The differences in thermal profiles between normal and leukemic cells exposed to anticancer drug evaluated by differential scanning calorimetry

Chronic lymphocytic leukemia (CLL) is a heterogenous disease with an imbalance between apoptosis and cell proliferation. Therefore, the main goal in CLL therapy is to induce apoptosis and effectively support this process in transformed B lymphocytes. In the current study, we have compared differential scanning calorimetry (DSC) profiles of nuclei isolated from CLL cells and normal mononuclear cells exposed to cladribine or fludarabine combined with mafosfamide (CM; FM), and additionally to CM combined with monoclonal antibody—rituximab (RCM) for 48 h, as well as in culture medium only (controls). Under current study, the mononuclear cells from peripheral blood (PBMCs) of healthy individuals have been included. The obtained results have shown the presence of thermal transition at 95 ± 5 °C in most of nuclear preparations (92.2 %) isolated from blood of CLL patients. This thermal characteristic parameter was changed after drug exposure, however, to a different extent. These thermal changes were accompanied by the decrease of cell viability, an elevation of apoptosis rate and the changes in expression/proteolysis of poly(ADP-ribose)polymerase-1—main marker of apoptosis. Importantly, in DSC profiles of nuclear preparations of PBMCs from blood of healthy donors exposed to investigated drug combinations and control CLL cells, the lack of such changes was observed. Our results confirmed that DSC technique complemented with other biological approaches could be helpful in tailoring therapy for CLL patients.Research was sponsored by Grant from the Polish National Science Centre (No. 2011/01/B/NZ/0102); Results of presented study were partially presented in oral presentation on 2nd Central and Eastern European Conference on Thermal Analysis and Calorimetry in Vilnius, Lithuania, 201

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2  M_{⊙} and 1.0  M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14  yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200]  Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2  M_{⊙}<1.0  M_{⊙} is f_{PBH}≡Ω_{PBH}/Ω_{DM}≲6%. This improves existing constraints on primordial black hole abundance by a factor of ∼3. The other is a dissipative dark matter model, in which fermionic dark matter can collapse and form black holes. The upper limit on the fraction of dark matter black holes depends on the minimum mass of the black holes that can be formed: the most constraining result is obtained at M_{min}=1  M_{⊙}, where f_{DBH}≡Ω_{DBH}/Ω_{DM}≲0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO???s and Advanced Virgo???s Third Observing Run

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M⊙ and 1.0 M⊙ in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q ≥ 0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^−1. This implies an upper limit on the merger rate of subsolar binaries in the range [220−24200] Gpc^−3 yr^−1,depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M⊙ < m PBH < 1.0 M⊙ is f PBH ≡ Ω PBH/Ω DM ≲ 6%. This improves existing constraints on primordial black hole abundance by a factor of ∼3. The other is a dissipative dark matter model, in which fermionic dark matter can collapse and form black holes. The upper limit on the fraction of dark matter black holes depends on the minimum mass of the black holes that can be formed: the most constraining result is obtained at M min = 1 M⊙, where f DBH ≡ Ω DBH/Ω DM ≲ 0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses