Adaptive Eigenvalue Computation - Complexity Estimates

This paper is concerned with the design and analysis of a fully adaptive eigenvalue solver for linear symmetric operators. After transforming the original problem into an equivalent one formulated on $\ell_2$, the space of square summable sequences, the problem becomes sufficiently well conditioned so that a gradient type iteration can be shown to reduce the error by some fixed factor per step. It then remains to realize these (ideal) iterations within suitable dynamically updated error tolerances. It is shown under which circumstances the adaptive scheme exhibits in some sense asymptotically optimal complexity.Comment: submitted to Math. Com

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapies with particular emphasis on tyrosine kinase inhibitors (TKIs). TKIs are a class of compounds that inhibits tyrosine kinases, thereby preventing the dissemination of growth signals and activation of key cellular proteins that are involved in cell growth and division. Because they have been shown to inhibit key kinases in both B cells and T cells that are involved in the pathophysiology of cGvHD, TKIs present new promising therapeutic approaches. Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy. Also, Janus Associated Kinases (JAK1 and JAK2) inhibitors, such as itacitinib (JAK1) and ruxolitinib (JAK1 and 2), are promising in the treatment of cGvHD. Herein, we present the current status and future directions of the use of these new drugs with particular spotlight on their targeting of specific intracellular signal transduction cascades important for cGvHD, in order to shed some light on their possible mode of actions

Statistical properties of 243^{243}Pu, and 242^{242}Pu(n,γ\gamma) cross section calculation

The level density and gamma-ray strength function (gammaSF) of 243Pu have been measured in the quasi-continuum using the Oslo method. Excited states in 243Pu were populated using the 242Pu(d,p) reaction. The level density closely follows the constant-temperature level density formula for excitation energies above the pairing gap. The gammaSF displays a double-humped resonance at low energy as also seen in previous investigations of actinide isotopes. The structure is interpreted as the scissors resonance and has a centroid of omega_{SR}=2.42(5)MeV and a total strength of B_{SR}=10.1(15)mu_N^2, which is in excellent agreement with sum-rule estimates. The measured level density and gammaSF were used to calculate the 242Pu(n,gamma) cross section in a neutron energy range for which there were previously no measured data.Comment: 9 pages, 8 figure

Chromatin accessibility dynamics across C. elegans development and ageing

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, more than 1000 promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements changes during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing

Vacancy Control in Acene Blends Links Exothermic Singlet Fission to Coherence

The fission of singlet excitons into triplet pairs in organic materials holds great technological promise, but the rational application of this phenomenon is hampered by a lack of understanding of its complex photophysics. Here, we use the controlled introduction of vacancies by means of spacer molecules in tetracene and pentacene thin films as a tuning parameter complementing experimental observables to identify the operating principles of different singlet fission pathways. Time-resolved spectroscopic measurements in combination with microscopic modelling enables us to demonstrate distinct scenarios, resulting from different singlet-to-triplet pair energy alignments. For pentacene, where fission is exothermic, coherent mixing between the photoexcited singlet and triplet-pair states is promoted by vibronic resonances, which drives the fission process with little sensitivity to the vacancy concentration. Such vibronic resonances do not occur for endothermic materials such as tetracene, for which we find fission to be fully incoherent; a process that is shown to slow down with increasing vacancy concentration