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Showing papers by "Agilent Technologies published in 2010"


Journal ArticleDOI
Leming Shi1, Gregory Campbell1, Wendell D. Jones, Fabien Campagne2  +198 moreInstitutions (55)
TL;DR: P predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans are generated.
Abstract: Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

753 citations


Journal ArticleDOI
29 Oct 2010-Science
TL;DR: This work identified 4.1 million “singly unique nucleotide” positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families, revealing extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species.
Abstract: Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million “singly unique nucleotide” positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

661 citations


Journal ArticleDOI
18 Feb 2010-Nature
TL;DR: It is shown that synaptic TCR–pMHC binding dynamics differ significantly from TCR’s binding in solution, and TCR affinity for pMHC was significantly elevated as the result of a large (about 100-fold) increase in the association rate, a likely consequence of complementary molecular orientation and clustering.
Abstract: The use of a novel FRET-based imaging system provides an in situ view of the kinetics of T-cell receptor (TCR) binding to peptide MHC complexes in their natural environment, the immunological synapse. Previously the mater of how containment in this environment would affect the molecular interactions that drive cell–cell interactions has been a matter of speculation. Now that they have been measured, both expected effects (enhanced association rate due to optimal orientation) and unexpected (a very active cytoskeletal component destabilizing TCR binding) are revealed. This work is of relevance to T-cell immunology and to in cell–cell interactions more generally. T lymphocytes, which are an integral part of most adaptive immune responses, recognize foreign antigens through the binding of antigenic peptide–major histocompatibility complex (pMHC) molecules on other cells to specific T-cell antigen receptors (TCRs). Using single-molecule microscopy and fluorescence resonance energy transfer, the kinetics of TCR–pMHC binding are now measured in situ, revealing accelerated kinetics and increased affinity when compared with solution measurements. The recognition of foreign antigens by T lymphocytes is essential to most adaptive immune responses. It is driven by specific T-cell antigen receptors (TCRs) binding to antigenic peptide–major histocompatibility complex (pMHC) molecules on other cells1. If productive, these interactions promote the formation of an immunological synapse2,3. Here we show that synaptic TCR–pMHC binding dynamics differ significantly from TCR–pMHC binding in solution. We used single-molecule microscopy and fluorescence resonance energy transfer (FRET) between fluorescently tagged TCRs and their cognate pMHC ligands to measure the kinetics of TCR–pMHC binding in situ. When compared with solution measurements, the dissociation of this complex was increased significantly (4–12-fold). Disruption of actin polymers reversed this effect, indicating that cytoskeletal dynamics destabilize this interaction directly or indirectly. Nevertheless, TCR affinity for pMHC was significantly elevated as the result of a large (about 100-fold) increase in the association rate, a likely consequence of complementary molecular orientation and clustering. In helper T cells, the CD4 molecule has been proposed to bind cooperatively with the TCR to the same pMHC complex. However, CD4 blockade had no effect on the synaptic TCR affinity, nor did it destabilize TCR–pMHC complexes, indicating that the TCR binds pMHC independently of CD4.

479 citations


Journal ArticleDOI
TL;DR: Surprisingly, untargeted metabolite profiling of Mtb growing on ¹³C-labeled carbon substrates revealed that Mtb could catabolize multiple carbon sources simultaneously to achieve enhanced monophasic growth.

315 citations


Journal ArticleDOI
TL;DR: It is shown that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies’ SurePrint® DNA microarray platform and the characterization of synthesis efficiency for such libraries is reported.
Abstract: We have achieved the ability to synthesize thousands of unique, long oligonucleotides (150mers) in fmol amounts using parallel synthesis of DNA on microarrays. The sequence accuracy of the oligonucleotides in such large-scale syntheses has been limited by the yields and side reactions of the DNA synthesis process used. While there has been significant demand for libraries of long oligos (150mer and more), the yields in conventional DNA synthesis and the associated side reactions have previously limited the availability of oligonucleotide pools to lengths <100 nt. Using novel array based depurination assays, we show that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies' SurePrint DNA microarray platform. We also demonstrate how depurination can be controlled and reduced by a novel detritylation process to enable the synthesis of high quality, long (150mer) oligonucleotide libraries and we report the characterization of synthesis efficiency for such libraries. Oligonucleotide libraries prepared with this method have changed the economics and availability of several existing applications (e.g. targeted resequencing, preparation of shRNA libraries, site-directed mutagenesis), and have the potential to enable even more novel applications (e.g. high-complexity synthetic biology).

313 citations


Journal ArticleDOI
TL;DR: This work uses high-fidelity DNA microchips, selective oligonucleotide pool amplification, optimized gene assembly protocols and enzymatic error correction to develop a method for highly parallel gene synthesis.
Abstract: Development of cheap, high-throughput and reliable gene synthesis methods will broadly stimulate progress in biology and biotechnology. Currently, the reliance on column-synthesized oligonucleotides as a source of DNA limits further cost reductions in gene synthesis. Oligonucleotides from DNA microchips can reduce costs by at least an order of magnitude, yet efforts to scale their use have been largely unsuccessful owing to the high error rates and complexity of the oligonucleotide mixtures. Here we use high-fidelity DNA microchips, selective oligonucleotide pool amplification, optimized gene assembly protocols and enzymatic error correction to develop a method for highly parallel gene synthesis. We tested our approach by assembling 47 genes, including 42 challenging therapeutic antibody sequences, encoding a total of ∼35 kilobase pairs of DNA. These assemblies were performed from a complex background containing 13,000 oligonucleotides encoding ∼2.5 megabases of DNA, which is at least 50 times larger than in previously published attempts.

296 citations


Journal ArticleDOI
07 May 2010-Science
TL;DR: It is shown that hybridization capture on microarrays can successfully recover more than a megabase of target regions from Neandertal DNA even in the presence of ~99.8% microbial DNA.
Abstract: Neandertals, our closest relatives, ranged across Europe and Southwest Asia before their extinction approximately 30,000 years ago. Green et al. (p. [710][1]) report a draft sequence of the Neandertal genome, created from three individuals, and compare it with genomes of five modern humans. The results suggest that ancient genomes of human relatives can be recovered with acceptably low contamination from modern human DNA. Because ancient DNA can be contaminated with microbial DNA, Burbano et al. (p. [723][2]) developed a target sequence capture approach to obtain 14 kilobases of Neandertal DNA from a fairly poorly preserved sample with a high microbial load. A number of genomic regions and genes were revealed as candidates for positive selection early in modern human history. The genomic data suggest that Neandertals mixed with modern human ancestors some 120,000 years ago, leaving traces of Neandertal DNA in contemporary humans. [1]: /lookup/doi/10.1126/science.1188021 [2]: /lookup/doi/10.1126/science.1188046

279 citations


Journal ArticleDOI
22 Jul 2010-Nature
TL;DR: Genetic and molecular evidence supports a model whereby PHF8 regulates zebrafish neuronal cell survival and jaw development in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB, which functions downstream of multiple signalling and developmental pathways.
Abstract: Mutations in the PHF8 gene, which encodes the plant homeo domain (PHD) finger protein 8, are connected to X-linked mental retardation associated with cleft lip and cleft palate. Two groups now report that the PHF8 protein is a histone demethylase with activity against H4K20me1 (histone H4 lysine 20). Qi et al. report a role for PHF8 in regulating gene expression, as well as in neuronal cell survival and craniofacial development in zebrafish. The results suggest there may be a link between histone methylation dynamics and X-linked mental retardation. Liu et al. show that PHF8 is linked to two distinct events during cell-cycle progression. PHF8 is recruited to the promoters of G1/S-phase genes where it removes H4K20me1 and contributes to gene activation, whereas dissociation of PHF8 from chromatin in prophase allows H4K20me1 to accumulate during mitosis. PHF8 is a JmjC domain-containing protein, the gene for which has been linked to X-linked mental retardation (XLMR). These authors demonstrate PHF8 to be a histone demethylase with activity against H4K20me1. It has a role in regulating gene expression as well as in neuronal cell survival and craniofacial development in zebrafish. The results suggest there may be a link between histone methylation dynamics and XLMR. X-linked mental retardation (XLMR) is a complex human disease that causes intellectual disability1. Causal mutations have been found in approximately 90 X-linked genes2; however, molecular and biological functions of many of these genetically defined XLMR genes remain unknown. PHF8 (PHD (plant homeo domain) finger protein 8) is a JmjC domain-containing protein and its mutations have been found in patients with XLMR and craniofacial deformities. Here we provide multiple lines of evidence establishing PHF8 as the first mono-methyl histone H4 lysine 20 (H4K20me1) demethylase, with additional activities towards histone H3K9me1 and me2. PHF8 is located around the transcription start sites (TSS) of ∼7,000 RefSeq genes and in gene bodies and intergenic regions (non-TSS). PHF8 depletion resulted in upregulation of H4K20me1 and H3K9me1 at the TSS and H3K9me2 in the non-TSS sites, respectively, demonstrating differential substrate specificities at different target locations. PHF8 positively regulates gene expression, which is dependent on its H3K4me3-binding PHD and catalytic domains. Importantly, patient mutations significantly compromised PHF8 catalytic function. PHF8 regulates cell survival in the zebrafish brain and jaw development, thus providing a potentially relevant biological context for understanding the clinical symptoms associated with PHF8 patients. Lastly, genetic and molecular evidence supports a model whereby PHF8 regulates zebrafish neuronal cell survival and jaw development in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB, which functions downstream of multiple signalling and developmental pathways3. Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR.

257 citations


Journal ArticleDOI
TL;DR: Pol III localization in other transformed and primary cell lines reveals previously uncharacterized and cell type–specific Pol III loci as well as one microRNA, suggesting that active chromatin gates Pol III accessibility to the genome.
Abstract: RNA polymerase (Pol) III transcribes many noncoding RNAs (for example, transfer RNAs) important for translational capacity and other functions. We localized Pol III, alternative TFIIIB complexes (BRF1 or BRF2) and TFIIIC in HeLa cells to determine the Pol III transcriptome, define gene classes and reveal 'TFIIIC-only' sites. Pol III localization in other transformed and primary cell lines reveals previously uncharacterized and cell type-specific Pol III loci as well as one microRNA. Notably, only a fraction of the in silico-predicted Pol III loci are occupied. Many occupied Pol III genes reside within an annotated Pol II promoter. Outside of Pol II promoters, occupied Pol III genes overlap with enhancer-like chromatin and enhancer-binding proteins such as ETS1 and STAT1. Moreover, Pol III occupancy scales with the levels of nearby Pol II, active chromatin and CpG content. These results suggest that active chromatin gates Pol III accessibility to the genome.

239 citations


Journal ArticleDOI
TL;DR: It is shown that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged.
Abstract: Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes, yet the importance of this aspect of genome organization is unclear. Here we show that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged. This conservation is both tissue-specific and independent of the genomic G+C content conservation. Moreover, we show that time of replication is globally conserved despite numerous large-scale genome rearrangements. We systematically identify rearrangement fusion points and demonstrate that replication time can be locally diverged at these loci. Conversely, rearrangements are shown to be correlated with early replication and physical chromosomal proximity. These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome.

170 citations


Journal ArticleDOI
TL;DR: A technique is demonstrated for polarization demultiplexing of arbitrary complex-modulated signals using data in Stokes space to find the best fit plane and the normal to it which contains the origin.
Abstract: A technique is demonstrated for polarization demultiplexing of arbitrary complex-modulated signals. The technique is based entirely on the observation of samples in Stokes space, does not involve demodulation and is modulation format independent. The data in Stokes space is used to find the best fit plane and the normal to it which contains the origin. This normal identifies the two orthogonal polarization states of transmission and the desired polarization alignment transformation matrix. The technique is verified experimentally and is compared with the constant modulus algorithm.

Journal ArticleDOI
TL;DR: The results raise the possibility that the relative expression of related miRNAs might serve as diagnostic indicators in defining the developmental state of embryonic cells and other stem cell lines, such as iPSCs, and raise the possibilities that mi RNAs bearing identical seed sequences could have specific functions during separable stages of early embryonic development.
Abstract: Studies of embryonic stem cells (ESCs) reveal that these cell lines can be derived from differing stages of embryonic development. We analyzed common changes in the expression of microRNAs (miRNAs)...

Journal ArticleDOI
TL;DR: The results demonstrate that the two genes together perform an essential function and that the effects of their single mutations are mostly masked by overlapping patterns of expression and redundant function as well as by compensation at the post-translational level.

Journal ArticleDOI
TL;DR: A method to accurately genotype these new insertions by mapping next-generation sequencing datasets to the breakpoint is developed, thereby providing a means to characterize copy-number status for regions previously inaccessible to single-nucleotide polymorphism microarrays.
Abstract: The extent of human genomic structural variation suggests that there must be portions of the genome yet to be discovered, annotated and characterized at the sequence level. We present a resource and analysis of 2,363 new insertion sequences corresponding to 720 genomic loci. We found that a substantial fraction of these sequences are either missing, fragmented or misassigned when compared to recent de novo sequence assemblies from short-read next-generation sequence data. We determined that 18-37% of these new insertions are copy-number polymorphic, including loci that show extensive population stratification among Europeans, Asians and Africans. Complete sequencing of 156 of these insertions identified new exons and conserved noncoding sequences not yet represented in the reference genome. We developed a method to accurately genotype these new insertions by mapping next-generation sequencing datasets to the breakpoint, thereby providing a means to characterize copy-number status for regions previously inaccessible to single-nucleotide polymorphism microarrays.

Journal ArticleDOI
TL;DR: New profiling studies of mRNA and microRNA expression for the 60 cell lines of the National Cancer Institute (NCI) Developmental Therapeutics program (DTP) drug screen using the 41,000-probe Agilent Whole Human Genome Oligo Microarray and the 15, thousands-feature AgILent Human microRNA Microarray V2 are presented.
Abstract: As part of the Spotlight on Molecular Profiling series, we present here new profiling studies of mRNA and microRNA expression for the 60 cell lines of the National Cancer Institute (NCI) Developmental Therapeutics program (DTP) drug screen (NCI-60) using the 41,000-probe Agilent Whole Human Genome Oligo Microarray and the 15,000-feature Agilent Human microRNA Microarray V2. The expression levels of approximately 21,000 genes and 723 human microRNAs were measured. These profiling studies include quadruplicate technical replicates for six and eight cell lines for mRNA and microRNA, respectively, and duplicates for the remaining cell lines. The resulting data sets are freely available and searchable online in our CellMiner database. The result indicates high reproducibility for both platforms and an essential biological similarity across the various cell types. The mRNA and microRNA expression levels were integrated with our previously published 1,429-compound database of anticancer activity obtained from the NCI DTP drug screen. Large blocks of both mRNAs and microRNAs were identified with predominately unidirectional correlations to approximately 1,300 drugs, including 121 drugs with known mechanisms of action. The data sets presented here will facilitate the identification of groups of mRNAs, microRNAs, and drugs that potentially affect and interact with one another.

Proceedings ArticleDOI
04 Nov 2010
TL;DR: In this paper, a 56-Gbaud PDM 16-QAM using electronic time-division multiplexing (ETDM) and a four-level-driven I/Q modulator is presented.
Abstract: We generate 56-Gbaud PDM 16-QAM using electronic time-division multiplexing (ETDM) and a four-level-driven I/Q modulator. The 448-Gb/s line-rate signal is transmitted over 1,200 km of ultra-large-area fiber and coherently received by two 32.5-GHz oscilloscopes with >5.5 effective bits.

Journal ArticleDOI
TL;DR: In this article, the authors present a review of current macro-nutrient assessment technologies by target compound (nitrogen, phosphorus, and potassium (NPK)) and by sensing approach (e.g., chemical, electrical, optical) with an eye towards the potential to create an integrated sensor capable of detecting the three macronutrients of primary interest.

Journal ArticleDOI
TL;DR: Significant transcriptional induction of several pathogenesis related genes in Xa21 challenged strains, as well as differential changes to GAD, PAL, ICL1 and Glutathione-S-transferase transcripts indicated limited correlation with metabolite changes under single time point global profiling conditions.
Abstract: Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), gives rise to devastating crop losses in rice. Disease resistant rice cultivars are the most economical way to combat the disease. The TP309 cultivar is susceptible to infection by Xoo strain PXO99. A transgenic variety, TP309_Xa21, expresses the pattern recognition receptor Xa21, and is resistant. PXO99 big up tri, openraxST, a strain lacking the raxST gene, is able to overcome Xa21-mediated immunity. We used a single extraction solvent to demonstrate comprehensive metabolomics and transcriptomics profiling under sample limited conditions, and analyze the molecular responses of two rice lines challenged with either PXO99 or PXO99 big up tri, openraxST. LC-TOF raw data file filtering resulted in better within group reproducibility of replicate samples for statistical analyses. Accurate mass match compound identification with molecular formula generation (MFG) ranking of 355 masses was achieved with the METLIN database. GC-TOF analysis yielded an additional 441 compounds after BinBase database processing, of which 154 were structurally identified by retention index/MS library matching. Multivariate statistics revealed that the susceptible and resistant genotypes possess distinct profiles. Although few mRNA and metabolite differences were detected in PXO99 challenged TP309 compared to mock, many differential changes occurred in the Xa21-mediated response to PXO99 and PXO99 big up tri, openraxST. Acetophenone, xanthophylls, fatty acids, alkaloids, glutathione, carbohydrate and lipid biosynthetic pathways were affected. Significant transcriptional induction of several pathogenesis related genes in Xa21 challenged strains, as well as differential changes to GAD, PAL, ICL1 and Glutathione-S-transferase transcripts indicated limited correlation with metabolite changes under single time point global profiling conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0218-7) contains supplementary material, which is available to authorized users.

Journal ArticleDOI
TL;DR: A software-defined real-time optical multiformat transmitter enabling format switching in the nanosecond regime without changing the transmitter hardware is demonstrated.
Abstract: We demonstrate a software-defined real-time optical multiformat transmitter. Here, eight different modulation formats are shown. Data rate and modulation formats are defined through software accessible look-up tables enabling format switching in the nanosecond regime without changing the transmitter hardware. No data are lost during the switching process. SP-64 quadrature amplitude modulation at 28 Gbd has been generated and tested. This allows us to generate a 336-Gb/s real-time pseudorandom bit sequence in a dual polarization setup.

Journal ArticleDOI
TL;DR: An overall decreasing trend of PFCs contaminations with depth was observed in both of two 60 cm sediment cores from the Zhujiang River and the Huangpu River each, and little attention has been focused on the distributions in urban river sediments from Chinese major metropolises such as Guangzhou and Shanghai so far.

Journal ArticleDOI
TL;DR: This study is a valuable indicator of the potential of LC/MS-MS for routine quantitative multi-residue analysis of pharmaceuticals in drinking water and wastewater samples and will make monitoring studies much easier to develop for water utilities across the US.

Journal ArticleDOI
TL;DR: Recombinant Rv1248c catalyzed consumption of alpha-ketoglutarate in a mycobacterial small molecule extract with matched production of 5-hydroxylevulinate (HLA) in a reaction predicted to require glyoxylate, and encodes an HOA synthase.

Journal ArticleDOI
TL;DR: Specific microRNAs are identified as attenuators of growth factor signaling and oncogenesis, in line with roles as suppressors of EGF receptor (EGFR) signaling, which is decreased in breast and in brain tumors driven by the EGFR or the closely related HER2.
Abstract: Epidermal growth factor (EGF) stimulates cells by launching gene expression programs that are frequently deregulated in cancer. MicroRNAs, which attenuate gene expression by binding complementary regions in messenger RNAs, are broadly implicated in cancer. Using genome-wide approaches, we showed that EGF stimulation initiates a coordinated transcriptional program of microRNAs and transcription factors. The earliest event involved a decrease in the abundance of a subset of 23 microRNAs. This step permitted rapid induction of oncogenic transcription factors, such as c-FOS, encoded by immediate early genes. In line with roles as suppressors of EGF receptor (EGFR) signaling, we report that the abundance of this early subset of microRNAs is decreased in breast and in brain tumors driven by the EGFR or the closely related HER2. These findings identify specific microRNAs as attenuators of growth factor signaling and oncogenesis.

Journal ArticleDOI
TL;DR: Yeast α-arrestins, Aly1 and Aly2, redistribute the Gap1 permease from endosomes to the cell surface and interact with clathrin/AP-1.
Abstract: Arrestins, known regulators of endocytosis, take on novel functions in nutrient-regulated endosomal recycling. Yeast α-arrestins, Aly1 and Aly2, redistribute the Gap1 permease from endosomes to the...

Journal ArticleDOI
TL;DR: This study confirmed that although sialyllactose is the major OS in bovine colostrum, several neutral OS species are present in significant abundance even at the third day of lactation.

Proceedings ArticleDOI
21 Mar 2010
TL;DR: In this article, a real-time all-optical FFT receiver for OFDM data with line rates of 5.4 Tbit/s or 10.8 T bit/s is presented.
Abstract: OFDM data with line rates of 5.4 Tbit/s or 10.8 Tbit/s are generated and decoded with a new real-time all-optical FFT receiver. Each of 75 carriers of a comb source is encoded with 18 GBd QPSK or 16-QAM.

Patent
29 Jun 2010
TL;DR: In this article, the same authors present a system and methods for using the same to obtain a chemical array layout, and a computer program product for executing the subject methods, as well as computer program products for executing these methods.
Abstract: Systems and methods for using the same to obtain a chemical array layout are provided. Also provided are computer program products for executing the subject methods.

Journal ArticleDOI
TL;DR: In this paper, the protein interaction network of Leishmaniasis major was predicted by using three validated methods: PSIMAP, PEIMAP and iPfam, and calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions.
Abstract: Background: Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease. Results: We have predicted the protein interaction network of Leishmania major by using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets. Conclusion: We have constructed the first protein interaction network of the Leishmania major parasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.

Journal ArticleDOI
TL;DR: Analytical expressions are derived for the power spectral density of orthogonal frequency division multiplex signals employing a cyclic prefix (CP-OFDM) or zero padding time guard interval and validated by inspecting the power spectra of some standardized OFDM signals.
Abstract: In this letter, analytical expressions are derived for the power spectral density (PSD) of orthogonal frequency division multiplex (OFDM) signals employing a cyclic prefix (CP-OFDM) or zero padding (ZP-OFDM) time guard interval. Under the relatively weak assumptions that (i) the data are independent and identically distributed on all OFDM subcarriers and (ii) the OFDM pulse shape is sufficiently localized in time, simple closed-form PSD expressions can be obtained. These expressions are then compared to existing OFDM PSD expressions and validated by inspecting the power spectra of some standardized OFDM signals.

Journal ArticleDOI
TL;DR: A 3 h procedure for preparing serum N-glycans and labeling them with 8-aminopyrene-1,3,6-trisulfonic acid (APTS) by sequential addition of reagents to the serum and incubation in a polymerase chain reaction (PCR) thermocycler is developed.
Abstract: We developed a 3 h procedure for preparing serum N-glycans and labeling them with 8-aminopyrene-1,3,6-trisulfonic acid (APTS) by sequential addition of reagents to the serum and incubation in a polymerase chain reaction (PCR) thermocycler. Moreover, we succeeded in analyzing these samples by capillary electrophoresis on three commercial microfluidics-based platforms: the MCE-202 MultiNA, the 2100 Bioanalyzer, and a modified prototype of the eGene system which were originally designed for nucleic acid separation and detection. Although these instruments use short separation channels, our technical improvements made it possible to reliably measure the N-glycans constituting GlycoHepatoTest. This test comprises a panel of biomarkers that allows follow-up of liver fibrosis patients starting from the early stage. In this way and for the first time, we demonstrate a clinical glycomics assay on an affordable, robust platform so that clinical chemistry laboratories can exploit glycomics in the diagnosis and monitoring of chronic liver disease. Another potential application is the rapid screening of the N-glycosylation of recombinant glycoproteins produced for pharmaceutical use.