509 research outputs found
Reaction rate for two--neutron capture by He
Recent investigations suggest that the neutrino--heated hot bubble between
the nascent neutron star and the overlying stellar mantle of a type--II
supernova may be the site of the r--process. In the preceding --process
building up the elements to , the He(2n,)He--
and He(,n)Be--reactions bridging the instability gap at
and could be of relevance. We suggest a mechanism for
He(2n,)He and calculate the reaction rate within the
+n+n approach. The value obtained is about a factor 1.6 smaller than
the one obtained recently in the simpler direct--capture model, but is at least
three order of magnitude enhanced compared to the previously adopted value. Our
calculation confirms the result of the direct--capture calculation that under
representative conditions in the --process the reaction path proceeding
through He is negligible compared to He(n,)Be.Comment: 13 pages, 4 postscript figures, to appear in "Zeitschrift f. Physik
A", changed internet address and filename, the uuencoded postscript file
including the figures is available at
ftp://is1.kph.tuwien.ac.at/pub/ohu/twoneutron.u
Halo Excitation of He in Inelastic and Charge-Exchange Reactions
Four-body distorted wave theory appropriate for nucleon-nucleus reactions
leading to 3-body continuum excitations of two-neutron Borromean halo nuclei is
developed. The peculiarities of the halo bound state and 3-body continuum are
fully taken into account by using the method of hyperspherical harmonics. The
procedure is applied for A=6 test-bench nuclei; thus we report detailed studies
of inclusive cross sections for inelastic He(p,p')He and
charge-exchange Li(n,p)He reactions at nucleon energy 50 MeV. The
theoretical low-energy spectra exhibit two resonance-like structures. The first
(narrow) is the excitation of the well-known three-body resonance. The
second (broad) bump is a composition of overlapping soft modes of
multipolarities whose relative weights depend on
transferred momentum and reaction type. Inelastic scattering is the most
selective tool for studying the soft dipole excitation mode.Comment: Submitted to Phys. Rev. C., 11 figures using eps
Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL
Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and
adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to
greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic
approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to
inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development.
Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71
ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block
copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty
pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor
development was observed in the hOPG group as compared to control groups. Marked bone lesions were
revealed by micro-computed tomography analyses in control groups whereas a normal bone microarchitecture
was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was
expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment
may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition.
In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor
and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the
relevance of blocking RANKL by OPG as a promising therapy in ES
Gene expression profiling of Ewing sarcoma tumours reveals the prognostic importance of tumourâstromal interactions: a report from the Children's Oncology Group
Relapse of Ewing sarcoma (ES) can occur months or years after initial remission, and salvage therapy for relapsed disease is usually ineffective. Thus, there is great need to develop biomarkers that can predict which patients are at risk for relapse so that therapy and postâtherapy evaluation can be adjusted accordingly. For this study, we performed whole genome expression profiling on two independent cohorts of clinically annotated ES tumours in an effort to identify and validate prognostic gene signatures. ES specimens were obtained from the Children's Oncology Group and whole genome expression profiling performed using Affymetrix Human Exon 1.0 ST arrays. Lists of differentially expressed genes between survivors and nonâsurvivors were used to identify prognostic gene signatures. An independent cohort of tumours from the EuroâEwing cooperative group was similarly analysed as a validation cohort. Unsupervised clustering of gene expression data failed to segregate tumours based on outcome. Supervised analysis of survivors versus nonâsurvivors revealed a small number of differentially expressed genes and several statistically significant gene signatures. Geneâspecific enrichment analysis demonstrated that integrin and chemokine genes were associated with survival in tumours where stromal contamination was present. Tumours that did not harbour stromal contamination showed no association of any genes or pathways with clinical outcome. Our results reflect the challenges of performing RNAâbased assays on archived bone tumour specimens. In addition, they reveal a key role for tumour stroma in determining ES prognosis. Future biological and clinical investigations should focus on elucidating the contribution of tumour:microâenvironment interactions on ES progression and response to therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111186/1/cjp29.pd
Targeted Morphoproteomic Profiling of Ewing's Sarcoma Treated with Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors: Response/Resistance Signatures
Insulin-like growth factor 1 receptor (IGF1R) targeted therapies have resulted in responses in a small number of patients with advanced metastatic Ewing's sarcoma. We performed morphoproteomic profiling to better understand response/resistance mechanisms of Ewing's sarcoma to IGF1R inhibitor-based therapy.This pilot study assessed two patients with advanced Ewing's sarcoma treated with IGF1R antibody alone followed by combined IGF1R inhibitor plus mammalian target of rapamycin (mTOR) inhibitor treatment once resistance to single-agent IGF1R inhibitor developed. Immunohistochemical probes were applied to detect p-mTOR (Ser2448), p-Akt (Ser473), p-ERK1/2 (Thr202/Tyr204), nestin, and p-STAT3 (Tyr 705) in the original and recurrent tumor. The initial remarkable radiographic responses to IGF1R-antibody therapy was followed by resistance and then response to combined IGF1R plus mTOR inhibitor therapy in both patients, and then resistance to the combination regimen in one patient. In patient 1, upregulation of p-Akt and p-mTOR in the tumor that relapsed after initial response to IGF1R antibody might explain the resistance that developed, and the subsequent response to combined IGF1R plus mTOR inhibitor therapy. In patient 2, upregulation of mTOR was seen in the primary tumor, perhaps explaining the initial response to the IGF1R and mTOR inhibitor combination, while the resistant tumor that emerged showed activation of the ERK pathway as well.Morphoproteomic analysis revealed that the mTOR pathway was activated in these two patients with advanced Ewing's sarcoma who showed response to combined IGF1R and mTOR inhibition, and the ERK pathway in the patient in whom resistance to this combination emerged. Our pilot results suggests that morphoproteomic assessment of signaling pathway activation in Ewing's sarcoma merits further investigation as a guide to understanding response and resistance signatures
Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.
METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible.
RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count â„13.0 Ă 103/ÎŒL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count \u3c250 \u3eĂ 103/ÎŒL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated â„4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count â„13.0 Ă 103/ÎŒL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration â„4 days following diarrhea onset (2.71 [1.18-6.21]).
CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring
Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function
It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signalling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/ÎČ (LXR/LXRÎČ), peroxisome proliferator-activated receptor Îł (PPAR-Îł), estrogen receptors α/ÎČ (ERα/ÎČ) and sterol regulatory element-binding proteins (SREBPs) in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed
T=1 states in Rb74 and their Kr74 analogs
Charge symmetry breaking effects that perturb analog symmetry between nuclei are usually small but are important in extracting reliable Fermi matrix elements from "superallowed" ÎČ decays and testing conserved vector current theory, especially for the heavier cases. We have used the Ca40(Ar36, pn)Rb74 and Ca40(Ca40,αpn)Rb74 reactions at 108, 123 and 160 MeV, respectively, to populate Rb74 and determine the analog distortion through comparison of T=1 states in Rb74 with their corresponding Kr74 levels. We have traced the analogs of the Kr74 ground-state band in Rb74 to a candidate spin J=8 state and determined the Coulomb energy differences. They are small and positive and increase smoothly with spin. New T=0 states were found that better delineate the deformed band structure and clarify the steps in deexcitation from high spin. A new T=0 band was found. No evidence was found for Îł decay to or from a low-lying JÏ=0+ state in Rb74 despite a careful search
Terminating states in the positive-parity structures of As 67
The energy levels and γ-ray decay scheme of the positive-parity states in the Tz=12 nucleus As67 have been studied by using the Ca40(Ar36,2αp)As67 reaction at a beam energy of 145 MeV. Two new band structures have been identified which can be connected to the previously known levels. The results for these bands are compared with configuration-dependent cranked Nilsson-Strutinsky calculations. The good level of agreement between theory and experiment suggests that these structures can be interpreted in terms of configurations that involve three g92 particles and that both possess noncollective terminating states
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