304 research outputs found
Control of atomic currents using a quantum stirring device
We propose a BEC stirring device which can be regarded as the incorporation
of a quantum pump into a closed circuit: it produces a DC circulating current
in response to a cyclic adiabatic change of two control parameters of an
optical trap. We demonstrate the feasibility of this concept and point out that
such device can be utilized in order to probe the interatomic interactions.Comment: 5 pages, 4 figures, uses epl2.cls, revised versio
Separable and non-separable multi-field inflation and large non-Gaussianity
In this paper we provide a general framework based on formalism to
estimate the cosmological observables pertaining to the cosmic microwave
background radiation for non-separable potentials, and for generic \emph{end of
inflation} boundary conditions. We provide analytical and numerical solutions
to the relevant observables by decomposing the cosmological perturbations along
the curvature and the isocurvature directions, \emph{instead of adiabatic and
entropy directions}. We then study under what conditions large bi-spectrum and
tri-spectrum can be generated through phase transition which ends inflation. In
an illustrative example, we show that large and
can be obtained for the case of separable and
non-separable inflationary potentials.Comment: 21 pages, 6 figure
Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity
<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R), has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs).</p> <p>Results</p> <p>VLPs were subjected to post-purification disassembly and reassembly (D/R) treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs) H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5) was greatly reduced.</p> <p>Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire</p> <p>HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres.</p> <p>Conclusions</p> <p>D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical properties of VLPs and to correlate the observed changes at the molecular level. Mapping of known antibody epitopes to the homology model explains the changes in antibody reactivity upon D/R. In particular, the H16.H5 epitope is partially occluded by intercapsomeric interactions involving the L1 C-terminal arm. The homology model allows a more precise mapping of antibody epitopes. This work provides a better understanding of VLPs in current vaccines and could guide the design of improved vaccines or therapeutics.</p
SeqGene: a comprehensive software solution for mining exome- and transcriptome- sequencing data
Abstract Background The popularity of massively parallel exome and transcriptome sequencing projects demands new data mining tools with a comprehensive set of features to support a wide range of analysis tasks. Results SeqGene, a new data mining tool, supports mutation detection and annotation, dbSNP and 1000 Genome data integration, RNA-Seq expression quantification, mutation and coverage visualization, allele specific expression (ASE), differentially expressed genes (DEGs) identification, copy number variation (CNV) analysis, and gene expression quantitative trait loci (eQTLs) detection. We also developed novel methods for testing the association between SNP and expression and identifying genotype-controlled DEGs. We showed that the results generated from SeqGene compares favourably to other existing methods in our case studies. Conclusion SeqGene is designed as a general-purpose software package. It supports both paired-end reads and single reads generated on most sequencing platforms; it runs on all major types of computers; it supports arbitrary genome assemblies for arbitrary organisms; and it scales well to support both large and small scale sequencing projects. The software homepage is http://seqgene.sourceforge.net.</p
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Genetic Variations and Haplotype Diversity of the UGT1 Gene Cluster in the Chinese Population
Vertebrates require tremendous molecular diversity to defend against numerous small hydrophobic chemicals. UDP-glucuronosyltransferases (UGTs) are a large family of detoxification enzymes that glucuronidate xenobiotics and endobiotics, facilitating their excretion from the body. The UGT1 gene cluster contains a tandem array of variable first exons, each preceded by a specific promoter, and a common set of downstream constant exons, similar to the genomic organization of the protocadherin (Pcdh), immunoglobulin, and T-cell receptor gene clusters. To assist pharmacogenomics studies in Chinese, we sequenced nine first exons, promoter and intronic regions, and five common exons of the UGT1 gene cluster in a population sample of 253 unrelated Chinese individuals. We identified 101 polymorphisms and found 15 novel SNPs. We then computed allele frequencies for each polymorphism and reconstructed their linkage disequilibrium (LD) map. The UGT1 cluster can be divided into five linkage blocks: Block 9 (UGT1A9), Block 9/7/6 (UGT1A9, UGT1A7, and UGT1A6), Block 5 (UGT1A5), Block 4/3 (UGT1A4 and UGT1A3), and Block 3β² UTR. Furthermore, we inferred haplotypes and selected their tagSNPs. Finally, comparing our data with those of three other populations of the HapMap project revealed ethnic specificity of the UGT1 genetic diversity in Chinese. These findings have important implications for future molecular genetic studies of the UGT1 gene cluster as well as for personalized medical therapies in Chinese
A Novel Statistic for Genome-Wide Interaction Analysis
Although great progress in genome-wide association studies (GWAS) has been made,
the significant SNP associations identified by GWAS account for only a few
percent of the genetic variance, leading many to question where and how we can
find the missing heritability. There is increasing interest in genome-wide
interaction analysis as a possible source of finding heritability unexplained by
current GWAS. However, the existing statistics for testing interaction have low
power for genome-wide interaction analysis. To meet challenges raised by
genome-wide interactional analysis, we have developed a novel statistic for
testing interaction between two loci (either linked or unlinked). The null
distribution and the type I error rates of the new statistic for testing
interaction are validated using simulations. Extensive power studies show that
the developed statistic has much higher power to detect interaction than
classical logistic regression. The results identified 44 and 211 pairs of SNPs
showing significant evidence of interactions with FDR<0.001 and
0.001<FDR<0.003, respectively, which were seen in two independent studies
of psoriasis. These included five interacting pairs of SNPs in genes LST1/NCR3,
CXCR5/BCL9L, and GLS2, some of which were located in the target sites of
miR-324-3p, miR-433, and miR-382, as well as 15 pairs of interacting SNPs that
had nonsynonymous substitutions. Our results demonstrated that genome-wide
interaction analysis is a valuable tool for finding remaining missing
heritability unexplained by the current GWAS, and the developed novel statistic
is able to search significant interaction between SNPs across the genome. Real
data analysis showed that the results of genome-wide interaction analysis can be
replicated in two independent studies
Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer
Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant
Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution
MicroRNA (miRNA)βmediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution
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