Protein identification by MALDI-TOF-MS peptide mapping: a new strategy

A new strategy for identifying proteins by MALDI-TOF-MS peptide mapping is reported. In contrast to current approaches, the strategy does not rely on a good relative or absolute mass accuracy as the criterion that discriminates false positive results. The protein sequence database is first searched for all proteins that match a minimum five of the submitted masses within the maximum expected relative errors when the default or externally determined calibration constants are used, for instance, +/-500 ppm. Typically, this search retrieves many thousand candidate sequences. Assuming initially that each of these is the correct protein, the relative errors of the matching peptide masses are calculated for each candidate sequence. Linear regression analysis is then performed of the calculated relative errors as a function of m/z for each candidate sequence, and the standard deviation to the regression is used to distinguish the correct sequence among the candidates. We show that this parameter is independent of whether the mass spectrometric data were internally or externally calibrated. The result is a search engine that renders internal spectrum calibration unnecessary and adapts to the quality of the raw data without user interference. This is made possible by a dynamic scoring algorithm, which takes into account the number of matching peptide masses, the percentage of the protein's sequence covered by these peptides and, as new parameter, the determined standard deviation. The lower the standard deviation, the less cleavage peptides are required for identification and vice versa. Performance of the new strategy is demonstrated and discussed. All necessary computing has been implemented in a computer program, free access to which is provided in the Internet.     

CAD/CAM技术在脚医学中的应用

将CAD／CAM技术与脚医学结合，研究开发脚支撑设计制造系统，包括脚底曲面数据的读取及处理，根据医疗规划完成三维脚支撑模型的构造，平衡及光滑处理，激光快速原型文件和铣削加工刀具轨迹的自动生成等。     

Apolipoprotein E isoforms in Alzheimer's disease pathology and etiology

The apolipoprotein E (apoE) epsilon4 allele increases risk of Alzheimer's disease (AD), perhaps by accelerating plaque formation, or by impairing neuron repair. Considerable evidence supports both mechanisms. AD patients with epsilon4 have more and earlier amyloid deposits than do patients without epsilon4. The same is true of non-demented control subjects. In vitro, all apoE isoforms inhibit amyloid beta protein (Abeta) aggregation, but apoE4 less effectively than apoE3. Transgenic amyloid-producing mice expressing apoE3 or apoE4 develop less Abeta deposition than apoE knockout mice. These observations are consistent with an effect of apoE isoforms on Abeta aggregation in AD. ApoE is important for neurite maintenance since apoE knockout mice lose neurites and suffer behavioral deficits with aging or treatment with excitotoxins. ApoE4 mice show similar defects, but apoE3 mice are normal. AD patients with epsilon4 show more neuritic deficits than epsilon3 carriers. ApoE epsilon4 also worsens neurological impairment in head injury, stroke, and multiple sclerosis. Thus, apoE4 is less effective at neurite maintenance. Perhaps epsilon4 increases AD risk by both mechanisms: allowing amyloid deposition and failing to repair neurites. In either case, introducing apoE3 or apoE2 into the brain, for example by gene therapy or cell grafts, might delay AD progression.     

Engineering Bacillus thuringiensis bioinsecticides with an indigenous site-specific recombination system

The cry genes of Bacillus thuringiensis encode a diverse group of crystal-forming proteins that exhibit insecticidal activity, particularly against the larvae of lepidopteran, coleopteran, and dipteran insects. The efficacy of B. thuringiensis-based biopesticides may be improved through the genetic manipulation of these genes. A gene transfer system has been developed for the introduction and maintenance of cloned insecticidal cry genes on small plasmids in B. thuringiensis. This vector system combines a B. thuringiensis plasmid replicon and an indigenous site-specific recombination system that allows for the selective removal of ancillary or foreign DNA from the recombinant bacterium after introduction of the Cry-encoding plasmid. The site-specific recombination system is useful for engineering strains with unique combinations of cry genes, resulting in new active ingredients with improved insecticidal properties.     

Analytical determination of eddy currents in a hollow sphereexcited by an arbitrary dipole

In this paper an analytical solution for the quasistationary eddy current distribution in a hollow sphere is presented using a divergence free vector potential derived from another spatial vector function by applying the curl operator. The field is excited by a dipole of arbitrary orientation and position. The dissipated power is also considered and hints are given for the analytical treatment of multishield problems excited by current loops     

Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.     

Lumped element networks for replacing sections of a buriedtransmission line

A buried transmission line formed by vertical conductors can function as a wave guiding structure in producing a part of the electromagnetic field distribution caused by a distributed source at the air-earth interface. Such a structure, when excited by an appropriate low-frequency source, is a viable EMP simulation technique for use with underground systems. In the developmental phase of such a technology, there exists a need to artificially elongate the buried line by using lumped element networks. In effect, such networks simulate the simulator plates and earth. The authors address such a network concept and its design considerations. The actual design, fabrication, and testing of an example network are also presented