266 research outputs found
Crossover of skyrmion and helical modulations in noncentrosymmetric ferromagnets
The coupling between angular (twisting) and longitudinal modulations arising
near the ordering temperature of noncentrosymmetric ferromagnets strongly
influences the structure of skyrmion states and their evolution in an applied
magnetic field. In the precursor states of cubic helimagnets, a continuous
transformation of skyrmion lattices into the saturated state is replaced by the
first-order processes accompanied by the formation of multidomain states.
Recently the effects imposed by dominant longitudinal modulations have been
reported in bulk MnSi and FeGe. Similar phenomena can be observed in the
precursor regions of cubic helimagnet epilayers and in easy-plane chiral
ferromagnets (e.g. in the hexagonal helimagnet CrNb3S6)
Skyrmionic textures in chiral magnets
In non-centrosymmetric magnets the chiral Dzyaloshinskii-Moriya exchange
stabilizes Skyrmion-strings as excitations which may condense into multiply
modulated phases. Such extended Skyrmionic textures are determined by the
stability of the localized "solitonic" Skyrmion cores and their geometrical
incompatibility which frustrates regular space-filling. We present numerically
exact solutions for Skyrmion lattices and formulate basic properties of the
Skyrmionic states.Comment: Conference information: The International Conference on Magnetism
(ICM), Karlsruhe, July 26 - 31, 200
Chiral Skyrmionic matter in non-centrosymmetric magnets
Axisymmetric magnetic strings with a fixed sense of rotation and nanometer
sizes (chiral magnetic vortices or Skyrmions) have been predicted to exist in a
large group of non-centrosymmetric crystals more than two decades ago. Recently
these extraordinary magnetic states have been directly observed in thin layers
of cubic helimagnet (Fe,Co)Si. In this report we apply our earlier theoretical
findings to review main properties of chiral Skyrmions, to elucidate their
physical nature, and to analyse these recent experimental results on
magnetic-field-driven evolution of Skyrmions and helicoids in chiral
helimagnets.Comment: 13 pages, 7 figures, invited talk - JEMS-2010 ( 23-28 August, Krakow,
Poland
Fluorocarbons Enhance Intracellular Delivery of Short STAT3-sensors and Enable Specific Imaging
Short oligonucleotide sequences are now being widely investigated for their potential therapeutic properties. The modification of oligonucleotide termini with short fluorinated residues is capable of drastically altering their behavior in complex in vitro and in vivo systems, and thus may serve to greatly enhance their therapeutic potential. The main goals of our work were to explore: 1) how modification of STAT3 transcription factor-binding oligodeoxynucleotide (ODN) duplexes (ODND) with one or two short fluorocarbon (FC)-based residues would change their properties in vitro and in vivo, and if so, how this would affect their intracellular uptake by cancer cells, and 2) the ability of such modified ODND to form non-covalent complexes with FC-modified carrier macromolecule. The latter has an inherent advantage of producing a 19F-specific magnetic resonance (MR) imaging signature. Thus, we also tested the ability of such copolymers to generate 19F-MR signals.
Materials and Methods. Fluorinated nucleic acid residues were incorporated into ODN by using automated synthesis or via activated esters on ODN 5\u27-ends. To quantify ODND uptake by the cells and to track their stability, we covalently labeled ODN with fluorophores using internucleoside linker technology; the FC-modified carrier was synthesized by acylation of pegylated polylysine graft copolymer with perfluoroundecanoic acid (M5-gPLL-PFUDA).
Results. ODN with a single FC group exhibited a tendency to form duplexes with higher melting points and with increased stability against degradation when compared to control non-modified ODNs. ODND carrying fluorinated residues showed complex formation with M5-gPLL-PFUDA as predicted by molecular dynamics simulations. Moreover, FC groups modulated the specificity of ODND binding to the STAT3 target. Finally, FC modification resulted in greater cell uptake (2 to 4 fold higher) when compared to the uptake of non-modified ODND as determined by quantitative confocal fluorescence imaging of A431 and INS-1 cells.
Conclusion. ODND modification with FC residues enables fine-tuning of protein binding specificity to double-strand binding motifs and results in an increased internalization by A431 and INS-1 cells in culture. Our results show that modification of ODN termini with FC residues is both a feasible and powerful strategy for developing more efficient nucleic acid-based therapies with the added benefit of allowing for non-invasive MR imaging of ODND therapeutic targeting and response
Proceedings of the third international molecular pathological epidemiology (MPE) meeting
Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields
Sensing of transcription factor binding via cyanine dye pair fluorescence lifetime changes
We designed and synthesized sensors for imaging transcription factor-DNA interactions using a complementary pair of 21-base pair long oligonucleotides (ODNs) carrying two internucleoside phosphate-linked cyanine fluorophores that can either engage in Forster\u27s resonance energy transfer (FRET) with fluorescence emission or assemble into a ground state quenched dimer with short fluorescence lifetimes (FL). Cyanine fluorophores were linked to ODNs within the NF-kappaB binding site. These sensors were tested in the presence of recombinant p50 and p65 NF-kappaB proteins or constitutively NF-kappaB activating HeLa cell lysates. By using a coherent light excitation source we followed changes in fluorescence lifetime of the donor (Cy5.5) at the donor\u27s excitation and emission light wavelengths, as well as the acceptor (800CW or Cy7 cyanine fluorophores) in FRET mode. We observed increases in the donor lifetime in both emitting (0.08-0.15 ns) and non-emitting quenched (0.21 ns) sensors in response to protein binding. The measurements of lifetimes in FRET mode in quenched pair-carrying ODN duplex sensors showed significant differences in FL of the acceptor cyanine fluorophore between NF-kappaB-containing and NF-kappaB-free samples but not in control sensors with ODN sequences that have decreased binding affinity to NF-kappaB. We anticipate that the observed effects will be instrumental for developing sensors enabling non-invasive imaging in cells that undergo activation of NF-kappaB
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