Transition metal complexes provide a promising avenue for the design of therapeutic and diagnostic agents, but the limited understanding of their cellular uptake is a roadblock to their effective ...application. Here, we examine the mechanism of cellular entry of a luminescent ruthenium(II) polypyridyl complex, Ru(DIP)2dppz2+ (where DIP = 4,7-diphenyl-1,10-phenanthroline and dppz = dipyridophenazine), into HeLa cells, with the extent of uptake measured by flow cytometry. No diminution of cellular uptake is observed under metabolic inhibition with deoxyglucose and oligomycin, indicating an energy-independent mode of entry. The presence of organic cation transporter inhibitors also does not significantly alter uptake. However, the cellular internalization of Ru(DIP)2dppz2+ is sensitive to the membrane potential. Uptake decreases when cells are depolarized with high potassium buffer and increases when cells are hyperpolarized with valinomycin. These results support passive diffusion of Ru(DIP)2dppz2+ into the cell.
The cellular uptake and localization of a Ru−octaarginine conjugate with and without an appended fluorescein are compared. The inherent luminescence of the Ru(II) dipyridophenazine complex allows ...observation of its uptake without the addition of a fluorophore. Ru−octaarginine−fluorescein stains the cytosol, nuclei, and nucleoli of HeLa cells under conditions where the Ru−octaarginine conjugate without fluorescein shows only punctate cytoplasmic labeling. At higher concentrations, however, Ru−octaarginine without the fluorescein tag does exhibit cytoplasmic, nuclear, and nucleolar staining. Attaching fluorescein to Ru−octaarginine lowers the threshold concentration required for diffuse cytoplasmic labeling and nuclear entry. Hence, the localization of the fluorophore-bound peptide cannot serve as a proxy for that of the free peptide.
The HOPE mass spectrometer of the Radiation Belt Storm Probes (RBSP) mission (renamed the Van Allen Probes) is designed to measure the
in situ
plasma ion and electron fluxes over 4
π
sr at each RBSP ...spacecraft within the terrestrial radiation belts. The scientific goal is to understand the underlying physical processes that govern the radiation belt structure and dynamics. Spectral measurements for both ions and electrons are acquired over 1 eV to 50 keV in 36 log-spaced steps at an energy resolution Δ
E
FWHM
/
E
≈15 %. The dominant ion species (H
+
, He
+
, and O
+
) of the magnetosphere are identified using foil-based time-of-flight (TOF) mass spectrometry with channel electron multiplier (CEM) detectors. Angular measurements are derived using five polar pixels coplanar with the spacecraft spin axis, and up to 16 azimuthal bins are acquired for each polar pixel over time as the spacecraft spins. Ion and electron measurements are acquired on alternate spacecraft spins. HOPE incorporates several new methods to minimize and monitor the background induced by penetrating particles in the harsh environment of the radiation belts. The absolute efficiencies of detection are continuously monitored, enabling precise, quantitative measurements of electron and ion fluxes and ion species abundances throughout the mission. We describe the engineering approaches for plasma measurements in the radiation belts and present summaries of HOPE measurement strategy and performance.
The last decade has seen a marked shift in how the internal structure of hadrons is understood. Modern experimental facilities, new theoretical techniques for the continuum bound-state problem and ...progress with lattice-regularised QCD have provided strong indications that soft quark+quark (diquark) correlations play a crucial role in hadron physics. For example, theory indicates that the appearance of such correlations is a necessary consequence of dynamical chiral symmetry breaking, viz. a corollary of emergent hadronic mass that is responsible for almost all visible mass in the universe; experiment has uncovered signals for such correlations in the flavour-separation of the proton’s electromagnetic form factors; and phenomenology suggests that diquark correlations might be critical to the formation of exotic tetra- and penta-quark hadrons. A broad spectrum of such information is evaluated herein, with a view to consolidating the facts and therefrom moving toward a coherent, unified picture of hadron structure and the role that diquark correlations might play.
We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
Despite general acceptance that the retinotopic organisation of human V4 (hV4) takes the form of a single, uninterrupted ventral hemifield, measured retinotopic maps of this visual area are often ...incomplete. Here, we test hypotheses that artefact from draining veins close to hV4 cause inverted BOLD responses that may serve to obscure a portion of the lower visual quarterfield-including the lower vertical meridian-in some hemispheres. We further test whether correcting such responses can restore the 'missing' retinotopic coverage in hV4. Subjects (N = 10) viewed bowtie, ring, drifting bar and full field flash stimuli. Functional EPIs were acquired over approximately 1.5h and analysed to reveal retinotopic maps of early visual cortex, including hV4. Normalised mean maps (which show the average EPI signal amplitude) were constructed by voxel-wise averaging of the EPI time course and used to locate venous eclipses, which can be identified by a decrease in the EPI signal caused by deoxygenated blood. Inverted responses are shown to cluster in these regions and correcting these responses improves maps of hV4 in some hemispheres, including restoring a complete hemifield map in one. A leftwards bias was found whereby 6/10 left hemisphere hV4 maps were incomplete, while this was the case in only 1/10 right hemisphere maps. Incomplete hV4 maps did not correspond with venous artefact in every instance, with incomplete maps being present in the absence of a venous eclipse and complete maps coexisting with a proximate venous eclipse. We also show that mean maps of upper surfaces (near the boundary between cortical grey matter and CSF) provide highly detailed maps of veins on the cortical surface. Results suggest that venous eclipses and inverted voxels can explain some incomplete hV4 maps, but cannot explain the remainder nor the leftwards bias in hV4 coverage reported here.
Exploring the cellular accumulation of metal complexes Puckett, Cindy A; Ernst, Russell J; Barton, Jacqueline K
Dalton transactions : an international journal of inorganic chemistry,
01/2010, Letnik:
39, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Transition metal complexes offer great potential as diagnostic and therapeutic agents, and a growing number of biological applications have been explored. To be effective, these complexes must reach ...their intended target inside the cell. Here we review the cellular accumulation of metal complexes, including their uptake, localization, and efflux. Metal complexes are taken up inside cells through various mechanisms, including passive diffusion and entry through organic and metal transporters. Emphasis is placed on the methods used to examine cellular accumulation, to identify the mechanism(s) of uptake, and to monitor possible efflux. Conjugation strategies that have been employed to improve the cellular uptake characteristics of metal complexes are also described.
The E12-14-012 experiment, performed in Jefferson Lab Hall A, has measured the (e, e'p) cross section in parallel kinematics using a natural titanium target. In this paper, we report the analysis of ...the dataset obtained in different kinematics for our solid natural titanium target. Data were obtained in a range of missing momentum and missing energy between 15 ≲ pm ≲ 250 MeV / c and 12 ≲ Em ≲ 80 MeV, respectively, and using an electron beam energy of 2.2 GeV. We measured the reduced cross section with ~7% accuracy as a function of both missing momentum and missing energy. Furthermore, our Monte Carlo simulation, including both a model spectral function and the effects of final-state interactions, satisfactorily reproduces the data.
The E12-14-012 experiment, performed in Jefferson Lab Hall A, has measured the $(e, e'p)$ cross section in parallel kinematics using a natural argon target. Here, we report the full results of the ...analysis of the data set corresponding to beam energy 2.222 GeV, and spanning the missing momentum and missing energy range $15 \lesssim p_m \lesssim 300$ MeV/c and $12 \lesssim E_m \lesssim 80$ MeV. The reduced cross section, determined as a function of $p_m$ and $E_m$ with $\approx$4\% accuracy, has been fitted using the results of Monte Carlo simulations involving a model spectral function and including the effects of final state interactions. The overall agreement between data and simulations turns out to be quite satisfactory ($\chi^2$/n.d.o.f.=1.9). Furthermore, the resulting spectral function will provide valuable new information, needed for the interpretation of neutrino interactions in liquid argon detectors.
The internal structure of nucleons (protons and neutrons) remains one of the greatest outstanding problems in modern nuclear physics. By scattering high-energy electrons off a proton we are able to ...resolve its fundamental constituents and probe their momenta and positions. Here we investigate the dynamics of quarks and gluons inside nucleons using deeply virtual Compton scattering (DVCS)-a highly virtual photon scatters off the proton, which subsequently radiates a photon. DVCS interferes with the Bethe-Heitler (BH) process, where the photon is emitted by the electron rather than the proton. We report herein the full determination of the BH-DVCS interference by exploiting the distinct energy dependences of the DVCS and BH amplitudes. In the regime where the scattering is expected to occur off a single quark, measurements show an intriguing sensitivity to gluons, the carriers of the strong interaction.
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