Observations of a doubly driven V system probed to a fourth level in laser-cooled rubidium

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Speculative devices for photo display

In this paper, we describe three purposefully provocative, digital photo display technologies designed for home settings. The three devices have been built to provoke questions around how digital photographs might be seen and interacted with in novel ways. They are also intended for speculation about the expressive resources afforded by digital technologies for displaying photos. It is hoped interactions with the devices will help researchers and designers reflect on new design possibilities. The devices are also being deployed as part of ongoing home-oriented field research

AutoClickChem: Click Chemistry in Silico

Academic researchers and many in industry often lack the financial resources available to scientists working in “big pharma.” High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu

Generating samples for association studies based on HapMap data

<p>Abstract</p> <p>Background</p> <p>With the completion of the HapMap project, a variety of computational algorithms and tools have been proposed for haplotype inference, tag SNP selection and genome-wide association studies. Simulated data are commonly used in evaluating these new developed approaches. In addition to simulations based on population models, empirical data generated by perturbing real data, has also been used because it may inherit specific properties from real data. However, there is no tool that is publicly available to generate large scale simulated variation data by taking into account knowledge from the HapMap project.</p> <p>Results</p> <p>A computer program (<it>gs</it>) was developed to quickly generate a large number of samples based on real data that are useful for a variety of purposes, including evaluating methods for haplotype inference, tag SNP selection and association studies. Two approaches have been implemented to generate dense SNP haplotype/genotype data that share similar local <it>linkage disequilibrium </it>(LD) patterns as those in human populations. The first approach takes haplotype pairs from samples as inputs, and the second approach takes patterns of haplotype block structures as inputs. Both quantitative and qualitative traits have been incorporated in the program. Phenotypes are generated based on a disease model, or based on the effect of a quantitative trait nucleotide, both of which can be specified by users. In addition to single-locus disease models, two-locus disease models have also been implemented that can incorporate any degree of epistasis. Users are allowed to specify all nine parameters in a 3 × 3 penetrance table. For several commonly used two-locus disease models, the program can automatically calculate penetrances based on the population prevalence and marginal effects of a disease that users can conveniently specify.</p> <p>Conclusion</p> <p>The program <it>gs </it>can effectively generate large scale genetic and phenotypic variation data that can be used for evaluating new developed approaches. It is freely available from the authors' web site at <url>http://www.eecs.case.edu/~jxl175/gs.html</url>.</p

High expression of Lewis(y/b )antigens is associated with decreased survival in lymph node negative breast carcinomas

INTRODUCTION: There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewis(y )and Lewis(b )antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewis(y/b )binding antibody that binds to native and extended Lewis(y )and Lewis(b )haptens, displaying no cross reactivity with H type 1, H type 2, Lewis(x )or normal blood group antigens. METHODS: Immunohistochemical detection of Lewis(y/b )was performed on 660 formalin-fixed, paraffin embedded breast tumour specimens using a streptavidin-biotin peroxidase technique. Tissue from these patients had previously been included in tissue microarrays. This cohort comprises a well characterized series of patients with primary operable breast cancer diagnosed between 1987 and 1992, obtained from the Nottingham Tenovus Primary Breast Carcinoma Series. This includes patients 70 years of age or less, with a mean follow up of 7 years. RESULTS: Of the breast carcinomas, 370 of 660 (56%) were negative for Lewis(y/b )expression, 110 (17%) cases showed a low level of expression (<25% of positive cells) and only 54 cases (8%) showed extensive expression of Lewis(y/b )(>75% of positive cells). We found significant positive associations between histological grade (p < 0.001), Nottingham Prognostic Index (p = 0.016), tumour type (p = 0.007) and the level of Lewis (y/b )expression. There was a significant correlation between the proportion of Lewis(y/b )positive tumour cells and survival in lymph-node negative patients (p = 0.006). CONCLUSION: The unique epitope recognised by SC101 mAb on Lewis(y/b )hapten is over-expressed on breast tumour tissue compared with normal breast. In this large series of invasive breast cancers, higher expression of Lewis(y/b )was more often found in high grade and poor prognosis tumours compared to good prognosis cancers. Moreover, in lymph node negative breast carcinomas, over-expression of Lewis(y/b )hapten was associated with significantly decreased patient survival

Immunophenotyping of Circulating T Helper Cells Argues for Multiple Functions and Plasticity of T Cells In Vivo in Humans - Possible Role in Asthma

BACKGROUND: The immune process driving eosinophilic and non-eosinophilic asthma is likely driven by different subsets of T helper (Th) cells. Recently, in vitro studies and animal studies suggest that Th cell subsets displays plasticity by changing their transcription factor or by expressing multiple transcription factors. Our aim was to determine whether individuals with asthma and elevated circulating eosinophils express signs of different regulatory immune mechanisms compared with asthmatics with low blood eosinophils and non-asthmatic control subjects. In addition, determine the relationship between eosinophilia and circulating Th cell subsets. METHODOLOGY/PRINCIPAL FINDINGS: Participants were selected from a random epidemiological cohort, the West Sweden Asthma Study. Immunophenotypes of fresh peripheral blood cells obtained from stable asthmatics, with and without elevated eosinophilic inflammation (EOS high and EOS low respectively) and control subjects, were determined by flow cytometry. No differences in the number of Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt) or Treg (FOXP3) cells were observed between the groups when analysing each subset separately. However, in all groups, each of the Th subsets showed expression of additional canonical transcription factors T-bet, GATA-3, RORγt and FOXP3. Furthermore, by in vitro stimulation with anti-CD3/anti-CD28 there was a significant increase of single expressing GATA-3(+) and co-expressing T-bet(+)GATA-3(+) cells in the EOS high asthmatics in comparison with control subjects. In addition, T-bet(-)GATA-3(+)RORγt(+)FOXP3(+) were decreased in comparison to the EOS low asthmatics. Finally, in a group of control subjects we found that the majority of proliferating Th cells (CD4(+)CD25(+)Ki67(+)) expressed three or four transcription factors. CONCLUSIONS: The ability of human Th cells to express several regulatory transcription factors suggests that these cells may display plasticity in vivo

Carpal tunnel syndrome and the "double crush" hypothesis: a review and implications for chiropractic

Upton and McComas claimed that most patients with carpal tunnel syndrome not only have compressive lesions at the wrist, but also show evidence of damage to cervical nerve roots. This "double crush" hypothesis has gained some popularity among chiropractors because it seems to provide a rationale for adjusting the cervical spine in treating carpal tunnel syndrome. Here I examine use of the concept by chiropractors, summarize findings from the literature, and critique several studies aimed at supporting or refuting the hypothesis. Although the hypothesis also has been applied to nerve compressions other than those leading to carpal tunnel syndrome, this discussion mainly examines the original application – "double crush" involving both cervical spinal nerve roots and the carpal tunnel. I consider several categories: experiments to create double crush syndrome in animals, case reports, literature reviews, and alternatives to the original hypothesis. A significant percentage of patients with carpal tunnel syndrome also have neck pain or cervical nerve root compression, but the relationship has not been definitively explained. The original hypothesis remains controversial and is probably not valid, at least for sensory disturbances, in carpal tunnel syndrome. However, even if the original hypothesis is importantly flawed, evaluation of multiple sites still may be valuable. The chiropractic profession should develop theoretical models to relate cervical dysfunction to carpal tunnel syndrome, and might incorporate some alternatives to the original hypothesis. I intend this review as a starting point for practitioners, educators, and students wishing to advance chiropractic concepts in this area

Disordered microbial communities in asthmatic airways.

A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls.We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2) surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients.The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways

Does Sleep Improve Your Grammar? : Preferential Consolidation of Arbitrary Components of New Linguistic Knowledge

We examined the role of sleep-related memory consolidation processes in learning new form-meaning mappings. Specifically, we examined a Complementary Learning Systems account, which implies that sleep-related consolidation should be more beneficial for new hippocampally dependent arbitrary mappings (e.g. new vocabulary items) relative to new systematic mappings (e.g. grammatical regularities), which can be better encoded neocortically. The hypothesis was tested using a novel language with an artificial grammatical gender system. Stem-referent mappings implemented arbitrary aspects of the new language, and determiner/suffix+natural gender mappings implemented systematic aspects (e.g. tib scoiffesh + ballerina, tib mofeem + bride; ked jorool + cowboy, ked heefaff + priest). Importantly, the determiner-gender and the suffix-gender mappings varied in complexity and salience, thus providing a range of opportunities to detect beneficial effects of sleep for this type of mapping. Participants were trained on the new language using a word-picture matching task, and were tested after a 2-hour delay which included sleep or wakefulness. Participants in the sleep group outperformed participants in the wake group on tests assessing memory for the arbitrary aspects of the new mappings (individual vocabulary items), whereas we saw no evidence of a sleep benefit in any of the tests assessing memory for the systematic aspects of the new mappings: Participants in both groups extracted the salient determiner-natural gender mapping, but not the more complex suffix-natural gender mapping. The data support the predictions of the complementary systems account and highlight the importance of the arbitrariness/systematicity dimension in the consolidation process for declarative memories