Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification

Cyclin D1 proto-oncogene is a key regulator of the mammalian cell-cycle acting at the restriction point in late G1. Amplification of the cyclin D1 locus, located on chromosome 11q13, as well as cyclin D1 protein overexpression have been reported in several human malignancies. The purpose of this study was to evaluate cyclin D1 gene copy status and protein expression during the multistep process of head and neck tumorigenesis, using a combination of fluorescence in situ hybridization and immunohistochemistry techniques. From 29 selected patients presenting with head and neck squamous carcinoma and whose tumor cytospins had been previously screened for presence (16 cases) or absence (13 cases) of amplification at the 11q13 band, we analysed 46 paraffin-embedded tissue specimens that demonstrated, besides the primary tumor, the presence of contiguous adjacent normal tissue and/or premalignant lesions. Of the 16 amplified cases, nine demonstrated a continuous progression from premalignant to invasive carcinoma and seven (77.7%) of these cases showed cyclin D1 gene amplification in premalignant lesions prior to development of invasive carcinoma. Increased cyclin D1 protein expression was observed in all 16 amplified tumors and five of the 13 (38.4%) non-amplified tumors. Interestingly, dysregulated cyclin D1 expression was also found in the premalignant lesions adjacent to all 16 amplified tumors, and it appeared to precede cyclin D1 gene amplification. In contrast no dysregulated expression was detected in the premalignant lesions of the non-amplified tumors. In conclusion, these findings provide strong evidence for early dysregulation of cyclin D1 expression during the tumorigenesis process and suggest that dysregulated increased expression precedes and possibly enables gene amplification.     

Effects of NAD or NADP on the stability of liver and pectoral muscle enzymes in 3-acetylpyridine treated quail by heat and trypsin

(1) The effects of long term treatment with 3-acetylpyridine on the stability of enzymes towards heat and trypsin treatment were studied. (2) In the liver NAD or NADP provided a similar degree of protection against heat inactivation at 55 degrees C for 6-phosphogluconate dehydrogenase (24%), glyceraldehyde-3-phosphate dehydrogenase (24%) and malic enzyme (20%), low level of protection of lactate dehydrogenase (13%) but didn't affect acetylcholinesterase at all. In the muscle, however, there was substantial protection against heat inactivation by coenzyme of glyceraldehyde-3-phosphate dehydrogenase (52%), an intermediate level of protection of lactate dehydrogenase (25%), low level of protection of 6-phosphogluconate dehydrogenase (17%) and malic enzyme (17%) and almost no protection of acetylcholinesterase. (3) In the susceptibility towards trypsin a low but similar degree of protection for dehydrogenases by coenzymes was observed in the liver whereas in the muscle there was substantial protection against trypsin inactivation by NAD of glyceraldehyde-3-phosphate dehydrogenase, an intermediate level of protection of 6-phosphogluconate dehydrogenase and malic enzyme and very little protection of lactate dehydrogenase but no protection of acetylcholinesterase. Among enzymes tested, glyceraldehyde-3-phosphate dehydrogenase showed the greatest protection against heat and trypsin inactivation by NAD. (4) The results suggest that the effect of 3-acetylpyridine treatment on the stability of muscle glyceraldehyde-3-phosphate dehydrogenase appears to be quite specific and selective.     

Membrane sterol composition modulates the pore forming activity of syringomycin E in human red blood cells

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.     

Influence of Neotyphodium coenophialum on copper concentration in tall fescue

Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity.     

边界对齐的平滑三维对称标架场

为了把广泛应用于网格四边形化和纹理合成的二维表面标架场拓展到三维,提出一种生成三维对称标架场的方法.不同于表面对称标架场(四对称方向场),二维标架场的对称性能用一个切平面的旋转角度来表示,而三维对称标架场的对称性却不能这样简单地表示.为了解决这个问题,利用球面函数来获得一个对称性表述,该表述对于绕任意一个轴的π/2旋转以及它们的复合是不变的.基于球面函数的表示可以获得一个有效的标架场光顺程度的度量,并以球面调和分析进行加速计算;基于一组边界约束,可以通过极小化这个度量函数来获得一个光顺的标架场,该标架场在表面上能很好地对齐法线.最后通过表面投影、流线追踪和奇异点来可视化这个标架场,并将这个光顺的标架场用于六面体网格生成,且讨论了它在生成高质量纯六面体网格方面的潜力,其与表面标架场在生成四边形网格方面的潜力是一致的.     

Simple Question Answering over Knowledge Graph Enhanced by Question Pattern Classification

Knowledge and Information Systems - Question answering over knowledge graph (KGQA), which automatically answers natural language questions by querying the facts in knowledge graph (KG), has drawn...     

基于MCGS的步进电机控制系统设计

设计了一种分层式的步进电机控制系统,现场控制层以AT89C52单片机为主控芯片,通过软件编程实现对步进电机的启停、正反转及调速控制,上位机监控层在工控组态软件MCGS平台下开发,操作界面直观友好,可以方便地对现场步进电机控制系统发布控制命令和参数;为解决现场控制层与监控层间数据交互问题,开发了基于MCGS的51单片机驱动构件;实际运行结果表明,整个系统实时性、稳定性良好,完全达到设计要求。     

Dynamics and genetic fuzzy neural network vibration control design of a smart flexible four-bar linkage mechanism

In this paper, a dynamic modeling method and an active vibration control scheme for a smart flexible four-bar linkage mechanism featuring piezoelectric actuators and strain gauge sensors are presented. The dynamics of this smart mechanism is described by the Discrete Time Transfer Matrix Method of Multibody System (MS-DTTMM). Then a nonlinear fuzzy neural network control is employed to suppress the vibration of this smart mechanism. For improving the dynamic performance of the fuzzy neural network, a genetic algorithm based on the MS-DTTMM is designed offline to tune the initial parameters of the fuzzy neural network. The MS-DTTMM avoids the global dynamics equations of the system, which results in the matrices involved are always very small, so the computational efficiency of the dynamic analysis and control system optimization can be greatly improved. Formulations of the method as well as a numerical simulation are given to demonstrate the proposed dynamic method and control scheme.     

Magnetic properties and microstructural characteristics of bulk Nd–Al–Fe–Co glassy alloys

Bulk Nd–Al–Fe–Co glassy alloys with diameter up to 5 mm were investigated by magnetic measurements, magnetic force microscopy (MFM) and high resolution electron microscopy (HREM) at room temperature. The results from the measurement of vibrating sample magnetometer show that these samples with compositions Nd₆₅Al₁₀Fe_25-xCo_x (x=0–10 at.%) and Nd₆₀Al₁₀Fe₂₀Co₁₀ display hard magnetic properties with H_C of 300 kAm⁻¹, M_S of 10 Am² kg⁻¹, and M_r of 7 Am² kg⁻¹. The MFM measurements of the Nd₆₀Al₁₀Fe₂₀Co₁₀ bulk metallic glass (BMG) reveal the existence of magnetic domains with a period of about 0.36 μm, and the ordered clusters with the averaged size of about 5 nm was observed by the HREM on the sample. The domain structure or cluster is believed to be associated with the appearance of hard-magnetic properties in this alloy system. The existence of the large-size domains demonstrates that magnetic moment of a great deal of ordered atomic clusters in the BMG has been aligned by exchange-coupling.