Biophysical Studies of Hairpin Polyamides with Broad-Spectrum Activity Against High-Risk Human Papillomaviruses

Human papillomavirus is a small dsDNA virus that infects mucosal and cutaneous epithelial tissues. Persistent infection with high-risk HPV is the main etiological agent in the development of cervical cancer worldwide. Although prophylactic vaccines against HPV are available, these preventative measures are type-specific and are ineffective against existing infections. Thus, there is a pressing need for antiviral drugs with a broad-spectrum activity against HPV to eradicate existing infections, no matter the subtype. Our group and collaborators have synthesized an extensive library of novel N-methylpyrrole/N-methylimidazole (Py/Im) hairpin polyamides (PAs) with broad-spectrum activities against three prevalent oncogenic-HPV types (HPV16, HPV18 and HPV31) without apparent cytotoxicity. Because Py/Im polyamides can be rationally designed to bind the minor groove of dsDNA in a sequence-dependent manner, these small molecules are attractive candidates as modulators of gene expression, as molecular probes for diagnostics and as antiviral agents for the selective elimination of dsDNA viruses. Despite the promise of applying these agents to treat HPV infections, much regarding their mechanism of action remains unexplained. Therefore, the overall goal of this dissertation is to investigate the DNA-binding properties of potent anti-HPV PAs under cell-free conditions and in HPV-harboring keratinocytes. Chapter 2 describes biophysical studies of anti-HPV hairpin polyamides (PA1 and PA25) using deoxyribonuclease I footprinting and affinity cleavage to interrogate the sequence specificity, binding sites and dissociation constants within the HPV18 Long Control Region. Chapter 3 extends these analyses to a new structural class of hairpin polyamides with tetramethylguanidinium (PA30) and guanidinium (PA31) substitutions on the N-terminus of PA1. Chapter 4 presents a detailed procedure to determine the genome-wide binding events of DNA-binding molecules in cell-free conditions using hydroxyl radical footprinting coupled to massively parallel DNA sequencing (·OH-Seq). In Chapter 5, ·OH-Seq and COSMIC-Seq have been employed to assess the binding occupancies of anti-HPV hairpin polyamides across the viral genomes in keratinocytes harboring HPV16 episomes. A deeper understanding of the molecular underpinnings of the ability of antiviral hairpin PAs to eliminate the HPV viral load may facilitate the development of a new generation of broad-spectrum antiviral treatments against this deadly virus

Recent progress in the development of a solar neutron tracking device (SONTRAC)

We report the results of recent calibration data analysis of a prototype scintillating fiber tracking detector system designed to perform imaging, spectroscopy and particle identification on 20 to 250 MeV neutrons and protons. We present the neutron imaging concept and briefly review the detection principle and the prototype description. The prototype detector system records ionization track data on an event-by-event basis allowing event selection criteria to be used in the off-line analysis. Images of acrylic phantoms from the analysis of recent proton beam calibrations are presented as demonstrations of the particle identification, imaging and energy measurement capabilities. The measured position resolution is \u3c 500 micrometers . The measured energy resolution is 14.2 percent at 35 MeV. The detection techniques employed can be applied to measurements in a variety of disciplines including solar and atmospheric physics, radiation therapy and nuclear materials monitoring. These applications are discussed briefly as are alternative detector configurations and future development plans

Ciclo De Confernencias De La Fundacion Educative Carlos M. Castaneda

El compromiso de la Fundación Educativa Carlos M. Castañeda es promover el periodismo de excelencia, la libertad de prensa y los derechos humanos, principios fundamentales por los que vivió, defendió y ejerció la profesión de periodista Carlos M. Castañeda, fundador, director y consejero de periódicos en América Latina, Miami y el Caribe. Además de su programa de becas encaminado a apoyar la educación de periodistas hispanohablantes, la FECMC organiza foros, conferencias y talleres sobre temas relacionados con la política, la economía y el periodismo para fortalecer la libertad de expresión y la democracia en nuestra América. Con este fin, la FECMC ofrecerá tres conferencias consecutivas los primeros tres sábados durante el mes de marzo de 2017 a las 3 pm en la librería Books & Books, de Coral Gables.https://digitalcommons.fiu.edu/cri_events/1326/thumbnail.jp

Kinetic modeling of the hydrotreatment of light cycle oil/diesel

A rigorous kinetic model of hydrodesulfurization (HDS) of complex mixtures such as light cycle oil (LCO) or diesel has been developed. An experimental setup was constructed to investigate the hydrotreatment of complex mixtures. The hydrodesulfurization of LCO on a commercial CoMo/Al2O3 (IMP) catalyst was investigated in a Robinson Mahoney perfectly mixed flow stationary basket reactor. An experimental investigation of the HDS of the dibenzothiophene (DBT) and substituted dibenzothiophenes in the LCO was carried out at temperatures between 290 and 330°C, space time for dibenzothiophene (W/F0 DBT) between 1000 and 6500 kgcat-h/kmol, and H2/HC molar ratio constant of 2.8. To avoid having to deal with a huge number of parameters in the model, a methodology based on structural contributions was applied. DENs and DENt are the denominators of the Hougen-Watson rate expressions for hydrodesulfurization of dibenzothiophene (DBT) and methyl-substituted dibenzothiophenes contained in the LCO. Both denominators comprise the concentration of all adsorbing species of the LCO multiplied by their adsorption equilibrium constants. The estimation of the denominators DENs and DENt was performed using the Levenberg-Marquardt algorithm and the results in terms of conversion for DBT, biphenyl and cyclohexylbenzene obtained in the hydrodesulfurization of the LCO. The evolution of DENs and DENt values with the composition was calculated for each LCO experiment. Structural contributions were taken from Vanrysselberghe and Froment for hydrogenolysis and hydrogenation of methyl-substituted dibenzothiophenes with a significant reduction in the number of parameters to be estimated in the HDS of the LCO. The multiplication factors, fsDBT, which are products of structural contributions for hydrogenolysis and hydrogenation of the mono- and dimethyl-dibenzothiophenes were also taken from Vanrysselberghe and Froment. These multiplication factors are based on experimental results with model components such as DBT, 4-Methyl dibenzothiophene and 4,6-Dimethyl dibenzothiophene. The results obtained in the modeling are in good agreement with the experimental data because the model reproduces very well the observed total conversions of DBT, conversions of DBT into biphenyl and conversions of DBT into cyclohexylbenzene as a function of temperature

A scintillating plastic fiber tracking detector for neutron and proton imaging and spectroscopy

We report the results of recent calibration data analysis of a prototype scintillating fiber tracking detector system designed to perform imaging, spectroscopy and particle identification on 20 to 250 MeV neutrons and protons. We present the neutron imaging concept and briefly review the detection principle and the prototype description. The prototype detector system records ionization track data on an event-by-event basis allowing event selection criteria to be used in the off-line analysis. Images of acrylic phantoms from the analysis of recent proton beam calibrations (14 to 65 MeV range) are presented as demonstrations of the particle identification, imaging and energy measurement capabilities. The measured position resolution is c 500 pm. The measured energy resolution (AE/E, FWHM) is 14.2% at 35 MeV. An effective technique for track identification and data compression is presented. The detection techniques employed can be applied to measurements in a variety of disciplines including solar and atmospheric physics, radiation therapy and nuclear materials monitoring. These applications are discussed briefly as are alternative detector configurations and future development plans

Latin America Goes Left

The article focuses on the status of the leftists in Latin America. The left has returned after long militaristic winters and democratic springs that has never had popular support. Latin America is divided between national populist like Venezuela's President Hugo Chavez and open trading of Brazil

Effect Of High-optical Excitation On The Ultrafast Electron Dynamics In Stacked-monolayer Graphene Samples

We report on transient absorption experiments performed at high optical excitation fluences and used to study the ultrafast dynamics in graphene. We employed a degenerated scheme of pump and probe at 800 nm (1.55 eV). The time resolution of our measurements was limited by the pulse duration similar to 100 fs. The samples were prepared by chemical vapor deposition (CVD) as single-layers on silica and, then staked layer-by-layer in order to make a stack of up to 5 graphene monolayers. We observed saturable absorption (SA) and fluence-dependent relaxation times. We see that the ultrafast carrier dynamics is composed by two decay mechanisms, one with response time of about 200 fs and a slower process of about 1 ps. The fast decay, due to both carrier-carrier and carrier-optical phonon scattering, becomes slower when the density of excited carrier was increased. We implemented a theoretical model and found that both the optical phonon rate emission and the optical phonon lifetime are affect by the pump fluence.9835Conference on Ultrafast Bandgap PhotonicsAPR 18-20, 2016Baltimore, M