Noncommutative Thermofield Dynamics

The real-time operator formalism for thermal quantum field theories, thermofield dynamics, is formulated in terms of a path-integral approach in non-commutative spaces. As an application, the two-point function for a thermal non-commutative $\lambda \phi^4$ theory is derived at the one-loop level. The effect of temperature and the non-commutative parameter, competing with one another, is analyzed.Comment: 13 pages; to be published in IJMP-A

Yang-Mills Action from Open Superstring Field Theory

We calculate the effective action for nonabelian gauge bosons up to quartic order using WZW-like open superstring field theory. After including level zero and level one contributions, we obtain with 75% accuracy the Yang-Mills quartic term. We then prove that the complete effective action reproduces the exact Yang-Mills quartic term by analytically performing a summation over the intermediate massive states.Comment: 10 page

Thermofield Dynamics for Twisted Poincare-Invariant Field Theories: Wick Theorem and S-matrix

Poincare invariant quantum field theories can be formulated on non-commutative planes if the statistics of fields is twisted. This is equivalent to state that the coproduct on the Poincare group is suitably twisted. In the present work we present a twisted Poincare invariant quantum field theory at finite temperature. For that we use the formalism of Thermofield Dynamics (TFD). This TFD formalism is extend to incorporate interacting fields. This is a non trivial step, since the separation in positive and negative frequency terms is no longer valid in TFD. In particular, we prove the validity of Wick's theorem for twisted scalar quantum field at finite temperature.Comment: v1: 25 pages, no figure v2: references added; typos corrected; typo in title correcte

Quantum Fields on the Groenewold-Moyal Plane

We give an introductory review of quantum physics on the noncommutative spacetime called the Groenewold-Moyal plane. Basic ideas like star products, twisted statistics, second quantized fields and discrete symmetries are discussed. We also outline some of the recent developments in these fields and mention where one can search for experimental signals.Comment: 50 pages, 3 figures. v2: published versio

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis.

peer reviewedSystemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released

Noncommutative effects in astrophysical objects: a survey

The main implications of noncommutativity over astrophysical objects are examined. Noncommutativity is introduced through a deformed dispersion relation $E^{2}=p^{2}c^{2}(1+\lambda E)^{2} + m^{2}c^{4}$ and the relevant thermodynamical quantities are calculated using the grand canonical ensemble formalism. These results are applied to simple physical models describing main-sequence stars, white-dwarfs and neutron stars. The stability of main-sequence stars and white dwarfs is discussed.Comment: 10 pages. Talk presented by C. Z. at the "First Mediterranean Conference on Classical and Quantum Gravity", Kolymbari (Crete, Greece), September 14-18, 2009. To appear in the Proceeding

Allogeneic hsct with reduced intensity conditioning regimens in high risk patients with myelofibrosis

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Impact of the rs1024611 polymorphism of ccl2 on the pathophysiology and outcome of primary myelofibrosis

Single nucleotide polymorphisms (SNPs) can modify the individual pro-inflammatory background and may therefore have relevant implications in the MPN setting, typified by aberrant cytokine production. In a cohort of 773 primary myelofibrosis (PMF), we determined the contribution of the rs1024611 SNP of CCL2—one of the most potent immunomodulatory chemokines—to the clinical and biological characteristics of the disease, demonstrating that male subjects carrying the homozygous genotype G/G had an increased risk of PMF and that, among PMF patients, the G/G genotype is an independent prognostic factor for reduced overall survival. Functional characterization of the SNP and the CCL2-CCR2 axis in PMF showed that i) homozygous PMF cells are the highest chemokine producers as compared to the other genotypes; ii) PMF CD34+ cells are a selective target of CCL2, since they uniquely express CCR2 (CCL2 receptor); iii) activation of the CCL2-CCR2 axis boosts pro-survival signals induced by driver mutations via Akt phosphorylation; iv) ruxolitinib effectively counteracts CCL2 production and down-regulates CCR2 expression in PMF cells. In conclusion, the identification of the role of the CCL2/CCR2 chemokine system in PMF adds a novel element to the pathophysiological picture of the disease, with clinical and therapeutic implications

Synergistic Cytotoxic Effect of Busulfan and the PARP Inhibitor Veliparib in Myeloproliferative Neoplasms

ABSTRACT Patients with high-risk myeloproliferative neoplasms (MPNs), and in particular myelofibrosis (MF), can be cured only with allogeneic hematopoietic stem cell transplantation (HSCT). Because MPNs and JAK2V617F-mutated cells show genomic instability, stalled replication forks, and baseline DNA double-strand breaks, DNA repair inhibition with poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors represents a potential novel therapy. Because the alkylating agent busulfan is integral in conditioning regimens for HSCT and leads to stalled replication forks through DNA strand cross-linking, we hypothesized that PARP inhibition with veliparib in combination with busulfan may lead to synergistic cytotoxicity in MPN cells. We first treated 2 MPN cell lines harboring the JAK2V617F mutation (SET2 and HEL) with veliparib at increasing concentrations and measured cell proliferation. SET2 and HEL cells were relatively sensitive to veliparib (IC50 of 11.3 μM and 74.2 μM, respectively). We next treated cells with increasing doses of busulfan in combination with 4 μM veliparib and found that the busulfan IC50 decreased from 27 μM to 4 μM in SET2 cells and from 45.1 μM to 28.1 μM in HEL cells. The mean combination index was .55 for SET2 cells and .40 for HEL cells. Combination treatment of SET2 cells caused G2M arrest in 53% of cells, compared with 30% with veliparib alone and 35% with busulfan alone. G2M arrest was associated with activation of the ATR-Chk1 pathway, as shown by an immunofluorescence assay for phosphorylated Chk1 (p-Chk1). We then tested in vivo the effect of combined low doses of busulfan and veliparib in a JAK2V617F MPN-AML xenotransplant model. Vehicle- and veliparib-treated mice had similar median survival of 39 and 40 days, respectively. Combination treatment increased median survival from 47 days (busulfan alone) to 50 days (P = .02). Finally, we tested the combined effect of busulfan and veliparib on CD34+ cells obtained from the bone marrow or peripheral blood of 5 patients with JAK2V617F-mutated and 2 patients with CALR-mutated MF. MF cells treated with the combination of veliparib and busulfan showed reduced colony formation compared with busulfan alone (87% versus 68%; P = .001). In contrast, treatment of normal CD34+ cells with veliparib did not affect colony growth. Here we show that in vivo confirmation that treatment with the PARP-1 inhibitor veliparib and busulfan results in synergistic cytotoxicity in MPN cells. Our data provide the rationale for testing novel pretransplantation conditioning regimens with combinations of PARP-1 inhibition and reduced doses of alkylators, such as busulfan and melphalan, for high-risk MPNs or MPN-derived acute myelogenous leukemia