Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia

The Abl kinase inhibitor imatinib mesylate is the preferred treatment for Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but is much less effective in CML blast crisis or Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). Here, we show that Bcr-Abl activated the Src kinases Lyn, Hck and Fgr in B-lymphoid cells. BCR-ABL1 retrovirus-transduced marrow from mice lacking all three Src kinases efficiently induced CML but not B-ALL in recipients. The kinase inhibitor CGP76030 impaired the proliferation of B-lymphoid cells expressing Bcr-Abl in vitro and prolonged survival of mice with B-ALL but not CML. The combination of CGP76030 and imatinib was superior to imatinib alone in this regard. The biochemical target of CGP76030 in leukemia cells was Src kinases, not Bcr-Abl. These results implicate Src family kinases as therapeutic targets in Ph(+) B-ALL and suggest that simultaneous inhibition of Src and Bcr-Abl kinases may benefit individuals with Ph(+) acute leukemia.     

BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling

In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.     

Mutations in SEC63 cause autosomal dominant polycystic liver disease

Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.     

MPLS自治系统中基于人工蜘蛛的重路由研究

提出了将一个MPLS自治网络按照自然界中蜘蛛网的形式转化为逻辑上的人工蜘蛛网络的思想,对网络内每个节点赋予了坐标,从而可以方便地对网络进行区域划分以及区域内寻路.在此基础上,提出了基于人工蜘蛛的动态分布式重路由算法(DDRAAS),以及改进的DDRAAS算法来实现MPLS网络中的快速重路由,通过仿真试验与传统的重路由算法作了比较,表明改进的DDRAAS算法在快速重路由方面具有较好的效果.     

Description of mechanism function about dehydration of cobalt oxalate dihydrate by multiple rates isotemperature method

0　IntroductionThetechnologyofthermalanalysishasbeenwidelyusedinthestudyofthermalbehaviorandthermalcharacterofsolidstatereaction ,theprimaryintentionofthermalanalysiskineticsistoestablishseparatevaluesofapparentactivationenergyE ,themostprobablemechanism g(α)andthepre exponentialfactorA ,meanwhilethedeterminationofg(α)hasgraduallybeenthefocusofthisfield .Inthisfield ,therearemostlygeneralkineticsmethodsused presently ,suchasCoats Redfern’s[1 ] integralmethod ,Achar’s[2 \〗differentialmet…     

The symmetric solutions of affiliated value model

0　IntroductionIntheprocessofR&Ditem ,thereisusuallycompetition .ManyfirmswanttoinvestR&Dtoobtainapatent.Lury[1 ] gaveanequilibriuminvestmentundertheconditionofone timeinvestmentandcontinuousinvestmentwhenthepayoffwasafixedprize.Ref.[2 ]analyzedtheeffectofinformationsharinginR&D .TherearemanyliteraturesaboutanalysisofR&DlevelswhenfirmscompeteinoutputmarketafterR&Dsucceeds[3 ,4] .Additionally ,todecideinvestmentlevel,therearemanyliteraturesaboutR&Ditem’spricing .MondherBellalah[5] ,K .…     

Change in the body temperature of healthy term infant over the first 72 hours of life

OBJECTIVE: To determine the range of body temperature in a group of healthy Chinese term neonates over the first 72 hours of life and to assess the influence of body weight, gestational age and route of delivery.METHOD: All 200 consecutive cases of neonates delivered at our hospital from March to August 2001 were included in this retrospective study. Temperatures were measured immediately after delivery, after 30 minutes, 1 hour, 2 hours, 8 hours and 15 hours and on the 2nd and 3rd day. Axillary temperatures ranging from 36.5 degrees C to 37 degrees C were regarded as normal. No cases of maternal fever or systemic infection of the newborns were discovered. All infants were discharged in good general condition. RESULTS: The mean rectal temperature at birth was 37.19 degrees C. The lowest average temperature was reached at 1 hour after delivery (36.54 degrees C) with a significant difference between natural delivery (36.48 degrees C) and section (36.59 degrees C) (P<0.05). Temperature subsequently rose to 36.70 degrees C at 8 hours and 36.78 degrees C at 15 hours (P<0.05). Hypothermia was seen in 51.8% and hypothermia in 42.5% of the patients. On the 3rd day after delivery, 96% of all temperatures were in the normal range. A significant relation was found between hypothermia and both low birth weight (P<0.001) and low gestational age (P<0.05). CONCLUSION: The reference range presently used did not include all physiological temperatures in the first 72 hours of life. Considering other factors, such as birth weight, route of delivery, gestational age and body temperature on the 2nd and 3rd day of life, may help to correctly assess the significance of temperatures beyond the reference range.     

Improving the precision of the keyword-matching pornographic text filtering method using a hybrid model

With the flooding of pornographic information on the Internet, how to keep people away from that offensive information is becoming one of the most important research areas in network information security. Some applications which can block or filter such information are used. Approaches in those systems can be roughly classified into two kinds: metadata based and content based. With the development of distributed technologies, content based filtering technologies will play a more and more important role in filtering systems. Keyword matching is a content based method used widely in harmful text filtering. Experiments to evaluate the recall and precision of the method showed that the precision of the method is not satisfactory, though the recall of the method is rather high. According to the results, a new pornographic text filtering model based on reconfirming is put forward. Experiments showed that the model is practical, has less loss of recall than the single keyword matching method, and has higher precision.     

Cellular automata modeling of pedestrian＇s crossing dynamics

Cellular automata modeling techniques and the characteristics of mixed traffic flow were used to derive the 2-dimensional model presented here for simulation of pedestrian's crossing dynamics. A conception of "stop point" is introduced to deal with traffic obstacles and resolve conflicts among pedestrians or between pedestrians and the other vehicles on the crosswalk. The model can be easily extended, is very efficient for simulation of pedestrian's crossing dynamics, can be integrated into traffic simulation software, and has been proved feasible by simulation experiments.     

Petrology, geochemistry and geodynamics of basic granulite from the Altay area, North Xinjiang, China

The basic granulite of the Altay orogenic belt occurs as tectonic lens in the Devonian medium- to lower-grade metamorphic beds through fault contact. The Altay granulite (AG) is an amphibole plagioclase two-pyroxene granulite and is mainly composed of two pyroxenes, plagioclase, amphibole and biotite. Its melano-minerals are rich in Mg/(Mg Fe^2 ),and its amphibole and biotite are rich in TiO2. The AG is rich in Mg/(Mg Fe^2 ), Al2O3 and depletion of U, Th and Rbcontents. The AG has moderate ∑REE and LREE-enriched with weak positive Eu anomaly. The AG shows island-arc pattern with negative Nb, P and Ti anomalies, reflecting that formation of the AG may be associated with subduction. Geochemical and mineral composition data reflect that the protolith of the AG is calc-alkaline basalt and formed by granulite facies metamorphism having peak P-T conditions of 750℃-780℃ and 0.6-0.7 Gpa. The AG formation underwent two stages was suggested. In the early stage of oceanic crustal subduction, calc-alkaline basalt with island-arc environment underwent granulite facies metamorphism to form the AG in deep crust, and in the late stage, the AG was thrust into the upper crust.