Specific inhibition of herpesvirus ribonucleotide reductase by a nonapeptide derived from the carboxy terminus of subunit 2

Ribonucleotide reductase, an essential enzyme for the synthesis of deoxyribonucleotides, is formed by the association of two nonidentical subunits in almost all prokaryotic and eukaryotic cells. The same model probably holds for the herpes simplex virus (HSV)-encoded ribonucleotide reductase; two polypeptides of relative molecular mass 136,000 (136K; H1) and 40K (H2) (referred to elsewhere as RR1 and RR2; see for example, Dutia et al.) have been associated with the viral enzyme by both genetic and immunological studies. Furthermore, DNA sequence analyses have shown significant stretches of amino-acid homology between these viral polypeptides and those of, respectively, subunit 1 (ref. 12) and subunit 2 (ref. 13) of the Escherichia coli and mammalian enzymes. To assess the involvement of the 40K polypeptide in reductase activity, we synthesized a nonapeptide corresponding to the sequence of its carboxy terminus with the intention of raising neutralizing antibodies specific for the viral activity (E.A.C. et al., in preparation). We report here the unexpected finding that the nonapeptide itself specifically inhibits the HSV ribonucleotide reductase activity in a reversible, non-competitive manner, and we suggest that it does this by impairment of the correct association of the two subunits. This phenomenon emphasizes the potential usefulness of synthetic peptides in probing critical sites involved in macromolecular interactions.     

Microring-Assisted Coupling Between Dissimilar Waveguides

The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators.     

彩色多普勒超声在腹壁下动脉穿支选择中的应用

验证彩色多普勒超声对腹壁下动脉穿支血管术前探查的有效性,寻找腹壁下动脉穿支术前优势穿支的选择标准。利用彩色多普勒超声探查腹壁下动脉穿支皮瓣行乳房再造患者52例,重点记录穿支血管穿腹直肌前鞘点的体表投影、口径、血流信息,并通过分析比较以上信息,选择优势穿支。结果52例患者腹壁下动脉穿支穿腹直肌前鞘点于超声下均可显示,平均每侧下腹部3支,距脐平均(5.7±2.09)cm,其中条件适用于显微外科的穿支平均口径(0.95±0.32)cm,血流峰速平均约16.4 cm/s,阻力指数平均0.7。术中优势穿支采用率92.31%。说明高频彩色多普勒超声适用于腹壁下动脉穿支皮瓣术前血管探查,可精确指导穿支的术前选择,辅助手术方案制定以及皮瓣设计。     

Tetrapod-like middle ear architecture in a Devonian fish

Few fossils show the incipient stages of complex morphological transformations. For example, the earliest stages in the remodelling of the spiracular tract and suspensorium (jaw suspension) of osteolepiform fishes into the middle ear of tetrapods have remained elusive. The most primitive known tetrapods show a middle ear architecture that is very different from osteolepiforms such as Eusthenopteron, with little indication of how this transformation took place. Here we present an analysis of tetrapod middle ear origins that is based on a detailed study of Panderichthys, the immediate sister taxon of tetrapods. We show that the spiracular region is radically transformed from osteolepiforms and represents the earliest stages in the origin of the tetrapod middle ear architecture. The posterior palatoquadrate of Panderichthys is completely tetrapod-like and defines a similarly tetrapod-like spiracular tract. The hyomandibula has lost its distal portion, representing a previously unrecognized advance towards a stapes-like morphology. This spiracular specialization suggests that the middle ear of early tetrapods evolved initially as part of a spiracular breathing apparatus.     

Efficacy of tumor cell vaccine after incorporating monophosphoryl lipid A (MPL) in tumor cell membranes containing tumor-associated ganglioside

Murine B16 melanoma expresses the ganglioside. GM₃. GM₃ shed from tumor cells is immunosuppressive and promotes tumor growth¹. Reduction or elimination of the shed GM₃ could be therapeutic, and the anti-GM₃ antibodies may reduce and clear the shed ganglioside. To test this hypothesis, mice were challenged with tumor cells, with or without inducing anti-GM₃ antibody response. Since gangliosides are poor immunogens and T-cell independent antigens, an adjuvant (monophosphoryl lipid A (MPL), a non-toxic lipid A ofSalmonella), directed against B-cells, was employed. MPL was incorporated onto liposomes and into the surface membrane of B16 mouse melanoma cells; both are rich in GM₃. C57BL/6J mice immunized with MPL-liposomes or MPL-B16 cells responded with elevated levels of anti-GM₃ IgM. Non-immunized mice or mice immunized with B16 cells alone or ganglioside GM₃ alone (without MPL) elicited poor anti-GM₃ IgM response, confirming the GM₃'s immunologic crypticity and MPL's immunopotentiating effect. MPL's immunopotentiating effect was improved by coupling it to melanoma cell membranes C57BL/6J mice were immunized with irradiated B16 alone or MPL alone or MPL-conjugated irradiated B16. After three weekly immunizations, each mouse received a challenge dose of viable syngeneic B16. Neither MPL alone nor B16 alone had a significant effect on tumor growth or host survival; however, administration of MPL-conjugated B16 cells significantly prevented tumor growth and prolonged survival. Our results indicate that MPL-incorporated B16 cells augment the anti-GM₃ IgM response, which may reverse GM₃-induced immunosuppression by eliminating tumor-derived GM₃, and restore immunocompetence.     

Effective Approach to Elevate the Intelligence of Management Decision System

Based on the sticking point of the low intelligence of the existing management decision system, this paper puts forward the idea of enriching and refining the knowledge of the system and endowing it with the ability to learn by means of adopting three types of heterogeneous knowledge representation and knowledge management measures. At length, this paper outlines the basic framework of an intelligence system for the sake of management decision problem.     

Simulation and uniform design-based automatic generation of risk scenarios

This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology.