Hypoxia-inducible Factor-dependent Breast Cancer-mesenchymal Stem Cell Bidirectional Signaling Promotes Metastasis.

published_or_final_versio

Universal Behavior of Lyapunov Exponents in Unstable Systems

We calculate the Lyapunov exponents in a classical molecular dynamics framework. The system is composed of few hundreds particles interacting either through Yukawa (Nuclear) or Slater-Kirkwood (Atomic) forces. The forces are chosen to give an Equation of State that resembles the nuclear and the atomic $^4He$ Equation Of State respectively near the critical point for liquid-gas phase transition. We find the largest fluctuations for an initial "critical temperature". The largest Lyapunov exponents $\lambda$ are always positive and can be very well fitted near this "critical temperature" with a functional form $\lambda\propto |T-T_c|^{-\omega}$, where the exponent $\omega=0.15$ is independent of the system and mass number. At smaller temperatures we find that $\lambda\propto T~ ^{0.4498}$, a universal behavior characteristic of an order to chaos transition.Comment: 11 pages, RevTeX, 3 figures not included available upon reques

Exactly Solvable Models: The Road Towards a Rigorous Treatment of Phase Transitions in Finite Systems

We discuss exact analytical solutions of a variety of statistical models recently obtained for finite systems by a novel powerful mathematical method, the Laplace-Fourier transform. Among them are a constrained version of the statistical multifragmentation model, the Gas of Bags Model and the Hills and Dales Model of surface partition. Thus, the Laplace-Fourier transform allows one to study the nuclear matter equation of state, the equation of state of hadronic and quark gluon matter and surface partitions on the same footing. A complete analysis of the isobaric partition singularities of these models is done for finite systems. The developed formalism allows us, for the first time, to exactly define the finite volume analogs of gaseous, liquid and mixed phases of these models from the first principles of statistical mechanics and demonstrate the pitfalls of earlier works. The found solutions may be used for building up a new theoretical apparatus to rigorously study phase transitions in finite systems. The strategic directions of future research opened by these exact results are also discussed.Comment: Contribution to the ``World Consensus Initiative III, Texas A & M University, College Station, Texas, USA, February 11-17, 2005, 21

A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3-internal tandem duplication mutations, 23% FLT3–tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively

Quantum gate algorithm for reference-guided DNA sequence alignment

Reference-guided DNA sequencing and alignment is an important process in computational molecular biology. The amount of DNA data grows very fast, and many new genomes are waiting to be sequenced while millions of private genomes need to be re-sequenced. Each human genome has 3.2 B base pairs, and each one could be stored with 2 bits of information, so one human genome would take 6.4 B bits or about 760 MB of storage (National Institute of General Medical Sciences). Today most powerful tensor processing units cannot handle the volume of DNA data necessitating a major leap in computing power. It is, therefore, important to investigate the usefulness of quantum computers in genomic data analysis, especially in DNA sequence alignment. Quantum computers are expected to be involved in DNA sequencing, initially as parts of classical systems, acting as quantum accelerators. The number of available qubits is increasing annually, and future quantum computers could conduct DNA sequencing, taking the place of classical computing systems. We present a novel quantum algorithm for reference-guided DNA sequence alignment modeled with gate-based quantum computing. The algorithm is scalable, can be integrated into existing classical DNA sequencing systems and is intentionally structured to limit computational errors. The quantum algorithm has been tested using the quantum processing units and simulators provided by IBM Quantum, and its correctness has been confirmed.Comment: 19 pages, 13 figure

Studies in the statistical and thermal properties of hadronic matter under some extreme conditions

The thermal and statistical properties of hadronic matter under some extreme conditions are investigated using an exactly solvable canonical ensemble model. A unified model describing both the fragmentation of nuclei and the thermal properties of hadronic matter is developed. Simple expressions are obtained for quantities such as the hadronic equation of state, specific heat, compressibility, entropy, and excitation energy as a function of temperature and density. These expressions encompass the fermionic aspect of nucleons, such as degeneracy pressure and Fermi energy at low temperatures and the ideal gas laws at high temperatures and low density. Expressions are developed which connect these two extremes with behavior that resembles an ideal Bose gas with its associated Bose condensation. In the thermodynamic limit, an infinite cluster exists below a certain critical condition in a manner similar to the sudden appearance of the infinite cluster in percolation theory. The importance of multiplicity fluctuations is discussed and some recent data from the EOS collaboration on critical point behavior of nuclei can be accounted for using simple expressions obtained from the model.Comment: 22 pages, revtex, includes 6 figures, submitted to Phys. Rev.

Heated nuclear matter, condensation phenomena and the hadronic equation of state

The thermodynamic properties of heated nuclear matter are explored using an exactly solvable canonical ensemble model. This model reduces to the results of an ideal Fermi gas at low temperatures. At higher temperatures, the fragmentation of the nuclear matter into clusters of nucleons leads to features that resemble a Bose gas. Some parallels of this model with the phenomena of Bose condensation and with percolation phenomena are discussed. A simple expression for the hadronic equation of state is obtained from the model.Comment: 12 pages, revtex, 1 ps file appended (figure 1

Event-by-Event Fluctuations in Heavy Ion Collisions and the QCD Critical Point

The event-by-event fluctuations of suitably chosen observables in heavy ion collisions at SPS, RHIC and LHC can tell us about the thermodynamic properties of the hadronic system at freeze-out. By studying these fluctuations as a function of varying control parameters, it is possible to learn much about the phase diagram of QCD. As a timely example, we stress the methods by which present experiments at the CERN SPS can locate the second-order critical endpoint of the first-order transition between quark-gluon plasma and hadron matter. Those event-by-event signatures which are characteristic of freeze-out in the vicinity of the critical point will exhibit nonmonotonic dependence on control parameters. We focus on observables constructed from the multiplicity and transverse momenta of charged pions. We first consider how the event-by-event fluctuations of such observables are affected by Bose-Einstein correlations, by resonances which decay after freeze-out and by fluctuations in the transverse flow velocity. We compare our thermodynamic predictions for such noncritical event-by-event fluctuations with NA49 data, finding broad agreement. We then focus on effects due to thermal contact between the observed pions and a heat bath with a given (possibly singular) specific heat, and due to the direct coupling between the critical fluctuations of the sigma field and the observed pions. We also discuss the effect of the pions produced in the decay of sigma particles just above threshold after freeze-out on the inclusive pion spectrum and on multiplicity fluctuations. We estimate the size of these nonmonotonic effects which appear near the critical point, including restrictions imposed by finite size and finite time, and conclude that they should be easily observable.Comment: 58 pages, 2 figures; to appear in Phys. Rev.