CiteULike: Author Davis

Genome sequence of the metazoan plant-parasitic nematode Meloidogyne incognita.

Pierre Abad — 2008-08-06T15:45:28-00:00

Nature biotechnology (27 July 2008)

Plant-parasitic nematodes are major agricultural pests worldwide and novel approaches to control them are sorely needed. We report the draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, including tomato, cotton and coffee. Most of the assembled sequence of this asexually reproducing nematode, totaling 86 Mb, exists in pairs of homologous but divergent segments. This suggests that ancient allelic regions in M. incognita are evolving toward effective haploidy, permitting new mechanisms of adaptation. The number and diversity of plant cell wall-degrading enzymes in M. incognita is unprecedented in any animal for which a genome sequence is available, and may derive from multiple horizontal gene transfers from bacterial sources. Our results provide insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.

Hypertext link integrity

Hugh Davis — 2008-07-09T21:12:35-00:00

ACM Comput. Surv. (1999)

MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.

IW Davis — 2007-12-12T13:40:49-00:00

Nucleic Acids Res, Vol. 35, No. Web Server issue. (1 July 2007)

MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis of any steric problems within the molecules as well as updated dihedral-angle diagnostics, and it can calculate and display the H-bond and van der Waals contacts in the interfaces between components. An integral step in the process is the addition and full optimization of all hydrogen atoms, both polar and nonpolar. New analysis functions have been added for RNA, for interfaces, and for NMR ensembles. Additionally, both the web site and major component programs have been rewritten to improve speed, convenience, clarity and integration with other resources. MolProbity results are reported in multiple forms: as overall numeric scores, as lists or charts of local problems, as downloadable PDB and graphics files, and most notably as informative, manipulable 3D kinemage graphics shown online in the KiNG viewer. This service is available free to all users at http://molprobity.biochem.duke.edu.

Genetics of Parkinsonism: a review

JR Vaughan — 2008-08-06T03:39:20-00:00

Annals of Human Genetics, Vol. 65, No. 2. (2001), pp. 111-126.

Idiopathic Parkinson's disease (IPD), a progressive neurodegenerative disorder, is a common cause of disability. No current therapies modify disease progression. The pathological hallmarks are the presence of Lewy bodies and massive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Two genes (SNCA and parkin) as well as two gene loci have now been implicated in the pathogenesis of familial PD. These represent significant progress in our understanding of the disease, considering the rarity of large families, low heritability in the general population and genetic heterogeneity. Mutations in a further gene, UCHL1, have been described in familial PD although the evidence for its role in PD is less clear. Knowledge of the genes described in PD to date should help to define molecular mechanisms of neurodegeneration in PD, as well as in other diseases where defects in protein handling may be a common feature. Nigral degeneration with Lewy body formation and the resulting clinical picture of PD may represent a final common pathway of a multifactorial disease process in which both environmental and genetic factors have a role. This review discusses the major advances in the field to date and illustrates how the existence of genetic factors has now become firmly established.

Do disparate mechanisms of duplication add similar genes to the genome?

Jerel Davis — 2005-08-12T14:19:22-00:00

Trends in Genetics, Vol. In Press, Corrected Proof

Gene duplication is the fundamental source of new genes. Biases in duplication have profound implications for the dynamics of gene content during evolution. In this article, we compare genes arising from whole gene duplication (WGD), smaller scale duplication (SSD) and singletons in Saccharomyces cerevisiae. Our results demonstrate that genes duplicated by WGD and SSD are similarly biased with respect to codon bias and evolutionary rate, although differing significantly in their functional constituency.

SMAD proteins control DROSHA-mediated microRNA maturation

Brandi Davis — 2008-06-12T04:36:14-00:00

Nature (11 June 2008)

Development of a performance assessment task and rubric to measure prospective secondary school mathematics teachers’ pedagogical content knowledge and skills

Hari Koirala — 2008-08-01T13:18:57-00:00

Journal of Mathematics Teacher Education, Vol. 11, No. 2. (18 April 2008), pp. 127-138.

Abstract The purpose of this paper is to share a performance assessment task and rubric designed to assess secondary school mathematics preservice teachers’ pedagogical content knowledge and skills. The assessment task and rubric were developed in collaboration with five education faculty, four arts and sciences faculty, and four high school teachers over a period of one year. Over this period, the group met more than 15 times and designed an assessment task and rubric to measure secondary school preservice teachers’ pedagogical content knowledge and skills. The assessment task and rubric were piloted at the end of the year and extensively revised using the pilot data. The redesigned task and rubric were successfully carried out in the second and subsequent years. Other teacher education programs can benefit from this assessment of teacher candidates’ pedagogical content knowledge and skills.

Brain Plasticity Mechanisms and Memory: A Party of Four

Elodie Bruel-Jungerman — 2008-04-24T22:12:17-00:00

Neuroscientist, Vol. 13, No. 5. (1 October 2007), pp. 492-505.

A defining characteristic of the brain is its remarkable capacity to undergo activity-dependent functional and morphological remodeling via mechanisms of plasticity that form the basis of our capacity to encode and retain memories. Today, it is generally accepted that the neurobiological substrate of memories resides in activity-driven modifications of synaptic strength and structural remodeling of neural networks activated during learning. Since the discovery of long-term potentiation, the role of synaptic strengthening in learning and memory has been the subject of considerable investigation, and numerous studies have provided new insights into how this form of plasticity can subserve memory function. At the same time, other studies have explored the contribution of synaptic elimination or weakening; synaptogenesis, the growth of new synaptic connections and synapse remodeling; and more recently, neurogenesis, the birth and growth of new neurons in the adult brain. In this review, based on work in the hippocampus, the authors briefly outline recent advances in their understanding of the mechanisms and functional role of these four types of brain plasticity in the context of learning and memory. While they have long been considered as alternative mechanisms of plasticity underlying the storage of long-term memories, recent evidence suggests that they are functionally linked, suggesting the mechanisms underlying plasticity in the brain required for the formation and retention of memories are multifaceted. NEUROSCIENTIST 13(5):492--505, 2007. DOI: 10.1177/1073858407302725 10.1177/1073858407302725

Open access publishing, article downloads, and citations: randomised controlled trial.

PM Davis — 2008-08-02T14:43:26-00:00

BMJ (Clinical research ed.), Vol. 337 (2008)

OBJECTIVE: To measure the effect of free access to the scientific literature on article downloads and citations. DESIGN: Randomised controlled trial. SETTING: 11 journals published by the American Physiological Society. PARTICIPANTS: 1619 research articles and reviews. MAIN OUTCOME MEASURES: Article readership (measured as downloads of full text, PDFs, and abstracts) and number of unique visitors (internet protocol addresses). Citations to articles were gathered from the Institute for Scientific Information after one year. INTERVENTIONS: Random assignment on online publication of articles published in 11 scientific journals to open access (treatment) or subscription access (control). RESULTS: Articles assigned to open access were associated with 89% more full text downloads (95% confidence interval 76% to 103%), 42% more PDF downloads (32% to 52%), and 23% more unique visitors (16% to 30%), but 24% fewer abstract downloads (-29% to -19%) than subscription access articles in the first six months after publication. Open access articles were no more likely to be cited than subscription access articles in the first year after publication. Fifty nine per cent of open access articles (146 of 247) were cited nine to 12 months after publication compared with 63% (859 of 1372) of subscription access articles. Logistic and negative binomial regression analysis of article citation counts confirmed no citation advantage for open access articles. CONCLUSIONS: Open access publishing may reach more readers than subscription access publishing. No evidence was found of a citation advantage for open access articles in the first year after publication. The citation advantage from open access reported widely in the literature may be an artefact of other causes.

Does free fluid on abdominal computed tomographic scan after blunt trauma require laparotomy?

MA Cunningham — 2008-08-02T00:55:26-00:00

The Journal of trauma, Vol. 44, No. 4. (April 1998)

BACKGROUND: Abdominal computed tomographic (CT) scans are used in the evaluation of blunt trauma. The purpose of this study was to determine if isolated intraperitoneal fluid seen on CT scan necessitates laparotomy. METHODS: Trauma registry records of patients who underwent abdominal computed tomography from January 1994 through January 1997 were studied. Data were reviewed for age, gender, CT scan interpretation, associated injuries, and operative findings. RESULTS: Abdominal injury was identified in 126 patients. Seventy-eight patients had evidence of solid-organ injury and 17 patients had extraperitoneal injury. Isolated intraperitoneal fluid was identified in 31 patients. All patients with isolated fluid underwent laparotomy; 29 of these procedures (94%) were therapeutic. Bowel injuries occurred in 18 patients and mesenteric injuries in 8 patients. Five patients had intraperitoneal bladder rupture, and undetected solid-organ injuries were found in two patients. Other organs injured included the stomach, pancreas, ovary, and uterus. CONCLUSION: Exploratory laparotomy was therapeutic in 94% of patients. Isolated intraperitoneal fluid on CT scan after blunt trauma mandates laparotomy.

Glycopeptides Related to β-Endorphin Adopt Helical Amphipathic Conformations in the Presence of Lipid Bilayers

M Dhanasekaran — 2008-08-01T18:52:40-00:00

J. Am. Chem. Soc., Vol. 127, No. 15. (20 April 2005), pp. 5435-5448.

Abstract: A series of glycosylated endorphin analogues designed to penetrate the blood-brain barrier (BBB) have been studied by circular dichroism and by 2D-NMR in the presence of water; TFE/water; SDS micelles; and in the presence of both neutral and anionic bicelles. In water, the glycopeptides showed only nascent helix behavior and random coil conformations. Chemical shift indices and nuclear Overhauser effects (NOE) confirmed helices in the presence of membrane mimics. NOE volumes provided distance constraints for molecular dynamics calculations used to provide detailed backbone conformations. In all cases, the glycopeptides were largely helical in the presence of membrane bilayer models (micelles or bicelles). Plasmon waveguide resonance (PWR) studies showed hen egg phosphatidyl choline (PC) bilayers produce amphipathic helices laying parallel to the membrane surface, with dissociation constants (KD) in the low nanomolar to micromolar concentration range. Two low-energy states are suggested for the glycosylated endorphin analogues, a flexible aqueous state and a restricted membrane bound state. Strong interactions between the glycopeptide amphipaths and membranes are crucial for penetration of the BBB via an endocytotic mechanism (transcytosis).

Mental Training Affects Distribution of Limited Brain Resources

Heleen Slagter — 2007-05-08T19:00:11-00:00

PLoS Biology, Vol. 5, No. 6. (1 June 2007), e138.

The information processing capacity of the human mind is limited, as is evidenced by the so-called “attentional-blink” deficit: When two targets (T1 and T2) embedded in a rapid stream of events are presented in close temporal proximity, the second target is often not seen. This deficit is believed to result from competition between the two targets for limited attentional resources. Here we show, using performance in an attentional-blink task and scalp-recorded brain potentials, that meditation, or mental training, affects the distribution of limited brain resources. Three months of intensive mental training resulted in a smaller attentional blink and reduced brain-resource allocation to the first target, as reflected by a smaller T1-elicited P3b, a brain-potential index of resource allocation. Furthermore, those individuals that showed the largest decrease in brain-resource allocation to T1 generally showed the greatest reduction in attentional-blink size. These observations provide novel support for the view that the ability to accurately identify T2 depends upon the efficient deployment of resources to T1. The results also demonstrate that mental training can result in increased control over the distribution of limited brain resources. Our study supports the idea that plasticity in brain and mental function exists throughout life and illustrates the usefulness of systematic mental training in the study of the human mind.

The ELF4 gene controls circadian rhythms and flowering time in Arabidopsis thaliana.

MR Doyle — 2006-03-22T13:16:41-00:00

Nature, Vol. 419, No. 6902. (5 September 2002), pp. 74-77.

Many plants use day length as an environmental cue to ensure proper timing of the switch from vegetative to reproductive growth. Day-length sensing involves an interaction between the relative length of day and night, and endogenous rhythms that are controlled by the plant circadian clock. Thus, plants with defects in circadian regulation cannot properly regulate the timing of the floral transition. Here we describe the gene EARLY FLOWERING 4 (ELF4), which is involved in photoperiod perception and circadian regulation. ELF4 promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles. elf4 mutants show attenuated expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a gene that is thought to function as a central oscillator component. In addition, elf4 plants transiently show output rhythms with highly variable period lengths before becoming arrhythmic. Mutations in elf4 result in early flowering in non-inductive photoperiods, which is probably caused by elevated amounts of CONSTANS (CO), a gene that promotes floral induction.

Developmental apraxia of speech: Determiners of differential diagnosis

Barbara Davis — 2008-08-01T14:45:31-00:00

Clinical Linguistics & Phonetics, Vol. 12, No. 1. (1998), pp. 25-45.

Developmental apraxia of speech (DAS) is a neurologically based disorder in the programming of sequential articulatory movements. This definition, based purely on motoric limitations, is fraught with controversy concerning aetiology, clinical manifestations, treatment, and even identification of the disorder as a separate clinical entity. An understanding of developmental apraxia depends on consistent utilization of a group of symptoms for diagnosis so that data-based results can be used to generate inferences about the disorder. Results from studies of children who are diagnosed with developmental apraxia, but who may not be apraxic, complicates application to theories attempting to account for observed symptoms. A longitudinal study of children with DAS has been under way at the University of Texas at Austin since 1985. Of 22 children referred as apraxic, a diagnosis has been confirmed in only four. Phonological and language evaluation data for five clients evaluated during this project are presented. One was diagnosed with developmental apraxia of speech. Each of the other four subjects were diagnosed with speech and/or language disorders without the presence of developmental apraxia of speech. Diagnostic results for all five are presented, to illustrate critical features for differential diagnosis of developmental apraxia.

The abundance threshold for plague as a critical percolation phenomenon

S Davis — 2008-07-31T19:26:43-00:00

Nature, Vol. 454, No. 7204., pp. 634-637.

Nonadaptive explanations for signatures of partial selective sweeps in Drosophila.

J Michael Macpherson — 2008-05-02T18:25:09-00:00

Molecular biology and evolution (16 January 2008)

A beneficial mutation which has nearly but not yet fixed in a population produces a characteristic haplotype configuration, called a partial selective sweep. Whether non-adaptive processes might generate similar haplotype configurations has not been previously explored. Here we consider five population genetic datasets taken from regions flanking high frequency transposable elements in North American strains of D. melanogaster, each of which appears to be consistent with the expectations of a partial selective sweep. We use coalescent simulations to explore whether incorporation of the species' demographic history, purifying selection against the element, or suppression of recombination caused by the element could generate putatively adaptive haplotype configurations. Where most of the datasets would be rejected as non-neutral under the standard neutral null model, only the dataset for which there is strong external evidence in support of an adaptive transposition appears to be non-neutral under the more complex null model, and in particular when demography is taken into account. High frequency, derived mutations from a recently-bottlenecked population, such as we study here, are of great interest to evolutionary genetics in the context of scans for adaptive events; we discuss the broader implications of our findings in this context.

Consortium to Establish a Registry for Alzheimer's Disease (CERAD): The first twenty years

Gerda Fillenbaum — 2008-03-20T15:35:56-00:00

Alzheimer's and Dementia, Vol. 4, No. 2. (March 2008), pp. 96-109.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded by the National Institute on Aging in 1986 to develop standardized, validated measures for the assessment of Alzheimer's disease (AD). The present report describes the measures that CERAD developed during its first decade and their continued use in their original and translated forms. These measures include clinical, neuropsychological, neuropathologic, and behavioral assessments of AD and also assessment of family history and parkinsonism in AD. An approach to evaluating neuroimages did not meet the standards desired. Further evaluations that could not be completed because of lack of funding (but where some materials are available) include evaluation of very severe AD and of service use and need by patient and caregiver. The information that was developed in the U.S. and abroad permits standardized assessment of AD in clinical practice, facilitates epidemiologic studies, and provides information valuable for individual and public health planning. CERAD materials and data remain available for those wishing to use them.

Neutron production from interactions of high-intensity ultrashort pulse laser with a planar deuterated polyethylene target

GM Petrov — 2008-07-31T09:09:29-00:00

Physics of Plasmas, Vol. 15, No. 7. (2008)

The deuteron acceleration from a planar uniform deuterated polyethylene (CD2) target was studied with a two-dimensional electromagnetic particle-in-cell method in the ultrarelativistic regime for peak laser intensities between 10^23 and 10^25 W/m2. Under identical conditions the deuteron energy and angular distributions are very different when compared to that produced from a double-layer target. The neutron production from D(d,n)–3He nuclear fusion reactions was also investigated with a three-dimensional Monte Carlo ion beam-target deposition model. The neutron yield and its angular distribution were studied as a function of peak laser intensity and laser pulse duration. A neutron yield of 10^4–10^6 neutrons per Joule laser energy is inferred from simulations of a 4 µm thick planar uniform CD2 target. The angular scattering of neutrons is found to be nonisotropic and has a significant component in the forward (laser propagation) direction.

Use of shotgun proteomics for the identification, confirmation, and correction of C. elegans gene annotations.

Gennifer E Merrihew — 2008-07-30T23:52:06-00:00

Genome research (24 July 2008)

We describe a general mass spectrometry-based approach for gene annotation of any organism and demonstrate its effectiveness using the nematode C. elegans. We detected 6,779 C. elegans proteins (67,047 peptides), including 384 that, although annotated in Wormbase WS150, lacked cDNA or other prior experimental support. We also identified 429 new coding sequences that were unannotated in WS150. Nearly half (192/429) of the new coding sequences were confirmed with RT-PCR data. Thirty-three (~8%) of the new coding sequences had been predicted to be pseudogenes, 151 (~35%) reveal apparent errors in gene models, and 245 (57%) appear to be novel genes. In addition, we verified 6,010 exon-exon splice junctions within existing Wormbase gene models. Our work confirms that mass spectrometry is a powerful experimental tool for annotating sequenced genomes. In addition, the collection of identified peptides should facilitate future proteomics experiments targeted at specific proteins of interest.

Oral contraceptives and libido in women.

AR Davis — 2008-07-30T18:38:40-00:00

Annual review of sex research, Vol. 15 (2004), pp. 297-320.

Oral contraceptives (OCs) provide safe, effective, and reversible contraception and are widely used by women for fertility control. Little is known about the effects of OCs on sexual functioning. This paper critically examines the published literature addressing the impact of OCs on sexual desire or libido. We reviewed 30 original research studies. In the retrospective, uncontrolled studies (n = 17), it was found that most women reported an increase in libido during OC use. In the uncontrolled, prospective studies (n = 4), it was found that most women reported little change in libido during OC use. In the prospective and cross-sectional controlled studies (n = 4), women using OCs reported both increased and decreased libido compared to non-OC users. The findings from randomized, placebo-controlled studies (n = 5) were mixed: In the most recent and well-conducted trial, a decrease in libido in OC users compared to placebo users was found. Overall, women experience positive effects, negative effects, as well as no effect on libido during OC use. Better-designed studies are needed to establish the independent, causal effects of OCs on libido.

A two-dimensional electromagnetic field algorithm for high-intensity laser-target interactions

GM Petrov — 2008-07-30T16:42:59-00:00

Computer Physics Communications, Vol. In Press, Accepted Manuscript

Colloidal gold and colloidal gold labelled wheat germ agglutinin as molecular probes for identification in mucin/chitosan complexes

I Fiebrig — 2008-07-30T15:00:50-00:00

Carbohydrate Polymers (June 1997), pp. 91-99.

Polyelectrolyte complex formation between pig gastric mucin and chitosan and its implications to mucoadhesion have recently been studied using techniques such as analytical ultracentrifugation, static light scattering and turbidimetry. The findings suggested the formation of large complexes, which were then visualised using electron microscopy. The present investigation employed electron microscopy combined with colloidal gold conjugates in order to identify and localize chitosan within the mucin/chitosan complex. Images of apparently dispersed chitosan molecules could be obtained using an anionic dye molecule, Orange II, which is known to interact stoichiometrically with the cationic sites on chitosan. Once chitosan was complexed with mucin, the colloidal gold labelled techniques revealed that chitosan is concentrated in the centre of the complex, surrounded by a possibly more hydrophilic layer of mucin.

HT06, tagging paper, taxonomy, Flickr, academic article, to read

Cameron Marlow — 2006-08-24T20:16:54-00:00

(2006), pp. 31-40.

In vitro activity and synergy of bismuth thiols and tobramycin against Burkholderia cepacia complex

Wilfredo Veloira — 2008-07-29T17:46:45-00:00

J. Antimicrob. Chemother., Vol. 52, No. 6. (1 December 2003), pp. 915-919.

Objectives: To determine the susceptibility of Burkholderia multivorans and Burkholderia cenocepacia to bismuth-thiols (BTs), and to examine the synergistic effects of tobramycin and subinhibitory concentrations of BTs against these organisms. Methods: The susceptibilities of 25 clinical isolates each of B. multivorans and B. cenocepacia to six BTs were measured by broth dilution in accordance with NCCLS protocols. Ten strains were selected to evaluate the antimicrobial interaction between BTs and tobramycin. Fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indices were calculated to assess synergy. Results: B. multivorans and B. cenocepacia showed a wide range of susceptibilities to BTs. Bismuth ethanedithiol (BisEDT) was one of the more potent BTs against these organisms (MIC50 7.8 microM), and was selected for synergy studies. Selected strains were highly resistant to tobramycin. The addition of subinhibitory concentrations of BisEDT (2 microM) reduced the MIC and MBC of tobramycin against all strains, achieving synergy in many instances. The FIC index was in the range 0.28-0.66 and the FBC in the range 0.12-0.85. Most strains became susceptible to tobramycin at clinically achievable concentrations in the presence of non-toxic BisEDT levels. Conclusions: Treatment with subinhibitory BisEDT and tobramycin reduces the MICs and MBCs for B. multivorans and B. cenocepacia. BTs may represent an important adjunctive therapy for resistant Burkholderia cepacia complex. 10.1093/jac/dkg471

Pervasive and Persistent Redundancy among Duplicated Genes in Yeast

Jedediah Dean — 2008-07-07T16:01:56-00:00

PLoS Genet, Vol. 4, No. 7. (4 July 2008), e1000113.

The loss of functional redundancy is the key process in the evolution of duplicated genes. Here we systematically assess the extent of functional redundancy among a large set of duplicated genes in Saccharomyces cerevisiae. We quantify growth rate in rich medium for a large number of S. cerevisiae strains that carry single and double deletions of duplicated and singleton genes. We demonstrate that duplicated genes can maintain substantial redundancy for extensive periods of time following duplication (∼100 million years). We find high levels of redundancy among genes duplicated both via the whole genome duplication and via smaller scale duplications. Further, we see no evidence that two duplicated genes together contribute to fitness in rich medium substantially beyond that of their ancestral progenitor gene. We argue that duplicate genes do not often evolve to behave like singleton genes even after very long periods of time.

Why do tagging systems work?

George Furnas — 2006-05-22T07:30:23-00:00

(2006), pp. 36-39.

Structure validation by Calpha geometry: phi,psi and Cbeta deviation.

SC Lovell — 2006-07-13T14:41:03-00:00

Proteins, Vol. 50, No. 3. (15 February 2003), pp. 437-450.

Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage).

Reproducibility Probability Score—incorporating measurement variability across laboratories for gene selection

Guixian Lin — 2006-12-12T03:05:10-00:00

Nature Biotechnology, Vol. 24, No. 12., pp. 1476-1477.

Quantum Metrology: Dynamics versus Entanglement

Sergio Boixo — 2008-07-28T09:06:01-00:00

Physical Review Letters, Vol. 101, No. 4. (2008)

A parameter whose coupling to a quantum probe of n constituents includes all two-body interactions between the constituents can be measured with an uncertainty that scales as 1/n3/2, even when the constituents are initially unentangled. We devise a protocol that achieves the 1/n3/2 scaling without generating any entanglement among the constituents, and we suggest that the protocol might be implemented in a two-component Bose-Einstein condensate.

Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis.

EA Winzeler — 2006-01-25T01:43:16-00:00

Science, Vol. 285, No. 5429. (6 August 1999), pp. 901-906.

The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.

Functional imaging of microdomains in cell membranes

James Duggan — 2008-07-28T00:29:03-00:00

European Biophysics Journal

Abstract The presence of microdomains or rafts within cell membranes is a topic of intense study and debate. The role of these structures in cell physiology, however, is also not yet fully understood with many outstanding problems. This problem is partly based on the small size of raft structures that presents significant problems to their in vivo study, i.e., within live cell membranes. But the structure and dynamics as well as the factors that control the assembly and disassembly of rafts are also of major interest. In this review we outline some of the problems that the study of rafts in cell membranes present as well as describing some views of what are considered the generalised functions of membrane rafts. We point to the possibility that there may be several different ‘types’ of membrane raft in cell membranes and consider the factors that affect raft assembly and disassembly, particularly, as some researchers suggest that the lifetimes of rafts in cell membranes may be sub-second. We attempt to review some of the methods that offer the ability to interrogate rafts directly as well as describing factors that appear to affect their functionality. The former include both near-field and far-field optical approaches as well as scanning probe techniques. Some of the advantages and disadvantages of these techniques are outlined. Finally, we describe our own views of raft functionality and properties, particularly, concerning the membrane dipole potential, and describe briefly some of the imaging strategies we have developed for their study.

On estimating treatment effects under non-compliance in randomized clinical trials: are intent-to-treat or instrumental variables analyses perfect solutions?

H Bang — 2008-07-27T09:55:58-00:00

Statistics in medicine, Vol. 26, No. 5. (28 February 2007), pp. 954-964.

In this report, we compared four estimators (intent-to-treat, as treated, per protocol, and instrumental variables estimators) that are conventionally considered for treatment effect estimation by simulation under different non-compliance scenarios in typical clinical trial settings. We found that intent-to-treat and instrumental variables estimators are not perfect and can be problematic in some situations although these two estimators carry desirable properties as we assume.

Building Web Services with Java : Making Sense of XML, SOAP, WSDL, and UDDI (2nd Edition) (Developer's Library)

Steve Graham — 2005-11-07T14:58:12-00:00

(28 June 2004)

Sams has assembled a team of experts in web services to provide you with a detailed reference guide on XML, SOAP, USDL and UDDI. Building Web Services with Java is in its second edition and it includes the newest standards for managing security, transactions, reliability and interoperability in web service applications. Go beyond the explanations of standards and find out how and why these tools were designed as they are and focus on practical examples of each concept. Download your source code from the publisher's website and work with a running example of a full enterprise solution. Learn from the best in Building Web Services with Java. Building Web Services with SOAP, XML, and UDDI assumes proficiency with Java and with distributed computing tools. Throughout the book, examples will be presented using Java and the Apache SOAP platform, although a set of sidebars will address .NET development, which Microsoft developers will use to deploy Web services. The book uses progressive disclosure to present an increasingly complex project as it moves through its development cycle. The final section of the book presents linking the completed project with other systems built in J2EE and .NET.

Thymic Selection Determines [gamma][delta] T Cell Effector Fate: Antigen-Naive Cells Make Interleukin-17 and Antigen-Experienced Cells Make Interferon [gamma]

Kirk Jensen — 2008-07-25T17:48:26-00:00

Immunity, Vol. 29, No. 1. (18 July 2008), pp. 90-100.

Summary [gamma][delta] T cells uniquely contribute to host immune defense, but how this is accomplished remains unclear. Here, we analyzed the nonclassical major histocompatibility complex class I T10 and T22-specific [gamma][delta] T cells in mice and found that encountering antigen in the thymus was neither required nor inhibitory for their development. But when triggered through the T cell receptor, ligand-naive lymphoid-[gamma][delta] T cells produced IL-17, whereas ligand-experienced cells made IFN-[gamma]. Immediately after immunization, a large fraction of IL-17+ [gamma][delta] T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17+ [alpha][beta] T cells. Thus, thymic selection determines the effector fate of [gamma][delta] T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive [gamma][delta] T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.

Cognitive functioning and postconcussive symptoms in trauma patients with and without mild TBI.

N Landre — 2007-05-09T19:42:06-00:00

Arch Clin Neuropsychol, Vol. 21, No. 4. (May 2006), pp. 255-273.

Although there is a large body of research on mild traumatic brain injury (MTBI), the portion that pertains to acute patients (those less than 1 month postinjury) is relatively small and yields inconsistent findings. The potential contribution of non-neurological factors, such as pain and emotional distress, to the clinical picture in this population is also lacking. To address these issues, the cognitive performance and symptom complaints of 37 hospitalized MTBI subjects were compared to those of 39 hospitalized trauma subjects, averaging 4.5 days postinjury. MTBI subjects performed significantly worse on all cognitive measures, but did not differ from trauma subjects in their report of postconcussive symptoms. Analyses also revealed that cognitive performance was unrelated to pain severity and emotional distress. Postconcussive symptoms were similarly unrelated to pain severity, but were consistently related to emotional distress. Results are discussed in terms of their etiological and treatment implications.

The relationship between Precision-Recall and ROC curves

Jesse Davis — 2008-01-20T14:54:47-00:00

(2006), pp. 233-240.

The turn in recent economics and return of orthodoxy

John Davis — 2008-07-25T14:44:48-00:00

Camb. J. Econ., Vol. 32, No. 3. (1 May 2008), pp. 349-366.

This paper examines change on the economics research frontier, and asks whether the current competition between new research programmes may be supplanted by a new single dominant approach in the future. The paper discusses whether economics tends to be dominated by a single approach or reflect a pluralism of approaches, and argues that, historically, it has alternated between the two. It argues that orthodoxy usually emerges from heterodoxy, and interprets the division between orthodoxy and heterodoxy in terms of a core-periphery distinction. Regarding recent economics, the paper maps out two different types of combinations of new research programmes as being synchronic or diachronic in nature. It treats the new research programmes as a new kind of heterodoxy, and asks how a new orthodoxy might arise out of this new heterodoxy and traditional heterodoxy. It discusses this question by advancing two views regarding how to different types of combinations in the new research programmes might consolidate along the lines of three shared commitments with traditional heterodoxy to form a new orthodoxy in economics. 10.1093/cje/bem048

A high-resolution atlas of nucleosome occupancy in Yeast

William Lee — 2007-10-01T04:57:32-00:00

Nature Genetics, Vol. 39, No. 10. (16 September 2007), pp. 1235-1244.

Paleogene island arc collision-related conglomerates, Yarlung-Tsangpo suture zone, Tibet

Aileen Davis — 2008-07-25T08:42:18-00:00

Sedimentary Geology, Vol. 150, No. 3-4. (1 July 2002), pp. 247-273.

Coarse clastic rocks in the Liuqu Conglomerate, formed in both terrestrial and subaqueous settings, record a Paleogene phase in the tectonic evolution of Tibet. Facies changes are commonly abrupt with rapid changes in clast types, grain size and stratal patterns. Sediments were derived from the leading (northern) edge of the Indian margin and a Late Jurassic-Cretaceous intraoceanic island arc that lay within Tethys. The coarse clastic sedimentary rocks of the Liuqu conglomerates are extremely proximal, but are locally offset relative to their original source terranes. They record aspects of the history of collision between these terranes and are interpreted to have been deposited in oblique-slip basins that developed along the zone of collision. The absence of clasts derived from terranes to the north of the Yarlung-Tsangpo suture suggests that basins associated with deposition of the Liuqu Conglomerate developed prior to the final collision between India and Asia.

DBAli tools: mining the protein structure space.

MA Marti-Renom — 2008-07-24T22:15:39-00:00

Nucleic acids research, Vol. 35, No. Web Server issue. (July 2007)

The DBAli tools use a comprehensive set of structural alignments in the DBAli database to leverage the structural information deposited in the Protein Data Bank (PDB). These tools include (i) the DBAlit program that allows users to input the 3D coordinates of a protein structure for comparison by MAMMOTH against all chains in the PDB; (ii) the AnnoLite and AnnoLyze programs that annotate a target structure based on its stored relationships to other structures; (iii) the ModClus program that clusters structures by sequence and structure similarities; (iv) the ModDom program that identifies domains as recurrent structural fragments and (v) an implementation of the COMPARER method in the SALIGN command in MODELLER that creates a multiple structure alignment for a set of related protein structures. Thus, the DBAli tools, which are freely accessible via the World Wide Web at http://salilab.org/DBAli/, allow users to mine the protein structure space by establishing relationships between protein structures and their functions.

The AnnoLite and AnnoLyze programs for comparative annotation of protein structures.

MA Marti-Renom — 2007-08-31T16:53:00-00:00

BMC Bioinformatics, Vol. 8 Suppl 4 (2007)

BACKGROUND: Advances in structural biology, including structural genomics, have resulted in a rapid increase in the number of experimentally determined protein structures. However, about half of the structures deposited by the structural genomics consortia have little or no information about their biological function. Therefore, there is a need for tools for automatically and comprehensively annotating the function of protein structures. We aim to provide such tools by applying comparative protein structure annotation that relies on detectable relationships between protein structures to transfer functional annotations. Here we introduce two programs, AnnoLite and AnnoLyze, which use the structural alignments deposited in the DBAli database. DESCRIPTION: AnnoLite predicts the SCOP, CATH, EC, InterPro, PfamA, and GO terms with an average sensitivity of ~90% and average precision of ~80%. AnnoLyze predicts ligand binding site and domain interaction patches with an average sensitivity of ~70% and average precision of ~30%, correctly localizing binding sites for small molecules in ~95% of its predictions. CONCLUSION: The AnnoLite and AnnoLyze programs for comparative annotation of protein structures can reliably and automatically annotate new protein structures. The programs are fully accessible via the Internet as part of the DBAli suite of tools at http://salilab.org/DBAli/.

Single-photon optical heterodyning

C Davis — 2008-07-24T17:09:43-00:00

Quantum Electronics, IEEE Journal of, Vol. 15, No. 1. (1979), pp. 26-29.

Optical heterodyning has been observed at the single-photon level by recording the sinusoidal variation in the probability for detection of a photoelectron from a photomultiplier tube illuminated with a FM laser and a local oscillator laser. The single-photon character of the heterodyne process was demonstrated by observation of beat signals at total power levels down to<tex>6 times 10^-15</tex>W where the spacing between photons emitted from the source laser was<tex>sim40 000</tex>times greater than their transit time through the apparatus.

Membrane nanotubes: dynamic long-distance connections between animal cells

Daniel Davis — 2008-05-23T14:16:01-00:00

Nature Reviews Molecular Cell Biology, Vol. 9, No. 6. (23 April 2008), pp. 431-436.

Dinosaurs and the Cretaceous Terrestrial Revolution

Graeme Lloyd — 2008-07-24T10:48:08-00:00

Proceedings of the Royal Society B: Biological Sciences

The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125-80Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR.

A General Strategy for Physics-Based Model Validation Illustrated with Earthquake Phenomenology, Atmospheric Radiative Transfer, and Computational Fluid Dynamics

Didier Sornette — 2008-07-23T16:02:53-00:00

(1 Oct 2007)

Validation is often defined as the process of determining the degree to which a model is an accurate representation of the real world from the perspective of its intended uses. Validation is crucial as industries and governments depend increasingly on predictions by computer models to justify their decisions. In this article, we survey the model validation literature and propose to formulate validation as an iterative construction process that mimics the process occurring implicitly in the minds of scientists. We thus offer a formal representation of the progressive build-up of trust in the model, and thereby replace incapacitating claims on the impossibility of validating a given model by an adaptive process of constructive approximation. This approach is better adapted to the fuzzy, coarse-grained nature of validation. Our procedure factors in the degree of redundancy versus novelty of the experiments used for validation as well as the degree to which the model predicts the observations. We illustrate the new methodology first with the maturation of Quantum Mechanics as the arguably best established physics theory and then with several concrete examples drawn from some of our primary scientific interests: a cellular automaton model for earthquakes, an anomalous diffusion model for solar radiation transport in the cloudy atmosphere, and a computational fluid dynamics code for the Richtmyer-Meshkov instability. This article is an augmented version of Sornette et al. [2007] that appeared in Proceedings of the National Academy of Sciences in 2007 (doi: 10.1073/pnas.0611677104), with an electronic supplement at URL <a href="http://www.pnas.org/cgi/content/full/0611677104/DC1.">this http URL</a> Sornette et al. [2007] is also available in preprint form at <a href="/abs/physics/0511219">physics/0511219</a>.

An integrated platform of genomic assays reveals small-molecule bioactivities

Shawn Hoon — 2008-07-23T04:16:43-00:00

Nat Chem Biol, Vol. 4, No. 8. (2008), pp. 498-506.

Genome-wide quantitative trait locus association scan of general cognitive ability using pooled DNA and 500K single nucleotide polymorphism microarrays

Butcher — 2008-04-29T10:48:47-00:00

Genes, Brain & Behavior, Vol. 7, No. 4. (June 2008), pp. 435-446.

Lags in vegetation response to greenhouse warming

Margaret Davis — 2008-07-22T18:15:45-00:00

Climatic Change, Vol. 15, No. 1. (1 October 1989), pp. 75-82.

Fossil pollen in sediments documents vegetation responses to climatic changes in the past. Beech (Fagus grandifolia), with animal-dispersed seeds, moved across Lake Michigan or around its southern margin, becoming established in Wisconsin about 1000 years after populations were established in Michigan. Hemlock (Tsuga canadensis), with wind-dispersed seeds, colonized a 50,000 km2 area in northern Michigan between 6000 and 5000 years ago. These tree species extended ranges northward at average rates of 20–25 km per century. To track climatic changes in the future, caused by the greenhouse effect, however, their range limit would need to move northward 100 km per °C warming, or about 300 km per century, an order of magnitude faster than range extension in the past. Yet range extension in the future would be less efficient than in the past, because advance disjunct colonies have been extirpated by human disturbance, and because the seed source is reduced due to reductions in tree populations following logging. Many species of trees may not be able to disperse rapidly enough to track climate, and woodland herbs, which have less efficient seed dispersal mechanisms, may be in danger of extinction.

Range Shifts and Adaptive Responses to Quaternary Climate Change

Margaret Davis — 2008-06-19T20:42:43-00:00

Science, Vol. 292, No. 5517. (27 April 2001), pp. 673-679.

10.1126/science.292.5517.673

Electromagnetic cloaking in the visible frequency range

II Smolyaninov — 2008-03-10T12:34:50-00:00

(10 Dec 2007)

Electromagnetic metamaterials provide unprecedented freedom and flexibility to introduce new devices, which control electromagnetic wave propagation in very unusual ways. Very recently theoretical design of an "invisibility cloak" has been suggested, which has been realized at microwave frequencies in a two-dimensional cylindrical geometry. In this communication we report on the experimental realization of the dielectric permittivity distribution required for non-magnetic cloaking in the visible frequency range.