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PubMed1991

Subjective evaluation of a prototype earmuff exhibiting flat and nonlinear attenuation characteristics.

Subjective user responses were obtained for a test earmuff exhibiting approximately flat (uniform) attenuation of about 25 dB from 500 to 8000 Hz for sound pressure levels (SPLs) less than 120 dB. At SPLs above 120 dB, the test earmuff exhibited nonlinear (level-dependent) attenuation characteristics such that noise reduction increased with increasing sound level. The study population consisted of police officers from the Raleigh, North Carolina, Police Department as they were performing arms requalification by executing a series of firing programs during two sequential and identical relays. The study subjects wore either the test earmuff or a comparable conventional earmuff during the first relay, then the alternate protector for the second relay with the order counterbalanced. Results indicated a significant preference for the test earmuff in three comparison areas: comfort, perceived hearing protection, and speech understanding. The study demonstrates that ammunition type and level of noise exposure contributed significantly to a preference in favor of the test earmuff. The subjects who used the quietest of the ammunition types rated the test earmuff significantly better than the remaining subjects with respect to speech understanding.

Adult↗
PubMed1998

Total and viable airborne bacterial load in two different agricultural environments using gas chromatography-tandem mass spectrometry and culture: a prototype study.

Airborne exposure to bacterial components found in agricultural environments can lead to pulmonary inflammation. Total (viable and nonviable) bacterial load was monitored in a stable and a dairy by a new approach, gas chromatography-tandem mass spectrometry measurement of muramic acid, a component of gram positive and gram negative bacterial peptidoglycan. Also used to assess the gram negative bacterial load were 3-hydroxy fatty acids, markers of bacterial lipopolysaccharide. Culture, an established procedure for assessing the viable bacterial portion of airborne dust, served as a basis for comparison. The muramic acid and 3-hydroxy fatty acid concentrations (total C12:0, C14:0, and C16:0) showed a correlation with an R2 of 0.81. Dust and muramic acid levels also correlated. However, although relative muramic acid levels were lower in the stable than the dairy, colony forming units (CFU) were considerably higher in the stable. The total bacterial load (estimated from muramic acid values) for both the stable and dairy was also higher than would have been predicted from culture. These results suggest that nonculture based approaches and culture provide complementary but independent measurements of airborne biopollution.

Agriculture↗
PubMedDate not supplied

4"-H-TSAO-T, a novel prototype in the HIV-1 specific TSAO family.

The first TSAO derivative that lacks the amino group at the 3'-spiro moiety has been prepared. This molecule retained its HIV-1 specificity (NNRTI characteristic) but did not select for any of the classical NNRTI-specific mutations in the NNRTI binding pocket, including 138-Lys (TSAO resistant strain).

Anti-HIV Agents↗
PubMed2003

Development and evaluation of a miniaturized procedure for determining the bonding index: a novel prototype for solid dosage formulation development.

The purpose of this study was a comparative evaluation of miniaturized vs. University of Minnesota's (i.e., U of Minn. = Hiestand's) procedures for determining the tensile strength, indentation hardness, and bonding index (BI), one out of three Indices of Tableting Performance (ITP). Tableting properties of six direct compression placebo formulations were determined by using a compaction simulator and a Texture Analyser TA-XT2I, or by following the U of Minn. method, which included a specially designed triaxial compression device, a computer-controlled mechanical stress-strain analyzer, and a dynamic pendulum impact apparatus. Miniaturization of the procedures to determine the ITP, as well as the ability to differentiate between materials while operating compaction cycles more comparable to standard tablet production conditions, enabled proper evaluation of each material's inherent tableting properties. Indentation diameter calculated via an empirical equation appeared to correlate well with, and provided acceptable precision of accuracy to, the determination of indentation diameter via standard optical microscopy methods. The miniaturized and U of Minn. procedure exhibited a significant degree of correlation when comparing the BI. However, the tensile strength and indentation hardness values were somewhat different due to the use of triaxial decompression for the U of Minn. procedure vs. standard compaction profiling for the miniaturized procedure. The present direct compression placebo formulation data gathered from the miniaturized procedures and compared with the U of Minn. method for determining the ITP suggest that both techniques yield similar conclusions. However, discrimination of out-of-die compaction properties determined via the miniaturized procedures, such as tensile strength and indentation hardness, appeared to associate more precisely with changes in strain rate, thus allowing better discrimination of particle-particle interactions and ductile-to-brittle characteristics as a function of compaction speed and pressure.

Chemistry, Pharmaceutical↗
PubMed1997

The Chlamydomonas mating type plus fertilization tubule, a prototypic cell fusion organelle: isolation, characterization, and in vitro adhesion to mating type minus gametes.

In the biflagellated alga Chlamydomonas, adhesion and fusion of the plasma membranes of gametes during fertilization occurs via an actin-filled, microvillus-like cell protrusion. Formation of this approximately 3-microm-long fusion organelle, the Chlamydomonas fertilization tubule, is induced in mating type plus (mt+) gametes during flagellar adhesion with mating type minus (mt-) gametes. Subsequent adhesion between the tip of the mt+ fertilization tubule and the apex of a mating structure on mt- gametes is followed rapidly by fusion of the plasma membranes and zygote formation. In this report, we describe the isolation and characterization of fertilization tubules from mt+ gametes activated for cell fusion. Fertilization tubules were detached by homogenization of activated mt+ gametes in an EGTA-containing buffer and purified by differential centrifugation followed by fractionation on sucrose and Percoll gradients. As determined by fluorescence microscopy of samples stained with a fluorescent probe for filamentous actin, the method yielded 2-3 x 10(6) fertilization tubules/microg protein, representing up to a 360-fold enrichment of these organelles. Examination by negative stain electron microscopy demonstrated that the purified fertilization tubules were morphologically indistinguishable from fertilization tubules on intact, activated mt+ gametes, retaining both the extracellular fringe and the internal array of actin filaments. Several proteins, including actin as well as two surface proteins identified by biotinylation studies, copurified with the fertilization tubules. Most importantly, the isolated mt+ fertilization tubules bound to the apical ends of activated mt- gametes between the two flagella, the site of the mt- mating structure; a single fertilization tubule bound per cell, binding was specific for gametes, and fertilization tubules isolated from trypsin-treated, activated mt+ gametes did not bind to activated mt- gametes.

Animals↗
PubMed1992

Prototype of dual energy x-ray tomodensimeter for lumbar spine bone mineral density measurement: choice of the reconstruction algorithm and first experimental results.

A dual-energy x-ray tomodensimeter adapted for the determination of bone mineral density (BMD) of the lumbar vertebrae has been directly developed from a typical dual-energy x-ray absorptiometer. This apparatus consists of two fundamental parts: a dual energy x-ray tube, and a multidetector made by an array of 24 NaI(T1) crystals. It provides both tomographic and non-tomographic (anteroposterior, lateral etc) measurement. The detection area is limited to 132 mm. In this condition, the choice of the best reconstruction algorithm in order to give a direct BDM is considered. Preliminary studies based on numerical simulated projections and hydroxyapatite phantoms demonstrated the superiority of algebraic reconstruction algorithms, such as conjugated gradient, in order to resolve the problems of (i) the impossibility of defining an internal calibration, and (ii) the potential for reconstruction errors due to the presence of bone structures located out of the detection area. The accuracy of BMD measurement is within 2%, with in vitro precision approximately 1%, and linearity characterized by a standard error of estimation (SEE) of 2 mg cm-3 in the range of lumbar BMD (less than 400 mg cm-3). Experimental data derived from two volunteers are presented.

Algorithms↗
PubMed1995

The experimental evaluation of a prototype rotating slat collimator for planar gamma camera imaging.

A collimator consisting of a series of parallel slats has been constructed and used in conjunction with a conventional gamma camera to collect one-dimensional projections of the radioisotope distribution being imaged. With the camera remaining stationary, the collimator was made to rotate continuously over the face of the detector and the projections acquired were used to reconstruct a planar image by the theory of computed tomography. The propagation of noise on image reconstruction was largely offset by the increased geometric efficiency that resulted from the enlarged solid angle of acceptance afforded by the slat collimator. For a uniform disc of activity the signal to noise ratio (SNR) at a point in an image reconstructed by convolution and backprojection is shown to be given by [formula:see text] and Q1(xi) is the one-dimensional filter function in Fourier space. Improved noise behaviour was observed for images acquired with the slat collimator compared to those acquired with a low-energy high-resolution (LEHR) collimator for small distributions of activity. Spatial resolution with the slat collimator was approximately equal to that obtained with an LEHR collimator and improved contrast was observed in images of small hot regions.

Biophysical Phenomena↗
PubMed2005

High-resolution imager for digital mammography: physical characterization of a prototype sensor.

The physical performance characteristics of a high-resolution sensor module for digital mammography were investigated. The signal response of the imager was measured at various detector entrance air kerma and was found to be linear. The spatial resolution was determined by measuring the presampling modulation transfer function, MTF(f), of the system. The noise power spectra, NPS(f), of the system were estimated using 26 kVp: Mo/Mo, 28 kVp: Mo/Rh and 30 kVp: Rh/Rh, with polymethyl methacrylate (PMMA) 'tissue equivalent material' of thickness 20, 45 and 57 mm for each of three x-ray spectra at detector entrance air kerma in the range between approximately 80.2 and 92.3 microGy. The noise equivalent quanta, NEQ(f), and detective quantum efficiencies, DQE(f), for the various spectral conditions were computed. In addition, dose dependence of NPS(f) and DQE(f) was studied at various detector entrance air kerma ranging from 9.4 to 169.7 microGy. A spatial resolution of about 10 cycles mm(-1) was obtained at the 10% MTF(f) level. A small increase in NEQ(f)was observed under higher energy spectral conditions while the DQE(f) decreased marginally. For a given spectrum, increasing PMMA filtration produced negligible change in DQE(f). The estimated DQE values at zero frequency were in the range between 0.45 and 0.55 under the conditions investigated in this study.

Equipment Design↗
PubMed2001

Prototype system for enhancing cystometric analysis with special emphasis on the pediatric population.

BACKGROUND AND PURPOSE: A urodynamic test system of improved accuracy and reliability was developed and implemented for enhancing cystometry. This system integrates known medical information, including the specialized problems of pediatric urodynamics, with the cystometric and imaging data. METHODS: After the requirements for the ideal cystometrogram test unit were established, a system was constructed, calibrated, and implemented in clinical practice. The patient's age, size, and sex are used to produce a patient-specific pressure-volume template for the cystometrogram test. RESULTS: This template showed the minimal and normal bladder capacities and the physiologically safe, equivocal, and dangerous pressure fields coded with symbolic colors. Different time averages of the pressure data were used to show bladder factors such as compliance and instability. The templates with data were presented automatically (therefore objectively) without operator intervention on monitors during testing and as printed copies on completion. CONCLUSIONS: The presentation of data in an easily understood format facilitates effective communication between the urologist, referring physician, and patient. Some of the physiological and statistical problems in pediatric urodynamic testing are efficiently and accurately resolved by this system, resulting in better analysis and diagnostic capabilities.

Automation↗
PubMed1990

Molecular differences between two immunologically related spumaretroviruses: the human prototype HSRV and the chimpanzee isolate SFV6.

A comparative study at the genomic and protein level was performed between two immunologically related spumaretroviruses, the human HSRV and the simian SFV6. Cross immunoprecipitation analysis with specific polyclonal and monoclonal antisera indicates shared antigenic determinants. However, restriction analysis of the viral DNAs and thermal stability of the hybrids demonstrate that HSRV and SFV6 are two different isolates.

Animals↗
PubMed1992

Nonnucleoside inhibitors of HIV-1 reverse transcriptase: nevirapine as a prototype drug.

Nevirapine, a dipyridodiazepinone, is a highly specific inhibitor of HIV-1 reverse transcriptase (RT) which exhibits an IC50 = 84nM in enzyme assays and IC50 = 40nM against HIV-1 replication in cell culture. This nonnucleoside inhibitor acts noncompetitively with respect to nucleoside triphosphates, template and primer suggesting that nevirapine does not bind to the active site of RT. Studies employing an azido analogue of nevirapine as a photoaffinity probe indicated that one molecule of inhibitor is sufficient to inactivate one molecule of heterodimeric enzyme and demonstrated that only the p66 subunit of p66/p51 heterodimeric RT is covalently labeled by this probe. When subjected to trypic mapping, Tyr 181 and Tyr 188 were labeled with probe and consequently these aromatic residues are apparently near or actually within the RT binding site for nevirapine. The extent to which Tyr 181 and Tyr 188 participate/contribute to nevirapine binding was determined by making amino acid substitutions at these positions using the corresponding residues from HIV-2 RT which is not sensitive to nevirapine. A change at either position dramatically decreased the enzymes' sensitivity to nevirapine, as well as to TIBO derivative and Merck L-693,593, indicating that both Tyr 181 and 188 are crucial for inhibitor-enzyme interaction. Cell culture selection in the continued presence of nevirapine results in the appearance of resistant HIV-1, Tyr 181 to Cys, raising the concern that combination drug therapy will be required in the clinic.

Amino Acid Sequence↗
PubMed1994

Immune responses induced by prototype vaccines for AIDS in rhesus monkeys.

A battery of assay systems was used to profile both humoral and cell-mediated immune responses induced by immunization with candidate vaccines consisting of recombinant simian immunodeficiency virus (SIV) glycoproteins rgp110 (nondenatured) with SAF-M adjuvant (gp110 + SAF-M) or rgp140 (denatured) with Freund's adjuvant (gp140 + FA). All of the monkeys became infected after intravenous challenge. However, 16 days following infection, viral antigenemia was reduced in both groups of vaccinates compared to controls. After 23 days antigenemia in the gp110 + SAF-M group remained at the same level as on day 16, whereas antigenemia in the gp140 + FA group was significantly reduced further than the level observed on day 16. Both vaccines induced blastogenic responses in PBMC cultures stimulated with rgp140, which decreased after repeated immunizations. Both vaccines induced high ELISA titers of IgG antibody against rgp140 that were equivalent to the titers in asymptomatic long-term survivors (LTSs). gp110 +/- SAF-M induced high titers of neutralizing antibody. In contrast, gp140 + FA failed to induce neutralizing antibody, suggesting that the natural conformation of the antigen may be essential for the induction of neutralizing antibody. High titers of antibodies capable of complement-mediated cytolysis (ACC) were induced by gp110 + SAF-M, whereas minimal ACC antibodies were induced by gp140 + FA. In spite of high titers of antibodies by ELISA, neither gp110 + SAF-M nor gp140 + FA vaccines induced detectable levels of antibody capable of antibody dependent cell-mediated cytolysis (ADCC). Detectable amounts of MHC class I-restricted, CD8+ cytotoxic T lymphocytes (CTLs) were not induced in immunized monkeys before challenge. After challenge and infection, antibody responses to glycoprotein (detected by ELISA and ACC) as well as glycoprotein-specific CTLs were induced in gp140 + FA vaccinates at levels higher than in nonimmunized control animals, indicating a priming effect by gp140 + FA immunization. No priming effect for ADCC antibody induction was observed in monkeys vaccinated with either gp110 + SAF-M or gp140 + FA. Rhesus monkey groups immunized with two different SIV envelope vaccines differed regarding potentially protective humoral and cell-mediated immune responses. The physical state of the immunogens, the type of adjuvant used, and/or the immunization protocol apparently affected these responses in both a qualitative and quantitative manner.

AIDS Vaccines↗
PubMed2005

Cryomacroscopy of vitrification, Part I: A prototype and experimental observations on the cocktails VS55 and DP6.

A new imaging device, termed a "cryomacroscope", is presented in this report. This device is designed to assist in exploring thermal and mechanical effects associated with large-scale vitrification and crystallization, with the current setup aimed at the range of 50 μm to 2 cm. The cryomacroscope is not intended as a substitute for the cryomicroscope, but as a complementary tool for the cryobiologist. A combination of cryomacroscopy and cryomicroscopy is suggested as a basis for multi-scale cryobiology studies. This report presents initial results on vitrification, crystallization, and fracture formation in the cryoprotectant cocktails DP6 and VS55. These results show some inconsistency in the tendency to form crystals, based on critical cooling and rewarming rates measured by means of a differential scanning calorimetric device (DSC) in parallel studies. This research is in its early stages, and comparative studies on biological materials are currently underway. Part II of this report (the companion paper) presents results for fracture formation in the cryoprotectant and discusses the mechanical stresses which promote these fractures. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

Journal Article↗
PubMed1998

An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery.

We have synthesized a linear, bifunctional peptide that comprises an integrin-targeting domain containing an arginine-glycine-aspartic acid tripeptide motif and a DNA-binding moiety consisting of a short stretch of 16 lysine residues. This peptide can form distinctive, condensed complexes with DNA and is capable of mediating its delivery and expression in a variety of mammalian cells in culture. Internalization is mediated by cell surface integrin receptors via a mechanism that is known to be phagocytic. We have analyzed the relationship between DNA and peptide and have investigated the conditions suitable for optimal gene delivery. The formation of condensed peptide DNA complexes leads to resistance to nuclease degradation. The level of reporter gene expression obtained is dependent on the peptide-to-DNA ratio and is enhanced in the presence of the endosomal buffer chloroquine, polyethyleneimine, and deactivated adenovirus during gene delivery. Under optimal conditions the levels of reporter gene expression obtained approach or even exceed those obtained with DNA delivered with the commercial liposome Lipofectamine. The ability to produce an efficient gene delivery system using small, easily modified, and well-defined constructs that have no constraint of particle size demonstrates the advantages of integrin-targeting peptides for gene transfer.

3T3 Cells↗
PubMed2005

A prototype prophylactic anti-influenza preparation in aerosol form on the basis of Abies sibirica polyprenols.

This research investigates a promising antiviral compound based on polyprenols from Siberian silver fir (Abies sibirica). The physico-chemical characteristics of a preparation developed in aerosol form and an estimation of its protective efficacy against aerosol challenge of laboratory animals are presented. It is shown that (1) by using a simple ultrasonic disperser one can obtain aerosol of three formulations studied with about 70% of its mass accumulated in the size range below 1.8 microm; (2) 40-100% of aerosol particles contain preparation for different formulations; (3) after delivering under specified schedules, the preparations as developed can protect up to 100% of mice against 5 LD(50) of influenza A/Aichi/2/68 (H3N2) virus aerosol infection. Animals inhaled twice the preparation doses (which were 100 times lower than injection ones of the same efficacy) and did not exceed 10 microg/mouse. It was shown that the mode of action of this immunomodulating preparation was nonspecific stimulation of immune cells' various activities.

Abies↗