Immunoblastic morphology as a possible prognostic indicator for the outcome of the patients with diffuse large B cell lymphoma in era of the rituximab based treatment: single centre experience

Recently the results from one large prospective study indicated that immunoblastic morphology and not immunohistohemical features predict the outcome of the Diffuse large B lymphoma (DLBL). In order to investigate the prediction value of the immunoblastic morphology (IB) as a possible prognostic indicator for the outcome of our DLBL patient treated with the Rituximab (R)-CHOP regimen we conducted a retrospective study. Our study enrolled 192 DLBL patients diagnosed and treated at the University Clinic of Hematology in the period between February 2002 and December 2007. They were all treated with R-CHOP regimen and the median follow-up of the patient was 36 months. We analyzed the biopsy samples immunohistochemically for markers of germinal center (BCL6), post-germinal center (MUM1) and apoptosis (BCL2).The patients were categorized as DLBL(132; 68.7%), IB(60; 31.2). The median overall survival time (OS) were 59.3 months in DLBL group and 42.2 months in IB group, and time to treatment (TT) were 56.8 and 30.6 months respectively for the IB group. The DLBL and IB groups were comparable regarding the age, gender distributions and all others already established prognostic parameters as performance status, advanced IPI, albumin level except for the low IPI 0-2 which was statistically associated with the DLBL group (p=.024). Our results did not show any statistical survival advantage and better outcome for the patient classified as DLBL when treated with R-CHOP and indicate that immunohistohemical markers do not really reflect the molecular diversity of the tumor.  Our work shows that IB morphology is a major risk factor in DLBL patients treated with R-CHOP. Therefore this morphology appears to capture some adverse molecular events that a currently hard to detect with routine diagnostic procedures.

Invaded cluster simulations of the XY model in two and three dimensions

The invaded cluster algorithm is used to study the XY model in two and three dimensions up to sizes 2000^2 and 120^3 respectively. A soft spin O(2) model, in the same universality class as the 3D XY model, is also studied. The static critical properties of the model and the dynamical properties of the algorithm are reported. The results are K_c=0.45412(2) for the 3D XY model and eta=0.037(2) for the 3D XY universality class. For the 2D XY model the results are K_c=1.120(1) and eta=0.251(5). The invaded cluster algorithm does not show any critical slowing for the magnetization or critical temperature estimator for the 2D or 3D XY models.Comment: 30 pages, 11 figures, problem viewing figures corrected in v

Ground state numerical study of the three-dimensional random field Ising model

The random field Ising model in three dimensions with Gaussian random fields is studied at zero temperature for system sizes up to 60^3. For each realization of the normalized random fields, the strength of the random field, Delta and a uniform external, H is adjusted to find the finite-size critical point. The finite-size critical point is identified as the point in the H-Delta plane where three degenerate ground states have the largest discontinuities in the magnetization. The discontinuities in the magnetization and bond energy between these ground states are used to calculate the magnetization and specific heat critical exponents and both exponents are found to be near zero.Comment: 10 pages, 6 figures; new references and small changes to tex

Lattice model of gas condensation within nanopores

We explore the thermodynamic behavior of gases adsorbed within a nanopore. The theoretical description employs a simple lattice gas model, with two species of site, expected to describe various regimes of adsorption and condensation behavior. The model includes four hypothetical phases: a cylindrical shell phase (S), in which the sites close to the cylindrical wall are occupied, an axial phase (A), in which sites along the cylinder's axis are occupied, a full phase (F), in which all sites are occupied, and an empty phase (E). We obtain exact results at T=0 for the phase behavior, which is a function of the interactions present in any specific problem. We obtain the corresponding results at finite T from mean field theory. Finally, we examine the model's predicted phase behavior of some real gases adsorbed in nanopores

Low-energy excitations in the three-dimensional random-field Ising model

The random-field Ising model (RFIM), one of the basic models for quenched disorder, can be studied numerically with the help of efficient ground-state algorithms. In this study, we extend these algorithm by various methods in order to analyze low-energy excitations for the three-dimensional RFIM with Gaussian distributed disorder that appear in the form of clusters of connected spins. We analyze several properties of these clusters. Our results support the validity of the droplet-model description for the RFIM.Comment: 10 pages, 9 figure

Critical aspects of the random-field Ising model

We investigate the critical behavior of the three-dimensional random-field Ising model (RFIM) with a Gaussian field distribution at zero temperature. By implementing a computational approach that maps the ground-state of the RFIM to the maximum-flow optimization problem of a network, we simulate large ensembles of disorder realizations of the model for a broad range of values of the disorder strength h and system sizes  = L3, with L ≤ 156. Our averaging procedure outcomes previous studies of the model, increasing the sampling of ground states by a factor of 103. Using well-established finite-size scaling schemes, the fourth-order’s Binder cumulant, and the sample-to-sample fluctuations of various thermodynamic quantities, we provide high-accuracy estimates for the critical field hc, as well as the critical exponents ν, β/ν, and γ̅/ν of the correlation length, order parameter, and disconnected susceptibility, respectively. Moreover, using properly defined noise to signal ratios, we depict the variation of the self-averaging property of the model, by crossing the phase boundary into the ordered phase. Finally, we discuss the controversial issue of the specific heat based on a scaling analysis of the bond energy, providing evidence that its critical exponent α ≈ 0−

Revisiting the scaling of the specific heat of the three-dimensional random-field Ising model

We revisit the scaling behavior of the specific heat of the three-dimensional random-field Ising model with a Gaussian distribution of the disorder. Exact ground states of the model are obtained using graph-theoretical algorithms for different strengths = 268 3 spins. By numerically differentiating the bond energy with respect to h, a specific-heat-like quantity is obtained whose maximum is found to converge to a constant in the thermodynamic limit. Compared to a previous study following the same approach, we have studied here much larger system sizes with an increased statistical accuracy. We discuss the relevance of our results under the prism of a modified Rushbrooke inequality for the case of a saturating specific heat. Finally, as a byproduct of our analysis, we provide high-accuracy estimates of the critical field hc = 2.279(7) and the critical exponent of the correlation exponent ν = 1.37(1), in excellent agreement to the most recent computations in the literature

Kinetic Monte Carlo simulations of flow-induced nucleation in polymer melts.

We derive a kinetic Monte Carlo algorithm to simulate flow-induced nucleation in polymer melts. The crystallisation kinetics are modified by both stretching and orientation of the amorphous chains under flow, which is modelled by a recent non-linear tube theory. Rotation of the crystallites under flow is modelled by a simultaneous Brownian dynamics simulation. Our kinetic Monte Carlo approach is highly efficient at simulating nucleation and is tractable even at low under-cooling. The simulations predict enhanced nucleation under both transient and steady state shear. Furthermore the model predicts the growth of shish-like elongated nuclei for sufficiently fast flows, which grow by a purely kinetic mechanism

Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA

BACKGROUND: Cystic fibrosis (CF) is a recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We previously described a first-in-class CFTR modulator that functions as an amplifier to selectively increase CFTR expression and function. The amplifier mechanism is distinct from and complementary to corrector and potentiator classes of CFTR modulators. Here we characterize the mechanism by which amplifiers increase CFTR mRNA, protein, and activity.; METHODS: Biochemical studies elucidated the action of amplifiers on CFTR mRNA abundance and translation and defined the role of an amplifier-binding protein that was identified using chemical proteomics.; RESULTS: Amplifiers stabilize CFTR mRNA through a process that requires only the translated sequence of CFTR and involves translational elongation. Amplifiers enrich ER-associated CFTR mRNA and increase its translational efficiency through increasing the fraction of CFTR mRNA associated with polysomes. Pulldowns identified the poly(rC)-binding protein 1 (PCBP1) as directly binding to amplifier. A PCBP1 consensus element was identified within the CFTR open reading frame that binds PCBP1. This sequence proved necessary for amplifier responsiveness.; CONCLUSIONS: Small molecule amplifiers co-translationally increase CFTR mRNA stability. They enhance translation through addressing the inherently inefficient membrane targeting of CFTR mRNA. Amplifiers bind directly to PCBP1, show enhanced affinity in the presence of bound RNA, and require a PCBP1 consensus element within CFTR mRNA to elicit translational effects. These modulators represent a promising new and mechanistically novel class of CFTR therapeutic. They may be useful as a monotherapy or in combination with other CFTR modulators. Copyright © 2020. Published by Elsevier B.V