837 research outputs found
Roles of sorcin in drug resistance in cancer: one protein, many mechanisms, for a novel potential anticancer drug target
The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules
Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies
Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of haematological cancers
GNO Solar Neutrino Observations: Results for GNOI
We report the first GNO solar neutrino results for the measuring period GNOI,
solar exposure time May 20, 1998 till January 12, 2000. In the present
analysis, counting results for solar runs SR1 - SR19 were used till April 4,
2000. With counting completed for all but the last 3 runs (SR17 - SR19), the
GNO I result is [65.8 +10.2 -9.6 (stat.) +3.4 -3.6 (syst.)]SNU (1sigma) or
[65.8 + 10.7 -10.2 (incl. syst.)]SNU (1sigma) with errors combined. This may be
compared to the result for Gallex(I-IV), which is [77.5 +7.6 -7.8 (incl.
syst.)] SNU (1sigma). A combined result from both GNOI and Gallex(I-IV)
together is [74.1 + 6.7 -6.8 (incl. syst.)] SNU (1sigma).Comment: submitted to Physics Letters B, June 2000. PACS: 26.65. +t ; 14.60
Pq. Corresponding author: [email protected] ; [email protected]
Complete results for five years of GNO solar neutrino observations
We report the complete GNO solar neutrino results for the measuring periods
GNO III, GNO II, and GNO I. The result for GNO III (last 15 solar runs) is
[54.3 + 9.9 - 9.3 (stat.)+- 2.3 (syst.)] SNU (1 sigma) or [54.3 + 10.2 - 9.6
(incl. syst.)] SNU (1 sigma) with errors combined. The GNO experiment is now
terminated after altogether 58 solar exposure runs that were performed between
May 20, 1998 and April 9, 2003. The combined result for GNO (I+II+III) is [62.9
+ 5.5 - 5.3 (stat.) +- 2.5 (syst.)] SNU (1 sigma) or [62.9 + 6.0 - 5.9] SNU (1
sigma) with errors combined in quadrature. Overall, gallium based solar
observations at LNGS (first in GALLEX, later in GNO) lasted from May 14, 1991
through April 9, 2003. The joint result from 123 runs in GNO and GALLEX is
[69.3 +- 5.5 (incl. syst.)] SNU (1 sigma). The distribution of the individual
run results is consistent with the hypothesis of a neutrino flux that is
constant in time. Implications from the data in particle- and astrophysics are
reiterated.Comment: 22 pages incl. 9 Figures and 8 Tables. to appear in: Physics Letters
B (accepted April 13, 2005) PACS: 26.65.+t ; 14.60.P
The CUORE cryostat: an infrastructure for rare event searches at millikelvin temperatures
The CUORE experiment is the world's largest bolometric experiment. The
detector consists of an array of 988 TeO2 crystals, for a total mass of 742 kg.
CUORE is presently taking data at the Laboratori Nazionali del Gran Sasso,
Italy, searching for the neutrinoless double beta decay of 130Te. A large
custom cryogen-free cryostat allows reaching and maintaining a base temperature
of about 10 mK, required for the optimal operation of the detector. This
apparatus has been designed in order to achieve a low noise environment, with
minimal contribution to the radioactive background for the experiment. In this
paper, we present an overview of the CUORE cryostat, together with a
description of all its sub-systems, focusing on the solutions identified to
satisfy the stringent requirements. We briefly illustrate the various phases of
the cryostat commissioning and highlight the relevant steps and milestones
achieved each time. Finally, we describe the successful cooldown of CUORE
Measurement of the diffractive structure function in deep inelastic scattering at HERA
This paper presents an analysis of the inclusive properties of diffractive
deep inelastic scattering events produced in interactions at HERA. The
events are characterised by a rapidity gap between the outgoing proton system
and the remaining hadronic system. Inclusive distributions are presented and
compared with Monte Carlo models for diffractive processes. The data are
consistent with models where the pomeron structure function has a hard and a
soft contribution. The diffractive structure function is measured as a function
of \xpom, the momentum fraction lost by the proton, of , the momentum
fraction of the struck quark with respect to \xpom, and of . The \xpom
dependence is consistent with the form \xpoma where
in all bins of and
. In the measured range, the diffractive structure function
approximately scales with at fixed . In an Ingelman-Schlein type
model, where commonly used pomeron flux factor normalisations are assumed, it
is found that the quarks within the pomeron do not saturate the momentum sum
rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil
Observation of hard scattering in photoproduction events with a large rapidity gap at HERA
Events with a large rapidity gap and total transverse energy greater than 5
GeV have been observed in quasi-real photoproduction at HERA with the ZEUS
detector. The distribution of these events as a function of the
centre of mass energy is consistent with diffractive scattering. For total
transverse energies above 12 GeV, the hadronic final states show predominantly
a two-jet structure with each jet having a transverse energy greater than 4
GeV. For the two-jet events, little energy flow is found outside the jets. This
observation is consistent with the hard scattering of a quasi-real photon with
a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil
Protons in near earth orbit
The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured
by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at
an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is
parameterized by a power law. Below the geomagnetic cutoff a substantial second
spectrum was observed concentrated at equatorial latitudes with a flux ~ 70
m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated
trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure
Search for antihelium in cosmic rays
The Alpha Magnetic Spectrometer (AMS) was flown on the space shuttle
Discovery during flight STS-91 in a 51.7 degree orbit at altitudes between 320
and 390 km. A total of 2.86 * 10^6 helium nuclei were observed in the rigidity
range 1 to 140 GV. No antihelium nuclei were detected at any rigidity. An upper
limit on the flux ratio of antihelium to helium of < 1.1 * 10^-6 is obtained.Comment: 18 pages, Latex, 9 .eps figure
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