The COMPASS Collaboration at CERN has measured the transverse spin azimuthal asymmetry of charged hadrons produced in semi-inclusive deep inelastic scattering using a 160 GeV mu + beam and a ...transversely polarised NH3 target. The Collins asymmetry of the proton was extracted in the Bjorken x range 0.003 < x < 0.7 . These new precise measurements confirm previous measurements from the COMPASS and HERMES Collaborations, which exhibit a definite effect in the valence quark region. The asymmetries for negative and positive hadrons are similar in magnitude and opposite in sign. They are compatible with model calculations in which the u-quark transversity is opposite in sign and somewhat larger than the d-quark transversity distribution function. The asymmetry is extracted as a function of Bjorken x, the relative hadron energy z and the hadron transverse momentum p T h . The high statistics and quality of the data also allow for more detailed investigations of the dependence on the kinematic variables. These studies confirm the leading-twist nature of the Collins asymmetry.
XIAP Overexpression in Human Islets Prevents Early Posttransplant Apoptosis and Reduces the Islet Mass Needed to Treat Diabetes
Juliet A. Emamaullee 1 2 ,
Ray V. Rajotte 1 3 ,
Peter Liston 4 ,
Robert ...G. Korneluk 4 ,
Jonathan R.T. Lakey 1 3 5 ,
A.M. James Shapiro 1 3 5 and
John F. Elliott 1 2
1 Alberta Diabetes Institute (ADI), University of Alberta, Edmonton, Alberta, Canada
2 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
3 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
4 Solange-Gauthier-Karsh Molecular Genetics Laboratory, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada
5 Clinical Islet Program, University of Alberta, Edmonton, Alberta, Canada
Address correspondence and reprint requests to Dr. John F. Elliott, 1-21 Medical Sciences Building, Department of Medical
Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. E-mail: john.elliott{at}ualberta.ca
Abstract
The Edmonton Protocol for treatment of type 1 diabetes requires islets from two or more donors to achieve euglycemia in a
single recipient, primarily because soon after portal infusion, the majority of the transplanted cells undergo apoptosis due
to hypoxia and hypoxia reperfusion injury. X-linked inhibitor of apoptosis protein (XIAP) is a potent endogenous inhibitor
of apoptosis that is capable of blocking the activation of multiple downstream caspases, and XIAP overexpression has previously
been shown to enhance engraftment of a murine β-cell line. In this study, human islets transduced with a XIAP-expressing recombinant
adenovirus were resistant to apoptosis and functionally recovered following in vitro stresses of hypoxia and hypoxia with
reoxygenation (models reperfusion injury). Furthermore Ad-XIAP transduction dramatically reduced the number of human islets
required to reverse hyperglycemia in chemically diabetic immunodeficient mice. These results suggest that by transiently overexpressing
XIAP in the immediate posttransplant period, human islets from a single donor might be used to effectively treat two diabetic
recipients.
GAL, galactosidase
Hu-XIAP, human XIAP
TUNEL, TdT-mediated dUTP nick-end labeling
XIAP, X-linked inhibitor of apoptosis protein
Footnotes
Accepted June 20, 2005.
Received April 18, 2005.
DIABETES
Despite the success of the Edmonton protocol for human islet transplantation, an alternate source of islet tissue must be developed if beta-cell replacement therapy is to see widespread application. ...Neonatal porcine islets (NPI) represent one potential source of tissue. When human or rodent islets are transplanted, the majority of cells undergo hypoxia-induce apoptosis soon after the grafts are placed in the recipient. In the present study, we investigated whether NPI were similarly sensitive to hypoxia.
NPI were exposed to hypoxia and hypoxia/reoxygenation using an in vitro hypoxic chamber. Afterwards, viability, frequency of apoptosis, and beta-cell function were evaluated. NPI and adult porcine islets were transplanted into chemically diabetic, immunodeficient mice and graft apoptosis was assessed 24 hours and seven days posttransplant.
NPI demonstrated a remarkable capacity to resist apoptosis and maintain insulin secretion despite severe stresses such as hypoxia/reoxygenation. One day after transplantation, NPI grafts showed limited apoptosis, confined to rare strongly insulin positive cells. In contrast, adult porcine islet grafts underwent widespread apoptosis. Western blotting revealed that NPI express high levels of at least one potent endogenous antiapoptotic protein (XIAP).
The majority of cells within transplanted human islets undergo apoptosis soon after portal infusion. In contrast, NPI have the capacity to resist this early posttransplant apoptosis, with likely reduced antigen release and diminished immune stimulation. NPI appear to contain a population of insulin-low to insulin-negative pre-beta-cells, which are resistant to hypoxia-induced apoptosis and still capable of differentiating into mature beta-cells.
We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ...⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.
The semi-inclusive difference asymmetry Ah+−h− for hadrons of opposite charge has been measured by the COMPASS experiment at CERN. The data were collected in the years 2002–2004 using a 160 GeV ...polarised muon beam scattered off a large polarised 6LiD target in the kinematic range 0.006<x<0.7 and 1<Q2<100 (GeV/c)2. In leading order QCD (LO) the deuteron asymmetry Ah+−h− measures the valence quark polarisation and provides an evaluation of the first moment of Δuv+Δdv which is found to be equal to 0.40±0.07(stat.)±0.06(syst.) over the measured range of x at Q2=10 (GeV/c)2. When combined with the first moment of g1d previously measured on the same data, this result favours a non-symmetric polarisation of light quarks Δu¯=−Δd¯ at a confidence level of two standard deviations, in contrast to the often assumed symmetric scenario Δu¯=Δd¯=Δs¯=Δs.
The inclusive double-spin asymmetry, A1p, has been measured at COMPASS in deep-inelastic polarised muon scattering off a large polarised NH3 target. The data, collected in the year 2007, cover the ...range Q2>1(GeV/c)2, 0.004<x<0.7 and improve the statistical precision of g1p(x) by a factor of two in the region x<0.02. The new proton asymmetries are combined with those previously published for the deuteron to extract the non-singlet spin-dependent structure function g1NS(x,Q2). The isovector quark density, Δq3(x,Q2), is evaluated from a NLO QCD fit of g1NS. The first moment of Δq3 is in good agreement with the value predicted by the Bjorken sum rule and corresponds to a ratio of the axial and vector coupling constants |gA/gV|=1.28±0.07(stat.)±0.10(syst.).
The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the π- π- π+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave ...analysis has been performed on a sample of 420,000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV2/c2. The well-known resonances a1(1260), a2(1320), and π2(1670) are clearly observed. In addition, the data show a significant natural-parity exchange production of a resonance with spin-exotic quantum numbers J(PC)=1-+ at 1.66 GeV/c2 decaying to ρπ. The resonant nature of this wave is evident from the mass-dependent phase differences to the J(PC)=2-+ and 1++ waves. From a mass-dependent fit a resonance mass of (1660±10(-64)(+0)) MeV/c2 and a width of (269±21(-64)(+42)) MeV/c2 are deduced, with an intensity of (1.7±0.2)% of the total intensity.
The Q-weak experiment at Jefferson Laboratory measured the parity violating asymmetry (
A
P
V
) in elastic electron-proton scattering at small momentum transfer squared (
Q
2
=0.025 (
G
e
V
/
c
)
2
...), with the aim of extracting the proton’s weak charge (
Q
W
p
) to an accuracy of 5 %. As one of the major uncertainty contribution sources to
Q
W
p
,
Q
2
needs to be determined to ∼1 % so as to reach the proposed experimental precision. For this purpose, two sets of high resolution tracking chambers were employed in the experiment, to measure tracks before and after the magnetic spectrometer. Data collected by the tracking system were then reconstructed with dedicated software into individual electron trajectories for experimental kinematics determination. The Q-weak kinematics and the analysis scheme for tracking data are briefly described here. The sources that contribute to the uncertainty of
Q
2
are discussed, and the current analysis status is reported.
Neonatal porcine pancreases may be a potential source of islets for transplantation into patients with type 1 diabetes; however, whether these cellular grafts will be susceptible to damage by human ...natural antibody-mediated rejection remains controversial. Although we and others have demonstrated that porcine islets bind human IgG and IgM, it remains unknown if they express the xenoreactive antigen Gal alpha(1,3)Gal beta(1,4)GlcNAc-R (Gal epitope). In this study, by using the Gal-specific lectin IB4 for immunohistochemistry and fluorescence-activated cell sorter (FACS) analysis, we determined which cell types present in porcine neonatal islet cell (NIC) aggregates express the Gal epitope and which ones are susceptible to lysis by activation of the human complement. After FACS analysis, 30.0 +/- 3.0% of porcine NICs were shown to express Gal, whereas 70.0 +/- 2.0% did not. Histological assessment of Gal-expressing cells revealed that 54.9 +/- 8.8% stained positive for either insulin or glucagon. In contrast, 68.8 +/- 8.4% of the Gal-negative population stained positive for the pancreatic hormones insulin and glucagon. Incubation of either the Gal-positive or -negative cells with human AB serum plus complement for 1.5 h resulted in the lysis of >90% of the cells. These results demonstrate that porcine NIC aggregates are composed of Gal-expressing cells and that expression of Gal is not restricted to nonendocrine cells. Furthermore, both Gal-positive and Gal-negative cells are susceptible to human antibody/complement-mediated cytolysis, suggesting that this form of immunological destruction is an obstacle that will need to be overcome before porcine NIC aggregates can be used clinically.
Azimuthal asymmetries in semi-inclusive production of positive (
h
+
) and negative hadrons (
h
−
) have been measured by scattering 160 GeV muons off longitudinally polarised deuterons at CERN. The ...asymmetries were decomposed in several terms according to their expected modulation in the azimuthal angle
φ
of the outgoing hadron. Each term receives contributions from one or several spin and transverse-momentum-dependent parton distribution and fragmentation functions. The amplitudes of all
φ
-modulation terms of the hadron asymmetries integrated over the kinematic variables are found to be consistent with zero within statistical errors, while the constant terms are nonzero and equal for
h
+
and
h
−
within the statistical errors. The dependencies of the
φ
-modulated terms versus the Bjorken momentum fraction
x
, the hadron fractional momentum
z
, and the hadron transverse momentum
were studied. The
x
dependence of the constant terms for both positive and negative hadrons is in agreement with the longitudinal double-spin hadron asymmetries, measured in semi-inclusive deep-inelastic scattering. The
x
dependence of the sin
φ
-modulation term is less pronounced than that in the corresponding HERMES data. All other dependencies of the
φ
-modulation amplitudes are consistent with zero within the statistical errors.
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