853 research outputs found
Momentum and Coordinate Space Three-nucleon Potentials
In this paper we give explicit formulae in momentum and coordinate space for
the three-nucleon potentials due to and meson exchange, derived
from off-mass-shell meson-nucleon scattering amplitudes which are constrained
by the symmetries of QCD and by the experimental data. Those potentials have
already been applied to nuclear matter calculations. Here we display additional
terms which appear to be the most important for nuclear structure. The
potentials are decomposed in a way that separates the contributions of
different physical mechanisms involved in the meson-nucleon amplitudes. The
same type of decomposition is presented for the TM force: the
, the chiral symmetry breaking and the nucleon pair terms are isolated.Comment: LATEX, 33 pages, 3 figures (available as postscript files upon
request
Blood transfusion in the critically ill: does storage age matter?
Morphologic and biochemical changes occur during red cell storage prior to product expiry, and these changes may hinder erythrocyte viability and function following transfusion. Despite a relatively large body of literature detailing the metabolic and structural deterioration that occurs during red cell storage, evidence for a significant detrimental clinical effect related to the transfusion of older blood is relatively less conclusive, limited primarily to observations in retrospective studies. Nonetheless, the implication that the transfusion of old, but not outdated blood may have negative clinical consequences demands attention. In this report, the current understanding of the biochemical and structural changes that occur during storage, known collectively as the storage lesion, is described, and the clinical evidence concerning the detrimental consequences associated with the transfusion of relatively older red cells is critically reviewed. Although the growing body of literature demonstrating the deleterious effects of relatively old blood is compelling, it is notable that all of these reports have been retrospective, and most of these studies have evaluated patients who received a mixture of red cell units of varying storage age. Until prospective studies have been completed and produce confirmative results, it would be premature to recommend any modification of current transfusion practice regarding storage age
Elevated Uptake of Plasma Macromolecules by Regions of Arterial Wall Predisposed to Plaque Instability in a Mouse Model
Atherosclerosis may be triggered by an elevated net transport of lipid-carrying
macromolecules from plasma into the arterial wall. We hypothesised that whether
lesions are of the thin-cap fibroatheroma (TCFA) type or are less fatty and more
fibrous depends on the degree of elevation of transport, with greater uptake leading
to the former. We further hypothesised that the degree of elevation can depend on
haemodynamic wall shear stress characteristics and nitric oxide synthesis. Placing
a tapered cuff around the carotid artery of apolipoprotein E -/- mice modifies
patterns of shear stress and eNOS expression, and triggers lesion development at
the upstream and downstream cuff margins; upstream but not downstream lesions
resemble the TCFA. We measured wall uptake of a macromolecular tracer in the
carotid artery of C57bl/6 mice after cuff placement. Uptake was elevated in the
regions that develop lesions in hyperlipidaemic mice and was significantly more
elevated where plaques of the TCFA type develop. Computational simulations and
effects of reversing the cuff orientation indicated a role for solid as well as fluid
mechanical stresses. Inhibiting NO synthesis abolished the difference in uptake
between the upstream and downstream sites. The data support the hypothesis that
excessively elevated wall uptake of plasma macromolecules initiates the
development of the TCFA, suggest that such uptake can result from solid and fluid
mechanical stresses, and are consistent with a role for NO synthesis. Modification
of wall transport properties might form the basis of novel methods for reducing
plaque rupture
Alterations of the retinoblastoma gene in metastatic breast cancer
Germline mutations affecting the retinoblastoma gene (RB1) predispose to inherited retinoblastomas but also other malignancies, including breast cancer. While somatic RB1 mutations have been detected in different malignancies, information about the potential role of RB1 mutations in breast cancer is limited. Recently, we discovered RB1 mutations to be associated with resistance to anthracyclines/mitomycin in primary breast cancer. The present work is the first report evaluating RB1 mutation and epigenetic status in metastatic breast cancer. Among 148 breast cancer samples analyzed by MLPA, four samples harbored intragenic deletions/duplications: Thus, exons 1â2 were deleted in two tumors and exons 21â23 in one tumor, while one sample harbored duplication of exons 18â23. The entire RB1 gene was duplicated in two tumors and multiple amplifications were revealed in one sample. Reduced copy number was observed in 17 samples (11.5%). No point mutation or promoter hypermethylation was discovered (n = 38 and 114 tumors analyzed, respectively). Interestingly, among seven tumors expressing lack of response to epirubicin, two samples harbored alterations in RB1, contrasting none out of 16 tumors with stable disease or an objective response (P = 0.08). In summary, the frequency of RB1 alterations in metastatic lesions was not increased when compared to primary breast cancer, indicating that RB1 alterations do not play a major role in metastatic development. While a non-significant association suggesting RB1 alterations to be linked to therapy resistance was observed, our data do not suggest a major role for RB1 alterations explaining acquired drug resistance
The deuteron: structure and form factors
A brief review of the history of the discovery of the deuteron in provided.
The current status of both experiment and theory for the elastic electron
scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic
Dual Anti-OX40/IL-2 Therapy Augments Tumor Immunotherapy via IL-2R-Mediated Regulation of OX40 Expression
The provision of T cell co-stimulation via members of the TNFR super-family, including OX40 (CD134) and 4-1BB (CD137), provides critical signals that promote T cell survival and differentiation. Recent studies have demonstrated that ligation of OX40 can augment T cell-mediated anti-tumor immunity in pre-clinical models and more importantly, OX40 agonists are under clinical development for cancer immunotherapy. OX40 is of particular interest as a therapeutic target as it is not expressed on naĂŻve T cells but rather, is transiently up-regulated following TCR stimulation. Although TCR engagement is necessary for inducing OX40 expression, the downstream signals that regulate OX40 itself remain unclear. In this study, we demonstrate that OX40 expression is regulated through a TCR and common gamma chain cytokine-dependent signaling cascade that requires JAK3-mediated activation of the downstream transcription factors STAT3 and STAT5. Furthermore, combined treatment with an agonist anti-OX40 mAb and IL-2 augmented tumor immunotherapy against multiple tumor types. Dual therapy was also able to restore the function of anergic tumor-reactive CD8 T cells in mice with long-term well-established (>5 wks) tumors, leading to increased survival of the tumor-bearing hosts. Together, these data reveal the ability of TCR/common gamma chain cytokine signaling to regulate OX40 expression and demonstrate a novel means of augmenting cancer immunotherapy by providing dual anti-OX40/common gamma chain cytokine-directed therapy
Comparison of germinal center markers CD10, BCL6 and human germinal center-associated lymphoma (HGAL) in follicular lymphomas
<p>Abstract</p> <p>Background</p> <p>Recently, human germinal center-associated lymphoma (HGAL) gene protein has been proposed as an adjunctive follicular marker to CD10 and BCL6.</p> <p>Methods</p> <p>Our aim was to evaluate immunoreactivity for HGAL in 82 cases of follicular lymphomas (FLs) - 67 nodal, 5 cutaneous and 10 transformed - which were all analysed histologically, by immunohistochemistry and PCR.</p> <p>Results</p> <p>Immunostaining for HGAL was more frequently positive (97.6%) than that for BCL6 (92.7%) and CD10 (90.2%) in FLs; the cases negative for bcl6 and/or for CD10 were all positive for HGAL, whereas the two cases negative for HGAL were positive with BCL6; no difference in HGAL immunostaining was found among different malignant subtypes or grades.</p> <p>Conclusions</p> <p>Therefore, HGAL can be used in the immunostaining of FLs as the most sensitive germinal center (GC)-marker; when applied alone, it would half the immunostaining costs, reserving the use of the other two markers only to HGAL-negative cases.</p
Twistor methods for AdS5
We consider the application of twistor theory to five-dimensional anti-de
Sitter space. The twistor space of AdS is the same as the ambitwistor space
of the four-dimensional conformal boundary; the geometry of this correspondence
is reviewed for both the bulk and boundary. A Penrose transform allows us to
describe free bulk fields, with or without mass, in terms of data on twistor
space. Explicit representatives for the bulk-to-boundary propagators of scalars
and spinors are constructed, along with twistor action functionals for the free
theories. Evaluating these twistor actions on bulk-to-boundary propagators is
shown to produce the correct two-point functions.Comment: 24 pages, 4 figures. v2: typos fixed, published versio
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A Search for Dark Higgs Bosons
Recent astrophysical and terrestrial experiments have motivated the proposal
of a dark sector with GeV-scale gauge boson force carriers and new Higgs
bosons. We present a search for a dark Higgs boson using 516 fb-1 of data
collected with the BABAR detector. We do not observe a significant signal and
we set 90% confidence level upper limits on the product of the Standard
Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots
for b/w printin
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