3,814 research outputs found
Overexpression of Both Human Sodium Iodide Symporter (NIS) and BRG1-Bromodomain Synergistically Enhances Radioiodine Sensitivity by Stabilizing p53 through NPM1 Expression.
Improved therapeutic strategies are required to minimize side effects associated with radioiodine gene therapy to avoid unnecessary damage to normal cells and radiation-induced secondary malignancies. We previously reported that codon-optimized sodium iodide symporter (oNIS) enhances absorption of I-131 and that the brahma-associated gene 1 bromodomain (BRG1-BRD) causes inefficient DNA damage repair after high-energy X-ray therapy. To increase the therapeutic effect without applying excessive radiation, we considered the combination of oNIS and BRG1-BRD as gene therapy for the most effective radioiodine treatment. The antitumor effect of I-131 with oNIS or oNIS+BRD expression was examined by tumor xenograft models along with functional assays at the cellular level. The synergistic effect of both BRG1-BRD and oNIS gene overexpression resulted in more DNA double-strand breaks and led to reduced cell proliferation/survival rates after I-131 treatment, which was mediated by the p53/p21 pathway. We found increased p53, p21, and nucleophosmin 1 (NPM1) in oNIS- and BRD-expressing cells following I-131 treatment, even though the remaining levels of citrulline and protein arginine deiminase 4 (PAD4) were unchanged at the protein level
Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.
This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic
Noise temperature measurements for axion haloscope experiments at IBS/CAPP
The axion was first introduced as a consequence of the Peccei-Quinn mechanism
to solve the CP problem in strong interactions of particle physics and is a
well motivated cold dark matter candidate. This particle is expected to
interact extremely weakly with matter and its mass is expected to lie in
eV range with the corresponding frequency roughly in GHz range. In 1983 P.
Sikivie proposed a detection scheme, so called axion haloscope, where axions
resonantly convert to photons in a tunable microwave cavity permeated by a
strong magnetic field. A major source of the experimental noise is attributed
to added noise by RF amplifiers, and thus precise understandings of amplifiers'
noise is of importance. We present the measurements of noise temperatures of
various low noise amplifiers broadly used for axion dark matter searches.Comment: 7 pages, 3 figure
Investigating photoexcitation-induced mitochondrial damage by chemotherapeutic corroles using multimode optical imaging
We recently reported that a targeted, brightly fluorescent gallium corrole (HerGa) is highly effective for breast tumor detection and treatment. Unlike structurally similar porphryins, HerGa exhibits tumor-targeted toxicity without the need for photoexcitation. We have now examined whether photoexcitation further modulates HerGa toxicity, using multimode optical imaging of live cells, including two-photon excited fluorescence, differential interference contrast (DIC), spectral, and lifetime imaging. Using two-photon excited fluorescence imaging, we observed that light at specific wavelengths augments the HerGa-mediated mitochondrial membrane potential disruption of breast cancer cells in situ. In addition, DIC, spectral, and fluorescence lifetime imaging enabled us to both validate cell damage by HerGa photoexcitation and investigate HerGa internalization, thus allowing optimization of light dose and timing. Our demonstration of HerGa phototoxicity opens the way for development of new methods of cancer intervention using tumor-targeted corroles
Mercury in Aquatic Systems of the Gulf Islands National Seashore, Southeastern USA
This study reports on levels and speciation of mercury (Hg) in different environmental compartments of selected park units in the Gulf Islands National Seashore (USA), and on potential rates of methyl-Hg (MMHg) formation and degradation in sediments. In the aqueous phase, total (THg) and MMHg concentrations ranged from 0.19 to 14.26 ng/L (n=32) an
Spatial and temporal characterization of a Bessel beam produced using a conical mirror
We experimentally analyze a Bessel beam produced with a conical mirror,
paying particular attention to its superluminal and diffraction-free
properties. We spatially characterized the beam in the radial and on-axis
dimensions, and verified that the central peak does not spread over a
propagation distance of 73 cm. In addition, we measured the superluminal phase
and group velocities of the beam in free space. Both spatial and temporal
measurements show good agreement with the theoretical predictions.Comment: 5 pages, 6 figure
Appearance of Half-Metallicity in the Quaternary Heusler Alloys
I report systematic first-principle calculations of the quaternary Heusler
alloys like Co[CrMn]Al, CoMn[AlSn] and
[FeCo]MnAl. I show that when the two limiting cases (x=0 or 1)
correspond to a half-metallic compound, so do the intermediate cases. Moreover
the total spin moment in scales linearly with the total number of
valence electrons (and thus with the concentration ) following the
relation , independently of the origin of the extra valence
electrons, confirming the Slater-Pauling behavior of the normal Heusler alloys.
Finally I discuss in all cases the trends in the atomic projected DOSs and in
the atomic spin moments.Comment: 4 pages, 3 figures, 2 Table
The falling chain of Hopkins, Tait, Steele and Cayley
A uniform, flexible and frictionless chain falling link by link from a heap
by the edge of a table falls with an acceleration if the motion is
nonconservative, but if the motion is conservative, being the
acceleration due to gravity. Unable to construct such a falling chain, we use
instead higher-dimensional versions of it. A home camcorder is used to measure
the fall of a three-dimensional version called an -slider. After
frictional effects are corrected for, its vertical falling acceleration is
found to be . This result agrees with the theoretical
value of for an ideal energy-conserving -slider.Comment: 17 pages, 5 figure
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