose self-administration induced only a transient potentiation of VTA glutamatergic signaling. Our data show that synaptic function in VTA DA neurons is readily but reversibly enhanced by natural reward-seeking behavior, while voluntary cocaine self-administration induced a persistent synaptic enhancement that is resistant to behavioral extinction. Such persistent synaptic potentiation in VTA DA neurons may represent a fundamental cellular phenomenon driving pathological drug-seeking behavior.

Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters

KJ Bowers — 2008-07-24T18:08:56-00:00

Supercomputing, 2006. SC '06. Proceedings of the ACM/IEEE SC 2006 Conference (2006), pp. 43-43.

Although molecular dynamics (MD) simulations of biomolecular systems often run for days to months, many events of great scientific interest and pharmaceutical relevance occur on long time scales that remain beyond reach. We present several new algorithms and implementation techniques that significantly accelerate parallel MD simulations compared with current state-of-the-art codes. These include a novel parallel decomposition method and message-passing techniques that reduce communication requirements, as well as novel communication primitives that further reduce communication time. We have also developed numerical techniques that maintain high accuracy while using single precision computation in order to exploit processor-level vector instructions. These methods are embodied in a newly developed MD code called Desmond that achieves unprecedented simulation throughput and parallel scalability on commodity clusters. Our results suggest that Desmond's parallel performance substantially surpasses that of any previously described code. For example, on a standard benchmark, Desmond's performance on a conventional Opteron cluster with 2K processors slightly exceeded the reported performance of IBM's Blue Gene/L machine with 32K processors running its Blue Matter MD code

Can practice guidelines safely reduce hospital length of stay? Results from a multicenter interventional study.

S Weingarten — 2008-07-23T14:38:17-00:00

The American journal of medicine, Vol. 105, No. 1. (July 1998), pp. 33-40.

BACKGROUND: Although practice guidelines about appropriate lengths of stay have been widely promulgated, their effects on patient outcomes are not clear. Our objective was to study the effects of length of stay practice guidelines on patient outcomes. PATIENTS AND METHODS: We performed a prospective, nonrandomized, interventional trial in six geographically distributed hospitals, among consecutively hospitalized "low-risk" patients with total hip replacement, hip fracture, or knee replacement. Case managers provided physicians with patient risk information based on guideline recommendations. We measured length of stay, compliance with recommended guideline length of stay, health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. RESULTS: A total of 560 patients were included in the study. For patients with knee replacement, there was a statistically significant increase in practice guideline compliance (27% baseline versus 53% intervention, P <0.0001) and reduction in length of stay (5.2 days versus 4.6 days, P <0.001) when compared with the baseline period. For hip replacement patients, there similarly was an increase in practice guideline compliance (66% baseline versus 82% intervention, P = 0.01) and reduction in length of stay (5.1 days versus 4.8 days, P = 0.03). Significant reductions in length of stay were not observed for patients recovering after hip fracture despite a significant increase in guideline compliance. There were few statistically significant changes in patient outcomes related to reductions in lengths of stay, including health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. For patients undergoing hip replacement, very short lengths of stay (shorter than the guideline recommendation) were associated with an increased rate of discharging patients to nursing homes and rehabilitation facilities (21% versus 7%, P = 0.01), and hip fracture patients with very short lengths of stay required more visits to the doctor after discharge (56% versus 25%, P = 0.04). CONCLUSION: Reductions in lengths of stay were most often associated with no significant change in patient outcomes. However, very short lengths of stay were associated with increased intensity of care following discharge for patients undergoing hip surgery, indicating possible cost shifting (the cost incurred by transferring patients to rehabilitation facilities may have been greater than had the patients remained in the acute care hospital for an additional 1 or 2 days and been sent directly home). These results emphasize the importance of monitoring the effects of cost containment and other systematic efforts to change patient care at the local level.

Can practice guidelines safely reduce hospital length of stay? Results from a multicenter interventional study

Scott Weingarten — 2008-07-23T14:33:50-00:00

The American Journal of Medicine, Vol. 105, No. 1. (July 1998), pp. 33-40.

Background: Although practice guidelines about appropriate lengths of stay have been widely promulgated, their effects on patient outcomes are not clear. Our objective was to study the effects of length of stay practice guidelines on patient outcomes. Patients and Methods: We performed a prospective, nonrandomized, interventional trial in six geographically distributed hospitals, among consecutively hospitalized "low-risk" patients with total hip replacement, hip fracture, or knee replacement. Case managers provided physicians with patient risk information based on guideline recommendations. We measured length of stay, compliance with recommended guideline length of stay, health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. Results: A total of 560 patients were included in the study. For patients with knee replacement, there was a statistically significant increase in practice guideline compliance (27% baseline versus 53% intervention, P <0.0001) and reduction in length of stay (5.2 days versus 4.6 days, P <0.001) when compared with the baseline period. For hip replacement patients, there similarly was an increase in practice guideline compliance (66% baseline versus 82% intervention, P = 0.01) and reduction in length of stay (5.1 days versus 4.8 days, P = 0.03). Significant reductions in length of stay were not observed for patients recovering after hip fracture despite a significant increase in guideline compliance. There were few statistically significant changes in patient outcomes related to reductions in lengths of stay, including health status, hospital readmission rates, return to emergency department, return to work and recreation, and patient satisfaction. For patients undergoing hip replacement, very short lengths of stay (shorter than the guideline recommendation) were associated with an increased rate of discharging patients to nursing homes and rehabilitation facilities (21% versus 7%, P = 0.01), and hip fracture patients with very short lengths of stay required more visits to the doctor after discharge (56% versus 25%, P = 0.04). Conclusion: Reductions in lengths of stay were most often associated with no significant change in patient outcomes. However, very short lengths of stay were associated with increased intensity of care following discharge for patients undergoing hip surgery, indicating possible cost shifting (the cost incurred by transferring patients to rehabilitation facilities may have been greater than had the patients remained in the acute care hospital for an additional 1 or 2 days and been sent directly home). These results emphasize the importance of monitoring the effects of cost containment and other systematic efforts to change patient care at the local level.

Single-Molecule DNA Sequencing of a Viral Genome

Timothy Harris — 2008-04-04T15:36:18-00:00

Science, Vol. 320, No. 5872. (4 April 2008), pp. 106-109.

The full promise of human genomics will be realized only when the genomes of thousands of individuals can be sequenced for comparative analysis. A reference sequence enables the use of short read length. We report an amplification-free method for determining the nucleotide sequence of more than 280,000 individual DNA molecules simultaneously. A DNA polymerase adds labeled nucleotides to surface-immobilized primer-template duplexes in stepwise fashion, and the asynchronous growth of individual DNA molecules was monitored by fluorescence imaging. Read lengths of >25 bases and equivalent phred software program quality scores approaching 30 were achieved. We used this method to sequence the M13 virus to an average depth of >150x and with 100% coverage; thus, we resequenced the M13 genome with high-sensitivity mutation detection. This demonstrates a strategy for high-throughput low-cost resequencing. 10.1126/science.1150427

Effects of Familial Alzheimer's Disease Mutations on the Folding Nucleation of the Amyloid beta-Protein.

Mary Griffin Krone — 2008-07-04T22:41:33-00:00

Journal of molecular biology (4 June 2008)

The effect of single amino acid substitutions associated with the Italian (E22K), Arctic (E22G), Dutch (E22Q) and Iowa (D23N) familial forms of Alzheimer's disease and cerebral amyloid angiopathy on the structure of the 21-30 fragment of the Alzheimer amyloid beta-protein (Abeta) is investigated by replica-exchange molecular dynamics simulations. The 21-30 segment has been shown in our earlier work to adopt a bend structure in solution that may serve as the folding nucleation site for Abeta. Our simulations reveal that the 24-28 bend motif is retained in all E22 mutants, suggesting that mutations involving residue E22 may not affect the structure of the folding nucleation site of Abeta. Enhanced aggregation in Abeta with familial Alzheimer's disease substitutions may result from the depletion of the E22-K28 salt bridge, which destabilizes the bend structure. Alternately, the E22 mutations may affect longer-range interactions outside the 21-30 segment that can impact the aggregation of Abeta. Substituting at residue D23, on the other hand, leads to the formation of a turn rather than a bend motif, implying that in contrast to E22 mutants, the D23N mutant may affect monomer Abeta folding and subsequent aggregation. Our simulations suggest that the mechanisms by which E22 and D23 mutations affect the folding and aggregation of Abeta are fundamentally different.

Mechanism of Na+/H+ Antiporting

Isaiah Arkin — 2007-09-15T18:49:15-00:00

Science, Vol. 317, No. 5839. (10 August 2007), pp. 799-803.

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model. 10.1126/science.1142824

Intuition in the context of discovery

Kenneth Bowers — 2008-07-02T11:34:39-00:00

Cognitive Psychology, Vol. 22, No. 1. (January 1990), pp. 72-110.

Most recent work concerned with intuition has emphasized the errors of intuitive judgment in the context of justification. The present research instead views intuition as informed judgment in the context of discovery. Two word tasks and a gestalt closure task were developed to investigate this concept of intuition. Two of these tasks demonstrated that people could respond discriminatively to coherence that they could not identify, and a third task demonstrated that this tacit perception of coherence guided people gradually to an explicit representation of it in the form of a hunch or hypothesis. While such hunches may surface quite suddenly into consciousness, we propose that the underlying cognitive processes which produce them are more continous than discontinuous in nature. Specifically, we argue that clues to coherence automatically activate the problem solver's relevant mnemonic and semantic networks. Eventually the level of patterned activation is sufficient to cross a threshold of consciousness, and at that point, it is represented as a hunch or hypothesis. The largely unconscious processes involved in generating hunches is quite different from the conscious processes required to test them--thereby vindicating the classical distinction between the context of discovery and the context of justification.

Theory of Laser Acceleration of Light-Ion Beams from Interaction of Ultrahigh-Intensity Lasers with Layered Targets

BJ Albright — 2008-07-01T13:18:43-00:00

Physical Review Letters, Vol. 97, No. 11. (2006)

Experiments at the LANL Trident facility demonstrated the production of monoenergetic ion beams from the interaction of an ultraintense laser with a target comprising a heavy ion substrate and thin layer of light ions. An analytic model is obtained that predicts how the mean energy and quality of monoenergetic ion beams and the energy of substrate ions vary with substrate material and light-ion layer composition and thickness. Dimensionless parameters controlling the dynamics are derived and the model is validated with particle-in-cell simulations and experimental data.

Monoenergetic and GeV ion acceleration from the laser breakout afterburner using ultrathin targets

L Yin — 2008-07-01T13:08:09-00:00

Physics of Plasmas, Vol. 14, No. 5. (2007)

A new laser-driven ion acceleration mechanism using ultrathin targets has been identified from particle-in-cell simulations. After a brief period of target normal sheath acceleration (TNSA) [S. P. Hatchett et al., Phys. Plasmas 7, 2076 (2000)], two distinct stages follow: first, a period of enhanced TNSA during which the cold electron background converts entirely to hot electrons, and second, the “laser breakout afterburner” (BOA) when the laser penetrates to the rear of the target where a localized longitudinal electric field is generated with the location of the peak field co-moving with the ions. During this process, a relativistic electron beam is produced by the ponderomotive drive of the laser. This beam is unstable to a relativistic Buneman instability, which rapidly converts the electron energy into ion energy. This mechanism accelerates ions to much higher energies using laser intensities comparable to earlier TNSA experiments. At a laser intensity of 10^21 W/cm^2, the carbon ions accelerate as a quasimonoenergetic bunch to 100 s of MeV in the early stages of the BOA with conversion efficiency of order a few percent. Both are an order of magnitude higher than those realized from TNSA in recent experiments [Hegelich et al., Nature 441, 439 (2006)]. The laser-plasma interaction then evolves to produce a quasithermal energy distribution with maximum energy of ~2 GeV.

Reading with optical magnifiers: page navigation strategies and difficulties.

A Bowers — 2008-06-27T12:46:32-00:00

Optometry and vision science : official publication of the American Academy of Optometry, Vol. 84, No. 1. (January 2007), pp. 9-20.

PURPOSE: To read efficiently with a simple hand or stand magnifier, people with visual impairment have to move (navigate) the device along each line (forward phase) and back to the correct position at the start of the next line (retrace phase). Page navigation difficulties have been implicated as limiting factors when reading with hand and stand magnifiers, but have not been objectively measured. METHODS: Magnifier movements were recorded using a 3SPACE Isotrak system for 43 participants with age-related macular degeneration (AMD) who read two short stories using their habitual hand or stand magnifier. Page navigation was quantified in terms of magnifier movements and navigation errors for the forward and retrace phases. Visual acuities and visual fields were measured, and magnifier usage and page navigation difficulties were surveyed. RESULTS: During the forward phase, participants primarily used either a straight (47%) or diagonal downward (46%) movement, whereas during the retrace phase, the majority (56%) used a downward movement. On average, forward navigation time was four times longer than retrace navigation time (p<0.001). The most common navigation error was incorrect positioning of the magnifier at the end of the retrace movement. Near word acuity correlated strongly with forward time (r=0.78), and moderately with retrace time (r=0.53) and forward errors (r=0.50). Vertical field of view correlated with retrace errors (r=-0.53). Participants' estimates of page navigation difficulties were not predictive of objective measures of performance. CONCLUSIONS: We quantified page navigation strategies and difficulties of people with AMD reading with magnifiers. Retrace, which presents the most common difficulty, is not well predicted by vision measures or magnifier characteristics; future studies should investigate the relationship between motor skills and navigation performance, and the impact of training or devices on reducing retrace navigation difficulties.

Preferred retinal locus and reading rate with four dynamic text presentation formats.

AR Bowers — 2008-06-26T09:52:58-00:00

Optometry and vision science : official publication of the American Academy of Optometry, Vol. 81, No. 3. (March 2004), pp. 205-213.

BACKGROUND: Electronic display devices hold the potential to improve access to written material by people with low vision. For those with central field loss, the optimal form of electronic text presentation may vary according to the location of the preferred retinal locus, but this has never been investigated. In this study, we examined the relationship between preferred retinal locus location and reading rate for four electronic display formats (rapid serial visual presentation, horizontal scroll, vertical scroll, and page). METHODS: Short sentences were presented in each format to 35 low-vision (most with central field loss) and 14 age-matched control subjects. Subjects read aloud to determine maximum oral reading rate and read silently to determine preferred silent reading rate. RESULTS: With the exception of page format, maximum oral reading rates were faster than silent preferred reading rates for both groups of subjects. For the low-vision group, there was no significant difference in maximum oral reading rates between the four display formats; and when reading at a preferred silent rate, page format was faster than the other three formats. Though page format was read more quickly, half of the low-vision subjects preferred the horizontal-scroll format. Contrary to our predictions, there was no significant effect of preferred retinal locus location (vertical vs. lateral) on reading rate and no significant interaction between preferred retinal locus location and display format. CONCLUSIONS: The differences between maximum oral and preferred silent reading rates and the lack of a relationship between reading rates and preferred display format reinforce the importance of patient preference in the evaluation and selection of a device or display format during rehabilitation.

Efficacy and safety of epoetin alfa in critically ill patients.

HL Corwin — 2008-05-26T13:56:16-00:00

The New England journal of medicine, Vol. 357, No. 10. (6 September 2007), pp. 965-976.

BACKGROUND: Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions. METHODS: In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline. RESULTS: As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86). CONCLUSIONS: The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov].).

A Structural Equation Modeling Approach to the Study of Stress and Psychological Adjustment in Emerging Adults

Kia Asberg — 2008-06-23T19:31:17-00:00

Child Psychiatry and Human Development

Abstract Today’s society puts constant demands on the time and resources of all individuals, with the resulting stress promoting a decline in psychological adjustment. Emerging adults are not exempt from this experience, with an alarming number reporting excessive levels of stress and stress-related problems. As a result, the present study addresses the need for a comprehensive model of emerging adult adjustment in the context of stress and coping variables and highlights the importance of accounting for differences between males and females in research concerning stress, social support, coping, and adjustment. Participants for this study are 239 college students (122 males and 117 females), the majority of whom are Caucasian. Results of structural equation modeling suggest that stress, social support, coping, and adjustment show unique patterns of relationships for males versus females. For both males and females, stress and social support show similar relationships to adjustment. In contrast, social support is related only to coping behaviors in females. Finally, social support appears to be a more important variable for female adjustment, whereas other coping behaviors appear to be more pertinent to male adjustment. Limitations and suggestions for future research will be discussed.

Anton, a special-purpose machine for molecular dynamics simulation

David Shaw — 2007-07-09T17:30:02-00:00

SIGARCH Comput. Archit. News, Vol. 35, No. 2. (May 2007), pp. 1-12.

Prolinks: a database of protein functional linkages derived from coevolution.

PM Bowers — 2005-08-25T13:33:08-00:00

Genome Biol, Vol. 5, No. 5. (2004)

The advent of whole-genome sequencing has led to methods that infer protein function and linkages. We have combined four such algorithms (phylogenetic profile, Rosetta Stone, gene neighbor and gene cluster) in a single database--Prolinks--that spans 83 organisms and includes 10 million high-confidence links. The Proteome Navigator tool allows users to browse predicted linkage networks interactively, providing accompanying annotation from public databases. The Prolinks database and the Proteome Navigator tool are available for use online at http://dip.doe-mbi.ucla.edu/pronav.

User embodiment in collaborative virtual environments

Steve Benford — 2007-08-03T11:05:27-00:00

(1995), pp. 242-249.

Physical and Genetic Structure of the Maize Genome Reflects Its Complex Evolutionary History.

Fusheng Wei — 2008-04-17T14:12:01-00:00

PLoS genetics, Vol. 3, No. 7. (20 July 2007)

Maize (Zea mays L.) is one of the most important cereal crops and a model for the study of genetics, evolution, and domestication. To better understand maize genome organization and to build a framework for genome sequencing, we constructed a sequence-ready fingerprinted contig-based physical map that covers 93.5% of the genome, of which 86.1% is aligned to the genetic map. The fingerprinted contig map contains 25,908 genic markers that enabled us to align nearly 73% of the anchored maize genome to the rice genome. The distribution pattern of expressed sequence tags correlates to that of recombination. In collinear regions, 1 kb in rice corresponds to an average of 3.2 kb in maize, yet maize has a 6-fold genome size expansion. This can be explained by the fact that most rice regions correspond to two regions in maize as a result of its recent polyploid origin. Inversions account for the majority of chromosome structural variations during subsequent maize diploidization. We also find clear evidence of ancient genome duplication predating the divergence of the progenitors of maize and rice. Reconstructing the paleoethnobotany of the maize genome indicates that the progenitors of modern maize contained ten chromosomes.

Extensive Concerted Evolution of Rice Paralogs and the Road to Regaining Independence

Xiyin Wang — 2008-01-29T17:18:25-00:00

Genetics, Vol. 177, No. 3. (1 November 2007), pp. 1753-1763.

Many genes duplicated by whole-genome duplications (WGDs) are more similar to one another than expected. We investigated whether concerted evolution through conversion and crossing over, well-known to affect tandem gene clusters, also affects dispersed paralogs. Genome sequences for two Oryza subspecies reveal appreciable gene conversion in the [~]0.4 MY since their divergence, with a gradual progression toward independent evolution of older paralogs. Since divergence from subspecies indica, [~]8% of japonica paralogs produced 57 MYA on chromosomes 11 and 12 have been affected by gene conversion and several reciprocal exchanges of chromosomal segments, while [~]70-MY-old "paleologs" resulting from a genome duplication (GD) show much less conversion. Sequence similarity analysis in proximal gene clusters also suggests more conversion between younger paralogs. About 8% of paleologs may have been converted since ricesorghum divergence [~]41 MYA. Domain-encoding sequences are more frequently converted than nondomain sequences, suggesting a sort of circularitythat sequences conserved by selection may be further conserved by relatively frequent conversion. The higher level of concerted evolution in the 57 MY-old segmental duplication may reflect the behavior of many genomes within the first few million years after duplication or polyploidization. 10.1534/genetics.107.073197

Demographic Responses to Habitat Fragmentation: Experimental Tests at the Landscape and Patch Scale

Jr — 2008-05-31T17:35:58-00:00

Ecology, Vol. 79, No. 3. (1998), pp. 969-980.

Does deep brain stimulation induce apathy in parkinson's disease?

L Kirsch-Darrow — 2008-05-31T10:28:37-00:00

Frontiers in bioscience : a journal and virtual library, Vol. 13 (2008), pp. 5316-5322.

Chronic deep brain stimulation (DBS) is an important therapeutic advancement for the treatment of motor symptoms in Parkinson's disease (PD). However, its effects on non-motor symptoms are not well understood. Several studies have reported motivational disturbances and apathy after DBS surgery. Recent studies are beginning to more carefully examine the relationship between DBS and apathy. This review summarizes and evaluates the current state of the literature on apathy after DBS surgery, discusses methodological limitations in the literature, and makes suggestions for future research.

A common, avoidable source of error in molecular dynamics integrators

Ross Lippert — 2008-02-22T19:25:32-00:00

The Journal of Chemical Physics, Vol. 126, No. 4. (2007)

Advancing ecological research with ontologies.

JS Madin — 2008-05-22T02:38:59-00:00

Trends in ecology & evolution (Personal edition), Vol. 23, No. 3. (March 2008), pp. 159-168.

Ecology is inherently cross-disciplinary, drawing together many types of information to address questions about the natural world. Finding and integrating relevant data to assist in these analyses is crucial, but is difficult owing to ambiguous terminology and the lack of sufficient information about datasets. Ontologies provide a formal mechanism for defining terms and their relationships, and can improve the location, interpretation and integration of data based on its inherent meaning. Ontologies have assisted other disciplines (e.g. molecular biology) in unifying and enriching descriptions of data, and ecology can benefit from similar approaches. We review ontology efforts in ecology, and describe how these can benefit research by enhancing the location and interpretation of relevant data for confronting crucial ecological questions.

The visitor as virtual archaeologist: explorations in mixed reality technology to enhance educational and social interaction in the museum

Tony Hall — 2008-05-08T17:26:25-00:00

(2001), pp. 91-96.

The midpoint method for parallelization of particle simulations

Kevin Bowers — 2008-02-11T16:45:07-00:00

The Journal of Chemical Physics, Vol. 124, No. 18. (2006)

Suppressive subtractive hybridization of and differences in gene expression content of calcifying and noncalcifying cultures of Emiliania huxleyi strain 1516.

B Nguyen — 2008-05-06T08:24:27-00:00

Applied and environmental microbiology, Vol. 71, No. 5. (May 2005), pp. 2564-2575.

The marine coccolithophorid Emiliania huxleyi is a cosmopolitan alga intensely studied in relation to global carbon cycling, biogeochemistry, marine ecology, and biomineralization processes. The biomineralization capabilities of coccolithophorids have attracted the attention of scientists interested in exploiting this ability for the development of materials science and biomedical and biotechnological applications. Although it has been well documented that biomineralization in E. huxleyi is promoted by growth under phosphate-limited conditions, the genes and proteins that govern the processes of calcification and coccolithogenesis remain unknown. Suppressive subtractive hybridization (SSH) libraries were constructed from cultures grown in phosphate-limited and phosphate-replete media as tester and driver populations for reciprocal SSH procedures. Positive clones from each of the two libraries were randomly selected, and dot blotting was performed for the analysis of expression patterns. A total of 513 clones from the phosphate-replete library and 423 clones from the phosphate-limited library were sequenced, assembled, and compared to sequences in GenBank using BLASTX. Of the 103 differentially expressed gene fragments from the phosphate-replete library, 34% showed significant homology to other known proteins, while only 23% of the 65 differentially expressed gene fragments from the phosphate-limited library showed homology to other proteins. To further assess mRNA expression, real-time RT-PCR analysis was employed and expression profiles were generated over a 14-day time course for three clones from the phosphate-replete library and five clones from the phosphate-limited library. The fragments isolated provide the basis for future cloning of full-length genes and functional analysis.

Scalable algorithms for molecular dynamics simulations on commodity clusters

Kevin Bowers — 2008-05-05T10:03:43-00:00

(2006)

Comparative physical mapping links conservation of microsynteny to chromosome structure and recombination in grasses

John Bowers — 2008-04-25T03:18:36-00:00

Proceedings of the National Academy of Sciences, Vol. 102, No. 37. (13 September 2005), pp. 13206-13211.

Nearly finished sequences for model organisms provide a foundation from which to explore genomic diversity among other taxonomic groups. We explore genome-wide microsynteny patterns between the rice sequence and two sorghum physical maps that integrate genetic markers, bacterial artificial chromosome (BAC) fingerprints, and BAC hybridization data. The sorghum maps largely tile a genomic component containing 41% of BACs but 80% of single-copy genes that shows conserved microsynteny with rice and partially tile a nonsyntenic component containing 46% of BACs but only 13% of single-copy genes. The remaining BACs are centromeric (4%) or unassigned (8%). The two genomic components correspond to cytologically discernible "euchromatin" and "heterochromatin." Gene and repetitive DNA distributions support this classification. Greater microcolinearity in recombinogenic (euchromatic) than nonrecombinogenic (heterochromatic) regions is consistent with the hypothesis that genomic rearrangements are usually deleterious, thus more likely to persist in nonrecombinogenic regions by virtue of Muller's ratchet. Interchromosomal centromeric rearrangements may have fostered diploidization of a polyploid cereal progenitor. Model plant sequences better guide studies of related genomes in recombinogenic than nonrecombinogenic regions. Bridging of 35 physical gaps in the rice sequence by sorghum BAC contigs illustrates reciprocal benefits of comparative approaches that extend at least across the cereals and perhaps beyond. 10.1073/pnas.0502365102

Taking the first steps towards a standard for reporting on phylogenies: Minimum Information About a Phylogenetic Analysis (MIAPA).

J Leebens-Mack — 2008-04-22T19:23:43-00:00

Omics : a journal of integrative biology, Vol. 10, No. 2. (2006), pp. 231-237.

In the eight years since phylogenomics was introduced as the intersection of genomics and phylogenetics, the field has provided fundamental insights into gene function, genome history and organismal relationships. The utility of phylogenomics is growing with the increase in the number and diversity of taxa for which whole genome and large transcriptome sequence sets are being generated. We assert that the synergy between genomic and phylogenetic perspectives in comparative biology would be enhanced by the development and refinement of minimal reporting standards for phylogenetic analyses. Encouraged by the development of the Minimum Information About a Microarray Experiment (MIAME) standard, we propose a similar roadmap for the development of a Minimal Information About a Phylogenetic Analysis (MIAPA) standard. Key in the successful development and implementation of such a standard will be broad participation by developers of phylogenetic analysis software, phylogenetic database developers, practitioners of phylogenomics, and journal editors.

Actor-oriented design of scientific workflows

S Bowers — 2008-04-22T11:55:51-00:00

(2005)

Scientific workflows are becoming increasingly important as a unifying mechanism for interlinking scientific data management, analysis, simulation, and visualization tasks. Scientific workflow systems are problem-solving environments, supporting scientists in the creation and execution of scientific workflows.

Collection-Oriented Scientific Workflows for Integrating and Analyzing Biological Data

Timothy Mcphillips — 2008-04-22T11:45:03-00:00

Data Integration in the Life Sciences (2006), pp. 248-263.

Steps in scientific workflows often generate collections of results, causing the data flowing through workflows to become increasingly nested. Because conventional workflow components (or actors) typically operate on simple or application-specific data types, additional actors often are required to manage these nested data collections. As a result, conventional workflows become increasingly complex as data becomes more nested. This paper describes a new paradigm for developing scientific workflows that transparently manages nested data collections. Collection-oriented workflows have a number of advantages over conventional approaches including simpler workflow designs (e.g., requiring fewer actors and control-flow constructs) that are invariant under changes in data nesting. Our implementation within the Kepler scientific workflow system enables the explicit representation of collections and collection schemas, concurrent operation over collection contents via multi-level pipeline parallelism, and allows collection-aware actors to be composed readily from conventional actors.

The history tablecloth: illuminating domestic activity

William Gaver — 2007-11-01T11:46:43-00:00

(2006), pp. 199-208.

From the Cover: Direct DNA binding by Brca1

Tanya Paull — 2008-04-16T06:15:14-00:00

Proceedings of the National Academy of Sciences, Vol. 98, No. 11. (22 May 2001), pp. 6086-6091.

10.1073/pnas.111125998

From the Disappearing Computer to Living Exhibitions: Shaping Interactivity in Museum Settings

John Bowers — 2008-02-11T18:55:05-00:00

The Disappearing Computer (2007), pp. 30-49.

While considerable technical ingenuity is being devoted to making the computer “disappear”, comparatively few research endeavours have concertedly explored the issues which arise when innovative artefacts are deployed in public settings. Innovations in “mixed reality”, “augmented reality” and “ubiquitous computing” tend to be confined to demonstrations, circumscribed trials or other controlled settings. However, a number of projects have begun to devote themselves to putting such technologies into the hands of the public and reflecting on the design and development issues that are encountered as a result. In particular, the SHAPE project was concerned with deploying innovative technologies in public settings, most notably museums. Over the course of our research, we developed an orientation to design which combines social scientific study, close collaboration with museum personnel and visitors, and a characteristic approach for technology deployment. In this chapter, we describe this orientation, exemplify it through accounts of the exhibitions the project has built at a number of museums in different European countries, and assess its broader implications for research on human-computer interaction, ubiquitous computing, and allied concerns.

Enhancing ubiquitous computing with user interpretation: field testing the home health horoscope

William Gaver — 2008-04-06T21:17:17-00:00

(2007), pp. 537-546.

User Embodiment in Collaborative Virtual Environments

Steve Benford — 2008-04-04T14:08:19-00:00

Vol. 1 (1995), pp. 242-249.

This paper explores the issue of user embodiment within collaborative virtual environments. By user embodiment we mean the provision of users with appropriate body images so as to represent them to others and also to themselves. By collaborative virtual environments we mean multi-user virtual reality systems which explicitly support co-operative work (although we argue that the results of our exploration may also be applied to other kinds of collaborative system). The main part of the paper...

Talk and embodiment in collaborative virtual environments

John Bowers — 2007-08-31T11:22:15-00:00

(1996), pp. 58-65.

The Ideological-Historical Context of an Educational Metaphor

CA Bowers — 2008-03-14T04:13:23-00:00

Theory into Practice, Vol. 18, No. 5. (1979), pp. 316-322.

Botulinum neurotoxin A blocks synaptic vesicle exocytosis but not endocytosis at the nerve terminal.

EA Neale — 2008-03-12T12:32:37-00:00

J Cell Biol, Vol. 147, No. 6. (13 December 1999), pp. 1249-1260.

The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K(+)-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K(+) depolarization, in the presence of Ca(2+), triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A-blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca(2+) is required for synaptic vesicle membrane retrieval.

Ultrahigh performance three-dimensional electromagnetic relativistic kinetic plasma simulation

KJ Bowers — 2008-03-06T18:48:54-00:00

Physics of Plasmas, Vol. 15, No. 5. (5 March 2008), pp. 055703-1-055703-7.

The algorithms, implementation details, and applications of VPIC, a state-of-the-art first principles 3D electromagnetic relativistic kinetic particle-in-cell code, are discussed. Unlike most codes, VPIC is designed to minimize data motion, as, due to physical limitations (including the speed of light!), moving data between and even within modern microprocessors is more time consuming than performing computations. As a result, VPIC has achieved unprecedented levels of performance. For example, VPIC can perform ~0.17 billion cold particles pushed and charge conserving accumulated per second per processor on IBM's Cell microprocessor—equivalent to sustaining Los Alamos's planned Roadrunner supercomputer at ~0.56 petaflop (quadrillion floating point operations per second). VPIC has enabled previously intractable simulations in numerous areas of plasma physics, including magnetic reconnection and laser plasma interactions; next generation supercomputers like Roadrunner will enable further advances.

siRNA target site secondary structure predictions using local stable substructures.

BS Heale — 2005-11-21T05:05:08-00:00

Nucleic Acids Res, Vol. 33, No. 3. (2005)

The crystal structure based model of the catalytic center of Ago2 revealed that the siRNA and the mRNA must be able to form an A-helix for correct positing of the scissile phosphate bond for cleavage in RNAi. This suggests that base pairing of the target mRNA with itself, i.e. secondary structure, must be removed before cleavage. Early on in the siRNA design, GC-rich target sites were avoided because of their potential to be involved in strong secondary structure. It is still unclear how important a factor mRNA secondary structure is in RNAi. However, it has been established that a difference in the thermostability of the ends of an siRNA duplex dictate which strand is loaded into the RNA-induced silencing complex. Here, we use a novel secondary structure prediction method and duplex-end differential calculations to investigate the importance of a secondary structure in the siRNA design. We found that the differential duplex-end stabilities alone account for functional prediction of 60% of the 80 siRNA sites examined, and that secondary structure predictions improve the prediction of site efficacy. A total of 80% of the non-functional sites can be eliminated using secondary structure predictions and duplex-end differential.

Automatic semantic activation of embedded words: Is there a "hat" in "that"?

Jeffrey Bowers — 2005-10-02T13:44:17-00:00

Journal of Memory and Language, Vol. 52, No. 1. (January 2005), pp. 131-143.

Participants semantically categorized target words that contain subsets (Experiment 1; e.g., target = hatch, subset = hat) or that are parts of supersets (Experiment 2; e.g., target = bee, superset = beer). In both experiments, the targets were categorized in a congruent condition (in which the subset-superset was associated with the same response, e.g., Does hatch refer to a human body part?) and an incongruent condition (in which the subset-superset was associated with a conflicting response, e.g., Does hatch refer to a piece of clothing?). Responses were slower and less accurate in the incongruent conditions, suggesting that subsets and supersets were processed to the level of meaning. Congruency effects occurred regardless of the position of the subset or superset (e.g., hatch, drama, howl), and in Experiment 1, were obtained for subsets that maintained (e.g., card) and changed their pronunciation (e.g., crown). Congruency effects were only found when the subsets were of higher frequency than the target. The implications for theories of word identification are discussed.

Many gene and domain families have convergent fates following independent whole-genome duplication events in Arabidopsis, Oryza, Saccharomyces and Tetraodon

Andrew Paterson — 2008-02-18T13:09:26-00:00

Trends in Genetics, Vol. 22, No. 11. (November 2006), pp. 597-602.

Genome duplication is potentially a good source of new genes, but such genes take time to evolve. We have found a group of `duplication-resistant' genes, which have undergone convergent restoration to singleton status following several independent genome duplications. Restoration of duplication-resistant genes to singleton status could be important to long-term survival of a polyploid lineage. Angiosperms show more frequent polyploidization and a higher degree of duplicate gene preservation than other paleopolyploids, making them well-suited to further study of duplication-resistant genes.

The influence of trade-off shape on evolutionary behaviour in classical ecological scenarios

Andrew Hoyle — 2008-02-15T15:48:02-00:00

Journal of Theoretical Biology, Vol. 250, No. 3. (7 February 2008), pp. 498-511.

Trade-off shapes are crucial to evolutionary outcomes. However, due to different ecological feedbacks their implications may depend not only on the trade-off being considered but also the ecological scenario. Here, we apply a novel geometric technique, trade-off and invasion plots (TIPs), to examine in detail how the shape of trade-off relationships affect evolutionary outcomes under a range of classic ecological scenarios including Lotka-Volterra type and host-parasite interactions. We choose models of increasing complexity in order to gain an insight into the features of ecological systems that determine the evolutionary outcomes. In particular we focus on when evolutionary attractors, repellors and branching points occur and how this depends on whether the costs are accelerating (benefits become `increasingly' costly), decelerating (benefits become `decreasingly' costly) or constant. In all cases strongly accelerating costs lead to attractors while strongly decelerating ones lead to repellors, but with weaker relationships, this no longer holds. For some systems weakly accelerating costs may lead to repellors and decelerating costs may lead to attractors. In many scenarios it is weakly decelerating costs that lead to branching points, but weakly accelerating and linear costs may also lead to disruptive selection in particular ecological scenarios. Using our models we suggest a classification of ecological interactions, based on three distinct criteria, that can produce one of four fundamental TIPs which allow for different evolutionary behaviour. This provides a baseline theory which may inform the prediction of evolutionary outcomes in similar yet unexplored ecological scenarios. In addition we discuss the implications of our results to a number of specific life-history trade-offs in the classic ecological scenarios represented by our models.

Zonal methods for the parallel execution of range-limited N-body simulations

Kevin Bowers — 2008-02-12T15:12:37-00:00

Journal of Computational Physics, Vol. 221, No. 1. (20 January 2007), pp. 303-329.

Particle simulations in fields ranging from biochemistry to astrophysics require the evaluation of interactions between all pairs of particles separated by less than some fixed interaction radius. The applicability of such simulations is often limited by the time required for calculation, but the use of massive parallelism to accelerate these computations is typically limited by inter-processor communication requirements. Recently, Snir [M. Snir, A note on N-body computations with cutoffs, Theor. Comput. Syst. 37 (2004) 295-318] and Shaw [D.E. Shaw, A fast, scalable method for the parallel evaluation of distance-limited pairwise particle interactions, J. Comput. Chem. 26 (2005) 1318-1328] independently introduced two distinct methods that offer asymptotic reductions in the amount of data transferred between processors. In the present paper, we show that these schemes represent special cases of a more general class of methods, and introduce several new algorithms in this class that offer practical advantages over all previously described methods for a wide range of problem parameters. We also show that several of these algorithms approach an approximate lower bound on inter-processor data transfer.

Cognitive and Situated Learning Perspectives in Theory and Practice

Paul Cobb — 2005-11-02T12:31:36-00:00

Educational Researcher, Vol. 28, No. 2. (1999), pp. 4-15.

In their recent exchange, Anderson, Reder, and Simon (1996, 1997) and Greeno (1997) frame the conflicts between cognitive theory and situated learning theory in terms of issues that are primarily of interest to educational psychologists. We attempt to broaden the debate by approaching this discussion of perspectives against the background of our concerns as educators who engage in classroom-based research and instructional design in collaboration with teachers. We first delineate the underlying differences between the two perspectives by distinguishing their central organizing metaphors. We then argue that the contrast between the two perspectives cannot be reduced to that of choosing between the individual and the social collective as the primary unit of analysis. Against this background, we compare the situated viewpoint we find useful in our work with the cognitive approach advocated by Anderson et al. by focusing on their treatments of meaning and instructional goals. Finally, we consider the potential contributions of the two perspectives to instructional practice by contrasting their differing formulations of the relationship between theory and practice.

Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype

Matthew State — 2008-01-27T22:18:17-00:00

Proceedings of the National Academy of Sciences, Vol. 100, No. 8. (15 April 2003), pp. 4684-4689.

Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dysregulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts. 10.1073/pnas.0730775100