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Title: Structural And Optical Properties Of Nanocrystalline Tio2 With Multiwalled Carbon Nanotubes And Its Photovoltaic Studies Using Ru(ii) Sensitizers.
Creator: Delekar, Sagar D., Dhodamani, Ananta G., More, Krantiveer V., Dongale, Tukaram D., Kamat, Rajanish K., Acquah, Steve F. A., Dalal, Naresh S., Panda, Dillip K.
Abstract/Description: In this study, the in situ sol-gel method has been deployed to prepare the titanium dioxide/multiwalled carbon nanotubes (TiO2/MWCNTs) nanocomposite (NCs) powders with varying content of MWCNTs (0.01-1.0 wt %), to construct the dye-sensitized solar cells (DSSCs). First, binder-free NCs were deposited on a transparent-conducting F:SnO2 (FTO) glass substrate by a doctor-blade technique and then anchored with Ru(II)-based dyes to either N719 or ruthenium phthalocyanine (RuPc). The structural and...
Show moreIn this study, the in situ sol-gel method has been deployed to prepare the titanium dioxide/multiwalled carbon nanotubes (TiO2/MWCNTs) nanocomposite (NCs) powders with varying content of MWCNTs (0.01-1.0 wt %), to construct the dye-sensitized solar cells (DSSCs). First, binder-free NCs were deposited on a transparent-conducting F:SnO2 (FTO) glass substrate by a doctor-blade technique and then anchored with Ru(II)-based dyes to either N719 or ruthenium phthalocyanine (RuPc). The structural and optical properties and interconnectivity of the materials within the composite are investigated thoroughly by various spectral techniques (XRD, XPS, Raman, FT-IR, and UV-vis), electron microscopy (HRTEM), and BET analysis. The experimental results suggest that the ratio of MWCNTs and TiO2 in NCs, morphology, and their interconnectivity influenced their structural, optical, and photovoltaic properties significantly. Finally, the photovoltaic performances of the assembled DSSCs with different content of MWCNTs to TiO2 films anchored with two different dyes were tested under one sun irradiation (100 mW/cm(2)). The measured current-voltage (IV) curve and incident photon-to-current conversion efficiency (IPCE) spectra of TiO2/0.1 wt % MWCNTs (T@0.1 C) for N719 dye show three times more power conversion efficiency (eta = 6.21%) which is opposed to an efficiency (eta = 2.07%) of T@0.1 C for RuPc dye under the same operating conditions.
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Date Issued: 2018-03
Identifier: FSU_libsubv1_wos_000427939400031, 10.1021/acsomega.7b01316
Format: Citation

Title: Cell Adhesion and Proliferation on the “Living” Surface of a Polyelectrolyte Multilayer.
Creator: Arias, Carlos B., Surmaitis, Richard L., Schlenoff, Joseph B.
Abstract/Description: The adhesion of living eukaryotic cells to a substrate, one of the most complex problems in surface science, requires adsorption of extracellular proteins such as fibronectin. Thin films of polyelectrolyte complex made layer-by-layer (polyelectrolyte multilayers or PEMUs) offer a high degree of control of surface charge and composition - interconnected and essential variables for protein adhesion. Fibroblasts grown on multilayers of poly(styrene sulfonate), PSS, and poly...
Show moreThe adhesion of living eukaryotic cells to a substrate, one of the most complex problems in surface science, requires adsorption of extracellular proteins such as fibronectin. Thin films of polyelectrolyte complex made layer-by-layer (polyelectrolyte multilayers or PEMUs) offer a high degree of control of surface charge and composition - interconnected and essential variables for protein adhesion. Fibroblasts grown on multilayers of poly(styrene sulfonate), PSS, and poly(diallyldimethylammonium), PDADMA, with increasing thickness exhibit good adhesion until the 12th layer of polyelectrolyte has been added, whereupon there is a sudden transition to nonadhesive behavior. This sharp change is due to the migration of excess positive charge to the surface – a previously unrecognized property of PEMUs. Precise radiotracer assays of adsorbed 125I-albumin, show how protein adsorption is related to multilayer surface charge. With more negative surface charge density from the sulfonates of PSS, more albumin adsorbs to the surface. However, a loosely-held or “soft corona” exchanges with serum protein under the Vroman effect, which is correlated with poor cell adhesion. A comprehensive view of cell adhesion highlights the central role of robust protein adhesion, which is required before any secondary effects of matrix stiffness on cell fate can come into play.
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Date Issued: 2016-05-18
Identifier: FSU_libsubv1_scholarship_submission_1540238895_2ac07ed1, 10.1021/acs.langmuir.6b00784
Format: Citation

Title: Modular Access To Functionalized 5-8-5 Fused Ring Systems Via A Photoinduced Cycloisomerization Reaction.
Creator: Salvati, Anna E., Law, James A., Liriano, Josue, Frederich, James H.
Abstract/Description: A 5-8-5 carbocyclic ring system forms the core of over 30 distinct natural products. Several members of this family have gained attention for their diverse activity in cell culture. In these cases, biological function is mediated by the arrangement of substituents around a conserved 5-8-5 nucleus. Despite the potential applications of this privileged substructure in medicinal chemistry, modular strategies for its assembly are underdeveloped. Herein, we describe a cycloisomerization reaction...
Show moreA 5-8-5 carbocyclic ring system forms the core of over 30 distinct natural products. Several members of this family have gained attention for their diverse activity in cell culture. In these cases, biological function is mediated by the arrangement of substituents around a conserved 5-8-5 nucleus. Despite the potential applications of this privileged substructure in medicinal chemistry, modular strategies for its assembly are underdeveloped. Herein, we describe a cycloisomerization reaction that forms the 5-8-5 framework directly. This strategy uniquely allows access to gram quantities of this valuable scaffold in four steps.
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Date Issued: 2018-06-28
Identifier: FSU_libsubv1_wos_000436027800011, 10.1039/c8sc00999f
Format: Citation

Title: Static and Dynamic Solution Behavior of a Polyzwitterion Using a Hofmeister Salt Series.
Creator: Delgado, Jose D., Schlenoff, Joseph
Abstract/Description: Polymers made from zwitterionic repeat units (bearing no net charge) have intriguing solution properties, especially in contrast to polyelectrolytes, such as an apparent indifference to salt concentration. These polyzwitterions, PZs, have come under renewed scrutiny because of their use in high performance antifouling coatings. Here, an amidosulfobetaine polymer was used to shed light on the complex and poorly-understood response of PZ solution conformation to ionic strength. A Hofmeister...
Show morePolymers made from zwitterionic repeat units (bearing no net charge) have intriguing solution properties, especially in contrast to polyelectrolytes, such as an apparent indifference to salt concentration. These polyzwitterions, PZs, have come under renewed scrutiny because of their use in high performance antifouling coatings. Here, an amidosulfobetaine polymer was used to shed light on the complex and poorly-understood response of PZ solution conformation to ionic strength. A Hofmeister anion series NaX, where X = SO4 2, Cl-, Br-, NO3-, ClO4- and SCN provided a systematic way to tune PZ/ion interactions. A consistent picture of PZ conformation emerged, where the role and location of counterions (how they pair with the polymer chain) depends on their position in the Hofmeister series. At least four regimes of PZ conformation/interaction as a function of ionic strength were observed, the last showing no change in coil size (hydrodynamic radius) as a function of ionic strength for all salts in the concentration range 0.6 M – 4 M. Hydrophobic (less hydrated) anions ClO4- and SCN yielded a clear minimum in coil size at lower [NaX] whereas PZ in solutions of hydrophilic ions SO4- and Cl showed only a hint of the much-discussed “antipolyelectrolyte” expansion of PZ with increasing [NaX]. Static light scattering results, when analyzed using Stockmeyer’s theory of scattering from multicomponent systems, revealed that NaX is associated with PZ with a corresponding increase in apparent molecular weight. Light scattering measurements at low [NaX] show solution ions are excluded from PZ coils dressed with hydrophobic NaX. DLS in salt-free solutions at elevated temperatures revealed substantial chain stiffening of PZ, thought to be caused by nearest-neighbor interactions between zwitterion groups. DLS yielded a fast mode in these salt free solutions, ascribed to soliton-like transport of waves of associated zwitterionic groups along the PZ backbone.
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Date Issued: 2017-05-25
Identifier: FSU_libsubv1_scholarship_submission_1540240683_30337f56, 10.1021/acs.macromol.7b00525
Format: Citation

Title: Water and the Glass Transition Temperature in a Polyelectrolyte Complex.
Creator: Fu, Jingcheng, Abbett, Rachel L., Fares, Hadi M., Schlenoff, Joseph B.
Abstract/Description: Hydrated polyelectrolyte complexes, H-PECs, have recently started attracting renewed interest as a class of highly solvated/plasticized blends. H-PECs are observed to undergo a transition in mechanical properties close to room temperature. Whether this is a true glass transition has been questioned recently: the material has an unusually low modulus in the “glassy” state and molecular dynamics simulations have suggested temperature-induced dehydration and water structure changes are...
Show moreHydrated polyelectrolyte complexes, H-PECs, have recently started attracting renewed interest as a class of highly solvated/plasticized blends. H-PECs are observed to undergo a transition in mechanical properties close to room temperature. Whether this is a true glass transition has been questioned recently: the material has an unusually low modulus in the “glassy” state and molecular dynamics simulations have suggested temperature-induced dehydration and water structure changes are responsible for the transition. Using in situ infrared spectroscopic methods on thin films of a widely-studied H-PEC we find no definitive evidence for changes in the hydration state of functional groups, the water content, or water structure below or above Tg for stoichiometric and nonstoichiometric H-PECs. These complexes represent a promising platform for fundamental studies of the glass transition, since the coupling between chains can be modified by “doping” the material with salt, which breaks ion pairing crosslinks. The Fox equation was used to estimate Tg’s for paired and unpaired oppositely-charged repeat units.
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Date Issued: 2017-09-22
Identifier: FSU_libsubv1_scholarship_submission_1540241093_22e4df52, 10.1021/acsmacrolett.7b00668
Format: Citation

Title: Towards Ion-Free Polyelectrolyte Multilayers: Cyclic Salt Annealing.
Creator: Fares, Hadi M., Ghoussoub, Yara E., Surmaitis, Richard L., Schlenoff, Joseph B.
Abstract/Description: Polyelectrolyte multilayers (PEMUs) are made from various combinations of polyanions and polycations. It is now understood that these ultrathin films of polyelectrolyte complex may also incorporate counterions derived from the solution from which the PEMU was deposited, or exchanged into the film post-assembly. If these ions are required to compensate nonstoichiometric ratios of polycation and polyanion they cannot leave the film and they exert considerable influence on film properties, such...
Show morePolyelectrolyte multilayers (PEMUs) are made from various combinations of polyanions and polycations. It is now understood that these ultrathin films of polyelectrolyte complex may also incorporate counterions derived from the solution from which the PEMU was deposited, or exchanged into the film post-assembly. If these ions are required to compensate nonstoichiometric ratios of polycation and polyanion they cannot leave the film and they exert considerable influence on film properties, such as modulus and permeability. These “extrinsic” charges also complicate fundamental studies on PEMUs. We report a method to remove almost all ionic content from a PEMU made of poly(diallyldimethylammonium chloride), PDADMAC, and poly(styrene sulfonate), PSS. In this method, a high salt concentration plasticizes the multilayer past its glass transition, dispersing all the buried excess PDADMA throughout the film. Exposure to a solution of PSS in a lower salt concentration consumes excess PDADMA near the surface without overcompensating with PSS. The process is repeated in a cyclic fashion, removing >95% of the ions charge present in the as-made PEMU.
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Date Issued: 2015-02-22
Identifier: FSU_libsubv1_scholarship_submission_1540241506_9d2111db, 10.1021/la504910y
Format: Citation

Title: Ion-Pairing Strength in Polyelectrolyte Complexes.
Creator: Fu, Jingcheng, Fares, Hadi M., Schlenoff, Joseph
Abstract/Description: Polyelectrolyte complexes, PECs, are spontaneously formed blends of polyelectrolytes bearing positive, Pol+, and negative, Pol-, repeat units. Many interesting PEC morphologies have been observed, ranging from dense precipitates to liquid-like coacervates to quasi-stable nanoparticles, depending on the identity of the polymers and the preparation conditions. While the number of polyelectrolytes available to synthesize these materials is large and increasing, the corresponding number of Pol+...
Show morePolyelectrolyte complexes, PECs, are spontaneously formed blends of polyelectrolytes bearing positive, Pol+, and negative, Pol-, repeat units. Many interesting PEC morphologies have been observed, ranging from dense precipitates to liquid-like coacervates to quasi-stable nanoparticles, depending on the identity of the polymers and the preparation conditions. While the number of polyelectrolytes available to synthesize these materials is large and increasing, the corresponding number of Pol+/Pol- combinations is vast. This work quantitatively compares the binding strengths between a selection of positive and negative polyelectrolytes by evaluating the extent to which ion pairs between them are broken by a common salt, KBr. Comparison of association constants or Gibbs free energies between different classes of ionic functionality reveals that more “hydrophilic” PECs are more weakly associated, small primary amines bind strongly, carboxylates bind weakly, and aromatic sulfonates interact more strongly than aliphatic ones. The use of “charge density” to predict binding strength is shown not to be justified. Ion diffusion coefficients through PECs also approximately follow water content and are inversely related to interaction strength.
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Date Issued: 2017-01-26
Identifier: FSU_libsubv1_scholarship_submission_1540239998_385e9eae, 10.1021/acs.macromol.6b02445
Format: Citation

Title: Equilibrium Overcompensation in Polyelectrolyte Complexes.
Creator: Fares, Hadi M., Schlenoff, Joseph
Abstract/Description: Association between positive, Pol+, and negative, Pol-, units on polyelectrolytes drive spontaneous formation of a range of morphologies, some with “fuzzy” structure but most essentially amorphous. An excess of one type of charge over the other, known as overcompensation or overcharging, is essential for certain types of processing, such as the formation of polyelectrolyte “multilayers” on substrates or “polyplex” nanoparticles in solution. In this work, uniform, stoichiometric, smooth thin...
Show moreAssociation between positive, Pol+, and negative, Pol-, units on polyelectrolytes drive spontaneous formation of a range of morphologies, some with “fuzzy” structure but most essentially amorphous. An excess of one type of charge over the other, known as overcompensation or overcharging, is essential for certain types of processing, such as the formation of polyelectrolyte “multilayers” on substrates or “polyplex” nanoparticles in solution. In this work, uniform, stoichiometric, smooth thin films of polyelectrolyte complex, PEC, from poly(diallyldimethylammonium), PDADMA, and poly(styrene sulfonate), PSS, were prepared starting from rough, nonstoichiometric multilayers of these materials. A narrow concentration range of added salt was found which promoted steady-state bulk overcompensation of PEC films in the presence of a large excess of polycation or polyanion without loss of PEC to solution. The extent of overcompensation, about 35% for PDADMA in 1.0 M NaCl and about 40% for PSS in 1.4 M NaCl, was independent of solution polymer concentration and only weakly dependent on salt concentration. A weak dependence of overcompensation on molecular weight was also determined. Erosion/instability of films for [NaCl] > 1.4 M was observed, with more prominent or faster erosion for higher molecular weight PSS. The mechanism for overcompensation in this entropically driven system was attributed to the formation of a Donnan ion equilibrium between the PEC and solution phases.
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Date Issued: 2017-05-09
Identifier: FSU_libsubv1_scholarship_submission_1540238171_d94189a0, 10.1021/acs.macromol.7b00665
Format: Citation

Title: Ion Environments in Mn2+ -Doped Polyelectrolyte Complexes: Dilute Magnetic Saloplastics.
Creator: Abhyankar, Nandita, Ghoussoub, Yara E., Wang, Qifeng, Dalal, Naresh S., Schlenoff, Joseph B.
Abstract/Description: Amorphous hydrated complexes of the polyelectrolytes poly(styrene sulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA) were doped with the spin-5/2 ion Mn2+. Xband electron paramagnetic resonance (EPR) measurements of the Mn2+ spins within this stoichiometric polyelectrolyte complex (PEC) revealed an octahedral coordination environment, similar to that observed in aqueous solutions of Mn2+. This octahedral symmetry of the [Mn(H2O)6] 2+ complexes, observed in the fully hydrated PECs, is...
Show moreAmorphous hydrated complexes of the polyelectrolytes poly(styrene sulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA) were doped with the spin-5/2 ion Mn2+. Xband electron paramagnetic resonance (EPR) measurements of the Mn2+ spins within this stoichiometric polyelectrolyte complex (PEC) revealed an octahedral coordination environment, similar to that observed in aqueous solutions of Mn2+. This octahedral symmetry of the [Mn(H2O)6] 2+ complexes, observed in the fully hydrated PECs, is somewhat distorted due to the wide range of ion pairs possible with sulfonate groups on PSS. As the Mn2+ concentration was increased, the linewidths were broadened, indicating the dominance of dipolar broadening over exchange narrowing in determining the linewidths, i.e. any exchange narrowing was masked by the large dipolar broadening. The calculated linewidths were used to estimate the strength of the dipolar interactions, and hence the distances between the Mn2+ spins, based on a simple model of regularly spaced spins. The distances calculated by this method were roughly comparable to the geometric average distances calculated on the basis of the Mn2+ concentrations and densities of the doped PEC samples. From a comparison of their EPR spectra, ion environments in the doped, fully hydrated PECs were found to be similar to those in hydrated classical ion exchange resins. EPR spectra before and after drying of the PECs indicate the replacement of octahedrally coordinated water by oxide anions from the polyanion chain, and the corresponding loss of the symmetric environment of Mn2+ ions.
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Date Issued: 2017-07-01
Identifier: FSU_libsubv1_scholarship_submission_1540239466_01912b85, 10.1021/acs.jpcb.6b02697
Format: Citation

Title: Ferromagnetic Quantum Critical Point In Cepd2p2 With Pd -> Ni Substitution.
Creator: Lai, Y., Bone, S. E., Minasian, S., Ferrier, M. G., Lezama-Pacheco, J., Mocko, V., Ditter, A. S., Kozimor, S. A., Seidler, G. T., Nelson, W. L., Chiu, Y.-C., Huang, K., Potter,...
Show moreLai, Y., Bone, S. E., Minasian, S., Ferrier, M. G., Lezama-Pacheco, J., Mocko, V., Ditter, A. S., Kozimor, S. A., Seidler, G. T., Nelson, W. L., Chiu, Y.-C., Huang, K., Potter, W., Graf, D., Albrecht-Schmitt, T. E., Baumbach, R. E.
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Abstract/Description: An investigation of the structural, thermodynamic, and electronic transport properties of the isoelectronic chemical substitution series Ce(Pd1-x Ni-x)(2)P-2 is reported, where a possible ferromagnetic quantum critical point is uncovered in the temperature-concentration (T-x) phase diagram. This behavior results from the simultaneous contraction of the unit cell volume, which tunes the relative strengths of the Kondo and Ruderman-KittelKasuya- Yosida (RKKY) interactions, and the introduction...
Show moreAn investigation of the structural, thermodynamic, and electronic transport properties of the isoelectronic chemical substitution series Ce(Pd1-x Ni-x)(2)P-2 is reported, where a possible ferromagnetic quantum critical point is uncovered in the temperature-concentration (T-x) phase diagram. This behavior results from the simultaneous contraction of the unit cell volume, which tunes the relative strengths of the Kondo and Ruderman-KittelKasuya- Yosida (RKKY) interactions, and the introduction of disorder through alloying. Near the critical region at x(cr) approximate to 0.7, the rate of contraction of the unit cell volume strengthens, indicating that the cerium f valence crosses over from trivalent to a noninteger value. Consistent with this picture, x-ray absorption spectroscopy measurements reveal that while CePd2P2 has a purely trivalent cerium f state, CeNi2P2 has a small (<10 %) tetravalent contribution. In a broad region around xcr, there is a breakdown of Fermi-liquid temperature dependences, signaling the influence of quantum critical fluctuations and disorder effects. Measurements of clean CePd2P2 furthermore showthat applied pressure has an initial effect similar to alloying on the ferromagnetic order. From these results, CePd2P2 emerges as a keystone system to test theories such as the Belitz-Kirkpatrick-Vojta model for ferromagnetic quantum criticality, where distinct behaviors are expected in the dirty and clean limits.
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Date Issued: 2018-06-06
Identifier: FSU_libsubv1_wos_000434256700002, 10.1103/PhysRevB.97.224406
Format: Citation

Title: A Rare Positively Charged Nicotinic Acid Disulfide: 2,2 '-dithiodinicotinic Acid Hydrochloride Monohydrate.
Creator: Chemey, Alexander T., McGuire, Chad M., Albrecht-Schmitt, Thomas E.
Abstract/Description: The title compound {systematic name: 3-carboxy-2-[2-(3-carboxypyridin-2-yl)disulfan-1-yl)]pyridin-1-ium chloride monohydrate}, C12H9N2O4S2+center dot Cl-center dot H2O, O, crystallizes in the triclinic space group P (1) over bar. A pair of 2-mercaptonicotinic acid moieties is connected by a 2,2'-disulfide bond with a dihedral angle of 78.79 (3)degrees. One of the N atom is protonated, as are both carboxylate groups, resulting in an overall +1 charge on the dimer. The structure comprises a...
Show moreThe title compound {systematic name: 3-carboxy-2-[2-(3-carboxypyridin-2-yl)disulfan-1-yl)]pyridin-1-ium chloride monohydrate}, C12H9N2O4S2+center dot Cl-center dot H2O, O, crystallizes in the triclinic space group P (1) over bar. A pair of 2-mercaptonicotinic acid moieties is connected by a 2,2'-disulfide bond with a dihedral angle of 78.79 (3)degrees. One of the N atom is protonated, as are both carboxylate groups, resulting in an overall +1 charge on the dimer. The structure comprises a zigzagging layer of the dimerized dithiodinicotinic acid rings, with charge-balancing chloride ions and water molecules between the layers. Hydrogen bonding between the chloride and water sites with the dimer appears to hold the structure together. Nearest neighbor nicotinic acid rings are offset when viewed down the a axis, suggesting no added stability from ring stacking. The asymmetric unit corresponds to the empirical formula of the compound, and it packs with two formula units per unit cell.
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Date Issued: 2018-06-01
Identifier: FSU_libsubv1_wos_000433880900013, 10.1107/S2056989018006916
Format: Citation

Title: Tropical Peatland Carbon Storage Linked To Global Latitudinal Trends In Peat Recalcitrance.
Creator: Hodgkins, Suzanne B., Richardson, Curtis J., Dommain, Rene, Wang, Hongjun, Glaser, Paul H., Verbeke, Brittany, Winkler, B. Rose, Cobb, Alexander R., Rich, Virginia I.,...
Show moreHodgkins, Suzanne B., Richardson, Curtis J., Dommain, Rene, Wang, Hongjun, Glaser, Paul H., Verbeke, Brittany, Winkler, B. Rose, Cobb, Alexander R., Rich, Virginia I., Missilmani, Malak, Flanagan, Neal, Ho, Mengchi, Hoyt, Alison M., Harvey, Charles F., Vining, S. Rose, Hough, Moira A., Moore, Tim R., Richard, Pierre J. H., De la Cruz, Florentino B., Toufaily, Joumana, Hamdan, Rasha, Cooper, William T., Chanton, Jeffrey P.
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Abstract/Description: Peatlands represent large terrestrial carbon banks. Given that most peat accumulates in boreal regions, where low temperatures and water saturation preserve organic matter, the existence of peat in (sub)tropical regions remains enigmatic. Here we examined peat and plant chemistry across a latitudinal transect from the Arctic to the tropics. Near-surface low-latitude peat has lower carbohydrate and greater aromatic content than near-surface high-latitude peat, creating a reduced oxidation...
Show morePeatlands represent large terrestrial carbon banks. Given that most peat accumulates in boreal regions, where low temperatures and water saturation preserve organic matter, the existence of peat in (sub)tropical regions remains enigmatic. Here we examined peat and plant chemistry across a latitudinal transect from the Arctic to the tropics. Near-surface low-latitude peat has lower carbohydrate and greater aromatic content than near-surface high-latitude peat, creating a reduced oxidation state and resulting recalcitrance. This recalcitrance allows peat to persist in the (sub)tropics despite warm temperatures. Because we observed similar declines in carbohydrate content with depth in high-latitude peat, our data explain recent field-scale deep peat warming experiments in which catotelm (deeper) peat remained stable despite temperature increases up to 9 degrees C. We suggest that high-latitude deep peat reservoirs may be stabilized in the face of climate change by their ultimately lower carbohydrate and higher aromatic composition, similar to tropical peats.
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Date Issued: 2018-09-07
Identifier: FSU_libsubv1_wos_000444014100015, 10.1038/s41467-018-06050-2
Format: Citation

Title: Pathogenic Tfg Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking And Axon Fasciculation.
Creator: Slosarek, Erin L., Schuh, Amber L., Pustova, Iryna, Johnson, Adam, Bird, Jennifer, Johnson, Matthew, Frankel, E. B., Bhattacharya, Nilakshee, Hanna, Michael G., Burke, Jordan E....
Show moreSlosarek, Erin L., Schuh, Amber L., Pustova, Iryna, Johnson, Adam, Bird, Jennifer, Johnson, Matthew, Frankel, E. B., Bhattacharya, Nilakshee, Hanna, Michael G., Burke, Jordan E., Ruhl, David A., Quinney, Kyle, Block, Samuel, Peotter, Jennifer L., Chapman, Edwin R., Sheets, Michael D., Butcher, Samuel E., Stagg, Scott M., Audhya, Anjon
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Abstract/Description: Length-dependent axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which...
Show moreLength-dependent axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP. We find that the TFG (p.R106C) mutation alters compaction of TFG ring complexes, which play a critical role in the export of cargoes from the endoplasmic reticulum (ER). Using CRISPR-mediated genome editing, we engineered human stem cells that express the mutant form of TFG at endogenous levels and identified specific defects in secretion from the ER and axon fasciculation following neuronal differentiation. Together, our data highlight a key role for TFG-mediated protein transport in the pathogenesis of HSP.
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Date Issued: 2018-08-28
Identifier: FSU_libsubv1_wos_000442923900005, 10.1016/j.celrep.2018.07.081
Format: Citation

Title: (tco4-)-tc-99 Remediation By A Cationic Polymeric Network.
Creator: Li, Jie, Dai, Xing, Zhu, Lin, Xu, Chao, Zhang, Duo, Silver, Mark A., Li, Peng, Chen, Lanhua, Li, Yongzhong, Zuo, Douwen, Zhang, Hui, Xiao, Chengliang, Chen, Jing, Diwu, Juan,...
Show moreLi, Jie, Dai, Xing, Zhu, Lin, Xu, Chao, Zhang, Duo, Silver, Mark A., Li, Peng, Chen, Lanhua, Li, Yongzhong, Zuo, Douwen, Zhang, Hui, Xiao, Chengliang, Chen, Jing, Diwu, Juan, Farha, Omar K., Albrecht-Schmitt, Thomas E., Chai, Zhifang, Wang, Shuao
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Abstract/Description: Direct removal of (TcO4-)-Tc-99 from the highly acidic solution of used nuclear fuel is highly beneficial for the recovery of uranium and plutonium and more importantly aids in the elimination of Tc-99 discharge into the environment. However, this task represents a huge challenge given the combined extreme conditions of super acidity, high ionic strength, and strong radiation field. Here we overcome this challenge using a cationic polymeric network with significant TcO4- uptake capabilities...
Show moreDirect removal of (TcO4-)-Tc-99 from the highly acidic solution of used nuclear fuel is highly beneficial for the recovery of uranium and plutonium and more importantly aids in the elimination of Tc-99 discharge into the environment. However, this task represents a huge challenge given the combined extreme conditions of super acidity, high ionic strength, and strong radiation field. Here we overcome this challenge using a cationic polymeric network with significant TcO4- uptake capabilities in four aspects: the fastest sorption kinetics, the highest sorption capacity, the most promising uptake performance from highly acidic solutions, and excellent radiation-resistance and hydrolytic stability among all anion sorbent materials reported. In addition, this material is fully recyclable for multiple sorption/desorption trials, making it extremely attractive for waste partitioning and emergency remediation. The excellent TcO4- uptake capability is elucidated by X-ray absorption spectroscopy, solid-state NMR measurement, and density functional theory analysis on anion coordination and bonding.
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Date Issued: 2018-08-01
Identifier: FSU_libsubv1_wos_000440413500007, 10.1038/s41467-018-05380-5
Format: Citation

Title: Diffusion of Sites versus Polymers in Polyelectrolyte Complexes and Multilayers.
Creator: Fares, Hadi, Schlenoff, Joseph
Abstract/Description: It has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites—charged polyelectrolyte repeat units balanced by counterions—within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of...
Show moreIt has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites—charged polyelectrolyte repeat units balanced by counterions—within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of poly(diallyldimethylammonium), PDADMA, and poly(styrenesulfonate), PSS, are at least 2 orders of magnitude faster than the diffusion of polyelectrolytes themselves. This is because site diffusion requires only local rearrangements of polyelectrolyte repeat units, placing far fewer kinetic limitations on the assembly of polyelectrolyte complexes in all of their forms. Site diffusion strongly depends on the salt concentration (ionic strength) of the environment, and diffusion of PDADMA sites is faster than that of PSS sites, accounting for the asymmetric nature of multilayer growth. Site diffusion is responsible for multilayer growth in the linear and into the exponential regimes, which explains how PDADMA can mysteriously “pass through” layers of PSS. Using quantitative relationships between site diffusion coefficient and salt concentration, conditions were identified that allowed the diffusion length to always exceed the film thickness, leading to full exponential growth over 3 orders of magnitude thickness. Both site and polymer diffusion were independent of molecular weight, suggesting that ion pairing density is a limiting factor. Polyelectrolyte complexes are examples of a broader class of dynamic bulk polymeric materials that (self-) assemble via the transport of cross-links or defects rather than actual molecules.
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Date Issued: 2017-10-05
Identifier: FSU_libsubv1_scholarship_submission_1543269470_f050f9b2, 10.1021/jacs.7b07905
Format: Citation

Title: Driving Forces for Oppositely Charged Polyioon Association in Aqueous Solution: Enthalpic, Entropic but Not Electrostatic.
Creator: Fu, Jingcheng, Schlenoff, Joseph
Abstract/Description: Driving forces for association between oppositely charged biological or synthetic polymers in aqueous solution have long been identified as electrostatic in origin. This attraction is broken down into an entropic component, due to loss of counterions, and an enthalpic component, stemming from Coulombic attraction between opposite charges. While the balance between entropic and enthalpic contributions shifts according to the conditions, the presence of exotherms or endotherms on mixing, though...
Show moreDriving forces for association between oppositely charged biological or synthetic polymers in aqueous solution have long been identified as electrostatic in origin. This attraction is broken down into an entropic component, due to loss of counterions, and an enthalpic component, stemming from Coulombic attraction between opposite charges. While the balance between entropic and enthalpic contributions shifts according to the conditions, the presence of exotherms or endotherms on mixing, though small, are viewed as signatures of Coulombic interactions which support theories of polyelectrolyte association rooted in continuum electrostatics. Here, a head-to-head comparison is made between mechanisms based on electrostatics and those based on specific ion pairing, or ion exchange. Using a Hofmeister series of counterions for a common polycation, poly(diallyldimethylammonium), enthalpy changes on association with poly(styrenesulfonate) are shown to derive from changes in water perturbation, revealed by Raman scattering studies of water O–H vibrations. The free energy for complexation is almost completely entropic over all salt concentrations.
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Date Issued: 2016-01-15
Identifier: FSU_libsubv1_scholarship_submission_1543268476_8c636203, 10.1021/jacs.5b11878
Format: Citation

Title: Saloplastics: Processing Compact Polyelectrolyte Complexes.
Creator: Schlenoff, Joseph, Schaaf, Pierre
Abstract/Description: Polyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion (exPECs). The presence of salt water is essential in plasticizing PECs to allow them to be reformed and fused. When hydrated, CoPECs are versatile, rugged, biocompatible, elastic materials with applications including bioinspired materials, supports for enzymes...
Show morePolyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion (exPECs). The presence of salt water is essential in plasticizing PECs to allow them to be reformed and fused. When hydrated, CoPECs are versatile, rugged, biocompatible, elastic materials with applications including bioinspired materials, supports for enzymes and (nano)composites. In this review, various methods for making CoPECs are described, as well as fundamental responses of CoPEC mechanical properties to salt concentration. Possible applications as synthetic cartilage, enzymatically active biocomposites, self‐healing materials, and magnetic nanocomposites are presented.
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Date Issued: 2015-03-13
Identifier: FSU_libsubv1_scholarship_submission_1543268228_25a15aaa, 10.1002/adma.201500176
Format: Citation

Title: Janus Nanofilms.
Creator: Ghoussoub, Yara, Schlenoff, Joseph
Abstract/Description: To make a two-dimensional Janus object, the perfluorinated anionic polyelectrolyte Nafion was adsorbed to the surface of ultrathin films of polyelectrolyte complex. Nafion changed the wetting characteristics of the polyelectrolyte multilayer (PEMU) of poly(diallyldimethylammonium) and poly(styrenesulfonate) from hydrophilic to hydrophobic. PEMUs assembled on aluminum substrates and terminated with Nafion could be released by exposure to alkali solution, producing free-floating films in the...
Show moreTo make a two-dimensional Janus object, the perfluorinated anionic polyelectrolyte Nafion was adsorbed to the surface of ultrathin films of polyelectrolyte complex. Nafion changed the wetting characteristics of the polyelectrolyte multilayer (PEMU) of poly(diallyldimethylammonium) and poly(styrenesulfonate) from hydrophilic to hydrophobic. PEMUs assembled on aluminum substrates and terminated with Nafion could be released by exposure to alkali solution, producing free-floating films in the 100 nm thickness regime. Water contact angle measurements showed a strong difference in hydrophilicity between the two sides of this Janus film, which was further characterized using atomic force microscopy and X-ray photoelectron spectroscopy (XPS). XPS revealed different fluorine contents on both sides of the PEMU, which could be translated to a Nafion gradient through the film. Fourier transform infrared spectroscopy showed the Nafion-containing films were much more resistant to decomposition by high salt concentration.
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Date Issued: 2016-04-07
Identifier: FSU_libsubv1_scholarship_submission_1543269187_3ddc9070, 10.1021/acs.langmuir.6b00672
Format: Citation

Title: Cell Resistant Zwitterionic Polyelectrolyte Coating Promotes Bacterial Attachment: and Adhesion Contradiction.
Creator: Martinez, Jessica, Kelly, Kris, Ghoussoub, Yara, Delgado, David, Keller, Thomas, Schlenoff, Joseph
Abstract/Description: AbstractPolymers of various architectures with zwitterionic functionality have recently been shown to effectively suppress nonspecific fouling of surfaces by proteins and prokaryotic (bacteria) or eukaryotic (mammalian) cells as well as other microorganisms and environmental contaminants. In this work, zwitterionic copolymers were used to make thin coatings on substrates with the layer-by-layer method. Polyelectrolyte multilayers, PEMUs, were built with [poly(allylamine hydrochloride)], PAH,...
Show moreAbstractPolymers of various architectures with zwitterionic functionality have recently been shown to effectively suppress nonspecific fouling of surfaces by proteins and prokaryotic (bacteria) or eukaryotic (mammalian) cells as well as other microorganisms and environmental contaminants. In this work, zwitterionic copolymers were used to make thin coatings on substrates with the layer-by-layer method. Polyelectrolyte multilayers, PEMUs, were built with [poly(allylamine hydrochloride)], PAH, and copolymers of acrylic acid and either the AEDAPS zwitterionic group 3-[2-(acrylamido)-ethyldimethyl ammonio] propane sulfonate (PAA-co-AEDAPS), or benzophenone (PAABp). Benzophenone allowed the PEMU to be toughened by photocrosslinking post-deposition. The attachment of two mammalian cell lines, rat aortic smooth muscle (A7r5) and mouse fibroblasts (3T3), and the biofilm-forming Gram-negative bacteria Escherichia coli was studied on PEMUs terminated with PAA-co-AEDAPS. Consistent with earlier studies, it is shown that PAH/PAA-co-AEDAPS PEMUs resist the adhesion of mammalian cells, but, contrary to our initial hypothesis, are bacterial adhesive and significantly so after maximizing the surface presentation of PAA-co-AEDAPS. This unexpected contrast in the adhesive behavior of prokaryotic and eukaryotic cells is explained by differences in adhesion mechanisms as well as different responses to the topology and morphology of the multilayer surface.
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Date Issued: 2016-02-12
Identifier: FSU_libsubv1_scholarship_submission_1543268983_2542ae09, 10.1039/C5BM00585J
Format: Citation

Title: The Polyelectrolyte Complex/Coacervate Continuum.
Creator: Schlenoff, Joseph, Wang, Qifeng
Abstract/Description: Stoichiometric polyelectrolyte complexes (PECs) of the strong polyelectrolytes poly(styrenesulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA) were dissociated and dissolved in aqueous KBr. Water was added to dilute the salt, allowing polyelectrolytes to reassociate. After appropriate equilibration, these mixtures yielded compositions spanning complexes (solid) to coacervates (elastic liquid) to dissolved solutions with increasing [KBr]. These compositions were defined by a ternary...
Show moreStoichiometric polyelectrolyte complexes (PECs) of the strong polyelectrolytes poly(styrenesulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA) were dissociated and dissolved in aqueous KBr. Water was added to dilute the salt, allowing polyelectrolytes to reassociate. After appropriate equilibration, these mixtures yielded compositions spanning complexes (solid) to coacervates (elastic liquid) to dissolved solutions with increasing [KBr]. These compositions were defined by a ternary polymer/water/salt phase diagram. For coacervates, transient microphase separation could be induced by a small departure from equilibration temperature. A boundary between complex and coacervate states was defined by the crossover point between loss and storage modulus. Salt ions within the complex/coacervate were identified as either ion paired with polyelectrolytes (“doping”) or unassociated. The fraction of ion pair cross-links between polyelectrolytes as a function of KBr concentration was used to account for viscosity using a model of “sticky” reptation.
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Date Issued: 2014-04-28
Identifier: FSU_libsubv1_scholarship_submission_1543267595_f3eff53c, 10.1021/ma500500q
Format: Citation

Title: Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues.
Creator: Khamis, Zahraa I, Iczkowski, Kenneth A, Man, Yan-Gao, Bou-Dargham, Mayassa J, Sang, Qing-Xiang Amy
Abstract/Description: Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate...
Show moreMatrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_26722363, 10.7150/jca.13067, PMC4679384, 26722363, 26722363, jcav07p0080
Format: Citation

Title: Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR-Cas system.
Creator: Elmore, Joshua R, Sheppard, Nolan F, Ramia, Nancy, Deighan, Trace, Li, Hong, Terns, Rebecca M, Terns, Michael P
Abstract/Description: CRISPR-Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that...
Show moreCRISPR-Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM.
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Date Issued: 2016-02-15
Identifier: FSU_pmch_26848045, 10.1101/gad.272153.115, PMC4762429, 26848045, 26848045, gad.272153.115
Format: Citation

Title: The sensitivity of fast muscle contractile function to the major components of the sarcomere Ca(2+)-cycling system.
Creator: Golding, C, Kelly, K, Kinsey, S T, Locke, B R
Abstract/Description: A reaction-diffusion model of a muscle sarcomere was developed to evaluate the sensitivity of force characteristics to diffusion and Ca(2+)-cycling components. The model compared well to experimental force measurements. Diffusion led to Ca(2+) gradients that enhanced maximal force and accelerated relaxation compared to when diffusion was infinitely fast. However, a modest increase in sarcomere length or radius led to a decrease in maximal force. Lowering the Ca(2+) release rate caused a lower...
Show moreA reaction-diffusion model of a muscle sarcomere was developed to evaluate the sensitivity of force characteristics to diffusion and Ca(2+)-cycling components. The model compared well to experimental force measurements. Diffusion led to Ca(2+) gradients that enhanced maximal force and accelerated relaxation compared to when diffusion was infinitely fast. However, a modest increase in sarcomere length or radius led to a decrease in maximal force. Lowering the Ca(2+) release rate caused a lower maximal force, but increasing the rate led to only modest gains in maximal force while incurring much greater ATP costs associated with reuptake. Greater parvalbumin binding rates decreased maximal force but enhanced relaxation, and this effect was magnified when Ca(2+) uptake rates were lowered as may occur during fatigue. These results show a physiological set of parameters that lead to a functional sarcomere of known dimensions and contractile function, and the effects of parameter variation on muscle function.
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Date Issued: 2016-04-01
Identifier: FSU_pmch_26774860, 10.1016/j.bpc.2016.01.001, PMC5003095, 26774860, 26774860, S0301-4622(15)30090-9
Format: Citation

Title: Predictive Sampling of Rare Conformational Events in Aqueous Solution: Designing a Generalized Orthogonal Space Tempering Method..
Creator: Lu, Chao, Li, Xubin, Wu, Dongsheng, Zheng, Lianqing, Yang, Wei
Abstract/Description: In aqueous solution, solute conformational transitions are governed by intimate interplays of the fluctuations of solute-solute, solute-water, and water-water interactions. To promote molecular fluctuations to enhance sampling of essential conformational changes, a common strategy is to construct an expanded Hamiltonian through a series of Hamiltonian perturbations and thereby broaden the distribution of certain interactions of focus. Due to a lack of active sampling of configuration response...
Show moreIn aqueous solution, solute conformational transitions are governed by intimate interplays of the fluctuations of solute-solute, solute-water, and water-water interactions. To promote molecular fluctuations to enhance sampling of essential conformational changes, a common strategy is to construct an expanded Hamiltonian through a series of Hamiltonian perturbations and thereby broaden the distribution of certain interactions of focus. Due to a lack of active sampling of configuration response to Hamiltonian transitions, it is challenging for common expanded Hamiltonian methods to robustly explore solvent mediated rare conformational events. The orthogonal space sampling (OSS) scheme, as exemplified by the orthogonal space random walk and orthogonal space tempering methods, provides a general framework for synchronous acceleration of slow configuration responses. To more effectively sample conformational transitions in aqueous solution, in this work, we devised a generalized orthogonal space tempering (gOST) algorithm. Specifically, in the Hamiltonian perturbation part, a solvent-accessible-surface-area-dependent term is introduced to implicitly perturb near-solute water-water fluctuations; more importantly in the orthogonal space response part, the generalized force order parameter is generalized as a two-dimension order parameter set, in which essential solute-solvent and solute-solute components are separately treated. The gOST algorithm is evaluated through a molecular dynamics simulation study on the explicitly solvated deca-alanine (Ala10) peptide. On the basis of a fully automated sampling protocol, the gOST simulation enabled repetitive folding and unfolding of the solvated peptide within a single continuous trajectory and allowed for detailed constructions of Ala10 folding/unfolding free energy surfaces. The gOST result reveals that solvent cooperative fluctuations play a pivotal role in Ala10 folding/unfolding transitions. In addition, our assessment analysis suggests that because essential conformational events are mainly driven by the compensating fluctuations of essential solute-solvent and solute-solute interactions, commonly employed "predictive" sampling methods are unlikely to be effective on this seemingly "simple" system. The gOST development presented in this paper illustrates how to employ the OSS scheme for physics-based sampling method designs.
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Date Issued: 2016-01-12
Identifier: FSU_pmch_26636477, 10.1021/acs.jctc.5b00953, PMC4968881, 26636477, 26636477
Format: Citation

Title: Free energy landscape of a minimalist salt bridge model.
Creator: Li, Xubin, Lv, Chao, Corbett, Karen M, Zheng, Lianqing, Wu, Dongsheng, Yang, Wei
Abstract/Description: Salt bridges are essential to protein stability and dynamics. Despite the importance, there has been scarce of detailed discussion on how salt bridge partners interact with each other in distinct solvent exposed environments. In this study, employing a recent generalized orthogonal space tempering (gOST) method, we enabled efficient molecular dynamics simulation of repetitive breaking and reforming of salt bridge structures within a minimalist salt-bridge model, the Asp-Arg dipeptide and...
Show moreSalt bridges are essential to protein stability and dynamics. Despite the importance, there has been scarce of detailed discussion on how salt bridge partners interact with each other in distinct solvent exposed environments. In this study, employing a recent generalized orthogonal space tempering (gOST) method, we enabled efficient molecular dynamics simulation of repetitive breaking and reforming of salt bridge structures within a minimalist salt-bridge model, the Asp-Arg dipeptide and thereby were able to map its detailed free energy landscape in aqueous solution. Free energy surface analysis shows that although individually-solvated states are more favorable, salt-bridge states still occupy a noticeable portion of the overall population. Notably, the competing forces, e.g. intercharge attractions that drive the formation of salt bridges and solvation forces that pull the charged groups away from each other, are energetically comparable. As the result, the salt bridge stability is highly tunable by local environments; for instance when local water molecules are perturbed to interact more strongly with each other, the population of the salt-bridge states is likely to increase. Our results reveal the critical role of local solvent structures in modulating salt-bridge partner interactions and imply the importance of water fluctuations on conformational dynamics that involves solvent accessible salt bridge formations.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_26300526, 10.1002/pro.2789, PMC4815310, 26300526, 26300526
Format: Citation

Title: Interfacing Microfluidics with Negative Stain Transmission Electron Microscopy.
Creator: Mukhitov, Nikita, Spear, John M, Stagg, Scott M, Roper, Michael G
Abstract/Description: A microfluidic platform is presented for preparing negatively stained grids for use in transmission electron microscopy (EM). The microfluidic device is composed of glass etched with readily fabricated features that facilitate the extraction of the grid poststaining and maintains the integrity of the sample. Utilization of this device simultaneously reduced environmental contamination on the grids and improved the homogeneity of the heavy metal stain needed to enhance visualization of...
Show moreA microfluidic platform is presented for preparing negatively stained grids for use in transmission electron microscopy (EM). The microfluidic device is composed of glass etched with readily fabricated features that facilitate the extraction of the grid poststaining and maintains the integrity of the sample. Utilization of this device simultaneously reduced environmental contamination on the grids and improved the homogeneity of the heavy metal stain needed to enhance visualization of biological specimens as compared to conventionally prepared EM grids. This easy-to-use EM grid preparation device provides the basis for future developments of systems with more integrated features, which will allow for high-throughput and dynamic structural biology studies.
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Date Issued: 2016-01-05
Identifier: FSU_pmch_26642355, 10.1021/acs.analchem.5b03884, PMC4730115, 26642355, 26642355
Format: Citation

Title: Single- and Multicompartment Hollow Polyelectrolyte Capsules by One-Step Spraying.
Creator: Wang, Qifeng, Schlenoff, Joseph
Abstract/Description: Polyelectrolyte complex microcapsules are prepared using a novel template‐ and surfactant‐free method. The microcapsules are produced spontaneously by ultrasonically spraying a solution of complex into a hot water reservoir, which enhances diffusion and relaxation of the polymer. The size and wall thickness of the microcapsules are precisely controlled. Encapsulation of polymers and nanoparticles by mixing them with polyelectrolyte solutions is demonstrated.
Date Issued: 2015-02-01
Identifier: FSU_libsubv1_scholarship_submission_1543267862_2543ec0f, 10.1002/adma.201405376
Format: Citation

Title: Noncompetitive affinity assays of glucagon and amylin using mirror-image aptamers as affinity probes.
Creator: Yi, Lian, Wang, Xue, Bethge, Lucas, Klussmann, Sven, Roper, Michael G
Abstract/Description: The ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of biostability of natural aptamers in a biological matrix. Using Spiegelmers as affinity probes, noncompetitive capillary electrophoresis affinity assays of glucagon and murine amylin were developed and optimized. The detection limit for glucagon was 6 pM and...
Show moreThe ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of biostability of natural aptamers in a biological matrix. Using Spiegelmers as affinity probes, noncompetitive capillary electrophoresis affinity assays of glucagon and murine amylin were developed and optimized. The detection limit for glucagon was 6 pM and for amylin was 40 pM. Glucagon-like peptide-1 and -2 did not interfere with the glucagon assay, while the amylin assay showed cross-reactivity to calcitonin gene related peptide. The developed assays were combined with a competitive immunoassay for insulin to measure glucagon, amylin, and insulin secretion from batches of islets after incubation with different glucose concentrations. The development of these assays is an important step towards incorporation into an online measurement system for monitoring dynamic secretion from single islets.
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Date Issued: 2016-03-21
Identifier: FSU_pmch_26881276, 10.1039/c5an02468d, PMC4783278, 26881276, 26881276
Format: Citation

Title: Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer.
Creator: Hoyne, Gerard, Rudnicka, Caroline, Sang, Qing-Xiang, Roycik, Mark, Howarth, Sarah, Leedman, Peter, Schlaich, Markus, Candy, Patrick, Matthews, Vance
Abstract/Description: Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and...
Show moreProstate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer. ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19. Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration. Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer.
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Date Issued: 2016-02-24
Identifier: FSU_pmch_26912236, 10.1186/s12885-016-2178-4, PMC4766641, 26912236, 26912236, 10.1186/s12885-016-2178-4
Format: Citation

Title: Wnt-YAP interactions in the neural fate of human pluripotent stem cells and the implications for neural organoid formation.
Creator: Bejoy, Julie, Song, Liqing, Li, Yan
Abstract/Description: Human pluripotent stem cells (hPSCs) have shown the ability to self-organize into different types of neural organoids (e.g., whole brain organoids, cortical spheroids, midbrain organoids etc.) recently. The extrinsic and intrinsic signaling elicited by Wnt pathway, Hippo/Yes-associated protein (YAP) pathway, and extracellular microenvironment plays a critical role in brain tissue morphogenesis. This article highlights recent advances in neural tissue patterning from hPSCs, in particular the...
Show moreHuman pluripotent stem cells (hPSCs) have shown the ability to self-organize into different types of neural organoids (e.g., whole brain organoids, cortical spheroids, midbrain organoids etc.) recently. The extrinsic and intrinsic signaling elicited by Wnt pathway, Hippo/Yes-associated protein (YAP) pathway, and extracellular microenvironment plays a critical role in brain tissue morphogenesis. This article highlights recent advances in neural tissue patterning from hPSCs, in particular the role of Wnt pathway and YAP activity in this process. Understanding the Wnt-YAP interactions should provide us the guidance to predict and modulate brain-like tissue structure through the regulation of extracellular microenvironment of hPSCs.
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Date Issued: 2016-01-02
Identifier: FSU_pmch_26901039, 10.1080/15476278.2016.1140290, PMC4882124, 26901039, 26901039
Format: Citation

Title: DNA Interactions Probed by Hydrogen-Deuterium Exchange (HDX) Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Confirm External Binding Sites on the Minichromosomal Maintenance (MCM) Helicase.
Creator: Graham, Brian W, Tao, Yeqing, Dodge, Katie L, Thaxton, Carly T, Olaso, Danae, Young, Nicolas L, Marshall, Alan G, Trakselis, Michael A
Abstract/Description: The archaeal minichromosomal maintenance (MCM) helicase from Sulfolobus solfataricus (SsoMCM) is a model for understanding structural and mechanistic aspects of DNA unwinding. Although interactions of the encircled DNA strand within the central channel provide an accepted mode for translocation, interactions with the excluded strand on the exterior surface have mostly been ignored with regard to DNA unwinding. We have previously proposed an extension of the traditional steric exclusion model...
Show moreThe archaeal minichromosomal maintenance (MCM) helicase from Sulfolobus solfataricus (SsoMCM) is a model for understanding structural and mechanistic aspects of DNA unwinding. Although interactions of the encircled DNA strand within the central channel provide an accepted mode for translocation, interactions with the excluded strand on the exterior surface have mostly been ignored with regard to DNA unwinding. We have previously proposed an extension of the traditional steric exclusion model of unwinding to also include significant contributions with the excluded strand during unwinding, termed steric exclusion and wrapping (SEW). The SEW model hypothesizes that the displaced single strand tracks along paths on the exterior surface of hexameric helicases to protect single-stranded DNA (ssDNA) and stabilize the complex in a forward unwinding mode. Using hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance MS, we have probed the binding sites for ssDNA, using multiple substrates targeting both the encircled and excluded strand interactions. In each experiment, we have obtained >98.7% sequence coverage of SsoMCM from >650 peptides (5-30 residues in length) and are able to identify interacting residues on both the interior and exterior of SsoMCM. Based on identified contacts, positively charged residues within the external waist region were mutated and shown to generally lower DNA unwinding without negatively affecting the ATP hydrolysis. The combined data globally identify binding sites for ssDNA during SsoMCM unwinding as well as validating the importance of the SEW model for hexameric helicase unwinding.
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Date Issued: 2016-06-10
Identifier: FSU_pmch_27044751, 10.1074/jbc.M116.719591, PMC4933441, 27044751, 27044751, M116.719591
Format: Citation

Title: Structural Influences: Cholesterol, Drug, and Proton Binding to Full-Length Influenza A M2 Protein..
Creator: Ekanayake, E Vindana, Fu, Riqiang, Cross, Timothy A
Abstract/Description: The structure and functions of the M2 protein from Influenza A are sensitive to pH, cholesterol, and the antiinfluenza drug Amantadine. This is a tetrameric membrane protein of 97 amino-acid residues that has multiple functions, among them as a proton-selective channel and facilitator of viral budding, replacing the need for the ESCRT proteins that other viruses utilize. Here, various amino-acid-specific-labeled samples of the full-length protein were prepared and mixed, so that only...
Show moreThe structure and functions of the M2 protein from Influenza A are sensitive to pH, cholesterol, and the antiinfluenza drug Amantadine. This is a tetrameric membrane protein of 97 amino-acid residues that has multiple functions, among them as a proton-selective channel and facilitator of viral budding, replacing the need for the ESCRT proteins that other viruses utilize. Here, various amino-acid-specific-labeled samples of the full-length protein were prepared and mixed, so that only interresidue (13)C-(13)C cross peaks between two differently labeled proteins representing interhelical interactions are observed. This channel is activated at slightly acidic pH values in the endosome when the His(37) residues in the middle of the transmembrane domain take on a +2 or +3 charged state. Changes observed here in interhelical distances in the N-terminus can be accounted for by modest structural changes, and no significant changes in structure were detected in the C-terminal portion of the channel upon activation of the channel. Amantadine, which blocks proton conductance by binding in the aqueous pore near the N-terminus, however, significantly modifies the tetrameric structure on the opposite side of the membrane. The interactions between the juxtamembrane amphipathic helix of one monomer and its neighboring monomer observed in the absence of drug are disrupted in its presence. However, the addition of cholesterol prevents this structural disruption. In fact, strong interactions are observed between cholesterol and residues in the amphipathic helix, accounting for cholesterol binding adjacent to a native palmitoylation site and near to an interhelix crevice that is typical of cholesterol binding sites. The resultant stabilization of the amphipathic helix deep in the bilayer interface facilitates the bilayer curvature that is essential for viral budding.
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Date Issued: 2016-03-29
Identifier: FSU_pmch_27028648, 10.1016/j.bpj.2015.11.3529, PMC4816700, 27028648, 27028648, S0006-3495(16)00152-1
Format: Citation

Title: A Non-Stem-Loop CRISPR RNA Is Processed by Dual Binding Cas6.
Creator: Shao, Yaming, Richter, Hagen, Sun, Shengfang, Sharma, Kundan, Urlaub, Henning, Randau, Lennart, Li, Hong
Abstract/Description: A subclass of recently discovered CRISPR repeat RNA in bacteria contains minimally recognizable structural features that facilitate an unknown mechanism of recognition and processing by the Cas6 family of endoribonucleases. Cocrystal structures of Cas6 from Methanococcus maripaludis (MmCas6b) bound with its repeat RNA revealed a dual site binding structure and a cleavage site conformation poised for phosphodiester bond breakage. Two non-interacting MmCas6b bind to two separate AAYAA motifs...
Show moreA subclass of recently discovered CRISPR repeat RNA in bacteria contains minimally recognizable structural features that facilitate an unknown mechanism of recognition and processing by the Cas6 family of endoribonucleases. Cocrystal structures of Cas6 from Methanococcus maripaludis (MmCas6b) bound with its repeat RNA revealed a dual site binding structure and a cleavage site conformation poised for phosphodiester bond breakage. Two non-interacting MmCas6b bind to two separate AAYAA motifs within the same repeat, one distal and one adjacent to the cleavage site. This bound structure potentially competes with a stable but non-productive RNA structure. At the cleavage site, MmCas6b supplies a base pair mimic to stabilize a short 2 base pair stem immediately upstream of the scissile phosphate. Complementary biochemical analyses support the dual-AAYAA binding model and a critical role of the protein-RNA base pair mimic. Our results reveal a previously unknown method of processing non-stem-loop CRISPR RNA by Cas6.
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Date Issued: 2016-04-05
Identifier: FSU_pmch_26996962, 10.1016/j.str.2016.02.009, PMC4823167, 26996962, 26996962, S0969-2126(16)00068-X
Format: Citation

Title: Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation.
Creator: Rea, Matthew, Jiang, Tingting, Eleazer, Rebekah, Eckstein, Meredith, Marshall, Alan G, Fondufe-Mittendorf, Yvonne N
Abstract/Description: Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown....
Show moreExposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone variants provides a first step toward an understanding of the functional significance of the diversity of histone structures, especially in inorganic arsenic-mediated gene expression and carcinogenesis.
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Date Issued: 2016-07-01
Identifier: FSU_pmch_27169413, 10.1074/mcp.M116.058412, PMC4937513, 27169413, 27169413, M116.058412
Format: Citation

Title: Multiplexing Fluorescence Anisotropy Using Frequency Encoding.
Creator: Schrell, Adrian M, Mukhitov, Nikita, Roper, Michael G
Abstract/Description: In this report, a method to multiplex fluorescence anisotropy measurements is described using frequency encoding. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and FITC-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz...
Show moreIn this report, a method to multiplex fluorescence anisotropy measurements is described using frequency encoding. As a demonstration of the method, simultaneous competitive immunoassays for insulin and glucagon were performed by measuring the ratio of bound and free Cy5-insulin and FITC-glucagon in the presence of their respective antibodies. A vertically polarized 635 nm laser was pulsed at 73 Hz and used to excite Cy5-insulin, while a vertically polarized 488 nm laser pulsed at 137 Hz excited FITC-glucagon. The total emission was split into parallel and perpendicular polarizations and collected onto separate photomultiplier tubes. The signals from each channel were demodulated using a fast Fourier transform, resolving the contributions from each fluorophore. Anisotropy calculations were carried out using the magnitude of the peaks in the frequency domain. The method produced the expected shape of the calibration curves with limits of detection of 0.6 and 5 nM for insulin and glucagon, respectively. This methodology could readily be expanded to other biological systems and further multiplexed to monitor increased numbers of analytes.
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Date Issued: 2016-08-16
Identifier: FSU_pmch_27440478, 10.1021/acs.analchem.6b02131, PMC4991543, 27440478, 27440478
Format: Citation

Title: Proteomic Upregulation of Fatty Acid Synthase and Fatty Acid Binding Protein 5 and Identification of Cancer- and Race-Specific Pathway Associations in Human Prostate Cancer Tissues.
Creator: Myers, Jennifer S, von Lersner, Ariana K, Sang, Qing-Xiang Amy
Abstract/Description: Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence...
Show moreProtein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States. In this study, age-, stage-, and Gleason score-matched prostate tumor specimen from African American and Caucasian American men, along with non-malignant adjacent prostate tissue from these same patients, were compared. Protein expression changes and altered pathway associations were identified in prostate cancer generally and in African American prostate cancer specifically. In comparing tumor to non-malignant samples, 45 proteins were significantly cancer-associated and 3 proteins were significantly downregulated in tumor samples. Notably, fatty acid synthase (FASN) and epidermal fatty acid-binding protein (FABP5) were upregulated in human prostate cancer tissues, consistent with their known functions in prostate cancer progression. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) was also upregulated in tumor samples. The Metastasis Associated Protein 3 (MTA3) pathway was significantly enriched in tumor samples compared to non-malignant samples. While the current experiment was unable to detect statistically significant differences in protein expression between African American and Caucasian American samples, differences in overrepresentation and pathway enrichment were found. Structural components (Cytoskeletal Proteins and Extracellular Matrix Protein protein classes, and Biological Adhesion Gene Ontology (GO) annotation) were overrepresented in African American but not Caucasian American tumors. Additionally, 5 pathways were enriched in African American prostate tumors: the Small Cell Lung Cancer, Platelet-Amyloid Precursor Protein, Agrin, Neuroactive Ligand-Receptor Interaction, and Intrinsic pathways. The protein components of these pathways were either basement membrane proteins or coagulation proteins.
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Date Issued: 2016-07-05
Identifier: FSU_pmch_27471561, 10.7150/jca.15860, PMC4964129, 27471561, 27471561, jcav07p1452
Format: Citation

Title: Wavy membranes and the growth rate of a planar chemical garden: Enhanced diffusion and bioenergetics..
Creator: Ding, Yang, Batista, Bruno, Steinbock, Oliver, Cartwright, Julyan H E, Cardoso, Silvana S S
Abstract/Description: To model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is...
Show moreTo model ion transport across protocell membranes in Hadean hydrothermal vents, we consider both theoretically and experimentally the planar growth of a precipitate membrane formed at the interface between two parallel fluid streams in a 2D microfluidic reactor. The growth rate of the precipitate is found to be proportional to the square root of time, which is characteristic of diffusive transport. However, the dependence of the growth rate on the concentrations of hydroxide and metal ions is approximately linear and quadratic, respectively. We show that such a difference in ionic transport dynamics arises from the enhanced transport of metal ions across a thin gel layer present at the surface of the precipitate. The fluctuations in transverse velocity in this wavy porous gel layer allow an enhanced transport of the cation, so that the effective diffusivity is about one order of magnitude higher than that expected from molecular diffusion alone. Our theoretical predictions are in excellent agreement with our laboratory measurements of the growth of a manganese hydroxide membrane in a microfluidic channel, and this enhanced transport is thought to have been needed to account for the bioenergetics of the first single-celled organisms.
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Date Issued: 2016-08-16
Identifier: FSU_pmch_27486248, 10.1073/pnas.1607828113, PMC4995959, 27486248, 27486248, 1607828113
Format: Citation

Title: Synthesis of "neoprofen", a rigidified analogue of ibuprofen, exemplifying synthetic methodology for altering the 3-D topology of pharmaceutical substances.
Creator: Ramsubhag, Ron R, Massaro, Chelsea L, Dadich, Christina M, Janeczek, Andrew J, Hoang, Tung T, Mazzio, Elizabeth A, Eyunni, Suresh, Soliman, Karam F A, Dudley, Gregory B
Abstract/Description: 3,3-Dimethylcyclopentanes (neopentylenes) are ubiquitous in Nature but largely absent from synthetic pharmaceutical libraries. Neopentylenes define a hydrophobic and rigid 3-D topology with distinct molecular pharmacology, as exemplified here with two neopentylene-fused analogues of the synthetic anti-inflammatory drug, ibuprofen.
Date Issued: 2016-08-16
Identifier: FSU_pmch_27492587, 10.1039/c6ob01351a, PMC5008855, 27492587, 27492587
Format: Citation

Title: Generalized Ensemble Sampling of Enzyme Reaction Free Energy Pathways.
Creator: Wu, D, Fajer, M I, Cao, L, Cheng, X, Yang, W
Abstract/Description: Free energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a...
Show moreFree energy path sampling plays an essential role in computational understanding of chemical reactions, particularly those occurring in enzymatic environments. Among a variety of molecular dynamics simulation approaches, the generalized ensemble sampling strategy is uniquely attractive for the fact that it not only can enhance the sampling of rare chemical events but also can naturally ensure consistent exploration of environmental degrees of freedom. In this review, we plan to provide a tutorial-like tour on an emerging topic: generalized ensemble sampling of enzyme reaction free energy path. The discussion is largely focused on our own studies, particularly ones based on the metadynamics free energy sampling method and the on-the-path random walk path sampling method. We hope that this minipresentation will provide interested practitioners some meaningful guidance for future algorithm formulation and application study.
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Date Issued: 2016-01-01
Identifier: FSU_pmch_27498634, 10.1016/bs.mie.2016.05.012, PMC4978182, 27498634, 27498634, S0076-6879(16)30047-7
Format: Citation

Title: Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance.
Creator: Martinez, Jessica S, Schlenoff, Joseph B, Keller, Thomas C S
Abstract/Description: Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked,...
Show morePolyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion and migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as 'leader' cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as 'follower' cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization.
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Date Issued: 2016-08-01
Identifier: FSU_pmch_27292313, 10.1016/j.yexcr.2016.06.002, PMC4967014, 27292313, 27292313, S0014-4827(16)30143-4
Format: Citation

Title: Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer.
Creator: Vallega, Karin A, Liu, NingNing, Myers, Jennifer S, Yu, Kaixian, Sang, Qing-Xiang Amy
Abstract/Description: African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels...
Show moreAfrican American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.
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Date Issued: 2016-06-17
Identifier: FSU_pmch_27314854, 10.1371/journal.pone.0157741, PMC4912107, 27314854, 27314854, PONE-D-16-17121
Format: Citation

Title: Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.
Creator: Dang, Xibei, Singh, Amar, Spetman, Brian D, Nolan, Krystal D, Isaacs, Jennifer S, Dennis, Jonathan H, Dalton, Stephen, Marshall, Alan G, Young, Nicolas L
Abstract/Description: Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free...
Show moreHistone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.
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Date Issued: 2016-09-02
Identifier: FSU_pmch_27431976, 10.1021/acs.jproteome.6b00414, PMC6261780, 27431976, 27431976
Format: Citation

Title: A flexible iron(II) complex in which zero-field splitting is resistant to structural variation.
Creator: Zadrozny, Joseph M., Greer, Samuel M., Hill, Stephen, Freedman, Danna E.
Abstract/Description: The relationship between electronic structure and zero-field splitting dictates key design parameters for magnetic molecules. In particular, to enable the directed synthesis of new electronic spin based qubits, developing complexes where zero-field splitting energies are invariant to structural changes is a critical challenge. Toward those ends, we report three salts of a new compound, a four-coordinate iron(II) complex [ Fe(C3S5)(2)](2-) ([(18-crown-6) K](+) (1), Ph4P+ (2), Bu4N+ (3)) with a...
Show moreThe relationship between electronic structure and zero-field splitting dictates key design parameters for magnetic molecules. In particular, to enable the directed synthesis of new electronic spin based qubits, developing complexes where zero-field splitting energies are invariant to structural changes is a critical challenge. Toward those ends, we report three salts of a new compound, a four-coordinate iron(II) complex [ Fe(C3S5)(2)](2-) ([(18-crown-6) K](+) (1), Ph4P+ (2), Bu4N+ (3)) with a continuous structural variation in a single parameter, the dihedral angle (theta(d)) between the two C3S52- ligands, as a function of counterion (theta(d) = 89.98(4)degrees for 1 to 72.41(2)degrees for 3). Electron paramagnetic resonance data for 1-3 reveal zero-field splitting parameters that are unusually robust to the structural variation. Mossbauer spectroscopic measurements indicate that the structural variation in theta(d) primarily affects the highest-energy 3d-orbitals (d(xz) and d(yz)) of the iron(II) ion. These orbitals have the smallest impact on the zero-field splitting parameters, thus the distortion has a minor effect on D and E. These results represent the first part of a directed effort to understand how spin state energies may be fortified against structural distortions for future applications of qubits in non-crystalline environments.
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Date Issued: 2016
Identifier: FSU_libsubv1_wos_000366826900047, 10.1039/c5sc02477c
Format: Citation

Title: Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent Markers and Cellular Secretion.
Creator: Yi, Lian, Bandak, Basel, Wang, Xue, Bertram, Richard, Roper, Michael G
Abstract/Description: Glucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with...
Show moreGlucose-stimulated insulin secretion from pancreatic β-cells within islets of Langerhans plays a critical role in maintaining glucose homeostasis. Although this process is essential for maintaining euglycemia, the underlying intracellular mechanisms that control it are still unclear. To allow simultaneous correlation between intracellular signal transduction events and extracellular secretion, an analytical system was developed that integrates fluorescence imaging of intracellular probes with high-speed automated insulin immunoassays. As a demonstration of the system, intracellular [Ca] ([Ca]) was measured by imaging Fura-2 fluorescence simultaneously with insulin secretion from islets exposed to elevated glucose levels. Both [Ca] and insulin were oscillatory during application of 10 mM glucose with temporal and quantitative profiles similar to what has been observed elsewhere. In previous work, sinusoidal glucose levels have been used to test the entrainment of islets while monitoring either [Ca] or insulin levels; using this newly developed system, we show unambiguously that oscillations of both [Ca] and insulin release are entrained to oscillatory glucose levels and that the temporal correlation of these are maintained throughout the experiment. It is expected that the developed analytical system can be expanded to investigate a number of other intracellular messengers in islets or other stimulus-secretion pathways in different cells.
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Date Issued: 2016-11-01
Identifier: FSU_pmch_27712062, 10.1021/acs.analchem.6b02404, PMC5089909, 27712062, 27712062
Format: Citation

Title: Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.
Creator: McKenna, Joseph P, Dhumpa, Raghuram, Mukhitov, Nikita, Roper, Michael G, Bertram, Richard
Abstract/Description: Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with...
Show morePancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.
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Date Issued: 2016-10-27
Identifier: FSU_pmch_27788129, 10.1371/journal.pcbi.1005143, PMC5082885, 27788129, 27788129, PCOMPBIOL-D-16-00306
Format: Citation

Title: Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues.
Creator: Khamis, Zahraa I., Iczkowski, Kenneth A., Man, Yan-Gao, Bou-Dargham, Mayassa J., Sang, Qing-Xiang Amy
Abstract/Description: Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate...
Show moreMatrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.
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Date Issued: 2016
Identifier: FSU_libsubv1_wos_000366281500011, 10.7150/jca.13067
Format: Citation

Title: Evolution of Physical and Electrochemical Properties of Polypyrrole during Extended Oxidation.
Creator: Schlenoff, Joseph B., Xu, Hong
Abstract/Description: The charge storage capacity and electrical conductivity of polypyrrole are followed through regimes of chemically reversible and irreversible electroactivity. Overoxidation of polypyrrole occurs at potentials in excess of 0.7 V vs. a saturated calomel electrode (SCE), as demonstrated by cyclic voltammetry of thin films. Material loss from polymer films as they are overoxidized is determined by in situ quartz microbalance experiments. The potential window for reversible electrochemistry in...
Show moreThe charge storage capacity and electrical conductivity of polypyrrole are followed through regimes of chemically reversible and irreversible electroactivity. Overoxidation of polypyrrole occurs at potentials in excess of 0.7 V vs. a saturated calomel electrode (SCE), as demonstrated by cyclic voltammetry of thin films. Material loss from polymer films as they are overoxidized is determined by in situ quartz microbalance experiments. The potential window for reversible electrochemistry in polypyrrole is compared to that for other conducting polymers. Reflectance FTIR of thick films reveals that hydroxyl groups, followed by carbonyls, result from overoxidation.
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Date Issued: 1992
Identifier: FSU_migr_chm_faculty_publications-0004, 10.1149/1.2221238
Format: Citation

Title: Exploring Background Mutational Processes To Decipher Cancer Genetic Heterogeneity.
Creator: Goncearenco, Alexander, Rager, Stephanie L., Li, Minghui, Sang, Qing-Xiang, Rogozin, Igor B., Panchenko, Anna R.
Abstract/Description: Much remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and...
Show moreMuch remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and underlying somatic cancer mutagenesis, analyzes mutational profiles of cancer samples, identifies the combinations of underlying mutagenic processes including those related to infidelity of DNA replication and repair machinery, and various other endogenous and exogenous mutagenic factors. As a result, the combination of mutagenic processes can be identified in any query sample with subsequent comparison to mutational profiles derived from malignant and benign samples. In addition, mutagen or cancer-specific mutational background models are applied to calculate expected DNA and protein site mutability to decouple relative contributions of mutagenesis and selection in carcinogenesis, thus elucidating the site-specific driving events in cancer. MutaGene is freely available at https://www.ncbi.nlm.nih.gov/projects/mutagene/.
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Date Issued: 2017-07-03
Identifier: FSU_libsubv1_wos_000404427000078, 10.1093/nar/gkx367
Format: Citation

Title: Local heterogeneities in cardiac systems suppress turbulence by generating multi-armed rotors.
Creator: Zhang, Zhihui, Steinbock, Oliver
Abstract/Description: Ventricular fibrillation is an extremely dangerous cardiac arrhythmia that is linked to rotating waves of electric activity and chaotically moving vortex lines. These filaments can pin to insulating, cylindrical heterogeneities which swiftly become the new rotation backbone of the local wave field. For thin cylinders, the stabilized rotation is sufficiently fast to repel the free segments of the turbulent filament tangle and annihilate them at the system boundaries. The resulting global wave...
Show moreVentricular fibrillation is an extremely dangerous cardiac arrhythmia that is linked to rotating waves of electric activity and chaotically moving vortex lines. These filaments can pin to insulating, cylindrical heterogeneities which swiftly become the new rotation backbone of the local wave field. For thin cylinders, the stabilized rotation is sufficiently fast to repel the free segments of the turbulent filament tangle and annihilate them at the system boundaries. The resulting global wave pattern is periodic and highly ordered. Our cardiac simulations show that also thicker cylinders can establish analogous forms of tachycardia. This process occurs through the spontaneous formation of pinned multi-armed vortices. The observed number of wave arms N depends on the cylinder radius and is associated to stability windows that for N = 2, 3 partially overlap. For N =. 1, 2, we find a small gap in which the turbulence is removed but the pinned rotor shows complex temporal dynamics. The relevance of our findings to human cardiology are discussed in the context of vortex pinning to more complex-shaped anatomical features and remodeled myocardium.
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Date Issued: 2016-05-12
Identifier: FSU_libsubv1_wos_000377191300001, 10.1088/1367-2630/18/5/053018
Format: Citation

Title: Linear and nonlinear dielectric theory for a slab: The connections between the phenomenological coefficients and the susceptibilities.
Creator: Fulton, Robert L.
Abstract/Description: The response of dielectric media to electromagnetic fields can be described by using either the response to a Maxwell field E or to an externally produced field E. The former response is measured by phenomenological (dielectric) coefficients and the latter by susceptibilities. With the purpose of clarifying some recent proposals, the connections between the linear (two-point) and first non-vanishing nonlinear (four-point) dielectric coefficients and the susceptibilities for media confined to...
Show moreThe response of dielectric media to electromagnetic fields can be described by using either the response to a Maxwell field E or to an externally produced field E. The former response is measured by phenomenological (dielectric) coefficients and the latter by susceptibilities. With the purpose of clarifying some recent proposals, the connections between the linear (two-point) and first non-vanishing nonlinear (four-point) dielectric coefficients and the susceptibilities for media confined to a slab are examined using a general procedure developed sometime ago. Unlike the relations found for correlations between a local polarization density and the integrated polarization densities (total polarizations), the point-point connections give rise to non-vanishing cross correlations between polarization densities which are parallel and perpendicular to the slab surfaces. The cross correlations in the two-point connections vanish when one polarization density is integrated to form the correlations between a local polarization density and the total polarization thereby losing angular information. The integrated parallel and perpendicular correlations remain different. When the four-point connections are similarly integrated most, but not all, cross correlations vanish. The angular correlations induced by the slab surfaces render the use of point-point correlations that are valid for isotropic media invalid for use in the integrated slab densities. In addition, the nonlinear fluctuations in the perpendicular components are drastically reduced relative to those in the parallel components or in isotropic media. Published by AIP Publishing.
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Date Issued: 2016-08-28
Identifier: FSU_libsubv1_wos_000383875500008, 10.1063/1.4961225
Format: Citation

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