A wafer level monitoring method for plasma-charging damage usingantenna PMOSFET test structure

A novel monitoring method for plasma-charging damage is proposed. This method performs a quick and accurate evaluation using antenna PMOSFET. It was found that not only hot-carrier (HC) lifetime but transistor parameters such as initial gate current and substrate current were changed according to the degree of plasma-charging damage. However, the present work suggests that monitoring the shift of drain current after a few seconds of HC stress is a more accurate method to indicate plasma-charging damage. The monitoring method using the present test structure is demonstrated to be useful for realizing highly reliable devices     

Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

Nasopharyngeal colonization in Costa Rican children during the first year of life

BACKGROUND: The establishment of the nasopharyngeal flora was followed in Costa Rican children from birth to 1 year of age. METHODS: Nasopharyngeal cultures were obtained at 1 (n = 413), 3 (n = 393), 6 (n = 376) and 12 months (n = 356) of age from children representative of the population in the Puriscal district. Weekly cultures were obtained from a subcohort of these children (n = 101). Mother-infant diads (n = 95) and preschool children (n = 208) attending day-care centers were also studied. RESULTS: The estimated proportion of colonized children in the population differed markedly depending on the frequency of culture. Quarterly cultures showed a slow increase in carrier rates from 3.9% for Haemophilus influenzae, 3.1% for Streptococcus pneumoniae and 6.5% for Moraxella catarrhalis at 1 month of age to 10.1% carrying H. influenzae and 19.4% carrying S. pneumoniae by the end of the first year. By quarterly culture the proportion of children colonized at least once was 36% for S. pneumoniae, 26% for H. influenzae and 28% for M. catarrhalis. In contrast weekly sampling showed that 95 to 100% of the children were colonized at least once during the first year of life with H. influenzae, S. pneumoniae or M. catarrhalis. Nasopharyngeal carriage of H. influenzae, S. pneumoniae and M. catarrhalis was low in the mothers, and very few mother-infant pairs carried identical bacteria at the same time. In contrast carrier rates were high in the siblings attending day care (H. influenzae 27.9%, S. pneumoniae 39.4%, both organisms 26.6%). Infants with siblings had significantly higher bacterial carriage at all ages than infants without siblings. CONCLUSIONS: Quarterly nasopharyngeal cultures showed that Costa Rican infants acquire their nasopharyngeal flora at a rate comparable with that for infants in developed countries and that siblings are an important source of the bacteria. Weekly samplings showed that virtually all children were colonized at least once during the first year of life.     

Role of the hemobiologist in the detection and prevention of post-transfusional hepatitis

To prevent post-transfusional hepatitis B and C, two epidemiologic studies were performed. The first, based on the frequencies distribution of hepatitis B virus serological markers versus sex and classes of age, has permitted the assessment of the profile of the infection in a population composed of 573 north vietnamese blood donors. There is no significant difference between men and women frequencies of HBs antigen (11.5%), anti-HBs antibody (70.2%) and anti-HBc antibody alone (3.8%), but a significant difference of no-marker frequencies: 7.8% and 17.9% in men and women respectively (X2 = 9.11; p = 0.010). The percentage of no-marker decreases when the mean age of each class increases. The second, using the increase of the serum alanine aminotransferase (ALAT) activity as an indirect marker of non-A, non-B hepatitis for determining in a population of more than 25,000 parisian blood donors, the percentage of donors eliminated. They are between 0.70 and 0.76 in women and 2.26 and 2.46 in men. These investigations can be applied to prevent the hepatitis B transmission in a population of 102 south vietnamese women in age to procreate or to determine the percentage of blood donors eliminated (3.12%) in a population of 2,950 Parisians composed in majority (50.9%) of new donors. The hemobiologist will have an important role to elaborate strategies for orientation of blood gifts with hepatitis B and C virus markers.     

Dimer interface of glutathione S-transferase from Arabidopsis thaliana: influence of the G-site architecture on the dimer interface and implications for classification

The three-dimensional structure of glutathione S-transferase from Arabidopsis thaliana has been solved at 2.2 A resolution (Reinemer et al., 1996). The enzyme forms a dimer of two identical subunits. The structure shows a new G-site architecture and a novel and unique dimer interface. Each monomer of the protein forms a separate G-site. Therefore, the requirements on the dimer interface are reduced. As a consequence, the interactions between the monomers are weaker and residues at the dimer interface are more variable. Thus, the dimer interface looses its relevance for a classification of plant glutathione S-transferases and the formation of heterodimers becomes even more difficult to predict.     

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.