A novel nonpeptide HIV-1 protease inhibitor: elucidation of the binding mode and its application in the design of related analogs.

HIV-1 protease has been identified as a significant target enzyme in AIDS research. While numerous peptide-derived inhibitors have been described, the identification of a nonpeptide inhibitor remains an important goal. Using an HIV-1 protease mass screening technique, 4-hydroxy-3-(3-phenoxypropyl)-2H-1-benzopyran-2-one (1) was identified as a nonpeptide competitive inhibitor of the enzyme. Employing a Monte Carlo-based docking procedure, the coumarin was docked in the active site of the enzyme, revealing a binding mode that was later confirmed by the X-ray crystal analysis. Several analogs were prepared to test the binding interactions and improve the overall binding affinity. The most active compound in the study was 4,7-dihydroxy-3-[4-(2-methoxyphenyl)butyl]-2H-1-benzopyran-2-one (31).

Formation of the local secondary structure of proteins: local sequence or environment.

An analysis of the occurrence of tetrapeptides in 35 globular proteins for alpha-helix, beta-structure and coil was performed. We concluded that: the conformation of a short polypeptide segment cannot be determined on the basis of the knowledge of the amino acid sequence only; local structures of a protein are formed as the result of interactions within the whole structural domain of the protein as well as interactions with the environment.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases. IV. Enthalpies of hydration of 5-alkyluracils.

Enthalpies of sublimation, DeltaH degrees (subl) and of solution in water, DeltaH degrees (sol) were determined for a series of crystalline 1,3-dimethyl-uracil derivatives substituted at the C5-ring carbon atom with alkyl groups (-C(n)H(2n+1), n = 2-4) and some of their C(5.6)-cyclooligomethylene analogues (-(CH2)(n)-, n = 3-5). From these data. enthalpies of hydration DeltaH degrees (hydr)= DeltaH degrees (sol) - DeltaH degrees (subl) were calculated and corrected for energies of cavity formation in pure liquid water in order to obtain enthalpies of interaction, DeltaH degrees (int) of the solutes with their hydration shells. The latter are discussed together with the recalculated DeltaH degrees (int) for variously methylated uracils, obtained previously according to a simplified correction procedure, in terms of perturbations in the energy and scheme of hydration of the diketopyrimidine ring brought about by alkyl substitution. It was found that each -CH2-group added with an alkyl substitution contributes favorably about -20 kJ mol(-1) toDeltaH degrees (int). This contribution is partially cancelled by the unfavorable contribution to DeltaH degrees (int) connected with removal of some water molecules bound in the first and subsequent hydration layers by an alkyl substituent. This is particularly evident on substitution at the polar side of the diketopyrimidine ring on which water molecules are expected to be bound specifically.

An observation on quartz resonator aging.

Aging and acceleration sensitivity of certain fabrication lots of quartz resonators show a trend that may arise from a common predominating mechanism, such as stresses arising from the mounting structure. The presence or absence of such a trend is discussed. As part of the work on bulk-acoustic-wave (BAW) resonators, a database of all known parameters of the resonators in question was assembled. Resonator processing and electrical parameters were examined for correlations with the acceleration sensitivity. A similar effort was being undertaken in regard to resonator aging, and possible correlations between the aging and acceleration sensitivities of the various resonators were examined. The results for two such fabrication lots are shown. The magnitude of the observed aging was typically in the 10(-10) per day range. The identity of the common contributor is unknown at the present time. It is likely that mounting related stresses are the common contributor.

Electrode-induced nonuniformities in the sweeping of alpha quartz.

Infrared absorption and scanning electron microscopic techniques show that color-center and/or electrode-metal introduction into quartz is influenced by the porosity of evaporated metal electrodes. Thermal-stress relief of electrode-metal films, during sweeping, normally causes porosity. If the porosity is extensive, H introduction predominates and color-center and electrode-metal introduction mechanisms are suppressed. Samples swept with evaporated Au/Cr electrodes relying on thermal stress-induced porosity sometimes displayed these sweeping nonuniformities. Nonuniformities were not found when samples were swept using evaporated Au-Cr electrodes containing periodic stripe openings. Uniform sweeping was also obtained using magnetron-sputtered amorphous Y-Ba-Cu-O films.

Designing for low acceleration sensitivity.

Recent advances in acceleration sensitivity measurement and modeling are discussed, with an emphasis on what these advances indicate in terms of designing for low acceleration sensitivity. The design suggestions are separated into two parts, namely, those that use the crystal resonator as a mechanical vibrator and those that use the crystal oscillator as an electronic circuit. Such topics as symmetry considerations, metallization, mounting etc., in both bulk acoustic wave (BAW) and surface acoustic wave (SAW) devices are discussed for the former, while for the latter the equivalent circuit modeling of crystal resonators and other loop components is addressed.

Theory and design of piezoelectric resonators immune to acceleration: present state of the art.

A typical low noise oscillator uses a crystal resonator as the frequency-determining element. An understanding of the fundamental nature of acceleration sensitivity in crystal oscillators resides primarily in understanding the behavior of the crystal resonator. The driving factor behind the acceleration-induced frequency shift is shown to be deformation of the resonator. The deformation drives two effects: an essentially linear change in the frequency-determining dimensions of the resonator and an essentially nonlinear effect of changing the velocity of the propagating wave. In this paper, the fundamental nature of acceleration sensitivity is reviewed and clarified, and attendant design guidance is developed for piezoelectric resonators. The basic properties of acceleration sensitivity and general design guidance are developed through the simple examples of "bulk acoustic wave (BAW) in a box" and "surface transverse wave (STW) in a box." These examples serve to clarify a number of concepts, including the role of mode shape and the basic difference between the BAW and STW cases. The design equations clarify the functional dependencies of the acceleration sensitivities on the full range of crystal resonator design and fabrication parameters.

Lithium tetraborate transducers.

Lithium tetraborate is a tetragonal material of considerable promise for frequency control and signal processing applications. It exhibits piezoelectric coupling values that fall between those of lithium niobate and quartz, but possesses orientations for which the temperature coefficient of frequency and delay time is zero for bulk and surface acoustic waves. The properties of two doubly rotated bulk wave resonator orientations having first- and second-order temperature coefficients equal to zero are discussed. These are suitable for shear and compressional wave transducers in applications where very low temperature sensitivity is required simultaneously with moderately strong piezocoupling coefficients.

Measured properties of doubly rotated dilithium tetraborate (Li(2)B(4)BO(7)) resonators and transducers.

Dilithium tetraborate plates, cut to the nominal angles of cut of (YXwl)40 degrees /33 degrees (TA-cut) and (YXwl)19 degrees /56 degrees (TC-cut), have been supplied by a crystal grower and have been processed into plate resonators. The mode spectra and electrical circuit parameters of the resonators have been examined for the fundamental, third, and fifth harmonics for all three thickness modes of the resonators. The observed values of frequency constants and piezoelectric coupling are in good agreement with the predicted values. The frequency-temperature behavior of the zero-temperature coefficient cuts has also been measured.

Pure-mode loci in piezoelectric plate resonators: application to materials evaluation in class 4 mm.

The accuracy of piezoelectric material evaluations can be enhanced by the use of pure-mode orientations, provided that exact analytic expressions for the pure-mode eigenvalues are known. The accuracy is enhanced by eliminating the need to extract constants from the differences in sums and products of measured quantities. It is necessary to adopt an approach for determining pure-mode loci in piezoelectric crystals which yields simple analytic expressions for the stiffness eigenvalues and provides a convenient engineering methodology for pure-mode sample set selection. The theory of simple thickness modes in piezoelectric plate vibrators is reviewed. The determination of pure-mode loci and its application to pure-mode sample set selection for dilithium tetraborate are presented. Thickness- and lateral-field excitation considerations are discussed.

Thermoelastic coefficients of alpha quartz.

Experimental measurements of alpha quartz thermal expansion as reported in the literature have been critically analyzed. A recommended set of best measured values over the temperature range -50 degrees C to +150 degrees C have been determined, as have values for the coefficient of thermal linear expansion (CTE) and the thermoelastic coefficients. The impact of using the coefficients on determinations of quartz material temperature coefficients and on the calculation of temperature coefficients of frequency for the case of the AT-cut is discussed.

A micromachined vibration isolation system for reducing the vibration sensitivity of surface transverse wave resonators.

A micromachined system has been developed for reducing the vibration sensitivity of surface transverse wave (STW) resonators. The isolation system consists of a support platform for mounting the STW resonator, four support arms, and a support rim. The entire isolation system measures 8 mm by 9 mm by 0.4 mm without the resonator mounted on the platform. The system acts as a passive vibration isolation system, decreasing the magnitude of high frequency (>1.2 kHz) vibrations. Finite element analysis is used to analyze the acceleration sensitivity of the mounted resonator. The isolation system is then modeled as a damped mass-spring system and the transmissibility of vibration from the support rim to the support platform is calculated. Multiplying the acceleration sensitivity of the resonator by the transmissibility results in the expected system vibration sensitivity. The isolation systems are fabricated using two sided bulk etching of (110) oriented silicon wafers. STW resonators were mounted on the isolation systems, and the isolated units were mounted on commercial hybrid oscillator substrates. Vibration sensitivity measurements were taken for vibrations with frequencies ranging from 100 Hz to 5 kHz. The measured data show that the system performs as expected with a low frequency (<500 Hz) vibration sensitivity of 1.8x10(-8)/g and a high frequency roll off of 12 dB/octave.

A multi-IDT input tunable surface acoustic wave filter.

Tunable surface acoustic wave (SAW) filters (TSF) have been widely used in the wireless telecommunication systems. A prototype of a multi-IDT (interdigital transducer) input TSF has been developed. The device consists of 11 IDT paralleled in the SAW propagation path. Different SAW filter configurations are realized by selecting or combining various IDTs, resulting in the tunability of both center frequency and 3 dB bandwidth. The center frequencies of the SAW filter range from 126.8 to 199.1 MHz; the 3 dB bandwidths range from 15.2 to 58.9 MHz. Impedance weighting methods have been applied. The passband ripple has been reduced from 6.44 to 1.37 dB after resistance weighting.

Determination of cross-reactant drugs with a new morphine radioimmunoassay procedure.

A study to determine the specificity of a new morphine radioimmunoassay (RIA) procedure was performed on 23 drugs of forensic science interest. Spiked whole blood and urine specimens were analyzed and the apparent morphine concentrations determined. All compounds analyzed showed low cross-reactivity, indicating a high specificity for morphine.

Perceived barriers to childhood immunization: a physician and parent survey in a southeastern urban/rural community.

PURPOSE: To identify physicians' and parents' perceptions of barriers to completing the immunization process by age 24 months. METHODS: A questionnaire hand-delivered to 110 physicians who treat children yielded a response rate of 83%. A telephone survey conducted with parents of a random sample of 2,100 children younger than three years of age selected from the county birth records yielded an adjusted response rate of 87%. RESULTS: Physicians' response fell into two categories: those with more and less than 90% up-to-date immunizations. Those with less than 90% indicated that parental knowledge is the primary reason. Those with more than 90% reported telephone follow-up for missed appointments. The top three barriers reported by parents; (1) waiting time at the clinic (33%), (2) child too ill at time of appointment (21%), and (3) insurance does not cover immunizations (16%). CONCLUSIONS: There is an opportunity for education intervention with physicians, policy makers, and parents in several key areas: (1) fact-based contraindications to immunizations, (2) effective means of follow-up, (3) accessibility to immunization for the under-insured, and (4) parental responsibility.

Apparatus for measurement of acoustic wave propagation under uniaxial loading with application to measurement of third-order elastic constants of piezoelectric single crystals.

We describe an apparatus for the measurement of acoustic wave propagation under uniaxial loading featuring a special mechanism designed to assure a uniform mechanical load on a cube-shaped sample of piezoelectric material. We demonstrate the utility of the apparatus by determining the effects of stresses on acoustic wave speed, which forms a foundation for the final determination of the third-order elastic constants of langasite and langatate single crystals. The transit time method is used to determine changes in acoustic wave velocity as the loading is varied. In order to minimize error and improve the accuracy of the wave speed measurements, the cross correlation method is used to determine the small changes in the time of flight. Typical experimental results are presented and discussed.