119 resultados para Amphiphilic helix


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Parallel strand models for base sequences d(A)(10). d(T)(10), d(AT)(5) . d(TA)(5), d(G(5)C(5)). d(C(5)G(5)), d(GC)(5) . d(CG)(5) and d(CTATAGGGAT). d(GATATCCCTA), where reverse Watson-Crick A-T pairing with two H-bonds and reverse Watson-Crick G-C pairing with one H-bond or with two H-bonds were adopted, and three models of d(T)(14). d(A)(14). d(T)(14) triple helix with different strand orientations were built up by molecular architecture and energy minimization. Comparisons of parallel duplex models with their corresponding B-DNA models and comparisons among the three triple helices showed: (i) conformational energies of parallel AT duplex models were a little lower, while for GC duplex models they were about 8% higher than that of their corresponding B-DNA models; (ii) the energy differences between parallel and B-type duplex models and among the three triple helices arose mainly from base stacking energies, especially for GC base pairing; (iii) the parallel duplexes with one H-bond G-C pairs were less stable than those with two H-bonds G-C pairs. The present paper includes a brief discussion about the effect of base stacking and base sequences on DNA conformations. (C) 1997 Academic Press Limited.

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It was expected that there are a coil (289 similar to 325) and two a helix (alpha(1)368 similar to 373, alpha(2)381 similar to 388) structures in p53 protein C-terminal region based on its mRNA secondary structure template and Chou-Fasman's protein secondary structure principle of prediction. The result was conformed by the other four methods of protein secondary structure prediction that are based on the multiple sequence alignment (accuracy = 73.20%). Combine with the 31 amino acids crystal structure of the oligomerization, the three dimensional conformation of p53 C-terminal 108 residues was built using the SGI INDIGO(2) computer. This structure further expounds the relationship among those biological function domains of p53 C- terminus at three-dimensional level.

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Five models for human interleukin-7 (HIL-7), HIL-9, HIL-13, HIL-15 and HIL-17 have been generated by SYBYL software package. The primary models were optimized using molecular dynamics and molecular mechanics methods. The final models were optimized using a steepest descent algorithm and a subsequent conjugate gradient method. The complexes with these interleukins and the common gamma chain of interleukin-2 receptor (IL-2R) were constructed and subjected to energy minimization. We found residues, such as Gln127 and Tyr103, of the common gamma chain of IL-2R are very important. Other residues, e.g. Lys70, Asn128 and Glu162, are also significant. Four hydrophobic grooves and two hydrophilic sites converge at the active site triad of the gamma chain. The binding sites of these interleukins interaction with the common gamma chain exist in the first helical and/or the fourth helical domains. Therefore, we conclude that these interleukins binds to the common gamma chain of IL-2R by the first and the fourth helix domain. Especially at the binding sites of some residues (lysine, arginine, asparagine, glutamic acid and aspartic acid), with a discontinuous region of the common gamma chain of IL-2R, termed the interleukins binding sites (103-210). The study of these sites can be important for the development of new drugs. (C) 2000 Elsevier Science B.V. All rights reserved.

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Anew integrated sequence-structure database, called IADE (Integrated ASTRAL-DSSP-EMBL), incorporating matching mRNA sequence, amino acid sequence, and protein secondary structural data, is constructed. It includes 648 protein domains. Based on the IADE database, we studied the relation between RNA stem-loop frequencies and protein secondary structure. It was found that the alpha-helices and beta-strands on proteins tend to be preferably "coded" by mRNA stem region, while the coils on proteins tend to be preferably "coded" by mRNA loop region. These tendencies are more obvious if we observe the structural words (SWs). An SW is defined by a four-amino-acid-fragment that shows the pronounced secondary structural (alpha-helix or beta-strand) propensity. It is demonstrated that the deduced correlation between protein and mRNA structure can hardly be explained as the stochastic fluctuation effect. (C) 2003 Wiley Periodicals, Inc.

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Natural levels of solar UVR were shown to break and alter the spiral structure of Arthrospira (Spirulina) platensis (Nordst.) Gomont during winter. However, this phenomenon was not observed during summer at temperatures of similar to 30 degrees C. Since little has been documented on the interactive effects of solar UV radiation (UVR; 280-400 nm) and temperature on cyanobacteria, the morphology, photosynthesis, and DNA damage of A. platensis were examined using two radiation treatments (PAR [400-700 nm] and PAB [PAR + UV-A + UV-B: 280-700]), three temperatures (15, 22, and 30 degrees C), and three biomass concentrations (100, 160, and 240 mg dwt [dry weight] . L-1). UVR caused a breakage of the spiral structure at 15 degrees C and 22 degrees C, but not at 30 degrees C. High PAR levels also induced a significant breakage at 15 degrees C and 22 degrees C, but only at low biomass densities, and to lesser extent when compared with the PAB treatment. A. platensis was able to alter its spiral structure by increasing helix tightness at the highest temperature tested. The photochemical efficiency was depressed to undetectable levels at 15 degrees C but was relatively high at 30 degrees C even under the treatment with UVR in 8 h. At 30 degrees C, UVR led to 93%-97% less DNA damage when compared with 15 degrees C after 8 h of exposure. UV-absorbing compounds were determined as negligible at all light and temperature combinations. The possible mechanisms for the temperature-dependent effects of UVR on this organism are discussed in this paper.

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m Background: Cross-species nuclear transfer has been shown to be a potent approach to retain the genetic viability of a certain species near extinction. However, most embryos produced by cross-species nuclear transfer were compromised because that they were unable to develop to later stages. Gene expression analysis of cross-species cloned embryos will yield new insights into the regulatory mechanisms involved in cross-species nuclear transfer and embryonic development. Results: A novel gene, K31, was identified as an up-regulated gene in fish cross-subfamily cloned embryos using SSH approach and RACE method. K31 complete cDNA sequence is 1106 base pairs (bp) in length, with a 342 bp open reading frame (ORF) encoding a putative protein of 113 amino acids (aa). Comparative analysis revealed no homologous known gene in zebrafish and other species database. K31 protein contains a putative transmembrane helix and five putative phosphorylation sites but without a signal peptide. Expression pattern analysis by real time RT-PCR and whole-mount in situ hybridization (WISH) shows that it has the characteristics of constitutively expressed gene. Sub-cellular localization assay shows that K31 protein can not penetrate the nuclei. Interestingly, over-expression of K31 gene can cause lethality in the epithelioma papulosum cyprinid (EPC) cells in cell culture, which gave hint to the inefficient reprogramming events occurred in cloned embryos. Conclusion: Taken together, our findings indicated that K31 gene is a novel gene differentially expressed in fish cross-subfamily cloned embryos and over-expression of K31 gene can cause lethality of cultured fish cells. To our knowledge, this is the first report on the determination of novel genes involved in nucleo-cytoplasmic interaction of fish cross-subfamily cloned embryos.

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Voltage-dependent anion channel (VDAC, also known as mitochondrial porin) is acknowledged to play an important role in stress-induced mammalian apoptosis. In this study, Paralichthys olivaceus VDAC (PoVDAC) gene was identified as a virally induced gene from Scophthalmus Maximus Rhabdovirus (SMRV)-infected flounder embryonic cells (FEC). The full length of PoVDAC cDNA is 1380 bp with an open reading frame of 852 bp encoding a 283 amino acid protein. The deduced PoVDAC contains one alpha-helix, 13 transmembrane beta-strands and one eukaryotic mitochondrial porin signature motif. Constitutive expression of PoVDAC was confirmed in all tested tissues by real-time PCR. Further expression analysis revealed PoVDAC mRNA was upregulated by viral infection. We prepared fish antiserum against recombinant VDAC proteins and detected the PoVDAC in heart lysates from flounder as a 32 kDa band on western blot. Overexpression of PoVDAC in fish cells induced apoptosis. Immunofluoresence localization indicated that the significant distribution changes of PoVDAC have occurred in virus-induced apoptotic cells. This is the first report on the inductive expression of VDAC by viral infection, suggesting that PoVDAC might be mediated flounder antiviral immune response through induction of apoptosis. (c) 2007 Elsevier Ltd. All rights reserved.

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We theoretically study the spatial behaviors of the spin precession in a two-dimensional electron system with spin-orbit interaction. Through analysis of interaction between the spin and the effective magnetic field in the system, we obtain the general conditions to generate a persistent spin helix and predict a persistent spin helix pattern in [001]-grown quantum wells. Particularly, we demonstrate that the phase of spin can be locked to propagate in a quantum well with SU(2) symmetry.

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Recent experiments indicated that disorder effect in deoxyribonucleic acid (DNA) may lead to a transition of the electronic hole transport mechanism from band resonant tunneling to thermally activated hopping. In this letter, based on Mott's variable-range hopping theory, we present a kinetic study for the hole transport properties of DNA molecules. Beyond the conventional argument in large-scale systems, our numerical study for finite-size DNA molecules reveals a number of unique features for: (i) the current-voltage characteristics, (ii) the temperature and length dependence, and (iii) the transition from conducting to insulating behaviors. (c) 2005 American Institute of Physics.

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A quantum chemistry based Green's function formulation of long-range charge transfer in deoxyribose nucleic acid (DNA) double helix is proposed. The theory takes into account the effects of DNA's electronic structure and its incoherent interaction with aqueous surroundings. In the implementation, the electronic tight-binding parameters for unsolvated DNA molecules are determined at the HF/6-31G* level, while those for individual nucleobase-water couplings are at a semiempirical level by fitting with experimental redox potentials. Numerical results include that: (i) the oxidative charge initially at the donor guanine site does hop sequentially over all guanine sites; however, the revealed rates can be of a much weaker distance dependence than that described by the ordinary Ohm's law; (ii) the aqueous surroundings-induced partial incoherences in thymine/adenine bridge bases lead them to deviate substantially from the superexchange regime; (iii) the time scale of the partially incoherent hole transport through the thymine/adenine pi stack in DNA is about 5 ps. (C) 2002 American Institute of Physics.

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可生物降解的两亲性嵌段共聚物PLA-PEG飞所制备的胶束或纳术粒子,作为潜在的药物控制释放体系弓!起人们广泛的兴趣。,方们授有寿比山于PEG链的空间位阴.效应可以避免单核噬菌体的吞噬,、并且可以通过控制可降解部分的降解行为实现药物的持续释放,使在微载体内所包载的药物分子持续释放出来。尽管高聚物的胶束和纳米粒子作为药物的胶体载体已作厂泛研究,但是对其本身物理化学性质与应用之间的联系研究甚少。因此本文对一系列PLLA和PEG两嵌段和三嵌段共聚物的自聚集行为进行了细致研究,得到了以卜结论:1.以花为"模型药物",通过荧光探针技术对一系列两亲性共聚物在水呀招夜和NaCI溶液种的胶束化行为进行了研究。这些共聚物是由一种新型氨钙催化利,以人分J,的聚乙二醇(PEG)为引发剂,引发丙交酷开环聚合得到,,其中囚定长度阴 PEG段分剐为44,104和113环氧乙烷早兀,PLLA的长没在15-280乳酸中元之间。由于氨钙准活性的特点,这些共聚物的分散度较低,均在1.1-1.3之间。其临界胶束浓度cmc发现随PLLA的含量增加I荆氏。具有同一PEG长度的两嵌段和三嵌段共聚物cmc值的截然差别为它们胶束的构型不同提供了证据。同时也发现了NaCI的加入对丫EG段和争LLA段较短洪聚物的cmc的降低有明掀笋作用,而对具有较长PEG段或较长PLLA段的共聚物的cmc基本上没有什么影响。2.通过荧光探余十技术测定花在这一系列共聚物胶束溶液锄勺配分系数在0.2*10~5至1.9*10~5之间,对于同-PEG段的共聚物,花在其胶柬相中的配分系数随PLLA的含量的增加而增加。另外发现NaCl的加入能够促进花在胶束相中的配分。3.通过透射电子显微镜研究了两嵌段共聚物水溶液胶束的形貌,发现胶束的粒径和分散度均随PLLA段的增加而增加:通过原子力显微镜研究"这些纳米粒子退火前后的形貌变化,发现退火后纳米粒子重新自聚集为类似于神经网络红脚乏的"纳米条带"结构,其中心为类似"神经元"的团簇结构,而周困为支化的车由突"分支结构,这与文献上提到的只有三嵌段共聚物能够形成支化的"纳米条带"结构截然不同,其自聚集机理在进,步研究之中。4.以亲水性的荧光素为荧光探针研究了两嵌段共聚物在甲苯中的胶束化行为,发现其clnc值随PLLA段的含量增加而降低,相对于PEG段,PLLA段在其胶宋化过程中起主要作用。通过1HNMR证明两嵌段共聚物在甲苯中的胶束具伯以PLLA段为"核"、PEG段为"壳"的"核-壳"结构,这种胶柬化行为通过溶解度参数的差异进行了解释。5.通过原子力显微镜发现,当这些胶束滴加在云母表面上经过热处理后,这些胶束重新自聚集成为规则的具有平缓隆起的纳米结构,这与由水中得到的胶柬热处理后的形貌截然不同,并对此进行了进一步解释。由XPS分析认为主要是PEG段覆盖在PLLA段表面。

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本论文主要研究了ABA和ABC型两亲性三嵌段共聚物在选择性稀溶液中的自组装行为,得到了多种形态新颖、结构复杂多样的胶束,研究了这些复杂胶束的形成过程,探讨了影响胶束形态的各种因素并通过适当的方法对胶束形态进行调控。研究了聚乙烯基毗陡(P4VP)/聚苯乙烯(PS)三嵌段共聚物P4VP-b-PS-b-P4VP在二氧六环/水中的自组装行为,成功得到了嵌段共聚物环状胶束,并通过实验研究了环状胶束的形成过程。结果表明,胶束形态依赖于退火时间的长短。随着退火时间的延长,胶束结构从棒状过渡到环形结构。以实验结果为基础提出了环状胶束形成的新的机理,即囊泡塌陷形成环。同时,通过改变实验条件还得到了一些新型的环状复合结构,如环套环形、鸟状、哑铃形、戒指形、网络状等结构,并得到了与计算机模拟一致的结果。通过不同的方法对ABA型三嵌段共聚物(P4VP-b-PS-b-P4VP)在选择性溶液中的自组装胶束形态进行调控:首先,详细研究了P4VP-b-PS-b-P4VP在不同的共溶剂中的自组装行为。结果表明通过单纯改变共溶剂的性质可以很方便地调节胶束的形态,得到了球、棒、囊泡等结构。并用混合溶剂的方法得到了长度和直径可控的纳米线胶束。同时,通过加入第二种选择性溶剂(核层嵌段PS的选择性溶剂甲苯)的方法使形成胶束的核层嵌段在胶核中的伸展程度增加,从而使胶束形态发生转变。其次,研究了加入表面活性剂十五烷基苯酚(PDP)以构建分子间氢键来调节P4VP-b-PS-b-P4VP的胶束形态。结果表明,通过调节PDP的加入量可以使胶束形态发生从球到棒,到网络状、再到囊泡结构的转变。通过实验对比系统地研究了PDP的加入对胶束形态转变的影响,提出了相应的形态转变机理。再次,研究了不同分子量的嵌段共聚物之间共混及共聚物与均聚物共混对胶束形态的影响。结果表明加入亲油嵌段的均聚物对共聚物胶束形态影响非常明显,胶束形态与加入的均聚物的分子量及加入量直接相关。同时得到了一些新形态的胶束,如海绵状、笼子状等。共聚物共混的研究结果表明:通过两种不同分子量的共聚物共混可以得到这两种共聚物胶束的过渡态结构。用共聚物混合的方法还可以得到一些具有生物模拟性的胶束结构,如乌贼状、章鱼状等。这加深了人们对囊泡的形成机理及各种胶束形态之间形态转变的认识。P4VP-b-PS-b-P4VP通过在二氧六环/水中的自组装形成了囊泡,结果表明囊泡的尺寸依赖于初始状态下共聚物在共溶剂中的浓度及退火时间。除得到常规的球形囊泡外,还得到一些非球形囊泡,如长条形、三角形、项链形等囊泡结构。结合计算机模拟的方法研究了囊泡的形成机理,发现这些不同结构的囊泡的形成是由于初始状态下密度涨落所引起的。研究了实验中经常出现的各种胶束形态共存现象的原因,发现体系中亚稳态的存在是多形态共存的重要原因之一。通过聚苯乙烯一左聚乙烯基毗睫一左聚氧乙烯(PS一b一PZVP一b一PEO)在THF/水中的二次自组装首次得到了一种具有生物模拟性的巨大的节状蠕虫胶束(SWM)。研究发现,SWM是由重复单元盘状结构和丝状结构相连组成的。最令人吃惊的是这种SWM与自然界中的一些生命体如蛆叫、蛹、昆虫类的幼虫结构非常相似。通过对SWM形成过程中的中间态胶束结构的深入研究发现SWM是由球形胶束通过二次自组装形成的。SWM的形成过程可以分为三个阶段:ABC三嵌段共聚物先组装形成球形结构;这些球型结构粘连在一起形成梭形的中间结构;这些梭状中间结构中的球经过重组和重新调整各嵌段的排布最终形成SWM。用所得到的嵌段共聚物胶束为模板,采用无电沉积的方法成功制备了各种形态的金属一有机高分子纳米复合材料。用简单的方法还得到了导电金属金一银的双金属纳米结构材料。这些纳米结构材料在微电子器件等领域有潜在应用价值。以上研究结果丰富了人们对嵌段共聚物在选择性介质中自组装行为的理解,为人们提供了对生物材料自组装本质的理解的依据。这在两亲性分子在溶液中自组装的基础研究方面以及基于这些自组装形态而构建结构及功能更复杂的纳米结构材料等方面都有一定的意义。

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本论文主要由3 个相对独立的部分组成: 西夫韦肽抗HIV 活性机制研究及其 联合用药和耐药性研究,盐肤木提取物及其化合物抗HIV 活性机制研究和精子 顶体反应抑制剂AGB 抗HIV 活性及机制研究。 HIV 侵入抑制剂是抗HIV 药物研发的热点。该类抑制剂靶定在病毒复制周 期早期,为HARRT 疗法提供了更多新的药物组合,且该类抑制剂对临床中已产 生的耐药毒株也有较好的抑制作用。目前FDA 批准上市的侵入抑制剂仅有T-20, 急需开发新一类的HIV-1 侵入抑制剂。西夫韦肽是由36 个氨基酸组成的多肽, 我们对西夫韦肽进行了一系列体外抗HIV 药效学的实验来研究西夫韦肽体外抗 HIV 活性以及作用机制。实验结果表明西夫韦肽对多种HIV 宿主细胞毒性小, 可以有效抑制HIV-1IIIB 诱导的C8166 细胞的病变效应,EC50 值仅为7.8ng/ml , TI 值大于 384,615;在不同的检测方法中,西夫韦肽均表现出了比T-20 更好的抑 制活性,EC50 值低了13-42 倍。在对HIV-1 临床分离株、耐药株、两株HIV-2 毒株和SIVmac239 的抑制活性研究表明西夫韦肽也可以很好地抑制 HIV-1 临床株 HIV-1KM018 的复制,EC50 值低至4.4ng/ml,对耐药株HIV-174V、HIV-2 和 SIVmac239 的复制也均有较好的抑制作用。 在机制研究中,我们发现西夫韦肽极有效地抑制HIV-1慢性感染H9细胞与 正常C8166细胞间的融合作用,EC50 低至0.4ng/ml,表明西夫韦肽可以以极低的 浓度有效抑制HIV进入宿主细胞。用GST-pull down 实验进一步验证了西夫韦肽 和T-20可以很好地与HR1结合而不能与HR2结合,作用机制就是特异地与gp41的 HR1结合从而抑制了6-Helix的形成,阻断了HIV的融合过程。由于HIV的高变异 性,单一药物治疗容易产生耐药性,最终导致治疗失败。因此在新药开发中进行 药物与作用靶不同的已上市药物体外联合用药和耐药性研究是非常必要的,将对 临床应用有指导意义,我们的实验结果表明西夫韦肽与AZT联合用药体外抗HIV-1作用较单独用药好,不同检测方法联合用药比单独使用西夫韦肽的效果好 8.3-9.4倍;耐药性研究表明其体外诱导耐药性产生的时间与T-20相仿,与T-20有 交叉耐药。 我国传统的中医药是个巨大的宝库,有丰富的临床经验,中医药治疗艾滋病 有着一定的潜力。从我国国情出发,利用中医药的独特性及经济性,开发传统的 具有我国特色的艾滋病治疗天然药物成为AIDS 防治工作的当务之急。盐肤木是 中国的本土植物,在我国民间用作传统医药有着悠久的历史。盐肤木茎提取物尤 其是石油醚提取部分RC-1 具有较好的抗HIV 活性,且作用于病毒复制周期的后 期,从中分离得到的化合物1、2、4、5 和6 都是RC-1 的活性成份;盐肤木茎 提取物乙酸乙酯提取物RC-2 中也有较好的抗HIV 作用,其中的化合物8、9、 10 和13 是抗HIV 的活性成分,且作用机制各不相同,这些有效化合物的抗HIV 机制值得进一步的研究。 杀微生物剂是一种局部用药于阴道或宫颈的药物制剂,由女性自主控制防止 性传播疾病病原体包括HIV 的感染,是近年来的研究热点之一。AGB(4`-乙酰胺 苯基 4-胍基苯甲酸酯)是顶体酶的抑制剂,我们的实验表明AGB 有很好的杀精 子作用,还具有体外抗HIV-1 的作用,作用机制主要是阻断HIV-1 进入细胞。

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人胚胎干细胞(human embryonic stem cells, hES细胞)来源于植入前胚胎的内细胞团,具有自我更新能力和发育全能性,能够在体内外分化为代表三个胚层的细胞类型。hES细胞来源的神经前体细胞(neural progenitor)对于研究胚胎早期的神经发育以及药物筛选和神经系统疾病的细胞替代性治疗具有重要意义。然而,许多因素影响了ES细胞的临床应用,如供体细胞不足、纯度低、异源物质污染等。 本研究采用同源饲养层培养的hES细胞在单层培养条件下高效地分化得到了神经前体细胞。主要结论如下:1)hES细胞在同源饲养层HAFi上培养八个月后仍保持ES细胞的各项表型特征和抗原特性。表明HAFi能够支持hES细胞的长期培养,从培养条件上避免了异源物质污染的可能性。2)单层贴壁分化的方法培养成分简单,不含血清和条件培养基,不需繁琐的筛选步骤就可以得到高比例的神经前体细胞(97.5%±0.83%)(P<0.05)。此外,成分确定的培养基是研究神经分化的分子机制的良好模型。3)hES细胞来源的神经前体细胞具有分化为神经元,星形胶质和少突胶质细胞的能力,并能够模拟体内神经发育的过程和分子表达模式。长期的传代培养中发现,随着培养时间的延长,nestin阳性的神经前体细胞比例下降,同时发育能力也发生了变化。在传代培养的早期,神经前体细胞发育为神经元的比例很高,几乎没有胶质细胞分化出来。随培养时间的延长,胶质细胞的比例逐渐上升。进一步研究发现具有bHLH (basic helix-loop-helix) 结构域的转录因子neurogenein2(Ngn2) 和olig2可能在这一变化中发挥了重要的作用。

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A bar on the Brazos River near Calvert, Texas, has been analyzed in order to determine the geologic meaning of certain grain size parameters and to study the behavior of the size fractions with transport. The bar consists of a strongly bimodal mixture of pebble gravel and medium to fine sand; there is a lack of material in the range of 0.5 to 2 mm, because the source does not supply particles of this size. The size distributions of the two modes, which were established in the parent deposits, are nearly invariant over the bar because the present environment of deposition only affects the relative proportions of the two modes, not the grain size properties of the modes themselves. Two proportions are most common; the sediment either contains no gravel or else contains about 60% gravel. Three sediment types with characteristic bedding features occur on the bar in constant stratigraphic order, with the coarsest at the base. Statistical analysis of the data is based on a series of grain size parameters modified from those of Inman (1952) to provide a more detailed coverage of non-normal size curves. Unimodal sediments have nearly normal curves as defined by their skewness and kurtosis. Non-normal kurtosis and skewness values are held to be the identifying characteristics of bimodal sediments even where such modes are not evident in frequency curves. The relative proportions of each mode define a systematic series of changes in numerical properties; mean size, standard deviation and skewness are shown to be linked in a helical trend, which is believed to be applicable to many other sedimentary suites. The equations of the helix may be characteristic of certain environments. Kurtosis values show rhythmic pulsations along the helix and are diagnostic of two-generation sediments.