Axion Cosmology Revisited

The misalignment mechanism for axion production depends on the temperature-dependent axion mass. The latter has recently been determined within the interacting instanton liquid model (IILM), and provides for the first time a well-motivated axion mass for all temperatures. We reexamine the constraints placed on the axion parameter space in the light of this new mass function. We find an accurate and updated constraint f_a \le 2.8(\pm2)\times 10^{11}\units{GeV} or m_a \ge 21(\pm2) \units{\mu eV} from the misalignment mechanism in the classic axion window (thermal scenario). However, this is superseded by axion string radiation which leads to f_a \lesssim 3.2^{+4}_{-2} \times 10^{10} \units{GeV} or m_a \gtrsim 0.20 ^{+0.2}_{-0.1} \units{meV}. In this analysis, we take care to precisely compute the effective degrees of freedom and, to fill a gap in the literature, we present accurate fitting formulas. We solve the evolution equations exactly, and find that analytic results used to date generally underestimate the full numerical solution by a factor 2-3. In the inflationary scenario, axions induce isocurvature fluctuations and constrain the allowed inflationary scale $H_I$. Taking anharmonic effects into account, we show that these bounds are actually weaker than previously computed. Considering the fine-tuning issue of the misalignment angle in the whole of the anthropic window, we derive new bounds which open up the inflationary window near $\theta_a \to \pi$. In particular, we find that inflationary dark matter axions can have masses as high as 0.01--1\units{meV}, covering the whole thermal axion range, with values of $H_I$ up to $10^9$GeV. Quantum fluctuations during inflation exclude dominant dark matter axions with masses above $m_a\lesssim 1$meV.Comment: 42 pages, 12 figures, version as accepted by Phys.Rev.

Temperature Dependence of Exciton Diffusion in Conjugated Polymers

The temperature dependence of the exciton dynamics in a conjugated polymer is studied using time-resolved spectroscopy. Photoluminescence decays were measured in heterostructured samples containing a sharp polymer-fullerene interface, which acts as an exciton quenching wall. Using a 1D diffusion model, the exciton diffusion length and diffusion coefficient were extracted in the temperature range of 4-293 K. The exciton dynamics reveal two temperature regimes: in the range of 4-150 K, the exciton diffusion length (coefficient) of ~3 nm (~1.5 × 10-4 cm2/s) is nearly temperature independent. Increasing the temperature up to 293 K leads to a gradual growth up to 4.5 nm (~3.2 × 10-4 cm2/s). This demonstrates that exciton diffusion in conjugated polymers is governed by two processes: an initial downhill migration toward lower energy states in the inhomogenously broadened density of states, followed by temperature activated hopping. The latter process is switched off below 150 K.

Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology

Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors. We find no evidence of mouse-specific clonal evolution in glioma PDOXs. Our cohort captures individual molecular genotypes for precision medicine including mutations in IDH1, ATRX, TP53, MDM2/4, amplification of EGFR, PDGFRA, MET, CDK4/6, MDM2/4, and deletion of CDKN2A/B, PTCH, and PTEN. Matched longitudinal PDOX recapitulate the limited genetic evolution of gliomas observed in patients following treatment. At the histological level, we observe increased vascularization in the rat host as compared to mice. PDOX-derived standardized glioma organoids are amenable to high-throughput drug screens that can be validated in mice. We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology