Universality of Phases in QCD and QCD-like Theories

We argue that the whole or the part of the phase diagrams of QCD and QCD-like theories should be universal in the large-N_c limit through the orbifold equivalence. The whole phase diagrams, including the chiral phase transitions and the BEC-BCS crossover regions, are identical between SU(N_c) QCD at finite isospin chemical potential and SO(2N_c) and Sp(2N_c) gauge theories at finite baryon chemical potential. Outside the BEC-BCS crossover region in these theories, the phase diagrams are also identical to that of SU(N_c) QCD at finite baryon chemical potential. We give examples of the universality in some solvable cases: (i) QCD and QCD-like theories at asymptotically high density where the controlled weak-coupling calculations are possible, (ii) chiral random matrix theories of different universality classes, which are solvable large-N (large volume) matrix models of QCD. Our results strongly suggest that the chiral phase transition and the QCD critical point at finite baryon chemical potential can be studied using sign-free theories, such as QCD at finite isospin chemical potential, in lattice simulations.Comment: v1: 35 pages, 6 figures; v2: 37 pages, 6 figures, minor improvements, conclusion unchanged; v3: version published in JHE

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Singular values of the Dirac operator in dense QCD-like theories

We study the singular values of the Dirac operator in dense QCD-like theories at zero temperature. The Dirac singular values are real and nonnegative at any nonzero quark density. The scale of their spectrum is set by the diquark condensate, in contrast to the complex Dirac eigenvalues whose scale is set by the chiral condensate at low density and by the BCS gap at high density. We identify three different low-energy effective theories with diquark sources applicable at low, intermediate, and high density, together with their overlapping domains of validity. We derive a number of exact formulas for the Dirac singular values, including Banks-Casher-type relations for the diquark condensate, Smilga-Stern-type relations for the slope of the singular value density, and Leutwyler-Smilga-type sum rules for the inverse singular values. We construct random matrix theories and determine the form of the microscopic spectral correlation functions of the singular values for all nonzero quark densities. We also derive a rigorous index theorem for non-Hermitian Dirac operators. Our results can in principle be tested in lattice simulations.Comment: 3 references added, version published in JHE

Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r(2 )= 0.8). A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r(2 )= 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types

The C. elegans Opa1 Homologue EAT-3 Is Essential for Resistance to Free Radicals

The C. elegans eat-3 gene encodes a mitochondrial dynamin family member homologous to Opa1 in humans and Mgm1 in yeast. We find that mutations in the C. elegans eat-3 locus cause mitochondria to fragment in agreement with the mutant phenotypes observed in yeast and mammalian cells. Electron microscopy shows that the matrices of fragmented mitochondria in eat-3 mutants are divided by inner membrane septae, suggestive of a specific defect in fusion of the mitochondrial inner membrane. In addition, we find that C. elegans eat-3 mutant animals are smaller, grow slower, and have smaller broodsizes than C. elegans mutants with defects in other mitochondrial fission and fusion proteins. Although mammalian Opa1 is antiapoptotic, mutations in the canonical C. elegans cell death genes ced-3 and ced-4 do not suppress the slow growth and small broodsize phenotypes of eat-3 mutants. Instead, the phenotypes of eat-3 mutants are consistent with defects in oxidative phosphorylation. Moreover, eat-3 mutants are hypersensitive to paraquat, which promotes damage by free radicals, and they are sensitive to loss of the mitochondrial superoxide dismutase sod-2. We conclude that free radicals contribute to the pathology of C. elegans eat-3 mutants

An Analysis of the Myocardial Transcriptome in a Mouse Model of Cardiac Dysfunction with Decreased Cholinergic Neurotransmission

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KDHOM hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function

Bananas as an Energy Source during Exercise: A Metabolomics Approach

This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41±0.22, 2.36±0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R2Y(cum) = 0.869, Q2(cum) = 0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways

Phase I–II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer

Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I–II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 μg) was given on days 3–12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m−2). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m−2, respectively, and the recommended doses were 50 and 80 mg m−2. Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 nonhaematologic toxicities except fot nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39–78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61–711 days) and 415 days (range: 74–801 days). This new regimen is promising for cervical cancer