Most natural (or biological) materials are complex composites whose mechanical properties are often outstanding, considering the weak constituents from which they are assembled. These complex structures, which have risen from hundreds of million years of evolution, are inspiring Materials Scientists in the design of novel materials.Their defining characteristics, hierarchy, multifunctionality, and self-healing capability, are illustrated. Self-organization is also a fundamental feature of many biological materials and the manner by which the structures are assembled from the molecular level up. The basic building blocks are described, starting with the 20 amino acids and proceeding to polypeptides, polysaccharides, and polypeptides-saccharides. These, on their turn, compose the basic proteins, which are the primary constituents of 'soft tissues' and are also present in most biominerals. There are over 1000 proteins, and we describe only the principal ones, with emphasis on collagen, chitin, keratin, and elastin. The 'hard' phases are primarily strengthened by minerals, which nucleate and grow in a biomediated environment that determines the size, shape and distribution of individual crystals. The most important mineral phases are discussed: hydroxyapatite, silica, and aragonite.Using the classification of Wegst and Ashby, the principal mechanical characteristics and structures of biological ceramics, polymer composites, elastomers, and cellular materials are presented. Selected systems in each class are described with emphasis on the relationship between their structure and mechanical response. A fifth class is added to this: functional biological materials, which have a structure developed for a specific function: adhesion, optical properties, etc.An outgrowth of this effort is the search for bioinspired materials and structures. Traditional approaches focus on design methodologies of biological materials using conventional synthetic 0079-6425/$ -see front matter Ó

Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3+CD4-CD8- lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte apoptosis. Each child had defective Fas-mediated T lymphocyte apoptosis associated with a unique, deleterious Fas gene mutation. One mutation appeared to cause a simple loss of function; however, four others had a dominant negative phenotype when coexpressed with normal Fas. Family studies demonstrated the inheritance of the mutant Fas alleles. The occurrence of Fas mutations together with abnormal T cell apoptosis in ALPS patients suggests an involvement of Fas in this recently recognized disorder of lymphocyte homeostasis and peripheral self-tolerance.

This paper describes the Magnetic Electron Ion Spectrometer (MagEIS) instruments aboard the RBSP spacecraft from an instrumentation and engineering point of view. There are four magnetic spectrometers aboard each of the two spacecraft, one low-energy unit (20-240 keV), two medium-energy units (80-1200 keV), and a high-energy unit (800-4800 keV). The high unit also contains a proton telescope (55 keV-20 MeV).The magnetic spectrometers focus electrons within a selected energy pass band upon a focal plane of several silicon detectors where pulse-height analysis is used to determine if the energy of the incident electron is appropriate for the electron momentum selected by the magnet. Thus each event is a two-parameter analysis, an approach leading to a greatly reduced background.The physics of these instruments are described in detail followed by the engineering implementation. The data outputs are described, and examples of the calibration results and early flight data presented.

The tumour suppressor gene PTEN, which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma Human Molecular Genetics, 1998, Vol. 7, No. 3 508 and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN, with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis in the group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.

No abstract

No abstract

No abstract

No abstract