Phonons, electronic charge response and electron-phonon interaction in the high-temperature superconductors

We investigate in the framework of linear response theory the complete phonon dispersion, phonon induced electronic charge response, electron-phonon interaction and dielectric and infrared properties of the high-temperature superconductors (HTSC's). In particular the experimentally observed strong renormalization of the in-plane oxygen bond-stretching modes (OBSM) which appear upon doping in the HTSC's is discussed. It is shown that the characteristic softening, indicating a strong EPI, is most likely a generic effect of the CuO plane and is driven by a nonlocal coupling of the displaced ions to the localized charge-fluctuations (CF's) at the Cu and O ions. The different behaviour of the OBSM during the insulator-metal transition via the underdoped phase is calculated and from a comparison of these modes conclusions about the electronic state in the HTSC's are drawn. The underdoped state is modelled in terms of a charge response which is insulator-like at the Cu and is competing with a metallic charge response at the O-network in the CuO plane. For the non-cuprate HTSC Ba-Bi-O also a strong renormalization of the OBSM is predicted. C-axis polarized infrared and Raman-active modes of the HTSC's are calculated in terms of CF's and anisotropic dipole-fluctuations and the problem of a metallic character of the BiO planes is studied.Interlayer phonons and their accompanying charge response are investigated. Depending on the interlayer coupling calculations are performed from the static, adiabatic- to the non-adiabatic regime.It is shown that phonon-plasmon mixing and a strong long-ranged non-adiabatic EPI becomes evident within a certain region around the c-axis. Both the OBSM and the non-adiabatic coupled c-axis phonon-plasmon modes are found to be important for pairing in the HTSC's.Comment: 65 pages,20 figures. Extended version to appear in Physica Status Solidi (b) 2004; figure 20 has been corrected; references have been adde

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Introduction

Introduction to Special Issue on John F. Kennedy