Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 A resolution

The only well-understood mechanism of zymogen activation is that of the serine proteinases, in which proteolytic cleavage leads to conformational changes resulting in a functional active site. A different mechanism is now unveiled by the crystal structure of pepsinogen. Salt bridges that stabilize the positioning of the N-terminal proenzyme segment across the active site of pepsin are disrupted at low pH, releasing the amino-terminal segment and thereby exposing the catalytic apparatus and the substrate-binding sites.     

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.     

Commercialization of research: so far

In June 1982, potential corporate investors attended a Harvard conference on biotechnology and the evolving research partnership between universities and industry. Molecular biologist Walter Gilbert spoke about the need to correct public misconceptions about technology transfer between industry and academia, and about the relationship between basic and applied research. Harvard president Derek Bok encouraged "bilateral" research agreements between corporations and universities and proposed conditions under which such agreements would operate. Bok also offered guidelines on individual faculty involvement in biotechnology firms and university investment in such firms, while Gilbert commented on the issue of patent rights in academically-sponsored research.     

Refinement of reduced-models for dynamic systems

A refinement procedure for the reduced models of structural dynamic systems is presented in this article. The refinement procedure is to ＂tune＂ the parameters of a reduced model, which could be obtained from any traditional model reduction scheme, into an improved reduced model. Upon the completion of the refinement, the improved reduced model matches the dynamic characteristics - the chosen structural frequencies and their mode shapes - of the full order model. Mathematically, the procedure to implement the model refinement technique is an application of the recently developed cross-model cross-mode （CMCM） method for model updating. A numerical example of reducing a 5-DOF （degree-of-freedom） classical mass-spring （or shear-building） model into a 3-DOF generalized mass-spring model is demonstrated in this article.     

Gas chromatographic method for the determination of hexaconazole residues in black tea

A highly reliable, quantitative and sensitive analytical method for determining the residues of the fungicide, hexaconazole in black tea is described. The proposed method is based on liquid-liquid extraction followed by gas chromatographic determination, using nitrogen phosphorus detector （GC-NPD） for the identification and quantitation of hexaconazole. The most appropriate solvent mixture for extracting hexaconazole residues from black tea was n-hexane：acetone at 1 ：1 （v/v）. The extract was cleaned up by adsorption column chromatography using activated florisil. Performance of the method was assessed by evaluating quality parameters such as recovery value, repeatability, reproducibility, linearity and limits of detection and quantitation. When the method was assessed for repeatability, the percentage of recovery ranged between 86% and 96% while the relative standard deviation was between 0.30% and 2.35%. In studies on reproducibility the recovery ranged from 81% to 85% and relative standard deviation from 1.68% to 5.13%, implying that the method was reliable. A field trial was conducted to verify the application of this method with real samples. Results prove that the validated method was suitable for extracting hexaconazole residues.     

地球物理流体力学基础

本书作者是美国加州大学洛杉矶分校地球科学教授，美国Boulder国家大气研究中心研究员，从事本学科教学和研究达30年之久。     

Content-Based Image Retrieval: Near Tolerance Rough Set Approach

<正>The problem considered in this paper is how to detect the degree of similarity in the content of digital images useful in image retrieval,i.e.,to what extent is the content of a query image similar to content of other images.The solution to this problem results from the detection of subsets that are rough sets contained in covers of digital images determined by perceptual tolerance relations(PTRs).Such relations are defined within the context of perceptual representative spaces that hearken back to work by J.H.Poincare on representative spaces as models of physical continua.Classes determined by a PTR provide content useful in content-based image retrieval(CBIR).In addition,tolerance classes provide a means of determining when subsets of image covers are tolerance rough sets(TRSs).It is the nearness of TRSs present in image tolerance spaces that provide a promising approach to CBIR,especially in cases such as satellite images or aircraft identification where there are subtle differences between pairs of digital images,making it difficult to quantify the similarities between such images.The contribution of this article is the introduction of the nearness of tolerance rough sets as an effective means of measuring digital image similarities and,as a significant consequence,successfully carrying out CBIR.     

The structural basis for membrane binding and pore formation by lymphocyte perforin

Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca(2+)-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.