231 research outputs found
Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space
Mortality of glioblastoma multiforme (GBM) has not improved over the
last two decades despite medical breakthroughs in the treatment of other
types of cancers. Nanoparticles hold tremendous promise to overcome the
pharmacokinetic challenges and off-target adverse effects. However, an
inhibitory effect of nanoparticles by themselves on metastasis has not
been explored. In this study, we developed transferrin-conjugated porous
silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting
GBM migration by means of a microfluidic-based migration chip. This
platform, designed to mimic the tight extracellular migration tracts in
brain parenchyma, allowed high-content time-resolved imaging of cell
migration. Tf@pSiNP were colloidally stable, biocompatible, and their
uptake into GBM cells was enhanced by receptor-mediated internalisation.
The migration of Tf@pSiNP-exposed cells across the confined
microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced
destabilisation of focal adhesions at the leading front may partially
explain the migration inhibition. More corroborating evidence suggests
that pSiNP uptake reduced the plasticity of GBM cells in reducing cell
volume, an effect that proved crucial in facilitating migration across
the tight confined tracts. We believe that the inhibitory effect of
Tf@pSiNP on cell migration, together with the drug-delivery capability
of pSiNP, could potentially offer a disruptive strategy to treat GBM.</p
Random Walks in Logarithmic and Power-Law Potentials, Nonuniversal Persistence, and Vortex Dynamics in the Two-Dimensional XY Model
The Langevin equation for a particle (`random walker') moving in
d-dimensional space under an attractive central force, and driven by a Gaussian
white noise, is considered for the case of a power-law force, F(r) = -
Ar^{-sigma}. The `persistence probability', P_0(t), that the particle has not
visited the origin up to time t, is calculated. For sigma > 1, the force is
asymptotically irrelevant (with respect to the noise), and the asymptotics of
P_0(t) are those of a free random walker. For sigma < 1, the noise is
(dangerously) irrelevant and the asymptotics of P_0(t) can be extracted from a
weak noise limit within a path-integral formalism. For the case sigma=1,
corresponding to a logarithmic potential, the noise is exactly marginal. In
this case, P_0(t) decays as a power-law, P_0(t) \sim t^{-theta}, with an
exponent theta that depends continuously on the ratio of the strength of the
potential to the strength of the noise. This case, with d=2, is relevant to the
annihilation dynamics of a vortex-antivortex pair in the two-dimensional XY
model. Although the noise is multiplicative in the latter case, the relevant
Langevin equation can be transformed to the standard form discussed in the
first part of the paper. The mean annihilation time for a pair initially
separated by r is given by t(r) \sim r^2 ln(r/a) where a is a microscopic
cut-off (the vortex core size). Implications for the nonequilibrium critical
dynamics of the system are discussed and compared to numerical simulation
results.Comment: 10 pages, 1 figur
The Yuan-Tseh Lee Array for Microwave Background Anisotropy
The Yuan-Tseh Lee Array for Microwave Background Anisotropy (AMiBA) is the
first interferometer dedicated to studying the cosmic microwave background
(CMB) radiation at 3mm wavelength. The choice of 3mm was made to minimize the
contributions from foreground synchrotron radiation and Galactic dust emission.
The initial configuration of seven 0.6m telescopes mounted on a 6-m hexapod
platform was dedicated in October 2006 on Mauna Loa, Hawaii. Scientific
operations began with the detection of a number of clusters of galaxies via the
thermal Sunyaev-Zel'dovich effect. We compare our data with Subaru weak lensing
data in order to study the structure of dark matter. We also compare our data
with X-ray data in order to derive the Hubble constant.Comment: accepted for publication in ApJ (13 pages, 7 figures); a version with
high resolution figures available at
http://www.asiaa.sinica.edu.tw/~keiichi/upfiles/AMiBA7/pho_highreso.pd
Color-Octet Production in the Decay
The direct production rate of in the decay is shown to be
dominated by the process followed by via
the color-octet mechanism proposed recently to explain the anomalous prompt
charmonium production at the Tevatron. We show that this plausibly dominant
process has a branching ratio compatible with the experimental data. Further
experimental study in this channel is important to test the significance of the
color-octet component of pair inside the system.Comment: 20 pages, Standard LaTeX, 2 figures; a couple of new processes added,
but conclusion unchange
Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth
Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with PluronicÂź F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface
Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1
Peer reviewe
Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies
We determine the relative rates of short GRBs in cluster and field early-type
galaxies as a function of the age probability distribution of their
progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the
difference in the growth of stellar mass in clusters and in the field, which
arises from the combined effects of the galaxy stellar mass function, the
early-type fraction, and the dependence of star formation history on mass and
environment. This approach complements the use of the early- to late-type host
galaxy ratio, with the added benefit that the star formation histories of
early-type galaxies are simpler than those of late-type galaxies, and any
systematic differences between progenitors in early- and late-type galaxies are
removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n =
-2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2,
corresponding to n ~ 0 - 1. This is similar to the value inferred from the
ratio of short GRBs in early- and late-type hosts, but it differs from the
value of n ~ -1 for NS binaries in the Milky Way. We stress that this general
approach can be easily modified with improved knowledge of the effects of
environment and mass on the build-up of stellar mass, as well as the effect of
globular clusters on the short GRB rate. It can also be used to assess the age
distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population
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