103 research outputs found
Design Equation: A Novel Approach to Heteropolymer Design
A novel approach to heteropolymer design is proposed. It is based on the
criterion by Kurosky and Deutsch, with which the probability of a target
conformation in a conformation space is maximized at low but finite
temperature. The key feature of the proposed approach is the use of soft spins
(fuzzy monomers) that leads to a design equation, which is an analog of the
Boltzmann machine learning equation in the design problem. We implement an
algorithm based on the design equation for the generalized HP model on the
3x3x3 cubic lattice and check its performance.Comment: 7 pages, 3 tables, 1 figures, uses jpsj.sty, jpsjbs1.sty, epsf.sty,
Submitted to J. Phys. Soc. Jp
Early Stages of Homopolymer Collapse
Interest in the protein folding problem has motivated a wide range of
theoretical and experimental studies of the kinetics of the collapse of
flexible homopolymers. In this Paper a phenomenological model is proposed for
the kinetics of the early stages of homopolymer collapse following a quench
from temperatures above to below the theta temperature. In the first stage,
nascent droplets of the dense phase are formed, with little effect on the
configurations of the bridges that join them. The droplets then grow by
accreting monomers from the bridges, thus causing the bridges to stretch.
During these two stages the overall dimensions of the chain decrease only
weakly. Further growth of the droplets is accomplished by the shortening of the
bridges, which causes the shrinking of the overall dimensions of the chain. The
characteristic times of the three stages respectively scale as the zeroth, 1/5
and 6/5 power of the the degree of polymerization of the chain.Comment: 11 pages, 3 figure
A hierarchical model for aging
We present a one dimensional model for diffusion on a hierarchical tree
structure. It is shown that this model exhibits aging phenomena although no
disorder is present. The origin of aging in this model is therefore the
hierarchical structure of phase space.Comment: 10 pages LaTeX, 4 postscript-figures include
Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients
FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia
The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294ā335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6
A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators.
BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes.
METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later.
RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, P = 0.011), a larger immediate increase in the diameter of the lumen (1.72 +/- 0.46 vs. 1.23 +/- 0.48 mm, P \u3c 0.001), and a larger luminal diameter immediately after the procedure (2.49 +/- 0.43 vs. 1.99 +/- 0.47 mm, P \u3c 0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 +/- 0.60 vs. 1.56 +/- 0.65 mm, P = 0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, P = 0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 percent of the patients in the stent group and 76.2 percent of those in the angioplasty group (P = 0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 percent vs. 15.4 percent, P = 0.06).
CONCLUSIONS: In selected patients, placement of an intracoronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion
DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma
In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2
Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas
Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients
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