Polarization Effects in Superdeformed Nuclei

A detailed theoretical investigation of polarization effects in superdeformed nuclei is performed. In the pure harmonic oscillator potential it is shown that when one particle (or hole) with the mass single-particle quadrupole moment q_{nu} is added to a superdeformed core, the change of the electric quadrupole moment can be parameterized as q_{eff}=e(bq_{nu}+a), and analytical expressions are derived for the two parameters, $a$ and $b$. Simple numerical expressions for q_{eff}(q_\nu}) are obtained in the more realistic modified oscillator model. It is also shown that quadrupole moments of nuclei with up to 10 particles removed from the superdeformed core of 152Dy can be well described by simply subtracting effective quadrupole moments of the active single-particle states from the quadrupole moment of the core. Tools are given for estimating the quadrupole moment for possible configurations in the superdeformed A 150-region.Comment: 28 pages including 9 figure

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p <0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Microscopic Properties of Superdeformed Nuclei

Many high spin rotational bands in superdeformed nuclei have been found in the A ~ 140-150 region, but so far no linking transitions to known normal-deformed states have been found in these nuclei. Therefore, configuration and spin assignments have to be based on indirect spectroscopic information. Identical bands were first discovered in this region of superdeformed shapes. At present, some identical bands have also been found at normal deformation, but such bands are more common at superdeformation. Recently lifetime measurements have given relative quadrupole moments with high accuracy. Spectroscopic quantities are calculated using the configuration constrained cranked Nilsson-Strutinsky model with the modified oscillator potential. In a statistical study the occurrence of identical bands is tested. Comparing superdeformed and normal deformed nuclei, the higher possibility for identical bands at superdeformation is understood from calculated reduced widths of the Egamma and J(2) distributions. The importance of high-N orbitals for identical bands is also discussed. Additivity of electric quadrupole moment contributions in the superdeformed A ~ 150 region is discussed with the nucleus 152Dy as a core. In analytic harmonic oscillator calculations, the effective electric quadrupole moment qeff, i.e. the change in the total quadrupole moment caused by the added particle, is expressed as a simple function of the single-particle mass quadrupole moment qv. Also in realistic calculations, simple relations between qeff and qv can be used to estimate the total electric quadrupole moment, e.g. for the nucleus 142Sm, by adding the effect of 10 holes, to the total electric quadrupole moment of 152Dy. Furthermore, tools are given for estimating the quadrupole moment for possible configurations in the superdeformed A ~ 150 region. For the superdeformed region around 143Eu, configuration and spin assignments are made based on effective alignments. The region is connected to, and compared with, previously investigated 146-153Gd nuclei. The two regions show similarities but it appears difficult to get consistent alignments in the whole region around 143Eu

Phase behavior of an ionic surfactant with mixed monovalent/polymeric counterions

A "complex salt" of cetyltrimethylammonium (CTA(+)) with short (30 repeating units) polyacrylate (PA(-)) counterions has been synthesized. The phase diagrams of its aqueous mixtures with either the surfactant cetyltrimethylammonium acetate (CTAAc), or the polyelectrolyte NaPA, have been studied by visual inspection through crossed polarizers and by small-angle X-ray scattering. Both of the ternary phase diagrams are strikingly simple, containing only micellar, cubic micellar, and hexagonal phases. In the CTAPA/CTAAc/water system, the surfactant forms essentially spherical micelles above ca. 50 wt % of water, regardless of the counterion composition, and the system may serve as a model for charged colloids with mixed monovalent/polymeric counterions. The interactions between micelles varies from repulsive to attractive as the fraction of monovalent counterions is dec eased. This results, first, in a liquid-liquid phase separation between a concentrated branch and a dilute branch of the micellar phase and, finally, a crystallization of micelles into a cubic (Pm3n) phase in equilibrium with essentially pure water. Small fractions of polymeric counterions "melt" the cubic phase. This is attributed to heterogeneity: A small proportion of micelle pairs that share polymeric counterions experience strong attractions. In CTAPA/NaPA/water mixtures, the micelle-micelle interactions switch from attractive to repulsive as the NaPA content is increased. A similar effect occurs with added NaAc. Monte Carlo simulations of interactions between surfactant aggregates neutralized by mixed polymeric and monovalent counterions qualitatively reproduce all experimental trends and show that the dominating source of the attraction between the aggregates is polyion bridging

Role of Interferon Regulatory Factor 3 in Type I Interferon Responses in Rotavirus-Infected Dendritic Cells and Fibroblasts

The main pathway for the induction of type I interferons (IFN) by viruses is through the recognition of viral RNA by cytosolic receptors and the subsequent activation of interferon regulatory factor 3 (IRF-3), which drives IFN-α/β transcription. In addition to their role in inducing an antiviral state, type I IFN also play a role in modulating adaptive immune responses, in part via their effects on dendritic cells (DCs). Many viruses have evolved mechanisms to interfere with type I IFN induction, and one recently reported strategy for achieving this is by targeting IRF-3 for degradation, as shown for rotavirus nonstructural protein 1 (NSP1). It was therefore of interest to investigate whether rotavirus-exposed DCs would produce type I IFN and/or mature in response to the virus. Our results demonstrate that IRF-3 was rapidly degraded in rotavirus-infected mouse embryonic fibroblasts (MEFs) and type I IFN was not detected in these cultures. In contrast, rotavirus induced type I IFN production in myeloid DCs (mDCs), resulting in their activation. Type I IFN induction in response to rotavirus was reduced in mDCs from IRF-3(−/−) mice, indicating that IRF-3 was important for mediating the response. Exposure of mDCs to UV-treated rotavirus induced significantly higher type I IFN levels, suggesting that rotavirus-encoded functions also antagonized the response in DCs. However, in contrast to MEFs, this action was not sufficient to completely abrogate type I IFN induction, consistent with a role for DCs as sentinels for virus infection