CiteULike: Author Clayton

Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine

DM Roden — 2008-08-19T21:33:44-00:00

Clin Pharmacol Ther, Vol. 84, No. 3. (21 May 2008), pp. 362-369.

A test of three hypotheses concerning attributions toward female promiscuity

Krisstal Clayton — 2008-08-19T00:06:09-00:00

The Social Science Journal, Vol. 44, No. 4. (2007), pp. 677-686.

We performed two experiments to test three alternative hypotheses concerning negative attributions toward sexually promiscuous females. The first two possibilities are based on female-to-female negative attributions. The first hypothesis, the Competition Hypothesis, states that females could be using a negative attribution towards other females for derogation purposes when in competition for a mate. Second, the Self-esteem Hypothesis states that females could be using negative attributions towards other females to build Self-esteem. Finally, according to the Social Norm Hypothesis, both males and females see female promiscuous behaviors as deviant thereby resulting in negative attributions towards the women who perform them. In both experiments, the Social Norm Hypothesis received more support than the other two hypotheses.

On emergence, agency, and organization

Kauffman — 2006-12-16T21:47:14-00:00

Biology and Philosophy, Vol. 21, No. 4. (September 2006), pp. 500-520.

Quantification of homozygosity in consanguineous individuals with autosomal recessive disease.

CG Woods — 2008-08-10T18:04:42-00:00

American journal of human genetics, Vol. 78, No. 5. (May 2006), pp. 889-896.

Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.

Variation of tandem repeats in the developmentally regulated procyclic acidic repetitive proteins of Trypanosoma brucei.

MR Mowatt — 2008-08-07T05:31:18-00:00

Molecular and cellular biology, Vol. 9, No. 3. (March 1989), pp. 1332-1335.

The procyclic acidic repetitive proteins (PARPs) of Trypanosoma brucei are developmentally regulated surface proteins encoded by a family of polymorphic genes. We have determined the complete nucleotide sequence of a novel member of the PARP gene family and investigated its expression. The amino acid sequence deduced from the parpA alpha gene showed a marked conservation of both the amino- and carboxy-terminal regions compared with other PARPs but revealed the substitution of a pentapeptide for the dipeptide repeating unit that is characteristic of all other PARPs. Northern hybridization analysis indicated that expression of the parpA alpha gene, like that of other members of this gene family, is confined to the procyclic stage of the T. brucei life cycle. This result implies coordinate regulation of the unlinked genetic loci that encode PARPs.

Whole-genome random sequencing and assembly of Haemophilus influenzae Rd.

RD Fleischmann — 2005-07-21T08:31:25-00:00

Science, Vol. 269, No. 5223. (28 July 1995), pp. 496-512.

An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.

Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.

E O'Meara — 2008-07-21T03:08:29-00:00

Circulation, Vol. 115, No. 24. (19 June 2007), pp. 3111-3120.

BACKGROUND: We wished to test previous hypotheses that sex-related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction (LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction. METHODS AND RESULTS: We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program using multivariable regression analyses. A total of 1188 women (50%) had a low LVEF (< or = 0.40), and 1212 had a preserved LVEF (> 0.40). Among the men, 3388 (65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women (51%) and 3465 men (67%) had an ischemic cause of their heart failure. All-cause mortality was 21.5% in women and 25.3% in men (adjusted hazard ratio [HR], 0.77; 95% CI, 0.69 to 0.86; P<0.001). Fewer women (30.4%) than men (33.3%) experienced cardiovascular death or heart failure hospitalization (adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P<0.001). The risks of sudden death (HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure (HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women (HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization (HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF. CONCLUSIONS: Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.

The mentality of crows: convergent evolution of intelligence in corvids and apes.

NJ Emery — 2005-04-24T21:07:35-00:00

Science, Vol. 306, No. 5703. (10 December 2004), pp. 1903-1907.

Discussions of the evolution of intelligence have focused on monkeys and apes because of their close evolutionary relationship to humans. Other large-brained social animals, such as corvids, also understand their physical and social worlds. Here we review recent studies of tool manufacture, mental time travel, and social cognition in corvids, and suggest that complex cognition depends on a "tool kit" consisting of causal reasoning, flexibility, imagination, and prospection. Because corvids and apes share these cognitive tools, we argue that complex cognitive abilities evolved multiple times in distantly related species with vastly different brain structures in order to solve similar socioecological problems.

Linda implementations in Java for concurrent systems: Research Articles

GC Wells — 2008-07-14T04:37:58-00:00

Concurr. Comput. : Pract. Exper., Vol. 16, No. 10. (August 2004), pp. 1005-1022.

Privacy, confidentiality, and electronic medical records.

RC Barrows — 2008-04-03T13:47:41-00:00

Journal of the American Medical Informatics Association : JAMIA, Vol. 3, No. 2. (r 1996), pp. 139-148.

The enhanced availability of health information in an electronic format is strategic for industry-wide efforts to improve the quality and reduce the cost of health care, yet it brings a concomitant concern of greater risk for loss of privacy among health care participants. The authors review the conflicting goals of accessibility and security for electronic medical records and discuss nontechnical and technical aspects that constitute a reasonable security solution. It is argued that with guiding policy and current technology, an electronic medical record may offer better security than a traditional paper record.

A Case Study of Domain-based Program Understanding

Richard Clayton — 2008-07-04T15:24:02-00:00

(1997)

Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.

H Williams — 2008-07-04T01:42:27-00:00

The Journal of allergy and clinical immunology, Vol. 103, No. 1 Pt 1. (January 1999), pp. 125-138.

BACKGROUND: Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES: We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS: A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS: Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS: Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.

Electron acceleration from the breaking of relativistic plasma waves

A Modena — 2008-02-29T03:55:57-00:00

Nature, Vol. 377, No. 6550. (19 October 1995), pp. 606-608.

Electrons in a plasma undergo collective wave-like oscillations near the plasma frequency. These plasma waves can have a range of wavelengths and hence a range of phase velocities. Of particular note are relativistic plasma waves, for which the phase velocity approaches the speed of light; the longitudinal electric field associated with such waves can be extremely large, and can be used to accelerate electrons (either injected externally or supplied by the plasma) to high energies over very short distances. The maximum electric field, and hence maximum acceleration rate, that can be obtained in this way is determined by the maximum amplitude of oscillation that can be supported by the plasma. When this limit is reached, the plasma wave is said to break. Here we report observations of relativistic plasma waves driven to breaking point by the Raman forward-scattering instability induced by short, high-intensity laser pulses. The onset of wave-breaking is indicated by a sudden increase in both the number and maximum energy (up to 44 MeV) of accelerated plasma electrons, as well as by the loss of coherence of laser light scattered from the plasma wave.

Ultrahigh-gradient acceleration of injected electrons by laser-excited relativistic electron plasma waves

CE Clayton — 2008-02-28T03:45:50-00:00

Physical Review Letters, Vol. 70, No. 1. (4 January 1993), 37.

High-gradient acceleration of externally injected 2.1-MeV electrons by a laser beat wave driven relativistic plasma wave has been demonstrated for the first time. Electrons with energies up to the detection limit of 9.1 MeV were detected when such a plasma wave was resonantly excited using a two-frequency laser. This implies a gradient of 0.7 GeV/m; corresponding to a plasma-wave amplitude of more than 8%. The electron signal was below detection threshold without injection or when the laser was operated on a single frequency.

Trapped electron acceleration by a laser-driven relativistic plasma wave

M Everett — 2007-12-10T21:49:03-00:00

Nature, Vol. 368, No. 6471. (7 April 1994), pp. 527-529.

THE aim of new approaches for high-energy particle acceleration is to push the acceleration rate beyond the limit (approx100 MeV m-1) imposed by radio-frequency breakdown in conventional accelerators. Relativistic plasma waves, having phase velocities very close to the speed of light, have been proposed as a means of accelerating charged particles, and this has recently been demonstrated. Here we show that the charged particles can be trapped by relativistic plasma waves—a necessary condition for obtaining the maximum amount of energy theoretically possible for such schemes. In our experiments, plasma waves are excited in a hydrogen plasma by beats induced by two collinear laser beams, the difference in whose frequencies matches the plasma frequency. Electrons with an energy of 2 MeV are injected into the excited plasma, and the energy spectrum of the exiting electrons is analysed. We detect electrons with velocities exceeding that of the plasma wave, demonstrating that some electrons are 'trapped' by the wave potential and therefore move synchronously with the plasma wave. We observe a maximum energy gain of 28 MeV, corresponding to an acceleration rate of about 2.8 GeV m-1.

Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis.

R Mistry — 2008-06-17T05:10:08-00:00

The Journal of infectious diseases, Vol. 195, No. 3. (1 February 2007), pp. 357-365.

BACKGROUND: The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, approximately 5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse. METHODS: We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples. CONCLUSIONS: A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs.

Exact Mass Measurement of Polar Organic Molecules at Low Resolution Using Electrospray Ionization and a Quadrupole Mass Spectrometer

AN Tyler — 2008-06-16T13:39:57-00:00

Anal. Chem., Vol. 68, No. 20. (15 October 1996), pp. 3561-3569.

Abstract: Hitherto, exact mass measurement experiments have usually been performed using high-resolution mass spectrometry. However, under the right circumstances, measurements with comparable accuracy may be made at low resolution. Here we demonstrate the use of a low-resolution single-quadrupole mass spectrometer to accurately mass measure organic samples analyzed by electrospray ionization, using a variety of glycol polymers for internal calibration. Results are presented from 11 samples which yield molecular signals in the m/z range 190-750, including data for positive, negative, and multiply-charged sample and reference ions. Replicate determinations of the masses of 12 ions gave values within 4.5 ppm (1.1 millimass units, mmu) of their calculated values, with standard deviations no larger than 3 ppm (1.7 mmu). From a total of 88 individual 1 min measurements, 83 were within 5 ppm, and 87 within 2 mmu of the theoretical mass. The accuracy, precision, and sensitivity shown here are comparable to those achievable using high-resolution mass spectrometers, with the added benefits of simpler instrumentation and analytical technique afforded by the quadrupole mass analyzer.

Plasma wakefield acceleration in self-ionized gas or plasmas

S Deng — 2007-04-23T19:41:00-00:00

Physical Review E, Vol. 68, No. 4. (14 October 2003), 047401.

Tunnel ionizing neutral gas with the self-field of a charged particle beam is explored as a possible way of creating plasma sources for a plasma wakefield accelerator [Bruhwiler et al. ; Phys. Plasmas (to be published)]. The optimal gas density for maximizing the plasma wakefield without preionized plasma is studied using the PIC simulation code OSIRIS [R. Hemker et al. ; in Proceeding of the Fifth IEEE Particle Accelerator Conference (IEEE; 1999); pp. 3672–3674]. To obtain wakefields comparable to the optimal preionized case; the gas density needs to be seven times higher than the plasma density in a typical preionized case. A physical explanation is given.

PTPN22 Trp620 explains the association of chromosome 1p13 with type 1 diabetes and shows a statistical interaction with HLA class II genotypes.

DJ Smyth — 2008-06-03T06:13:38-00:00

Diabetes, Vol. 57, No. 6. (June 2008), pp. 1730-1737.

OBJECTIVE: The disease association of the common 1858C>T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves' disease. Some studies have reported additional associated SNPs independent of rs2476601/Trp(620), suggesting that it may not be the sole causal variant in the region and that the relative risk of rs2476601/Trp(620) is greater in lower risk by HLA class II genotypes than in the highest risk class II risk category. RESEARCH DESIGN AND METHODS: We resequenced PTPN22 and used these and other data to provide >150 SNPs to evaluate the association of the PTPN22 gene and its flanking chromosome region with type 1 diabetes in a minimum of 2,000 case subjects and 2,400 control subjects. RESULTS: Due to linkage disequilibrium, we were unable to distinguish between rs2476601/Trp(620) (P = 2.11 x10(-87)) and rs6679677 (P = 3.21 x10(-87)), an intergenic SNP between the genes putative homeodomain transcription factor 1 and round spermatid basic protein 1. None of the previously reported disease-associated SNPs proved to be independent of rs2476601/Trp(620). We did not detect any interaction with age at diagnosis or sex. However, we found that rs2476601/Trp(620) has a higher relative risk in type 1 diabetic case subjects carrying lower risk HLA class II genotypes than in those carrying higher risk ones (P = 1.36 x 10(-4) in a test of interaction). CONCLUSIONS: In our datasets, there was no evidence for allelic heterogeneity at the PTPN22 locus in type 1 diabetes, indicating that the SNP rs2476601/Trp(620) remains the best candidate in this chromosome region in European populations. The heterogeneity of rs2476601/Trp(620) disease risk by HLA class II genotype is consistent with previous studies, and the joint effect of the two loci is still greater in the high-risk group.

The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease

David Clayton — 2008-05-28T21:28:34-00:00

Trends in Neurosciences, Vol. 21, No. 6. (1 June 1998), pp. 249-254.

Synuclein proteins are produced, in vertebrates, by three genes. They share structural resemblance to apolipoproteins, but are abundant in the neuronal cytosol and present in enriched amounts at presynaptic terminals. Synucleins have been specifically implicated in three diseases: Alzheimer's (AD), Parkinson's (PD) and breast cancer. In AD, a peptide derived from [alpha]-synuclein forms an intrinsic component of plaque amyloid. In PD, an [alpha]-synuclein allele is genetically linked to several independent familial cases, and the protein appears to accumulate in Lewy bodies. In breast cancer, increased expression of [gamma]-synuclein correlates with disease progression. In songbirds, [alpha]-synuclein expression is correlated with plasticity in the developing song control system. Although the normal function of synucleins is unknown, a role in membrane plasticity seems likely.

Tryptophan Rotamer Distributions in Amphipathic Peptides at a Lipid Surface

Andrew Clayton — 2008-05-20T07:56:16-00:00

Biophys. J., Vol. 76, No. 6. (1 June 1999), pp. 3235-3242.

The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. We describe the use of frequency domain fluorescence spectroscopy to determine the conformational and environmental changes associated with the interaction of single tryptophan amphipathic peptides with a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide known to associate with lipid bilayers. The peptides contain a single tryptophan located at positions 2, 3, 7, 12, or 14 in the sequence. In aqueous solution, the peptides are unstructured and a triple-exponential function is required to fit the decay data. Association of the peptides with small unilamellar vesicles composed of egg phosphatidylcholine reduces the complexity of the fluorescence decays to a double exponential function, with a reduced dependence of the preexponential amplitude on peptide sequence. The data are interpreted in terms of a rotamer model in which the modality and relative proportions of the lifetime components are related to the population distribution of tryptophan [chi]1 rotamers about the C[alpha]-C[beta] bond. Peptide secondary structure and the disposition of the tryptophan residue relative to the lipid and aqueous phases in the peptide-lipid complex affect the local environment of tryptophan and influence the distribution of side-chain rotamers. The results show that measurement of the temporal decay of tryptophan emission provides a useful adjunct to other biophysical techniques for investigating peptide-lipid and protein-membrane interactions.

Visual discrimination of local surface structure: Slant, tilt, and curvedness

Farley Norman — 2008-05-18T23:47:32-00:00

Vision Research, Vol. 46, No. 6-7. (March 2006), pp. 1057-1069.

In four experiments, observers were required to discriminate interval or ordinal differences in slant, tilt, or curvedness between designated probe points on randomly shaped curved surfaces defined by shading, texture, and binocular disparity. The results reveal that discrimination thresholds for judgments of slant or tilt typically range between 4° and 10°; that judgments of one component are unaffected by simultaneous variations in the other; and that the individual thresholds for either the slant or tilt components of orientation are approximately equal to those obtained for judgments of the total orientation difference between two probed regions. Performance was much worse, however, for judgments of curvedness, and these judgments were significantly impaired when there were simultaneous variations in the shape index parameter of curvature.

The Audacity of Hope

Dewey Clayton — 2008-05-11T02:46:03-00:00

Journal of Black Studies, Vol. 38, No. 1. (1 September 2007), pp. 51-63.

As the Democratic candidate for the U.S. Senate from Illinois, Barack Obama electrified the country with his keynote address at the Democratic National Convention in 2004. After having served only 2 years in his first term as a U.S. senator from Illinois, Senator Obama in 2007 announced his candidacy for president of the United States of America. He is the rising star in the Democratic Party and regularly draws huge crowds at his campaign events. He is only the third African American of a major political party to run for the office of the president. Obama is extremely charismatic and appeals to voters across racial lines and party lines. The heart of his campaign is a message of hope that transcends race and attempts to bring a divided country together. 10.1177/0021934707305057

Updating conspectus for a digital age

Peter Clayton — 2008-05-11T01:05:22-00:00

Library Collections, Acquisitions, and Technical Services, Vol. 26, No. 3. ( 2002), pp. 253-258.

The RLG Conspectus is a method of describing collection strengths in a standardized manner. Introduced at the end of the print-only era, its promise has never been fulfilled, and interest in it is clearly waning. The authors' view is that, while it has limitations as a tool facilitating coordinated regional and national collection development, it should still be useful in its primary role of collection description. However, in its present form it is collection-centered rather than resource access-centered, and now urgently needs to be updated to take into account the availability of digital data if it is to be of continuing relevance to the library community. This article proposes just such an updated version of Conspectus.

A guide to modelling cardiac electrical activity in anatomically detailed ventricles

RH Clayton — 2008-01-15T11:59:48-00:00

Progress in Biophysics and Molecular Biology, Vol. In Press, Corrected Proof

One of the most recent trends in cardiac electrophysiology is the development of integrative anatomically accurate models of the heart, which include description of cardiac activity from sub-cellular and cellular level to the level of the whole organ. In order to construct this type of model, a researcher needs to collect a wide range of information from books and journal articles on various aspects of biology, physiology, electrophysiology, numerical mathematics and computer programming. The aim of this methodological article is to survey recent developments in integrative modelling of electrical activity in the ventricles of the heart, and to provide a practical guide to the resources and tools that are available for work in this exciting and challenging area.

Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes.

WS Davidson — 2008-05-07T07:31:47-00:00

The Journal of biological chemistry, Vol. 273, No. 16. (17 April 1998), pp. 9443-9449.

alpha-Synuclein is a highly conserved presynaptic protein of unknown function. A mutation in the protein has been causally linked to Parkinson's disease in humans, and the normal protein is an abundant component of the intraneuronal inclusions (Lewy bodies) characteristic of the disease. alpha-Synuclein is also the precursor to an intrinsic component of extracellular plaques in Alzheimer's disease. The alpha-synuclein sequence is largely composed of degenerate 11-residue repeats reminiscent of the amphipathic alpha-helical domains of the exchangeable apolipoproteins. We hypothesized that alpha-synuclein should associate with phospholipid bilayers and that this lipid association should stabilize an alpha-helical secondary structure in the protein. We report that alpha-synuclein binds to small unilamellar phospholipid vesicles containing acidic phospholipids, but not to vesicles with a net neutral charge. We further show that the protein associates preferentially with vesicles of smaller diameter (20-25 nm) as opposed to larger (approximately 125 nm) vesicles. Lipid binding is accompanied by an increase in alpha-helicity from 3% to approximately 80%. These observations are consistent with a role in vesicle function at the presynaptic terminal.

Domesticated nature: Motivations for gardening and perceptions of environmental impact

Susan Clayton — 2008-05-06T03:43:50-00:00

Journal of Environmental Psychology, Vol. 27, No. 3. (September 2007), pp. 215-224.

Gardening is a popular pastime in the United States, worth investigating because of its potential for important effects on the individual as well as on the ecosystem. The present study was designed to investigate motivations for gardening and their relationship to attitudes toward nature and to gardening practices. Understanding such motivations may inform attempts to promote more sustainable gardening practices. One hundred twenty-six visitors to a garden center completed a survey about benefits from gardening, uses of their yard and concerns underlying their gardening practices. Results suggested that appreciation for nature was a significant motivation for gardening, but that social concerns and uses were also important. Both nature uses and social uses of the yard were associated with satisfaction. In general, respondents did not make a strong connection between their own private yards and the natural environment. Using the yard to appreciate nature, though, was associated with ecological considerations and concerns. A concern with practical issues like cost and ease of maintenance was negatively correlated with using the yard to appreciate nature, and was unconnected with satisfaction. Implications for encouraging sustainable gardening practices are discussed.

The genome of the kinetoplastid parasite, Leishmania major.

AC Ivens — 2007-05-09T11:29:53-00:00

Science, Vol. 309, No. 5733. (15 July 2005), pp. 436-442.

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.

Functional identification of sensory mechanisms required for developmental song learning

Sarah London — 2008-04-26T06:19:24-00:00

Nature Neuroscience, Vol. 11, No. 5. (06 April 2008), pp. 579-586.

Functional and molecular characterisation of mammary side population cells.

AJ Alvi — 2008-04-24T14:50:43-00:00

Breast cancer research : BCR, Vol. 5, No. 1. (2003)

BACKGROUND: Breast cancer is thought to arise in mammary epithelial stem cells. However, the identity of these stem cells is unknown. METHODS: Studies in the haematopoetic and muscle systems show that stem cells have the ability to efflux the dye Hoechst 33342. Cells with this phenotype are referred to as the side population (SP). We have adapted the techniques from the haematopoetic and muscle systems to look for a mammary epithelial SP. RESULTS: Of mammary epithelial cells isolated from both the human and mouse mammary epithelia, 0.2-0.45% formed a distinct SP. The SP was relatively undifferentiated but grew as typical differentiated epithelial clones when cultured. Transplantation of murine SP cells at limiting dilution into cleared mammary fat pads generated epithelial ductal and lobuloalveolar structures. CONCLUSION: These data demonstrate the existence of an undifferentiated SP in human and murine mammary epithelium. Purified SP cells are a live single-cell population that retain the ability to differentiate in vitro and in vivo. Studies of haematopoetic cells have suggested that the SP phenotype constitutes a universal stem cell marker. This work therefore has implications for mammary stem cell biology.

Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I

Tiziana Di Pucchio — 2008-04-20T05:29:38-00:00

Nature Immunology, Vol. 9, No. 5. (30 March 2008), pp. 551-557.

The HELP system.

TA Pryor — 2008-04-17T05:12:20-00:00

Journal of medical systems, Vol. 7, No. 2. (April 1983), pp. 87-102.

Bringing HELP to the clinical laboratory--use of an expert system to provide automatic interpretation of laboratory data.

PD Clayton — 2008-04-17T05:11:34-00:00

Annals of clinical biochemistry, Vol. 24 Suppl 1 (1987), pp. 5-11.

In domains where the types of data which are to be interpreted are relatively constrained (as in the case of specific laboratory test results), our modular data-driven approach can be very productive and well received by the clinical recipient of the data. The computer rarely surpasses the knowledge of an experts result from lack of communication, imperfect memory, oversight or multiple decision-makers caring for the same patient. In such cases, most of the alerts are immediately recognized as valid, so the need for elaborate explanations is not a high priority. On the other hand, a non-specialist is alerted to the need for additional investigation, tests or collaborative support, by the fact that a reminder or diagnosis that s/he had not previously considered, appears. In other words, for the expert, a data-driven system provides unceasing oversight in high-volume low-yielded situations where a small number of mistakes may uncommonly occur for reasons which are not related to the lack of knowledge of the provider. For the non-specialist the system suggests that the patient may have problems in a domain for which the physician needs additional support. In the present state of the art, we do not think that total reliance on the computer-contained knowledge is the ultimate source of this additional support; providing the awareness of the need may be the most important contribution. Once you know that you need help, it is usually obtainable. In a discussion about how computer systems have failed, Friedman and Gustafson made the following observation.(ABSTRACT TRUNCATED AT 250 WORDS)

On the knowledge required to understand a program

R Clayton — 2008-04-16T07:50:47-00:00

Reverse Engineering, 1998. Proceedings. Fifth Working Conference on (1998), pp. 69-78.

This paper is concerned with the units of knowledge used in understanding programs. A pilot study was conducted wherein a short, but complex, program was examined looking for knowledge atoms, the units from which program understanding is built. The resulting atoms were categorized along three orthogonal axes of knowledge type, design decision used, and the type of analysis required to uncover the atom. The results are discussed relative to several approaches to program understanding taken from the research literature

GENOME-WIDE ASSOCIATION STUDIES: THEORETICAL AND PRACTICAL CONCERNS

William Wang — 2006-07-17T15:39:55-00:00

Nat Rev Genet, Vol. 6, No. 2. (February 2005), pp. 109-118.

Recent Resurgence of Mumps in the United States.

Gustavo H Dayan — 2008-04-13T23:27:46-00:00

The New England journal of medicine, Vol. 358, No. 15. (10 April 2008), pp. 1580-1589.

BACKGROUND: The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS: We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS: A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS: Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps. Copyright 2008 Massachusetts Medical Society.

BUSINESS OFFICE FEATURE: Focus on Careers: EXODUS TO ASIA: Research Opportunities Abound

Julie Clayton — 2008-04-10T15:05:12-00:00

Science, Vol. 319, No. 5870. (21 March 2008), pp. 1691-1696.

10.1126/science.319.5870.1691

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

KE Nelson — 2005-11-19T21:38:53-00:00

Nature, Vol. 399, No. 6734. (27 May 1999), pp. 323-329.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

2007-11-01T06:11:56-00:00

Nat Genet, Vol. 39, No. 11. (November 2007), pp. 1329-1337.

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

The Songbird Neurogenomics (SoNG) Initiative: community-based tools and strategies for study of brain gene function and evolution

Kirstin Replogle — 2008-03-19T00:14:12-00:00

BMC Genomics, Vol. 9, No. 1. (2008)

BACKGROUND:Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts.RESULTS:We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in ESTIMA:Songbird. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500-15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a aCommunity Collaborationa mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations.CONCLUSIONS:Immediately, these results set the foundation for a coordinated set of 25 planned experiments by 16 research groups probing fundamental links between genome, brain, evolution and behavior in songbirds. Energetic application of genomic resources to research using songbirds should help illuminate how complex neural and behavioral traits emerge and evolve.

Use of unphased multilocus genotype data in indirect association studies.

D Clayton — 2008-03-27T16:26:34-00:00

Genet Epidemiol, Vol. 27, No. 4. (December 2004), pp. 415-428.

It is usually assumed that detection of a disease susceptability gene via marker polymorphisms in linkage disequilibrium with it is facilitated by consideration of marker haplotypes. However, capture of the marker haplotype information requires resolution of gametic phase, and this must usually be inferred statistically. Recently, we questioned the value of the marker haplotype information, and suggested that certain analyses of multivariate marker data, not based on haplotypes explicitly and not requiring resolution of gametic phase, are often more powerful than analyses based on haplotypes. Here, we review this work and assess more carefully the situations in which our conclusions might apply. We also relate these analyses to alternative approaches to haplotype analysis, namely those based on haplotype similarity and those inspired by cladistics.

The complete genome sequence of the gastric pathogen Helicobacter pylori.

JF Tomb — 2005-03-09T21:22:52-00:00

Nature, Vol. 388, No. 6642. (7 August 1997), pp. 539-547.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Approximate Inference in Generalized Linear Mixed Models

NE Breslow — 2008-03-17T09:41:47-00:00

Journal of the American Statistical Association, Vol. 88, No. 421. (1993), pp. 9-25.

Statistical approaches to overdispersion, correlated errors, shrinkage estimation, and smoothing of regression relationships may be encompassed within the framework of the generalized linear mixed model (GLMM). Given an unobserved vector of random effects, observations are assumed to be conditionally independent with means that depend on the linear predictor through a specified link function and conditional variances that are specified by a variance function, known prior weights and a scale factor. The random effects are assumed to be normally distributed with mean zero and dispersion matrix depending on unknown variance components. For problems involving time series, spatial aggregation and smoothing, the dispersion may be specified in terms of a rank deficient inverse covariance matrix. Approximation of the marginal quasi-likelihood using Laplace's method leads eventually to estimating equations based on penalized quasilikelihood or PQL for the mean parameters and pseudo-likelihood for the variances. Implementation involves repeated calls to normal theory procedures for REML estimation in variance components problems. By means of informal mathematical arguments, simulations and a series of worked examples, we conclude that PQL is of practical value for approximate inference on parameters and realizations of random effects in the hierarchical model. The applications cover overdispersion in binomial proportions of seed germination; longitudinal analysis of attack rates in epilepsy patients; smoothing of birth cohort effects in an age-cohort model of breast cancer incidence; evaluation of curvature of birth cohort effects in a case-control study of childhood cancer and obstetric radiation; spatial aggregation of lip cancer rates in Scottish counties; and the success of salamander matings in a complicated experiment involving crossing of male and female effects. PQL tends to underestimate somewhat the variance components and (in absolute value) fixed effects when applied to clustered binary data, but the situation improves rapidly for binomial observations having denominators greater than one.

Confirming the Revised C-terminal Domain of the MscL Crystal Structure

Joshua Maurer — 2008-03-10T17:42:06-00:00

Biophys. J. (7 March 2008), biophysj.107.127365.

The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the M. tuberculosis homologue (Tb), a model of the E. coli homologue (Ec), and most recently a revised crystal structure of Tb-MscL (2OAR). In order to understand which of these structures represents a physiological conformation, we measured the impact of mutations to the C-terminal domain on the thermal stability of Tb-MscL using circular dichroism and performed molecular dynamics simulations of the original and the revised crystal structures of Tb-MscL. Our results imply that this region is helical and adopts an alpha-helical bundle conformation similar to that observed in the Ec-MscL model and the revised Tb-MscL crystal structure. 10.1529/biophysj.107.127365

The Significance of the Categories "Part" and "Whole" for the Epistemology of Theology

Wolfhart Pannenberg — 2008-03-10T17:15:09-00:00

The Journal of Religion, Vol. 66, No. 4. (1986), pp. 369-385.