bluuebunny/crossref_metadata_2025 huggingface dataset:
Applications of CCTO supercapacitor in energy storage and electronics
Authors: Pandey R. K. , Stapleton W. A. , Tate J. , Bandyopadhyay A. K. , Sutanto I. , Sprissler S. , Lin S.
Published: June 2013

Since the discovery of colossal dielectric constant in CCTO supercapacitor in 2000, development of its practical application to energy storage has been of great interest. In spite of intensive efforts, there has been thus far, no report of proven application. The object of this research is to understand the reason for this lack of success and to find ways to overcome this limitation. Reported herein is the synthesis of our research in ceramic processing of this material and its characterization, particularly with the objective of identifying potential applications. Experimental results have shown that CCTO's permittivity and loss tangent, the two most essential dielectric parameters of fundamental importance for the efficiency of a capacitor device, are intrinsically coupled. They increase or decrease in tandem. Therefore, efforts to simultaneously retain the high permittivity while minimizing the loss tangent of CCTO might not succeed unless an entirely non-typical approach is taken for processing this material. Based on the experimental results and their analysis, it has been identified that it is possible to produce CCTO bulk ceramics with conventional processes having properties that can be exploited for fabricating an efficient energy storage device (EDS). We have additionally identified that CCTO can be used for the development of efficient solid state capacitors of Class II type comparable to the widely used barium titanate (BT) capacitors. Based on high temperature studies of the resistivity and the Seebeck coefficient it is found that CCTO is a wide bandgap n-type semiconductor material which could be used for high temperature electronics. The temperature dependence of the linear thermal expansion of CCTO shows the presence of possible phase changes at 220 and 770 °C the origin of which remains unexplained.
Structural Diversity and Magnetic Properties of Five Cu(II) Complexes with Mixed Naphthalene-Based Dicarboxyl Tecton and Different N-Donor Co-Ligands
Authors: Wen Jiong , Hu Jing-Yun , Sañudo E. Carolina , Chen Min , Liu Chun-Sen
Published: June 2013

Five new Cu(ii) complexes have been prepared by employing 2,3-naphthalenedicarboxylic acid (H2ndc) and different N-donor co-ligands, namely, [Cu(ndc)(H2O)]n (1), [Cu(ndc)(H2O)2]n (2), {[Cu1.5(ndc)(OH)(H2O)2]·2.5H2O}n (3), {[Cu(ndc)(phen)(H2O)]·CH3OH}n (4) (phen = 1,10-phenanthroline), and {[Cu2(H0.5ndc)2(4bpy)3](ClO4)·2H2O}n (5) (4bpy = 4,4′-bipyridine). Complex 1 displays a two-dimensional (2D) (4,6)-connected (32.44)2(34.42.64.75)(34.43.64.74) coordination network. Complex 2 shows a 2D 3-connected hcb network which is further interlinked via the interlayered C–H⋯π interactions to result in a three-dimensional (3D) supramolecular network. Complex 3 is a one-dimensional (1D) coordination chain which is further interlinked by the C–H⋯π and π⋯π interactions to lead to the formation of the final 3D supramolecular network. When the N-donor co-ligands phen and 4,4′-bipyridine (4bpy) were introduced, the 1D complex 4 and the 4-connected sql layered complex 5 were constructed, respectively. The final supramolecular frameworks of 4 (2D) and 5 (3D) are extended by hydrogen-bonding and C–H⋯π interactions. The structural diversity of the complexes was triggered by different reaction conditions and N-donor co-ligands. Moreover, the magnetic properties of the complexes have also been investigated and discussed.
N-Heterocyclic Silylene (NHSi) Rhodium and Iridium Complexes: Synthesis, Structure, Reactivity, and Catalytic Ability
Authors: Stoelzel Miriam , Präsang Carsten , Blom Burgert , Driess Matthias
Published: June 2013

Reaction of the zwitterionic N-heterocyclic silylene (NHSi) 1 L′Si: (L′ = [HC(CMeNAr)(C(CH2)NAr)], Ar = 2,6-iPr2C6H3) with HCl at low temperatures affords the kinetically stable 1,4-addition product of 1, LSiCl (L = [HC(CMeNAr)2], Ar = 2,6-iPr2C6H3) (9a), which upon reaction with [Rh(Cl)cod]2 and [Ir(Cl)cod]2 (cod = 1,5-cyclooctadiene) selectively affords the NHSi complexes [L(Cl)Si:→Rh(Cl)cod] (10a) and [L(Cl)Si:→Ir(Cl)cod] (10b), respectively. The latter were employed as pre-catalysts in the catalytic reduction of amides in the presence of silanes. Remarkably, they show strikingly different activities and selectivities. While complex 10a yields selectively the C–O cleavage product, 10b affords both cleavage products (C–O and C–N). Moreover, the total conversion of the catalytic amide reduction with 10b is significantly higher than the conversion with a benchmark system [Ir(Cl)cod]2 highlighting the enhanced catalytic activity afforded by the coordination of the NHSi ligand. Introducing the hydride source Li[HBEt3] into the catalytic reactions retards the catalyst performance due to a competitive decomposition pathway. This appears to occur via a H-shift onto the cod ligand with concomitant liberation of cyclooctene, which is also presented. The different reactivity of 10a and 10b towards nucleophiles such as MeLi is also discussed. The reaction of 10a with MeLi affords an intractable array of products, while the reaction of 10b with one equivalent of MeLi selectively affords [L(Cl)Si:→Ir(CH3)cod] (14) with selective methylation at the Ir centre. The analogous reaction with two equivalents of 10b affords the double methylated product [L(CH3)Si:→Ir(CH3)cod] (15).
B-Methyl Amine Borane Derivatives: Synthesis, Characterization, and Hydrogen Release
Authors: Campbell Patrick G. , Ishibashi Jacob S. A. , Zakharov Lev N. , Liu Shih-Yuan
Published: June 2013

We describe the synthesis of MeH2N–BH2Me (3) and H3N–BH2Me (4) as potential hydrogen storage materials with 6.8 wt-% and 8.9 wt-% capacity, respectively. Compounds 3 and 4 readily release 2 equivalents of H2 at 80°C in the presence of a CoCl2 catalyst to furnish the corresponding trimerized borazine derivatives. Regeneration of 3 from its spent fuel material can be accomplished using a simple two-step process: activation with formic acid followed by reduction with LiAlH4.
A Facile Eco-Friendly One-Pot Five-Component Synthesis of Novel 1,2,3-Triazole-Linked Pentasubstituted 1,4-Dihydropyridines and their Biological and Photophysical Studies
Authors: Singh Harjinder , Sindhu Jayant , Khurana Jitender M. , Sharma Chetan , Aneja Kamal R.
Published: June 2013

An eco-friendly one-pot five-component synthesis of novel 1,2,3-triazole-linked pentasubstituted 1,4-dihydropyridines under ultrasonic and microwave irradiation in polyethylene glycol (PEG) 400 is described. All newly synthesised compounds were evaluated for antibacterial activity, antifungal activity, antioxidant activity, and photophysical properties. Antimicrobial activity was evaluated against six microbial strains. All compounds exhibited antifungal activity against Aspergillus niger and Aspergillus flavus and moderate antibacterial activity against Gram positive bacteria (Staphylococcus aureus and Bacillus subtilis). Antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. All compounds showed good to moderate antioxidant activity. Furthermore all new compounds showed strong fluorescence in solution.
Preconsolidation pressure, soil water retention characteristics, and texture of Latosols in the Brazilian Cerrado
Authors: Severiano Eduardo da Costa , César de Oliveira Geraldo , Junior Moacir de Souza Dias , Curi Nilton , Costa Kátia Aparecida de Pinho , Carducci Carla Eloize
Published: June 2013

In the Brazilian Cerrado Biome, Latosols (Oxisols) predominate on gently sloping areas and are highly suitable for the development of mechanised agriculture. However, inappropriate management may lead to reduced crop yields and environmental degradation. We examined the relationships between compression behaviour and texture of Latosols to support decisions on the sustainable use and management of agricultural land. We collected soil samples in 10 Latosols with variable textures under native vegetation and determined the oxide content, bulk and particle density, total porosity, water retention curves, and preconsolidation pressure at different water potentials to develop preconsolidation pressure models. Our results showed that soil texture influenced soil physical properties, that is, an increase in the clay content enhanced the total porosity and water retention and decreased bulk density. Consequently, the susceptibility of these soils to compaction increased with an increase in the clay content. Considering the characteristics of the machinery used in intensive Brazilian agriculture, the compaction risk of these soils was considered high, despite the differences in resistance of the soils. In clayey and very clayey soils, some additional compaction is almost inevitable, even when the water content is low. Thus, caution is required in the evaluation of structural changes after mechanised field operations.
Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls
Authors: Kesler Shelli R. , Wefel Jeffrey S. , Hosseini S. M. Hadi , Cheung Maria , Watson Christa L. , Hoeft Fumiko
Published: June 2013

Breast cancer (BC) chemotherapy is associated with cognitive changes including persistent deficits in some individuals. We tested the accuracy of default mode network (DMN) resting state functional connectivity patterns in discriminating chemotherapy treated (C+) from non–chemotherapy (C−) treated BC survivors and healthy controls (HC). We also examined the relationship between DMN connectivity patterns and cognitive function. Multivariate pattern analysis was used to classify 30 C+, 27 C−, and 24 HC, which showed significant accuracy for discriminating C+ from C− (91.23%,
P
< 0.0001) and C+ from HC (90.74%,
P
< 0.0001). The C− group did not differ significantly from HC (47.06%,
P
= 0.60). Lower subjective memory function was correlated (
P
< 0.002) with greater hyperplane distance (distance from the linear decision function that optimally separates the groups). Disrupted DMN connectivity may help explain long-term cognitive difficulties following BC chemotherapy.
Amphetamine actions at the serotonin transporter rely on the availability of phosphatidylinositol-4,5-bisphosphate
Authors: Buchmayer Florian , Schicker Klaus , Steinkellner Thomas , Geier Petra , Stübiger Gerald , Hamilton Peter J. , Jurik Andreas , Stockner Thomas , Yang Jae-Won , Montgomery Therese , Holy Marion , Hofmaier Tina , Kudlacek Oliver , Matthies Heinrich J. G. , Ecker Gerhard F. , Bochkov Valery , Galli Aurelio , Boehm Stefan , Sitte Harald H.
Published: June 2013

Nerve functions require phosphatidylinositol-4,5-bisphosphate (PIP
2
) that binds to ion channels, thereby controlling their gating. Channel properties are also attributed to serotonin transporters (SERTs); however, SERT regulation by PIP
2
has not been reported. SERTs control neurotransmission by removing serotonin from the extracellular space. An increase in extracellular serotonin results from transporter-mediated efflux triggered by amphetamine-like psychostimulants. Herein, we altered the abundance of PIP
2
by activating phospholipase-C (PLC), using a scavenging peptide, and inhibiting PIP
2
-synthesis. We tested the effects of the verified scarcity of PIP
2
on amphetamine-triggered SERT functions in human cells. We observed an interaction between SERT and PIP
2
in pull-down assays. On decreased PIP
2
availability, amphetamine-evoked currents were markedly reduced compared with controls, as was amphetamine-induced efflux. Signaling downstream of PLC was excluded as a cause for these effects. A reduction of substrate efflux due to PLC activation was also found with recombinant noradrenaline transporters and in rat hippocampal slices. Transmitter uptake was not affected by PIP
2
reduction. Moreover, SERT was revealed to have a positively charged binding site for PIP
2
. Mutation of the latter resulted in a loss of amphetamine-induced SERT-mediated efflux and currents, as well as a lack of PIP
2
-dependent effects. Substrate uptake and surface expression were comparable between mutant and WT SERTs. These findings demonstrate that PIP
2
binding to monoamine transporters is a prerequisite for amphetamine actions without being a requirement for neurotransmitter uptake. These results open the way to target amphetamine-induced SERT-dependent actions independently of normal SERT function and thus to treat psychostimulant addiction.
Probing vasoocclusion phenomena in sickle cell anemia via mesoscopic simulations
Authors: Lei Huan , Karniadakis George E.
Published: June 2013

Vasoocclusion crisis is a key hallmark of sickle cell anemia. Although early studies suggest that this crisis is caused by blockage of a single elongated cell, recent experiments have revealed that vasoocclusion is a complex process triggered by adhesive interactions among different cell groups in multiple stages. However, the quantification of the biophysical characteristics of sickle cell anemia remains an open issue. Based on dissipative particle dynamics, we develop a multiscale model for the sickle red blood cells (SS-RBCs), accounting for diversity in both shapes and cell rigidities, to investigate the precise mechanism of vasoocclusion. First, we investigate the adhesive dynamics of a single SS-RBC in shear flow and static conditions, and find that the different cell groups (SS2: young-deformable SS-RBCs, ISCs: rigid-irreversible SS-RBCs) exhibit heterogeneous adhesive behavior due to the diverse cell morphologies and membrane rigidities. We quantify the observed adhesion behavior (in static conditions) in terms of a balance of free energies due to cell adhesion and deformation, and propose a power law that relates the free-energy increase as a function of the contact area. We further simulate postcapillary flow of SS-RBC suspensions with different cell fractions. The more adhesive SS2 cells interact with the vascular endothelium and trap ISC cells, resulting in vasoocclusion in vessels less than

depending on the hematocrit. Under inflammation, adherent leukocytes may also trap ISC cells, resulting in vasoocclusion in even larger vessels.
Nucleostemin deletion reveals an essential mechanism that maintains the genomic stability of stem and progenitor cells
Authors: Meng Lingjun , Lin Tao , Peng Guang , Hsu Joseph K. , Lee Sun , Lin Shiaw-Yih , Tsai Robert Y. L.
Published: June 2013

Stem and progenitor cells maintain a robust DNA replication program during the tissue expansion phase of embryogenesis. The unique mechanism that protects them from the increased risk of replication-induced DNA damage, and hence permits self-renewal, remains unclear. To determine whether the genome integrity of stem/progenitor cells is safeguarded by mechanisms involving molecules beyond the core DNA repair machinery, we created a nucleostemin (a stem and cancer cell-enriched protein) conditional-null allele and showed that neural-specific knockout of nucleostemin predisposes embryos to spontaneous DNA damage that leads to severe brain defects in vivo. In cultured neural stem cells, depletion of nucleostemin triggers replication-dependent DNA damage and perturbs self-renewal, whereas overexpression of nucleostemin shows a protective effect against hydroxyurea-induced DNA damage. Mechanistic studies performed in mouse embryonic fibroblast cells showed that loss of nucleostemin triggers DNA damage and growth arrest independently of the p53 status or rRNA synthesis. Instead, nucleostemin is directly recruited to DNA damage sites and regulates the recruitment of the core repair protein, RAD51, to hydroxyurea-induced foci. This work establishes the primary function of nucleostemin in maintaining the genomic stability of actively dividing stem/progenitor cells by promoting the recruitment of RAD51 to stalled replication-induced DNA damage foci.
Transformation of epithelial cells through recruitment leads to polyclonal intestinal tumors
Authors: Thliveris Andrew T. , Schwefel Brittany , Clipson Linda , Plesh Lauren , Zahm Christopher D. , Leystra Alyssa A. , Washington Mary Kay , Sullivan Ruth , Deming Dustin A. , Newton Michael A. , Halberg Richard B.
Published: June 2013

Intestinal tumors from mice and humans can have a polyclonal origin. Statistical analyses indicate that the best explanation for this source of intratumoral heterogeneity is the presence of interactions among multiple progenitors. We sought to better understand the nature of these interactions. An initial progenitor could recruit others by facilitating the transformation of one or more neighboring cells. Alternatively, two progenitors that are independently initiated could simply cooperate to form a single tumor. These possibilities were tested by analyzing tumors from aggregation chimeras that were generated by fusing together embryos with unequal predispositions to tumor development. Strikingly, numerous polyclonal tumors were observed even when one genetic component was highly, if not completely, resistant to spontaneous tumorigenesis in the intestine. Moreover, the observed number of polyclonal tumors could be explained by the facilitated transformation of a single neighbor within 144 μm of an initial progenitor. These findings strongly support recruitment instead of cooperation. Thus, it is conceivable that these interactions are necessary for tumors to thrive, so blocking them might be a highly effective method for preventing the formation of tumors in the intestine and other tissues.
Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion
Authors: Hägglund Martin , Dougherty Kimberly J. , Borgius Lotta , Itohara Shigeyoshi , Iwasato Takuji , Kiehn Ole
Published: June 2013

Neural networks in the spinal cord known as central pattern generators produce the sequential activation of muscles needed for locomotion. The overall locomotor network architectures in limbed vertebrates have been much debated, and no consensus exists as to how they are structured. Here, we use optogenetics to dissect the excitatory and inhibitory neuronal populations and probe the organization of the mammalian central pattern generator. We find that locomotor-like rhythmic bursting can be induced unilaterally or independently in flexor or extensor networks. Furthermore, we show that individual flexor motor neuron pools can be recruited into bursting without any activity in other nearby flexor motor neuron pools. Our experiments differentiate among several proposed models for rhythm generation in the vertebrates and show that the basic structure underlying the locomotor network has a distributed organization with many intrinsically rhythmogenic modules.
Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds
Authors: McGary Kriston L. , Slot Jason C. , Rokas Antonis
Published: June 2013

Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as “double neighbor gene pairs” (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD
50
doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates.
Structural basis of cargo recognitions for class V myosins
Authors: Wei Zhiyi , Liu Xiaotian , Yu Cong , Zhang Mingjie
Published: June 2013

Class V myosins (MyoV), the most studied unconventional myosins, recognize numerous cargos mainly via the motor’s globular tail domain (GTD). Little is known regarding how MyoV-GTD recognizes such a diverse array of cargos specifically. Here, we solved the crystal structures of MyoVa-GTD in its apo-form and in complex with two distinct cargos, melanophilin and Rab interacting lysosomal protein-like 2. The apo-MyoVa-GTD structure indicates that most mutations found in patients with Griscelli syndrome, microvillus inclusion disease, or cancers or in “dilute” rodents likely impair the folding of GTD. The MyoVa-GTD/cargo complex structure reveals two distinct cargo-binding surfaces, one primarily via charge–charge interaction and the other mainly via hydrophobic interactions. Structural and biochemical analysis reveal the specific cargo-binding specificities of various isoforms of mammalian MyoV as well as very different cargo recognition mechanisms of MyoV between yeast and higher eukaryotes. The MyoVa-GTD structures resolved here provide a framework for future functional studies of vertebrate class V myosins.
Sipros/ProRata: a versatile informatics system for quantitative community proteomics
Authors: Wang Yingfeng , Ahn Tae-Hyuk , Li Zhou , Pan Chongle
Published: June 2013

Summary: Sipros/ProRata is an open-source software package for end-to-end data analysis in a wide variety of community proteomics measurements. A database-searching program, Sipros 3.0, was developed for accurate general-purpose protein identification and broad-range post-translational modification searches. Hybrid Message Passing Interface/OpenMP parallelism of the new Sipros architecture allowed its computation to be scalable from desktops to supercomputers. The upgraded ProRata 3.0 performs label-free quantification and isobaric chemical labeling quantification in addition to metabolic labeling quantification. Sipros/ProRata is a versatile informatics system that enables identification and quantification of proteins and their variants in many types of community proteomics studies.

Availability: Both programs are freely available under the GNU GPL license at Sipros.omicsbio.org and ProRata.omicsbio.org.

Contact:  panc@ornl.gov

Supplementary information:  Supplementary data are available at Bioinformatics online.
Multilabel classification for exploiting cross-resistance information in HIV-1 drug resistance prediction
Authors: Heider Dominik , Senge Robin , Cheng Weiwei , Hüllermeier Eyke
Published: June 2013

Motivation: Antiretroviral treatment regimens can sufficiently suppress viral replication in human immunodeficiency virus (HIV)-infected patients and prevent the progression of the disease. However, one of the factors contributing to the progression of the disease despite ongoing antiretroviral treatment is the emergence of drug resistance. The high mutation rate of HIV can lead to a fast adaptation of the virus under drug pressure, thus to failure of antiretroviral treatment due to the evolution of drug-resistant variants. Moreover, cross-resistance phenomena have been frequently found in HIV-1, leading to resistance not only against a drug from the current treatment, but also to other not yet applied drugs. Automatic classification and prediction of drug resistance is increasingly important in HIV research as well as in clinical settings, and to this end, machine learning techniques have been widely applied. Nevertheless, cross-resistance information was not taken explicitly into account, yet.

Results: In our study, we demonstrated the use of cross-resistance information to predict drug resistance in HIV-1. We tested a set of more than 600 reverse transcriptase sequences and corresponding resistance information for six nucleoside analogues. Based on multilabel classification models and cross-resistance information, we were able to significantly improve overall prediction accuracy for all drugs, compared with single binary classifiers without any additional information. Moreover, we identified drug-specific patterns within the reverse transcriptase sequences that can be used to determine an optimal order of the classifiers within the classifier chains. These patterns are in good agreement with known resistance mutations and support the use of cross-resistance information in such prediction models.

Contact:  dominik.heider@uni-due.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Optimizing multiple sequence alignments using a genetic algorithm based on three objectives: structural information, non-gaps percentage and totally conserved columns
Authors: Ortuño Francisco M. , Valenzuela Olga , Rojas Fernando , Pomares Hector , Florido Javier P. , Urquiza Jose M. , Rojas Ignacio
Published: June 2013

Motivation: Multiple sequence alignments (MSAs) are widely used approaches in bioinformatics to carry out other tasks such as structure predictions, biological function analyses or phylogenetic modeling. However, current tools usually provide partially optimal alignments, as each one is focused on specific biological features. Thus, the same set of sequences can produce different alignments, above all when sequences are less similar. Consequently, researchers and biologists do not agree about which is the most suitable way to evaluate MSAs. Recent evaluations tend to use more complex scores including further biological features. Among them, 3D structures are increasingly being used to evaluate alignments. Because structures are more conserved in proteins than sequences, scores with structural information are better suited to evaluate more distant relationships between sequences.

Results: The proposed multiobjective algorithm, based on the non-dominated sorting genetic algorithm, aims to jointly optimize three objectives: STRIKE score, non-gaps percentage and totally conserved columns. It was significantly assessed on the BAliBASE benchmark according to the Kruskal–Wallis test (P < 0.01). This algorithm also outperforms other aligners, such as ClustalW, Multiple Sequence Alignment Genetic Algorithm (MSA-GA), PRRP, DIALIGN, Hidden Markov Model Training (HMMT), Pattern-Induced Multi-sequence Alignment (PIMA), MULTIALIGN, Sequence Alignment Genetic Algorithm (SAGA), PILEUP, Rubber Band Technique Genetic Algorithm (RBT-GA) and Vertical Decomposition Genetic Algorithm (VDGA), according to the Wilcoxon signed-rank test (P < 0.05), whereas it shows results not significantly different to 3D-COFFEE (P > 0.05) with the advantage of being able to use less structures. Structural information is included within the objective function to evaluate more accurately the obtained alignments.

Availability: The source code is available at http://www.ugr.es/∼fortuno/MOSAStrE/MO-SAStrE.zip.

Contact:  fortuno@ugr.es

Supplementary Information:  Supplementary material is available at Bioinformatics online.
Linc2GO: a human LincRNA function annotation resource based on ceRNA hypothesis
Authors: Liu Ke , Yan Zhangming , Li Yuchao , Sun Zhirong
Published: June 2013

Summary: Large numbers of long intergenic non-coding RNA (lincRNA) have been detected through high-throughput sequencing technology. However, currently we still know very little about their functions. Therefore, a lincRNA function annotation database is needed to facilitate the study in this field. In this article, we present Linc2GO, a web resource that aims to provide comprehensive functional annotations for human lincRNA. MicroRNA-mRNA and microRNA-lincRNA interaction data were integrated to generate lincRNA functional annotations based on the ‘competing endogenous RNA hypothesis’. To the best of our knowledge, Linc2GO is the first database that makes use of the ‘competing endogenous RNA hypothesis’ to predict lincRNA functions.

Availability: Freely available at http://www.bioinfo.tsinghua.edu.cn/~liuke/Linc2GO/index.html

Contact:  sunzhr@mail.tsinghua.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
The human genome contracts again
Authors: Pavlichin Dmitri S. , Weissman Tsachy , Yona Golan
Published: June 2013

Summary: The number of human genomes that have been sequenced completely for different individuals has increased rapidly in recent years. Storing and transferring complete genomes between computers for the purpose of applying various applications and analysis tools will soon become a major hurdle, hindering the analysis phase. Therefore, there is a growing need to compress these data efficiently. Here, we describe a technique to compress human genomes based on entropy coding, using a reference genome and known Single Nucleotide Polymorphisms (SNPs). Furthermore, we explore several intrinsic features of genomes and information in other genomic databases to further improve the compression attained. Using these methods, we compress James Watson’s genome to 2.5 megabytes (MB), improving on recent work by 37%. Similar compression is obtained for most genomes available from the 1000 Genomes Project. Our biologically inspired techniques promise even greater gains for genomes of lower organisms and for human genomes as more genomic data become available.

Availability: Code is available at sourceforge.net/projects/genomezip/

Contact:  golan.yona@stanford.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Differential gene expression analysis using coexpression and RNA-Seq data
Authors: Yang Ei-Wen , Girke Thomas , Jiang Tao
Published: June 2013

Motivation: RNA-Seq is increasingly being used for differential gene expression analysis, which was dominated by the microarray technology in the past decade. However, inferring differential gene expression based on the observed difference of RNA-Seq read counts has unique challenges that were not present in microarray-based analysis. The differential expression estimation may be biased against low read count values such that the differential expression of genes with high read counts is more easily detected. The estimation bias may further propagate in downstream analyses at the systems biology level if it is not corrected.

Results: To obtain a better inference of differential gene expression, we propose a new efficient algorithm based on a Markov random field (MRF) model, called MRFSeq, that uses additional gene coexpression data to enhance the prediction power. Our main technical contribution is the careful selection of the clique potential functions in the MRF so its maximum a posteriori estimation can be reduced to the well-known maximum flow problem and thus solved in polynomial time. Our extensive experiments on simulated and real RNA-Seq datasets demonstrate that MRFSeq is more accurate and less biased against genes with low read counts than the existing methods based on RNA-Seq data alone. For example, on the well-studied MAQC dataset, MRFSeq improved the sensitivity from 11.6 to 38.8% for genes with low read counts.

Availability: MRFSeq is implemented in C and available at http://www.cs.ucr.edu/~yyang027/mrfseq.htm

Contact:  yyang027@ucr.edu or jiang@cs.ucr.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Co-regulation in embryonic stem cells via context-dependent binding of transcription factors
Authors: Lee Yuju , Zhou Qing
Published: June 2013

Motivation: With the accumulation of genome-wide binding data for many transcription factors (TFs) in the same cell type or cellular condition, it is of great current interest to systematically infer the complex regulatory logic among multiple TFs. In particular, ChIP-Seq data have been generated for 14 core TFs critical to the maintenance and reprogramming of mouse embryonic stem cells (ESCs). This provides a great opportunity to study the regulatory collaboration and interaction among these TFs and with other unknown co-regulators.

Results: In combination with liquid association among gene expression profiles, we develop a computational method to predict context-dependent (CD) co-egulators of these core TFs in ESCs from pairwise binding datasets. That is, co-occupancy between a core TF and a predicted co-regulator depends on the presence or absence of binding sites of another core TF, which is regarded as a binding context. Unbiased external validation confirms that the predicted CD binding of a co-regulator is reliable. Our results reveal a detailed CD co-regulation network among the 14 core TFs and provide many other potential co-regulators showing strong agreement with the literature.

Availability: See www.stat.ucla.edu/~zhou/CMF for software and source code.

Contact:  zhou@stat.ucla.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
cisExpress: motif detection in DNA sequences
Authors: Triska Martin , Grocutt David , Southern James , Murphy Denis J. , Tatarinova Tatiana
Published: June 2013

Motivation: One of the major challenges for contemporary bioinformatics is the analysis and accurate annotation of genomic datasets to enable extraction of useful information about the functional role of DNA sequences. This article describes a novel genome-wide statistical approach to the detection of specific DNA sequence motifs based on similarities between the promoters of similarly expressed genes. This new tool, cisExpress, is especially designed for use with large datasets, such as those generated by publicly accessible whole genome and transcriptome projects. cisExpress uses a task farming algorithm to exploit all available computational cores within a shared memory node. We demonstrate the robust nature and validity of the proposed method. It is applicable for use with a wide range of genomic databases for any species of interest.

Availability:  cisExpress is available at www.cisexpress.org.

Contact:  tatiana.tatarinova@usc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Mechanistic insights into mutually exclusive splicing in dynamin 1
Authors: Suyama Mikita
Published: June 2013

Summary: Mutually exclusive splicing is a strictly regulated pattern of alternative splicing. A specific group of mutually exclusive splicing events has been shown to be regulated by the formation of specific RNA secondary structures. This type of regulation has been shown to exist only in arthropods. The present study involved a detailed sequence analysis of human gene structures that undergo mutually exclusive splicing, which showed that this type of regulation may also occur in dynamin 1 in mammals. A phylogenetic analysis revealed that the dynamin 1 orthologs in invertebrates did not share the same sequence features, which suggests that the regulatory mechanism has independently evolved in the mammalian lineage. Therefore, the emergence of this elaborate mechanism for mutually exclusive splicing may be attributable to mechanistic convergence.

Contact:  mikita@bioreg.kyushu-u.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fungibility and Consumer Choice: Evidence from Commodity Price Shocks*
Authors: Hastings Justine S. , Shapiro Jesse M.
Published: June 2013

We formulate a test of the fungibility of money based on parallel shifts in the prices of different quality grades of a commodity. We embed the test in a discrete-choice model of product quality choice and estimate the model using panel microdata on gasoline purchases. We find that when gasoline prices rise, consumers substitute to lower octane gasoline, to an extent that cannot be explained by income effects. Across a wide range of specifications, we consistently reject the null hypothesis that households treat “gas money” as fungible with other income. We compare the empirical fit of three psychological models of decision making. A simple model of category budgeting fits the data well, with models of loss aversion and salience both capturing important features of the time series.
Identification of ovarian cancer driver genes by using module network integration of multi-omics data
Authors: Gevaert Olivier , Villalobos Victor , Sikic Branimir I. , Plevritis Sylvia K.
Published: June 2013

The increasing availability of multi-omics cancer datasets has created a new opportunity for data integration that promises a more comprehensive understanding of cancer. The challenge is to develop mathematical methods that allow the integration and extraction of knowledge from large datasets such as The Cancer Genome Atlas (TCGA). This has led to the development of a variety of omics profiles that are highly correlated with each other; however, it remains unknown which profile is the most meaningful and how to efficiently integrate different omics profiles. We developed AMARETTO, an algorithm to identify cancer drivers by integrating a variety of omics data from cancer and normal tissue. AMARETTO first models the effects of genomic/epigenomic data on disease-specific gene expression. AMARETTO's second step involves constructing a module network to connect the cancer drivers with their downstream targets. We observed that more gene expression variation can be explained when using disease-specific gene expression data. We applied AMARETTO to the ovarian cancer TCGA data and identified several cancer driver genes of interest, including novel genes in addition to known drivers of cancer. Finally, we showed that certain modules are predictive of good versus poor outcome, and the associated drivers were related to DNA repair pathways.
A sticky situation: the unexpected stability of malaria elimination
Authors: Smith David L. , Cohen Justin M. , Chiyaka Christinah , Johnston Geoffrey , Gething Peter W. , Gosling Roly , Buckee Caroline O. , Laxminarayan Ramanan , Hay Simon I. , Tatem Andrew J.
Published: June 2013

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination's ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system's increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination's stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.
Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine
Authors: Biswas Gautam , Sankara Dieudonne P. , Agua-Agum Junerlyn , Maiga Alhousseini
Published: June 2013

Dracunculiasis, commonly known as guinea worm disease, is a nematode infection transmitted to humans exclusively via contaminated drinking water. The disease prevails in the most deprived areas of the world. No vaccine or medicine is available against the disease: eradication is being achieved by implementing preventive measures. These include behavioural change in patients and communities—such as self-reporting suspected cases to health workers or volunteers, filtering drinking water and accessing water from improved sources and preventing infected individuals from wading or swimming in drinking-water sources—supplemented by active surveillance and case containment, vector control and provision of improved water sources. Efforts to eradicate dracunculiasis began in the early 1980s. By the end of 2012, the disease had reached its lowest levels ever. This paper reviews the progress made in eradicating dracunculiasis since the eradication campaign began, the factors influencing progress and the difficulties in controlling the pathogen that requires behavioural change, especially when the threat becomes rare. The challenges of intensifying surveillance are discussed, particularly in insecure areas containing the last foci of the disease. It also summarizes the broader benefits uniquely linked to interventions against dracunculiasis.
Vacated niches, competitive release and the community ecology of pathogen eradication
Authors: Lloyd-Smith James O.
Published: June 2013

A recurring theme in the epidemiological literature on disease eradication is that each pathogen occupies an ecological niche, and eradication of one pathogen leaves a vacant niche that favours the emergence of new pathogens to replace it. However, eminent figures have rejected this view unequivocally, stating that there is no basis to fear pathogen replacement and even that pathogen niches do not exist. After exploring the roots of this controversy, I propose resolutions to disputed issues by drawing on broader ecological theory, and advance a new consensus based on robust mechanistic principles. I argue that pathogen eradication (and cessation of vaccination) leads to a ‘vacated niche’, which could be re-invaded by the original pathogen if introduced. Consequences for other pathogens will vary, with the crucial mechanisms being competitive release, whereby the decline of one species allows its competitors to perform better, and evolutionary adaptation. Hence, eradication can cause a quantitative rise in the incidence of another infection, but whether this leads to emergence as an endemic pathogen depends on additional factors. I focus on the case study of human monkeypox and its rise following smallpox eradication, but also survey how these ideas apply to other pathogens and discuss implications for eradication policy.
Modern contraceptive behaviour of Indian women: is spousal violence a constraint?
Authors: Debnath Avijit , Roy Niranjan , Mazumder Nazira
Published: June 2013

Purpose

The main goal of the paper is to study the effect of intimate partner violence on wives' participation in adopting modern contraceptive as a method of family planning in India.

Design/methodology/approach

The authors' analysis uses data from the NFHS‐III (2005‐2006) based on a nationally representative sample of 109,041 households, and 124,385 women (15‐49 years). The sample covers 99 percent of India's population living in all 29 states. Both bivariate and multivariate techniques have been used to analyze data. The bivariate analysis in the form of scatter diagram has been used to examine the association between “use of modern contraceptive” and “spousal violence”, while multivariate analysis in the form of logistic regression has been carried out to assess this association after controlling other variables.

Findings

The study reveals that spousal violence negatively affects wives' participation in adoption of modern contraceptive, but that their knowledge of contraceptive, religion, and level of women empowerment should be taken into account as well. Women with higher knowledge about contraceptive have been found to use more modern contraceptive. Muslim women have relatively lower modern contraceptive prevalence rate and they have an inclination for traditional methods. Similarly, modern contraceptive prevalence is lower among women who enjoy relatively higher empowerment. In fact, it has been found from the study that women empowerment has a high positive correlation with traditional contraceptive prevalence rate.

Originality/value

This paper is the first attempt at examining the association between spousal violence and contraceptive behaviour in India on a national basis covering every corner of the country. The findings of the study clearly stress the importance of spousal violence prevention measures as supplemental to family planning measures. However, it will be erroneous to assume that mere passing of bills in the parliament and making laws will solve the problem which is deeply rooted in the society.
Basic equality as a post‐revolutionary requisite
Authors: Doomen Jasper
Published: June 2013

Purpose

The Arab Spring poses challenges to governments of the countries involved; the author aims to present a way to respond to them. To this end, the notion of “basic equality” is proffered as a decisive element to be realized in a democratic form of government, democracy itself being necessary if one seeks to evade a return to the former forms of government.

Design/methodology/approach

No single answer suffices to realize stable while generally acceptable forms of government; basic equality is shown to be a necessary starting point in each case, to be supplemented by specific policies. The practical implications of the article's analysis are evidenced in the limitations governments must recognize and warrant: through legislation, basic equality is to be realized.

Findings

People's (formal) equality must be acknowledged. It may be difficult to reconcile this demand with, for example, religious convictions, but it is not necessary to compromise what one believes. One need only act in accordance with the dictates of formal equality, which is the corollary of basic equality. For example, an employer only has to treat his employees equally, and may, accordingly, not distinguish between race, gender or religion, but he is not required to believe that people are, in some fundamental sense, equal.

Originality/value

Equal treatment has often been proposed as a “moral” directive. The author presents a realistic alternative to this approach while realizing a state of affairs in which people are treated equally. Since this alternative is based on their self‐interest, this will lead to both a convincing theory and a viable practice.