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61.
Shahaf G Barak M Zuckerman NS Swerdlin N Gorfine M Mehr R 《Journal of theoretical biology》2008,255(2):210-222
During the immune response, the generation of memory B lymphocytes in germinal centers involves affinity maturation of the cells’ antigen receptors, based on somatic hypermutation of receptor genes and antigen-driven selection of the resulting mutants. Affinity maturation is vital for immune protection, and is the basis of humoral immune learning and memory. Lineage trees of somatically hypermutated immunoglobulin genes often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation in germinal centers. Here, we derive the quantitative relationships between parameters characterizing affinity maturation dynamics (proliferation, differentiation and mutation rates, initial affinity of the Ig to the antigen, and selection thresholds) and the mathematical properties of lineage trees, using a computer simulation which combines mathematical models for all mature B cell populations, stochastic models of hypermutation and selection, lineage tree generation and measurement of graphical tree characteristics. We identified seven key lineage tree properties, and found correlations of these with initial clone affinity and with the selection threshold. These two parameters were found to be the main factors affecting lineage tree shapes in both primary and secondary response trees. The results also confirm that recycling from centrocytes back to centroblasts is highly likely. 相似文献
62.
Melamed O Barak O Silberberg G Markram H Tsodyks M 《Journal of computational neuroscience》2008,25(2):308-316
The synchronous oscillatory activity characterizing many neurons in a network is often considered to be a mechanism for representing,
binding, conveying, and organizing information. A number of models have been proposed to explain high-frequency oscillations,
but the mechanisms that underlie slow oscillations are still unclear. Here, we show by means of analytical solutions and simulations
that facilitating excitatory (E
f) synapses onto interneurons in a neural network play a fundamental role, not only in shaping the frequency of slow oscillations,
but also in determining the form of the up and down states observed in electrophysiological measurements. Short time constants and strong E
f synapse-connectivity were found to induce rapid alternations between up and down states, whereas long time constants and weak E
f synapse connectivity prolonged the time between up states and increased the up state duration. These results suggest a novel role for facilitating excitatory synapses onto interneurons in controlling
the form and frequency of slow oscillations in neuronal circuits. 相似文献
63.
MOSIX is a cluster management system that supports preemptive process migration. This paper presents the MOSIX Direct File System Access (DFSA), a provision that can improve the performance of cluster file systems by allowing a migrated process to directly access files in its current location. This capability, when combined with an appropriate file system, could substantially increase the I/O performance and reduce the network congestion by migrating an I/O intensive process to a file server rather than the traditional way of bringing the file's data to the process. DFSA is suitable for clusters that manage a pool of shared disks among multiple machines. With DFSA, it is possible to migrate parallel processes from a client node to file servers for parallel access to different files. Any consistent file system can be adjusted to work with DFSA. To test its performance, we developed the MOSIX File-System (MFS) which allows consistent parallel operations on different files. The paper describes DFSA and presents the performance of MFS with and without DFSA. 相似文献
64.
Robert Manasherob Arieh Zaritsky Eitan Ben-Dov Deepak Saxena Ze'ev Barak Monica Einav 《Current microbiology》2001,43(5):355-364
The gene coding for the accessory protein P19 of Bacillus thuringiensis subsp. israelensis was expressed in Escherichia coli and its product was characterized. To investigate its putative role in δ-endotoxin crystallization as a P20-like polypeptide,
each of the two encoding genes, p20 and p19, was cloned for inducible expression coordinatively with cyt1Aa. The latter is known to kill its transgenic host. P20 but not P19 stabilized Cyt1Aa and protected the host cells from its
lethal effect. Neither GroEL nor GroES, expressed in trans, affected Cyt1Aa as did P20. The function of P20 is thus more specific than that of the chaperones, but that of P19 remains
enigmatic. The correct sequence of p19, confirmed in all five isolates of B. thuringiensis subsp. israelensis, does not explain the slow electrophoretic mobility of its 179 amino acids product.
Received: 5 March 2001 / Accepted: 3 April 2001 相似文献
65.
66.
Barak Rotblat Liron Belanis Hong Liang Roni Haklai Galit Elad-Zefadia John F. Hancock Yoel Kloog Sarah J. Plowman 《PloS one》2010,5(8)
H-Ras is a binary switch that is activated by multiple co-factors and triggers several key cellular pathways one of which is MAPK. The specificity and magnitude of downstream activation is achieved by the spatio-temporal organization of the active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability. 相似文献
67.
68.
Y Har-Shai N Hai A Taran S Mayblum A Barak E Tzur I Schafer R David E David S Linn 《Plastic and reconstructive surgery》2001,108(7):1982-1989
This article reports on the sensitivity and positive predictive value of clinical diagnosis of benign and malignant skin tumors by expert plastic surgeons in an Israeli clinic. Most published reports have focused on the sensitivity of clinicians' diagnoses, a general measure of the physician's skill that does not predict the rate of accuracy of a physician's diagnoses. Our study of 835 lesions in 778 patients, one of the largest Israeli series, assesses the clinical diagnosis of malignant and benign skin tumors and is one of the few that provide information on the positive predictive value, the measure that is of interest to both physicians and patients. The majority of tumors were benign (56.8 percent), 31.6 percent were malignant, and 11.6 percent were premalignant. Among the 474 benign lesions, 46 percent were nevi. The most common nevi subclass was compound nevi (53 percent), 9 percent of the nevi were dysplastic, and 5 percent were blue nevi. The most common malignant tumor was basal cell carcinoma, accounting for 78 percent of malignant tumors.Although sensitivity for clinical diagnosis of malignancy was 91.3 percent, the positive predictive value for clinical diagnosis of malignancy was 71.3 percent. The sensitivity rate for clinically diagnosing premalignant tumors was 42.3 percent, whereas the positive predictive value for these diagnoses was higher (64.1 percent). The sensitivity rate for diagnosis of all benign lesions was 85.9 percent, and the positive predictive value was 94.2 percent. The sensitivity rate for diagnosis of all nevi was 87.6 percent, and the positive predictive value was 85.7 percent: i.e., only seven of the 218 pathologically proven diagnoses of nevi (3.2 percent) were falsely diagnosed as malignant lesions. Even more interestingly, five of the 223 clinical diagnoses of nevi (2.2 percent) were pathologically proven to be malignant melanomas, and seven were found to be premalignant lesions (3.1 percent). It was concluded that publications which report only on the sensitivity neglect to provide information of interest regarding the positive predictive value. Often, positive predictive value is qualitatively different from the sensitivity, and thus relying only on the sensitivity may lead to incorrect evaluation of a clinical judgment, which may result in erroneous surgical decisions. 相似文献
69.
70.
Uptake of choline by the isolated perfused rat liver 总被引:1,自引:0,他引:1