On the macroion virial contribution to the osmotic pressure in charge-stabilized colloidal suspensions

Our interest goes to the different virial contributions to the equation of state of charged colloidal suspensions. Neglect of surface effects in the computation of the colloidal virial term leads to spurious and paradoxical results. This pitfall is one of the several facets of the danger of a naive implementation of the so called One Component Model, where the micro-ionic degrees of freedom are integrated out to only keep in the description the mesoscopic (colloidal) degrees of freedom. On the other hand, due incorporation of wall induced forces dissolves the paradox brought forth in the naive approach, provides a consistent description, and confirms that for salt-free systems, the colloidal contribution to the pressure is dominated by the micro-ionic one. Much emphasis is put on the no salt case but the situation with added electrolyte is also discussed

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

Investigation of the Mechanisms of 6-Li-Induced Reactions Far Above the Coulomb Barrier

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

Study of star-forming galaxies in SDSS up to redshift 0.4: I. Metallicity evolution

The chemical composition of the gas in galaxies versus cosmic time provides a very important tool for understanding galaxy evolution. Although there are many studies at high redshift, they are rather scarce at lower redshifts. However, low redshift studies can provide important clues about the evolution of galaxies, furnishing the required link between local and high redshift universe. In this work we focus on the metallicity of the gas of star-forming galaxies at low redshift, looking for signs of chemical evolution. To analyze the metallicity contents star-forming galaxies of similar luminosities and masses at different redshifts. With this purpose, we present a study of the metallicity of relatively massive (log(M_star/M_sun)>10.5) star forming galaxies from SDSS--DR5 (Sloan Digital Sky Survey--Data Release 5), using different redshift intervals from 0.04 to 0.4. We used data processed with the STARLIGHT spectral synthesis code, correcting the fluxes for dust extinction, estimating metallicities using the R_23 method, and segregating the samples with respect to the value of the [NII]6583/[OII]3727 line ratio in order to break the R_23 degeneracy selecting the upper branch. We analyze the luminosity and mass-metallicity relations, and the effect of the Sloan fiber diameter looking for possible biases. By dividing our redshift samples in intervals of similar magnitude and comparing them, significant signs of metallicity evolution are found. Metallicity correlates inversely with redshift: from redshift 0 to 0.4 a decrement of ~0.1 dex in 12+log(O/H) is found.Comment: 11 pages, 9 figures, Accepted for publication in A&

XMM-Newton and Deep Optical Observations of the OTELO fields: the Groth-Westphal Strip

OTELO (OSIRIS Tunable Emission Line Object Survey) will be carried out with the OSIRIS instrument at the 10 m GTC telescope at La Palma, and is aimed to be the deepest and richest survey of emission line objects to date. The deep narrow-band optical data from OSIRIS will be complemented by means of additional observations that include: (i) an exploratory broad-band survey that is already being carried out in the optical domain, (ii) FIR and sub-mm observations to be carried with the Herschel space telescope and the GTM, and (iii) deep X-Ray observations from XMM-Newton and Chandra.Here we present a preliminary analysis of public EPIC data of one of the OTELO targets,the Groth-Westphal strip, gathered from the XMM-Newton Science Archive (XSA). EPIC images are combined with optical BVRI data from our broadband survey carried out with the 4.2m WHT at La Palma. Distance-independent diagnostics (involving X/O ratio, hardness ratios, B/T ratio) are tested.Comment: 2 pages, 2 figures, uses graphicx package. To appear in proceedings of "The X-Ray Universe 2005", San Lorenzo del Escorial, Spain, September 26-30, 200

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

Thioglycosides as inhibitors of hSGLT1 and hSGLT2: Potential therapeutic agents for the control of hyperglycemia in diabetes

The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by SGLT1 or SGLT2, represents a promising therapeutic approach. Therefore, the aim of the present study was to evaluate the effect of thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected Chinese hamster ovary (CHO) cells expressing human SGLT1 and SGLT2 were used. The inhibitory effect of thioglycosides was assessed in transport studies and membrane potential measurements, using α-methyl-glucoside uptake and fluorescence resonance energy transfer, respectively. We found that some thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically, thioglycoside I (phenyl-1'-thio-β-D-glucopyranoside) inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1'-thio-β-D-galacto-pyranoside) had a pronounced inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating competitive inhibition as the mechanism of action. Therefore, these thioglycosides represent promising therapeutic agents for the control of hyperglycemia in patients with diabetes