基于科学思维的英语文学教学:跨学科的视角

本文阐述基于科学思维过程的英语文学教学策略,即英语文学作品以综合课程的形式应用于教学实践活动.其要点是从优秀文学作品中选取需要解决问题的情境,从跨学科的视角来审视作品中的矛盾和冲突.教师们通过分析这些问题情境教给学生科学的思维方法.其教学策略的重点在于提出问题和做出决策.这些用于跨学科教学策略的文学作品是关注真实世界的起点.生活中面临的两难问题通过基于科学思维的文学教学而获得理性的解释或合理的解决.     

Antibodies to a scrapie prion protein

Scrapie is a slow infection of the nervous system which progresses in the absence of any apparent immune response. The recent development of a large-scale purification protocol for scrapie prions made it possible to obtain substantial quantities of electrophoretically purified prion protein (PrP 27-30) and we report here on the successful production of a rabbit antiserum to PrP 27-30. The antiserum reacted with PrP 27-30 and several lower molecular weight proteins as shown by Western blots; it did not react with protein preparations from uninfected brains. Discrete structures in the subependymal region of scrapie-infected hamster brains were stained immunocytochemically. These same structures also stained with Congo red dye and showed green birefringence with polarized light, a characteristic of purified prion rods. This staining pattern suggests that they are amyloid plaques.     

Ipr1 gene mediates innate immunity to tuberculosis

An estimated eight million people are infected each year with the pathogen Mycobacterium tuberculosis, and more than two million die annually. Yet only about 10% of those infected develop tuberculosis. Genetic variation within host populations is known to be significant in humans and animals, but the nature of genetic control of host resistance to tuberculosis remains poorly understood. Previously we mapped a new genetic locus on mouse chromosome 1, designated sst1 (for supersusceptibility to tuberculosis 1). Here we show that this locus mediates innate immunity in sst1 congenic mouse strains and identify a candidate gene, Intracellular pathogen resistance 1 (Ipr1), within the sst1 locus. The Ipr1 gene is upregulated in the sst1 resistant macrophages after activation and infection, but it is not expressed in the sst1 susceptible macrophages. Expression of the Ipr1 transgene in the sst1 susceptible macrophages limits the multiplication not only of M. tuberculosis but also of Listeria monocytogenes and switches a cell death pathway of the infected macrophages from necrosis to apoptosis. Our data indicate that the Ipr1 gene product might have a previously undocumented function in integrating signals generated by intracellular pathogens with mechanisms controlling innate immunity, cell death and pathogenesis.     

Computational redesign of endonuclease DNA binding and cleavage specificity

The reprogramming of DNA-binding specificity is an important challenge for computational protein design that tests current understanding of protein-DNA recognition, and has considerable practical relevance for biotechnology and medicine. Here we describe the computational redesign of the cleavage specificity of the intron-encoded homing endonuclease I-MsoI using a physically realistic atomic-level forcefield. Using an in silico screen, we identified single base-pair substitutions predicted to disrupt binding by the wild-type enzyme, and then optimized the identities and conformations of clusters of amino acids around each of these unfavourable substitutions using Monte Carlo sampling. A redesigned enzyme that was predicted to display altered target site specificity, while maintaining wild-type binding affinity, was experimentally characterized. The redesigned enzyme binds and cleaves the redesigned recognition site approximately 10,000 times more effectively than does the wild-type enzyme, with a level of target discrimination comparable to the original endonuclease. Determination of the structure of the redesigned nuclease-recognition site complex by X-ray crystallography confirms the accuracy of the computationally predicted interface. These results suggest that computational protein design methods can have an important role in the creation of novel highly specific endonucleases for gene therapy and other applications.     

Control of the carrier-envelope phases of a synchronously pumped femtosecond optical parametric oscillator and its applications

The intrinsic synchronization, multi-color outputs and related carrier-envelope phases （CEP） among pulses bring advantages to synchronously pumped femtosecond optical parametric oscillators and the pumping sources for broadband frequency comb generation and ultrashort waveform coherent syn-thesis. In this paper, we discuss our latest research results in this field, which cover the following as-pects： the phase relationship and energy conservation law in an OPO and related experimental verifi-cation; control of the pumping Ti-sapphire femtosecond laser＇s CEP by self-referencing technology, and its repetition-rate locking by piezoelectric transducer （PZT）; CEP locking of the pulses from the OPO by beating the non-phase-matched visible outputs against pump supercontinuum to obtain a driving signal for a fast PZT on the OPO end mirror; the generation of a broadband frequency comb spanning from 400 nm to 2.4 μm with 1.2 kHz bandwidth; and the realization of coherent interference between phase controlled pump pulses and signal second harmonic pulses.