Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules.     

利用能量原理研究单壁碳纳米管的剪切模量

利用能量方法研究了单壁碳纳米管（SWCNT）的剪切模量．采用分子力学理论得出了受扭矩作用下单壁碳纳米管的总势能;通过总势能与相应的薄壁圆筒的扭转变形能比较,推导出了单壁碳纳米管剪切模量的计算公式;碳纳米管剪切模量的计算结果与现有的研究结果相符,从而证实了本文计算公式正确有效．     

自调式镦压挤胀复合液压机的研制

从力学原理、设计原理、整机结构、关键零部件的设计和工作程序,系统地介绍了自调式镦压挤胀复合液压机．由于压机设计了顶出缸对下活动横梁调节限位结构,回程拉杆对上镦压横梁的复位结构及镦压缸和气液储能器之间的连通协调结构,这不仅使该液压机结构紧凑,同时节省了上镦压横梁的回程液压缸、下活动横梁的镦压缸,并简化了上凸模与上镦压模分设的液压系统,而且解决了直齿圆柱齿轮在塑性成形过程中齿顶难以充满、齿根易出现微裂纹,以及成形压力过大和模具寿命过低的问题．     

基于拉格朗日系统中约束力思想的编队卫星构形非线性控制方法

借鉴经典动力学中约束力的思想,提出了一种编队卫星构形精确保持的非线性控制方法．该方法首先将非线性和摄动条件下编队卫星构形保持问题转换为带有完整约束的拉格朗日动力学系统,然后将问题转换为一组微分代数方程,通过求解微分代数方程,确定编队卫星构形保持的非线性控制律．由于借鉴了约束力的思想,该方法自然地利用了编队卫星动力学系统的力学特性,具有节省能量和高精度的特点．通过对线性和非线性条件下空间圆编队卫星构形保持问题的仿真,验证了提出的非线性控制方法的这些特性．     

PPAR γ partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK

Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2 in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological responses of the ligands. Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009     

Structural characterization of two papaya chitinases, a family GH19 of glycosyl hydrolases

Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19 of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II stretches was examined in the context of their resistance against proteolytic degradation. Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006     

Seborrhea-like dermatitis with psoriasiform elements caused by a mutation in ZNF750, encoding a putative C2H2 zinc finger protein

We describe an Israeli Jewish Moroccan family presenting with autosomal dominant seborrhea-like dermatosis with psoriasiform elements, including enhanced keratinocyte proliferation, parakeratosis, follicular plugging, Pityrosporum ovale overgrowth and dermal CD4 lymphocyte infiltrate. We mapped the disease gene to a 0.5-cM region overlapping the PSORS2 locus (17q25) and identified a frameshift mutation in ZNF750, which encodes a putative C2H2 zinc finger protein. ZNF750 is normally expressed in keratinocytes but not in fibroblasts and is barely detectable in CD4 lymphocytes.     

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006