583 research outputs found
Induction of Cytotoxic Oxidative Stress by d-Alanine in Brain Tumor Cells Expressing Rhodotorula gracilis d-Amino Acid Oxidase: A Cancer Gene Therapy Strategy
Overview summary Gene-directed enzyme prodrug therapy (GDEPT) is an antineoplastic treatment strategy designed to overcome the systemic toxicity of chemotherapy by specifically expressing a foreign enzyme in malignant cells that converts a nontoxic prodrug into a cytotoxic metabolite. The relative inefficiency of current in situ gene transfer methodology suggests that enzyme/prodrug combinations that produce membrane permeable metabolites will elicit a more favorable therapeutic response. Ideally, the agent produced by the transduced cell “factories” would be cytotoxic toward both proliferating and quiescent cells. We describe a novel GDEPT approach using d-amino acid oxidase from the red yeast Rhodotorula gracilis and d-alanine as a substrate that generates hydrogen peroxide, a reactive metabolite of oxygen that has both these characteristics. We also demonstrate the ability to sensitize tumor cells to this GDEPT protocol by manipulating cellular antioxidant pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63220/1/hum.1998.9.2-185.pd
THE COST STRUCTURE OF MICROFINANCE INSTITUTIONS IN EASTERN EUROPE AND CENTRAL ASIA
Microfinance institutions are important, particularly in developing countries, because they expand the frontier of financial intermediation by providing loans to those traditionally excluded from formal financial markets. This paper presents the first systematic statistical examination of the performance of MFIs operating in Eastern Europe and Central Asia. A cost function is estimated for MFIs in the region from 1999-2004. First, the presence of subsidies is found to be associated with higher MFI costs. When output is measured as the number of loans made, we find that MFIs become more efficient over time and that MFIs involved in the provision of group loans and loans to women have lower costs. However, when output is measured as volume of loans rather than their number, this last finding is reversed. This may be due to the fact that such loans are smaller in size; thus for a given volume more loans must be made.http://deepblue.lib.umich.edu/bitstream/2027.42/40195/3/wp809.pd
Small Phase Space Structures and their Relevance to Pulsed Quantum Evolution: the Stepwise Ionization of the Excited Hydrogen Atom in a Microwave Pulse
Experiments have shown that the microwave ionization probability of a highly
excited almost monodimensional hydrogen atom subjected to a microwave pulse
sometimes grows in steps when the peak electric field of the pulse is
increased. Classical pulsed simulations display the same steps, which have been
traced to phase-space metamorphoses. Quantum numerical calculations again
exhibit the same ionization steps. I show that the time-sequence of two level
interactions, responsible for the observed steps in the quantum picture, is
strictly related to the classical phase space structures generated by the above
mentioned metamorphoses.Comment: 46 pages, 23 figure
Comparing the hierarchy of keywords in on-line news portals
The tagging of on-line content with informative keywords is a widespread
phenomenon from scientific article repositories through blogs to on-line news
portals. In most of the cases, the tags on a given item are free words chosen
by the authors independently. Therefore, relations among keywords in a
collection of news items is unknown. However, in most cases the topics and
concepts described by these keywords are forming a latent hierarchy, with the
more general topics and categories at the top, and more specialised ones at the
bottom. Here we apply a recent, cooccurrence-based tag hierarchy extraction
method to sets of keywords obtained from four different on-line news portals.
The resulting hierarchies show substantial differences not just in the topics
rendered as important (being at the top of the hierarchy) or of less interest
(categorised low in the hierarchy), but also in the underlying network
structure. This reveals discrepancies between the plausible keyword association
frameworks in the studied news portals
JOYS+: mid-infrared detection of gas-phase SO emission in a low-mass protostar. The case of NGC 1333 IRAS2A: hot core or accretion shock?
JWST/MIRI has sharpened our infrared eyes toward the star formation process.
This paper presents the first mid-infrared detection of gaseous SO emission
in an embedded low-mass protostellar system. MIRI-MRS observations of the
low-mass protostellar binary NGC 1333 IRAS2A are presented from the JWST
Observations of Young protoStars (JOYS+) program, revealing emission from the
SO asymmetric stretching mode at 7.35 micron. The results are
compared to those derived from high-angular resolution SO data obtained
with ALMA. The SO emission from the band is predominantly located
on au scales around the main component of the binary, IRAS2A1. A
rotational temperature of K is derived from the lines. This is
in good agreement with the rotational temperature derived from pure rotational
lines in the vibrational ground state (i.e., ) with ALMA ( K).
However, the emission of the lines is not in LTE given that the total
number of molecules predicted by a LTE model is found to be a factor
higher than what is derived for the state. This
difference can be explained by a vibrational temperature that is K
higher than the derived rotational temperature of the state. The
brightness temperature derived from the continuum around the band of
SO is K, which confirms that the level is not
collisionally populated but rather infrared pumped by scattered radiation. This
is also consistent with the non-detection of the bending mode at 18-20
micron. Given the rotational temperature, the extent of the emission (
au in radius), and the narrow line widths in the ALMA data (3.5 km/s), the
SO in IRAS2A likely originates from ice sublimation in the central hot core
around the protostar rather than from an accretion shock at the disk-envelope
boundary.Comment: 19 pages, 17 figures, accepted for publication in A&A, abstract
abbreviate
Discovery of extreme particle acceleration in the microquasar Cygnus X-3
The study of relativistic particle acceleration is a major topic of
high-energy astrophysics. It is well known that massive black holes in active
galaxies can release a substantial fraction of their accretion power into
energetic particles, producing gamma-rays and relativistic jets. Galactic
microquasars (hosting a compact star of 1-10 solar masses which accretes matter
from a binary companion) also produce relativistic jets. However, no direct
evidence of particle acceleration above GeV energies has ever been obtained in
microquasar ejections, leaving open the issue of the occurrence and timing of
extreme matter energization during jet formation. Here we report the detection
of transient gamma-ray emission above 100 MeV from the microquasar Cygnus X-3,
an exceptional X-ray binary which sporadically produces powerful radio jets.
Four gamma-ray flares (each lasting 1-2 days) were detected by the AGILE
satellite simultaneously with special spectral states of Cygnus X-3 during the
period mid-2007/mid-2009. Our observations show that very efficient particle
acceleration and gamma-ray propagation out of the inner disk of a microquasar
usually occur a few days before major relativistic jet ejections. Flaring
particle energies can be thousands of times larger than previously detected
maximum values (with Lorentz factors of 105 and 102 for electrons and protons,
respectively). We show that the transitional nature of gamma-ray flares and
particle acceleration above GeV energies in Cygnus X-3 is clearly linked to
special radio/X-ray states preceding strong radio flares. Thus gamma-rays
provide unique insight into the nature of physical processes in microquasars.Comment: 29 pages (including Supplementary Information), 8 figures, 2 tables
version submitted to Nature on August 7, 2009 (accepted version available at
http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature08578.pdf
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