Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

You said it before and you'll say it again: Expectations of consistency in communication.

Repeated reference creates strong expectations in addressees that a speaker will continue to use the same expression for the same object. The authors investigate the root reason for these expectations by comparing a cooperativeness-based account (Grice, 1975) with a simpler consistency-based account. In two eye-tracking experiments, the authors investigated the expectations underlying the effect of precedents on comprehension. The authors show that listeners expect speakers to be consistent in their use of expressions even when these expectations cannot be motivated by the assumption of cooperativeness. The authors conclude that though this phenomenon seems to be motivated by cooperativeness, listeners' expectation that speakers be consistent in their use of expressions is governed by a general expectation of consistency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Finite-element analysis for magnetic resonance image artifact evaluation

The static magnetic field of a magnetic resonance imaging scanner can be distorted by the presence of materials, perturbing the spatial encoding process in magnetic resonance imaging and often resulting in image artifacts. The relationship between the image artifact size and magnetic susceptibility of the material specimen is of interest to engineers for the design of devices that are to be compatible with the imaging volume of the scanner. In this study, a finite-element method was used to simulate the distorted magnetic field of samples with different susceptibilities. With the knowledge of the external- and self- magnetic field interactions, a Lorentz correction was applied to compute the magnetic field deviation. The simulated results were then validated by the corresponding experimental magnetic resonance images.     

The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia

Venetoclax, a B-cell lymphoma (BCL-2) inhibitor, in combination with hypomethylating agents has become the new standard of care in elderly and unfit patients with acute myeloid leukemia, with significantly improved overall survival and quality of life. Studies of venetoclax combined with high-dose chemotherapy are emerging with evidence of higher rates of molecular remission. Recently, a growing number of publications bring forth the use of venetoclax in patients with acute lymphoblastic leukemia (ALL). In the current review, we present the biological rationale of BCL-2 inhibition in ALL, how the interplay of BH3 proteins modulate the response and the current clinical experience with various combinations.     

Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.     

微型计算机HDD日常使用与维护

微型计算机使用十分普遍、本文对比分析硬盘驱动器与软盘驱动器的物理结构、电气结构及价格比等，讨论提高整机使用效率、防治病毒的措施。     

Modeling the Combining Site of the Human Asialoglycoprotein Receptor

A model for the carbohydrate recognition domain (CRD) and combining site of the human asialoglycoprotein (ASGP) receptor has been computed on the basis of the close sequence homology with the mannose-binding lectin (MBP), whose three-dimensional structure in complex with a ligand has been determined by crystallographic methods (Weis, W.I.; Drickamer, K.; Hendrickson, W.A. Nature 1992, 360: 127). Within the limitations of modeling methods, the model is compatible with data on ligand binding of the family C-type lectins, of which the MBP and the ASGP receptor are members. The model derived can serve as a guide for designing site-directed mutagenesis experiments in order to further elucidate the origins of specificity of the ASGP receptor toward galactose. In particular, the model focuses attention on the possible role of position 207 (MBP sequence numbering) in promoting galactose binding.     

Sleeved co-clustering of lagged data

The paper focuses on mining clusters that are characterized by a lagged relationship between the data objects. We call such clusters lagged co-clusters. A lagged co-cluster of a matrix is a submatrix determined by a subset of rows and their corresponding lag over a subset of columns. Extracting such subsets may reveal an underlying governing regulatory mechanism. Such a regulatory mechanism is quite common in real-life settings. It appears in a variety of fields: meteorology, seismic activity, stock market behavior, neuronal brain activity, river flow, and navigation, but a limited list of examples. Mining such lagged co-clusters not only helps in understanding the relationship between objects in the domain, but assists in forecasting their future behavior. For most interesting variants of this problem, finding an optimal lagged co-cluster is NP-complete problem. We present a polynomial-time Monte-Carlo algorithm for mining lagged co-clusters. We prove that, with fixed probability, the algorithm mines a lagged co-cluster which encompasses the optimal lagged co-cluster by a maximum 2 ratio columns overhead and completely no rows overhead. Moreover, the algorithm handles noise, anti-correlations, missing values, and overlapping patterns. The algorithm is extensively evaluated using both artificial and real-world test environments. The first enable the evaluation of specific, isolated properties of the algorithm. The latter (river flow and topographic data) enable the evaluation of the algorithm to efficiently mine relevant and coherent lagged co-clusters in environments that are temporal, i.e., time reading data and non-temporal.