Genomic analyses with biofilter 2.0: knowledge driven filtering, annotation, and model development

BACKGROUND: The ever-growing wealth of biological information available through multiple comprehensive database repositories can be leveraged for advanced analysis of data. We have now extensively revised and updated the multi-purpose software tool Biofilter that allows researchers to annotate and/or filter data as well as generate gene-gene interaction models based on existing biological knowledge. Biofilter now has the Library of Knowledge Integration (LOKI), for accessing and integrating existing comprehensive database information, including more flexibility for how ambiguity of gene identifiers are handled. We have also updated the way importance scores for interaction models are generated. In addition, Biofilter 2.0 now works with a range of types and formats of data, including single nucleotide polymorphism (SNP) identifiers, rare variant identifiers, base pair positions, gene symbols, genetic regions, and copy number variant (CNV) location information. RESULTS: Biofilter provides a convenient single interface for accessing multiple publicly available human genetic data sources that have been compiled in the supporting database of LOKI. Information within LOKI includes genomic locations of SNPs and genes, as well as known relationships among genes and proteins such as interaction pairs, pathways and ontological categories. Via Biofilter 2.0 researchers can: • Annotate genomic location or region based data, such as results from association studies, or CNV analyses, with relevant biological knowledge for deeper interpretation • Filter genomic location or region based data on biological criteria, such as filtering a series SNPs to retain only SNPs present in specific genes within specific pathways of interest • Generate Predictive Models for gene-gene, SNP-SNP, or CNV-CNV interactions based on biological information, with priority for models to be tested based on biological relevance, thus narrowing the search space and reducing multiple hypothesis-testing. CONCLUSIONS: Biofilter is a software tool that provides a flexible way to use the ever-expanding expert biological knowledge that exists to direct filtering, annotation, and complex predictive model development for elucidating the etiology of complex phenotypic outcomes

Ferroelectric photovoltaic properties in doubly substituted (Bi0.9La0.1)(Fe0.97Ta0.03)O3 thin films

This work was supported by the DOE-EPSCoR Grant No. DE-FG02-08ER46526. Acknowledgment is also due to NSF Grant No. #1002410 for providing fellowships to R.K.K., D.B., and J.S.Y.Doubly substituted [Bi0.9La0.1][Fe0.97Ta0.03]O3 (BLFTO) films were fabricated on Pt/TiO2/SiO2/Si substrates by pulsed laser deposition. The ferroelectric photovoltaic properties of ZnO:Al/BLFTO/Pt thin film capacitor structures were evaluated under white light illumination. The open circuit voltage and short circuit current density were observed to be ∼0.20 V and ∼1.35 mA/cm2, respectively. The band gap of the films was determined to be ∼2.66 eV, slightly less than that of pure BiFeO3 (2.67 eV). The PVproperties of BLFTO thin films were also studied for various pairs of planar electrodes in different directions in polycrystalline thin films.Publisher PDFPeer reviewe

Cyclin D1 integrates G9a-mediated histone methylation.

Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle progression and mitochondrial metabolism. Herein, we show that cyclin D1 enhanced H3K9 dimethylation though direct association with G9a. Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a-induced H3K9me2 of histones, and for NL-LAD interaction. The finding that cyclin D1 is required for recruitment of G9a to target genes in chromatin and for H3K9 dimethylation, identifies a novel mechanism coordinating protein methylation

Switching ferroelectric domain configurations using both electric and magnetic fields in Pb(Zr,Ti)O3–Pb(Fe,Ta)O3 single-crystal lamellae

Thin single-crystal lamellae cut from Pb(Zr,Ti)O(3)–Pb(Fe,Ta)O(3) ceramic samples have been integrated into simple coplanar capacitor devices. The influence of applied electric and magnetic fields on ferroelectric domain configurations has been mapped, using piezoresponse force microscopy. The extent to which magnetic fields alter the ferroelectric domains was found to be strongly history dependent: after switching had been induced by applying electric fields, the susceptibility of the domains to change under a magnetic field (the effective magnetoelectric coupling parameter) was large. Such large, magnetic field-induced changes resulted in a remanent domain state very similar to the remanent state induced by an electric field. Subsequent magnetic field reversal induced more modest ferroelectric switching

Magnetic control of large room-temperature polarization

Numerous authors have referred to room-temperature magnetic switching of large electric polarizations as The Holy Grail of magnetoelectricity.We report this long-sought effect using a new physical process of coupling between magnetic and ferroelectric relaxor nano-regions. Here we report magnetic switching between the normal ferroelectric state and the ferroelectric relaxor state. This gives both a new room-temperature, single-phase, multiferroic magnetoelectric, PbZr0.46Ti0.34Fe0.13W0.07O3, with polarization, loss (<4%), and resistivity (typically 108 -109 ohm.cm) equal to or superior to BiFeO3, and also a new and very large magnetoelectric effect: switching not from +Pr to negative Pr with applied H, but from Pr to zero with applied H of less than a Tesla. This switching of the polarization occurs not because of a conventional magnetically induced phase transition, but because of dynamic effects: Increasing H lengthens the relaxation time by x500 from 100 ?s, and it couples strongly the polarization relaxation and spin relaxations. The diverging polarization relaxation time accurately fits a modified Vogel-Fulcher Equation in which the freezing temperature Tf is replaced by a critical freezing field Hf that is 0.92 positive/negative 0.07 Tesla. This field dependence and the critical field Hc are derived analytically from the spherical random bond random field (SRBRF) model with no adjustable parameters and an E2H2 coupling. This device permits 3-state logic (+Pr,0,negative Pr) and a condenser with >5000% magnetic field change in its capacitance.Comment: 20 pages, 5 figure

Ferroelectric Phase Transitions in Three-Component Short-Period Superlattices Studied by Ultraviolet Raman Spectroscopy

Vibrational spectra of three-component BaTiO3SrTiO3CaTiO3 short-period superlattices grown by pulsed laser deposition with atomic-layer control have been investigated by ultraviolet Raman spectroscopy. Monitoring the intensity of the first-order phonon peaks in Raman spectra as a function of temperature allowed determination of the ferroelectric phase transition temperature, Tc. Raman spectra indicate that all superlattices remain in the tetragonal ferroelectric phase with out-of-plane polarization in the entire temperature range below Tc. The dependence of Tc on the relative thicknesses of ferroelectric (BaTiO3) to non-ferroelectric materials (SrTiO3 and CaTiO3) has been studied. The highest Tc was found in superlattices having the largest relative amount of BaTiO3, provided that the superlattice maintains its coherency with the substrate. Strain relaxation leads to a significant decrease in the ferroelectric phase transition temperature

Magnetic switching of ferroelectric domains at room temperature in multiferroic PZTFT

Single-phase magnetoelectric multiferroics are ferroelectric materials that display some form of magnetism. In addition, magnetic and ferroelectric order parameters are not independent of one another. Thus, the application of either an electric or magnetic field simultaneously alters both the electrical dipole configuration and the magnetic state of the material. The technological possibilities that could arise from magnetoelectric multiferroics are considerable and a range of functional devices has already been envisioned. Realising these devices, however, requires coupling effects to be significant and to occur at room temperature. Although such characteristics can be created in piezoelectric-magnetostrictive composites, to date they have only been weakly evident in single-phase multiferroics. Here in a newly discovered room temperature multiferroic, we demonstrate significant room temperature coupling by monitoring changes in ferroelectric domain patterns induced by magnetic fields. An order of magnitude estimate of the effective coupling coefficient suggests a value of ~1 × 10(−7) sm(−1)

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel