Characteristics of the readback signal in digital magnetic recording

A theoretical treatment for the readback process in digital magnetic recording is presented. Three major factors, namely, the medium constantswhich defines the extent of the surface charge density, the head-to-medium spacingd, and the read head gap2 g,are taken into consideration. A general solution giving the characteristics of pulse readback signal is shown as a function ofs,dandg. Both amplitude and pulse width of the readback signal are arranged as a product of the medium loss, spacing loss, and gap loss, making it easy to describe the influence of each factor separately. The final value of the amplitude and the pulse width is proportional to that of the recorded surface charge density. Spacing loss simply depends on the ratio ofd/s; gap loss depends on the ratio ofg/(s + d). Theoretical results are compared with experiments which show good agreement for a wide combination ofs,d, andg.     

Optimally weighted wavelet transform based on supervised training for detection of microcalcifications in digital mammograms

We are developing a computer-aided diagnosis (CAD) scheme for detection of clustered microcalcifications in digital mammograms. The use of an empirically chosen wavelet and scale combination for detection of microcalcifications as an initial step of the CAD scheme has been reported by us previously. In this study, we developed a technique for optimizing the weights at individual scales in the wavelet transform to improve the performance of our CAD scheme based on the supervised learning method. In the learning process, an error function was formulated to represent the difference between a desired output and the reconstructed image obtained from weighted wavelet coefficients for a given mammogram. The error function was then minimized by modifying the weights for wavelet coefficients by means of a conjugate gradient algorithm. The Least Asymmetric Daubechies' wavelets were optimized with 297 regions of interest (ROIs) as a training set by a jackknife method. The performance of the optimally weighted wavelets was evaluated by means of receiver-operating characteristic (ROC) analysis by use of the above set of ROIs. The analysis yielded an average area under the ROC curve of 0.92, which outperforms the difference-image technique used in our existing CAD scheme, as well as the partial reconstruction method used in our previous study.     

Protein structural similarities predicted by a sequence-structure compatibility method

A method for protein structure prediction has been developed, which evaluates the compatibility of an amino acid sequence with known 3-dimensional structures and identifies the most likely structure. The method was applied to a large number of sequences in a database, and the structures of the following proteins were predicted: (1) shikimate kinase (SKase), (2) the hydrophilic subunit of mannose permease (IIABMan), (3) rat tyrosine aminotransferase (Tyr AT), and (4) threonine dehydratase (TDH). The functional and evolutionary implications of the predictions are discussed. (1) The structural similarity between SKase and adenylate kinase was predicted. Alignment of their sequences reveals that the ATP-binding type A sequence motif and 2 ATP-binding arginine residues are conserved. The prediction suggests a similarity in their functional mechanisms as well as an evolutionary relationship. (2) The structural similarity between IIABMan and galactose/glucose-binding protein (GGBP) was predicted. The IIA and IIB domains are aligned with the N- and C-terminal domains of GGBP, respectively. The 2 phosphorylated residues, His 10 and His 175, of IIABMan are threaded onto loops located in the substrate-binding cleft of GGBP. The prediction accounts for the phosphoryl transfer from His 10 to His 175, and to the sugar substrate. (3) The structural similarity between rat Tyr AT and Escherichia coli aspartate AT was predicted, as well as (4) the structural similarity between TDH and the tryptophan synthase beta subunit. Predictions (3) and (4) support the previous predictions based on observations of the functional similarities between the proteins.     

The full expression of the ity phenotype in ityr mice requires C3 activation by Salmonella lipopolysaccharide

Our previous study has shown that the rapid and sufficient activation of complement by Salmonella lipopolysaccharide occurs in genetically resistant (Ityr) A/J mice. To assess whether the level of complement activation by a virulent strain of Salmonella typhimurium regulates the level of murine natural resistance, we compared levels of serum complement activation by S. typhimurium and kinetics of serum-opsonized S. typhimurium grown in macrophages using several strains of resistant (Ityr) and susceptible (Itys) mice. Itys macrophages killed intracellular S. typhimurium to the same extent as did Ityr macrophages when the pathogen was opsonized with Ityr serum. Opsonization of S. typhimurium with Itys serum reduced intracellular killing activity in Ityr macrophages to the same level as seen with Itys macrophages. Incubation of S. typhimurium with 25% Mg2+ EGTA (5 mm MgCl2-3 mm ethylene glycol-bis (beta-aminotheyl either)-N,N,N',N'-tetraacetic acid)-chelated Ityr serum resulted in higher levels of C3 deposition onto the surface of this bacteria, C3b generation and also C3 consumption, compared with that with Mg2+ EGTA-chelated Itys serum. Opsonization of S. typhimurium with A/J serum prior to infection increased early resistance in Itys mice. Infection with a virulent strain of S. typhimurium induced the expression of interleukin-10 (IL-10) mRNA at higher levels in C57BL/6 mice than in A/J mice. However, opsonization of S. typhimurium with A/J serum decreased bacterial growth in the spleen of C57BL/6 mice to the same level as observed for A/J mice in association with decreased expression levels of IL-10 mRNA. Moreover, administration of anti-C3 antibodies reduced the resistance of A/J mice in association with a decrease in serum levels of C3. These results indicate that the high level of complement activation via the alternative pathway in Ityr serum by a virulent strain of S. typhimurium reduces the virulence of this pathogen, which may contribute to the full expression of Ity phenotype in Ityr mice.     

Free D-serine, D-aspartate and D-alanine in central nervous system and serum in mutant mice lacking D-amino acid oxidase

We have examined whether D-amino acid oxidase (DAO) regulates free D-serine content using mutant ddY/DAO- mice lacking DAO activity. We find that the content of D-serine in the serum and cerebellum of mutant mice is much higher than that of normal mice, whereas a slight but significant difference in the cerebral D-serine level is observed between the two strains. These results suggest that, although DAO may participate in the catabolism of D-serine in the cerebellum and periphery, there appears to be other mechanisms for catabolism of endogenous D-serine in the brain.     

Conformational properties of the guanine-binding site of ribonuclease T1 inferred from the X-ray structure and protein engineering

Recognition by ribonuclease T₁ of guanine bases via multidentatehydrogen bonding and stacking interactions appears to be mediatedmainly by a short peptide segment formed by one stretch of aheptapeptide, Tyr⁴²-Asn⁴³-Asn⁴⁴-Tyr⁴⁵-Gly⁴⁶-Gly⁴⁷-Phe⁴⁸. Thesegment displays a unique folding of the polypeptide chain—consistingof a reverse turn, Asn⁴⁴-Tyr⁴⁵-Glu⁴⁶-Gly⁴⁷, stabilized by ahydrogen-bond network involving the side chain of Asn⁴⁴, themain-chain atoms of Asn⁴⁴, Gly⁴⁷ and Phe⁴⁸ and one water molecule.The segment is connected to the C terminus of a ß-strandand expands into a loop region between Asn⁴³ and Ser⁵⁴. Lowvalues for the crystallographic thermal parameters of the segmentindicate that the structure has a rigidity comparable to thatof a ß-pleated sheet. Replacement of Asn⁴⁴ with alanineleads to a far lower enzymatic activity and demonstrates thatthe side chain of Asn⁴⁴ plays a key role in polypeptide foldingin addition to a role in maintaining the segment structure.Substitution of Asn⁴³ by alanine to remove a weak hydrogen bondto the guanine base destabilized the transition state of thecomplex by 6.3 kJ/mol at 37°C. In contrast, mutation ofGlu⁴⁶ to alanine to remove a strong hydrogen bond to the guaninebase caused a destabilization of the complex by 14.0 kJ/mol.A double-mutant enzyme with substitutions of Asn⁴³ by a histidineand Asn⁴⁴ by an aspartic acid, to reproduce the natural substitutionsfound in ribonuclease M_s, showed an activity and base specificitysimilar to that of the wild-type ribonuclease M_s. The segmenttherefore appears to be well conserved in several fungal ribonucleases.     

KB-R7785, a novel matrix metalloproteinase inhibitor, exerts its antidiabetic effect by inhibiting tumor necrosis factor-alpha production

It has been suggested that tumor necrosis factor-alpha (TNF-alpha) is a key mediator of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). TNF-alpha is synthesized as a membrane-bound precursor; this is proteolytically processed to an active form by a matrix metalloproteinase (MMP)-like enzyme. In this study, we have used KKAy mice which show insulin resistance like NIDDM to investigate the effects of KB-R7785, a novel MMP inhibitor, on blood glucose and insulin levels. Subcutaneous administration of KB-R7785 at 100 mg/kg twice daily (i.e., 200 mg/kg/day) for 4 weeks resulted in a significant decrease in plasma glucose levels which was observed after 3 weeks. Oral administration of pioglitazone (20 mg/kg twice daily or 40 mg/kg/day for 4 weeks), an agent known to ameliorate insulin sensitivity, significantly decreased plasma glucose levels during the treatment period. KB-R7785, but not pioglitazone, also significantly decreased plasma insulin levels. Lipopolysaccharide (LPS) increased plasma TNF-alpha levels to a significantly greater degree in KKAy mice than in normal C57BL mice; this was inhibitable in KKAy mice by KB-R7785. In contrast, pioglitazone did not affect the LPS-induced increase in plasma TNF-alpha levels in KKAy mice. These results suggest that KB-R7785 exerts its antidiabetic effect by ameliorating insulin sensitivity through the inhibition of TNF-alpha production.     

S.A.W. right-angle reflection coefficient from metal strip array reflector on y-cut LiNbO3

The s.a.w. reflection coefficient of the metal strip has been measured on y-cut LiNbO3 for waves reflected through 90° from the z into the x direction. The maximum value of the reflection coefficient of a metal strip is 0.020, when the width/periodicity ratio of the metal strips is about 0.3.     

Comparative studies of glycoprotein Ib in heparin coated and nonheparin coated extracorporeal circulation circuits

Contact between blood and artificial materials has various effects on blood. Impairment of platelet function is an especially important and well known effect, but its precise mechanism is not clearly understood. The authors constructed a circulation model to investigate the effect of extracorporeal circulation on platelet membrane glycoproteins (GPs), especially GP Ib, and to compare the changes in GP Ib in heparin coated (group C) and nonheparin coated (group N) circuits. As determined by flow cytometry, GP Ib in both groups decreased on initiating circulation, but the decrease in group N was significantly larger than that in group C. There was no observed change in GP IIb/IIIa levels in either group. The extent of shear stress induced platelet aggregation significantly decreased during circulation in both groups. Decreases in the extent of shear stress induced platelet aggregation were significantly less with the use of heparin coated circuits. In addition, the amount of GP Ib in the high speed pellet decreased progressively during circulation in both groups. In contrast, the amount of GP Ib in the Triton insoluble (low speed) pellet increased dramatically during circulation. However, expression of GP Ib in the Triton soluble platelet fraction was low in both groups. From the results, it was concluded that the cause of the decrease in platelet function during extracorporeal circulation is attributable to the internalization of GP Ib from the platelet surface inside the platelet. It also can be said that a heparin coated circuit is one effective means of controlling this change.