Helsinki Institute for Information Technology

About: Helsinki Institute for Information Technology is a facility organization based out in Espoo, Finland. It is known for research contribution in the topics: Population & Bayesian network. The organization has 630 authors who have published 1962 publications receiving 63426 citations.

RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses.

Abstract: Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations, RUNX1 mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate that PHF6 and BCORL1 mutations, IKZF1 deletions, and AID/RAG-mediated rearrangements are enriched in RUNX1mut BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primary RUNX1mut CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity of RUNX1mut blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells from RUNX1mut patients to be highly responsive for mTOR-, BCL2-, and VEGFR inhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygous RUNX1-/- and heterozygous RUNX1-/mut BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role of RUNX1 mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treating RUNX1mut BP-CML patients.

Automatical Composition of Lyrical Songs

Abstract: We address the challenging task of automatically composing lyrical songs with matching musical and lyrical features, and we present the first prototype, M.U. SicusApparatus, to accomplish the task. The focus of this paper is especially on generation of art songs (lieds). The proposed approach writes lyrics first and then composes music to match the lyrics. The crux is that the music composition subprocess has access to the internals of the lyrics writing subprocess, so the music can be composed to match the intentions and choices of lyrics writing, rather than just the surface of the lyrics. We present some example songs composed by M.U. Sicus, and we outline first steps towards a general system combining both music composition and writing of lyrics.

Contrasting the impact of cytotoxic and cytostatic drug therapies on tumour progression

Abstract: A tumour grows when the total division (birth) rate of its cells exceeds their total mortality (death) rate. The capability for uncontrolled growth within the host tissue is acquired via the accumulation of driver mutations which enable the tumour to progress through various hallmarks of cancer. We present a mathematical model of the penultimate stage in such a progression. We assume the tumour has reached the limit of its present growth potential due to cell competition that either results in total birth rate reduction or death rate increase. The tumour can then progress to the final stage by either seeding a metastasis or acquiring a driver mutation. We influence the ensuing evolutionary dynamics by cytotoxic (increasing death rate) or cytostatic (decreasing birth rate) therapy while keeping the effect of the therapy on net growth reduction constant. Comparing the treatments head to head we derive conditions for choosing optimal therapy. We quantify how the choice and the related gain of optimal therapy depends on driver mutation, metastasis, intrinsic cell birth and death rates, and the details of cell competition. We show that detailed understanding of the cell population dynamics could be exploited in choosing the right mode of treatment with substantial therapy gains.

Resilient connections for SSH and TLS

Abstract: Disconnection of an SSH shell or a secure application session due to network outages or travel is a familiar problem to many Internet users today In this paper, we extend the SSH and TLS protocols to support resilient connections that can span several sequential TCP connections The extensions allow sessions to survive both changes in IP addresses and long periods of disconnection Our design emphasizes deployability in real-world environments, and addresses many of the challenges identified in previous work, including assumptions made about network middleboxes such as firewalls and NATs We have also implemented the extensions in the OpenSSH and PureTLS software packages and tested them in practice