Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure.

Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA.     

Primary Structural and Quantitative Analysis of Infeasible Solution to Job shop Scheduling Problem

1　IntroductionTheJobShopSchedulingProblemisawell-knownNP-hardproblem,whichattractslotsofmathematiciansallovertheworldspendingmuchtimeandenergyinthisfield.Uptonowtherearemanyefficientheuristicalgorithms,whichhadalreadybeendeveloped,buttheinfeasiblesolutioncertainlypossessesthemajorityofsearchspacewhichhasinfluencedtheefficiencyofthesealgorithms.Atthemoment,noonehasbeenfoundtobededicatingtothequantitativeanalysisoftheinfeasiblesolutionproblem.InthispaperthestructureofinfeasiblesolutiontoJSS…     

以Aliquat336为流动载体的乳状液膜迁移和分离Mo（Ⅵ）的研究

用Aliquat336—Span80—煤油乳状液膜体系 ,研究Mo(Ⅵ )的迁移行为。在适宜条件下 ,5min内Mo(Ⅵ )的迁移率可达 96%以上 ,并能与Fe2 、Cu2 、Co2 、Ni2 、Zn2 、Cd2 、Mn2 等常见离子分离     

二尖瓣疾病的超声脉冲多普勒诊断

用脉冲多普勒超声心动图对10例正常人和20例二尖瓣疾病患者作了检查,并对两种情况下二尖瓣日的血流频谱参数作了分析。在这些病人中,男8例,女12例。平均年龄32岁(年龄范围5—52岁)。手术证实18例风心病,2例先心病,脉冲多普勒检查结果与手术结果基本一致,对正常和有病变的二尖瓣口血流频谱作的分析和比较表明:二尖瓣狭窄和二尖瓣返流频谱不仅其频谱形态可与正常人区别,而且它们的各项参数如峰值速度、血流加速度和减速度等均有明显差异。总之,超声脉冲多普勒心动图诊断二尖瓣狭窄和关闭不全是准确可靠的,这种技术比M型和B型具有更多的优点。     

Mechanisms underlying celiac disease and its neurologic manifestations

The extra-intestinal manifestations of celiac disease (CD), including ataxia and peripheral neuropathy, are increasingly being recognized as the presenting symptoms of this autoimmune disease. Although there is a greater understanding of the pathogenesis of the intestinal lesions in CD the mechanisms behind the neurologic manifestations of CD have not been elucidated. In this article, the authors review the cellular and molecular mechanisms behind the histopathologic changes in the intestine, discuss the presentation and characteristics of neurologic manifestations of CD, review the data on the mechanisms behind these manifestations, and discuss the diagnosis and treatment of CD. Molecular mimicry and intermolecular help may play a role in the development of neurologic complications.Received 11 March 2004; received after revision 29 October 2004; accepted 12 November 2004     

Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia

Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis. Abundant scientific and clinical evidence, including the lack of convincing clinical activity of early FLT3 inhibitors, suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.     

A low density of 0.8 g cm(-3) for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid 617 Patroclus is the only known binary Trojan. The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system's centre of mass, describing a roughly circular orbit. Using this orbital information, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(-3). The components of 617 Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the Solar System.     

大升角内螺旋槽加工新方法

大升角、小尺寸内螺旋槽的加工存在诸多干涉,其加工是一个难题.在分析了不同加工情况如平行轴加工、交错轴加工,使用不同加工刀具时,刀具的回转面截形的设计和计算;提出了使用圆弧刀具进行逼近加工的方法,经计算分析表明,只要在允许误差范围内,此方法是可行的;在此基础上,利用典型软件如I-DEAS软件的Program files功能、UG软件的加工模块,针对不同加工情况进行了螺旋槽加工的计算机仿真,如刀具路径仿真,加工误差分析,检验刀具设计的正确性等.     

基于收益率与风险比率的期货套期保值策略研究

引入目标收益率作为衡量套期保值行为盈亏的界线,建立基于改进的收益率与风险比率相对数最大化的期货套期保值优化决策模型。使得单位风险下组合期望收益率大于目标收益率的收益程度最大,从理论上推导出空头和多头套期保值的最优套期比率,并与传统套期比作比较,求出了空头和多头在传统最优套期比基础上的调整量。给出了当目标收益率满足一定条件时,空头和多头套期保值的最优套期比公式。     

图像处理技术在乘用车侧面碰撞试验中的应用

多媒体计算机序列图像运动分析系统与摄影测量学理论相结合,成为较完善的非接触动态测量系统.在乘用车侧面碰撞试验中采用图像采集和数字图像处理技术,结合直接线性变换(direct liner transformation,DLT)算法,分析碰撞试验中标示点的变形量,提高乘用车侧面碰撞强度,为汽车被动安全性研究提供依据.